Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi

Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessmentmore » by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo, the relationship between radial SOS and cortical porosity can be utilized and a porosity based radial SOS estimate could be implemented to determine cortical thickness. This would constitute a step toward individualized quantitative ultrasound diagnostics of osteoporosis.« less

Cranial electrotherapy stimulation and transcranial pulsed current stimulation: a computer based high-resolution modeling study.

PubMed

Datta, Abhishek; Dmochowski, Jacek P; Guleyupoglu, Berkan; Bikson, Marom; Fregni, Felipe

2013-01-15

The field of non-invasive brain stimulation has developed significantly over the last two decades. Though two techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)--are becoming established tools for research in neuroscience and for some clinical applications, related techniques that also show some promising clinical results have not been developed at the same pace. One of these related techniques is cranial electrotherapy stimulation (CES), a class of transcranial pulsed current stimulation (tPCS). In order to understand further the mechanisms of CES, we aimed to model CES using a magnetic resonance imaging (MRI)-derived finite element head model including cortical and also subcortical structures. Cortical electric field (current density) peak intensities and distributions were analyzed. We evaluated different electrode configurations of CES including in-ear and over-ear montages. Our results confirm that significant amounts of current pass the skull and reach cortical and subcortical structures. In addition, depending on the montage, induced currents at subcortical areas, such as midbrain, pons, thalamus and hypothalamus are of similar magnitude than that of cortical areas. Incremental variations of electrode position on the head surface also influence which cortical regions are modulated. The high-resolution modeling predictions suggest that details of electrode montage influence current flow through superficial and deep structures. Finally we present laptop based methods for tPCS dose design using dominant frequency and spherical models. These modeling predictions and tools are the first step to advance rational and optimized use of tPCS and CES. Copyright © 2012 Elsevier Inc. All rights reserved.

Validation of cortical bone mineral density distribution using micro-computed tomography.

PubMed

Mashiatulla, Maleeha; Ross, Ryan D; Sumner, D Rick

2017-06-01

Changes in the bone mineral density distribution (BMDD), due to disease or drugs, can alter whole bone mechanical properties such as strength, stiffness and toughness. The methods currently available for assessing BMDD are destructive and two-dimensional. Micro-computed tomography (μCT) has been used extensively to quantify the three-dimensional geometry of bone and to measure the mean degree of mineralization, commonly called the tissue mineral density (TMD). The TMD measurement has been validated to ash density; however parameters describing the frequency distribution of TMD have not yet been validated. In the current study we tested the ability of μCT to estimate six BMDD parameters: mean, heterogeneity (assessed by the full-width-at-half-maximum (FWHM) and the coefficient of variation (CoV)), the upper and lower 5% cutoffs of the frequency distribution, and peak mineralization) in rat sized femoral cortical bone samples. We used backscatter scanning electron microscopy (bSEM) as the standard. Aluminum and hydroxyapatite phantoms were used to identify optimal scanner settings (70kVp, and 57μA, with a 1500ms integration time). When using hydroxyapatite samples that spanned a broad range of mineralization levels, high correlations were found between μCT and bSEM for all BMDD parameters (R 2 ≥0.92, p<0.010). When using cortical bone samples from rats and various species machined to mimic rat cortical bone geometry, significant correlations between μCT and bSEM were found for mean mineralization (R 2 =0.65, p<0.001), peak mineralization (R 2 =0.61, p<0.001) the lower 5% cutoff (R 2 =0.62, p<0.001) and the upper 5% cutoff (R 2 =0.33, p=0.021), but not for heterogeneity, measured by FWHM (R 2 =0.05, p=0.412) and CoV (R 2 =0.04, p=0.469). Thus, while mean mineralization and most parameters used to characterize the BMDD can be assessed with μCT in rat sized cortical bone samples, caution should be used when reporting the heterogeneity. Copyright © 2017 Elsevier Inc. All rights reserved.

HttQ111/+ Huntington's Disease Knock-in Mice Exhibit Brain Region-Specific Morphological Changes and Synaptic Dysfunction.

PubMed

Kovalenko, Marina; Milnerwood, Austen; Giordano, James; St Claire, Jason; Guide, Jolene R; Stromberg, Mary; Gillis, Tammy; Sapp, Ellen; DiFiglia, Marian; MacDonald, Marcy E; Carroll, Jeffrey B; Lee, Jong-Min; Tappan, Susan; Raymond, Lynn; Wheeler, Vanessa C

2018-01-01

Successful disease-modifying therapy for Huntington's disease (HD) will require therapeutic intervention early in the pathogenic process. Achieving this goal requires identifying phenotypes that are proximal to the HTT CAG repeat expansion. To use Htt CAG knock-in mice, precise genetic replicas of the HTT mutation in patients, as models to study proximal disease events. Using cohorts of B6J.HttQ111/+ mice from 2 to 18 months of age, we analyzed pathological markers, including immunohistochemistry, brain regional volumes and cortical thickness, CAG instability, electron microscopy of striatal synapses, and acute slice electrophysiology to record glutamatergic transmission at striatal synapses. We also incorporated a diet perturbation paradigm for some of these analyses. B6J.HttQ111/+ mice did not exhibit significant neurodegeneration or gliosis but revealed decreased striatal DARPP-32 as well as subtle but regional-specific changes in brain volumes and cortical thickness that parallel those in HD patients. Ultrastructural analyses of the striatum showed reduced synapse density, increased postsynaptic density thickness and increased synaptic cleft width. Acute slice electrophysiology showed alterations in spontaneous AMPA receptor-mediated postsynaptic currents, evoked NMDA receptor-mediated excitatory postsynaptic currents, and elevated extrasynaptic NMDA currents. Diet influenced cortical thickness, but did not impact somatic CAG expansion, nor did it show any significant interaction with genotype on immunohistochemical, brain volume or cortical thickness measures. These data show that a single HttQ111 allele is sufficient to elicit brain region-specific morphological changes and early neuronal dysfunction, highlighting an insidious disease process already apparent in the first few months of life.

The Effect of Transcranial Direct Current Stimulation (tDCS) Electrode Size and Current Intensity on Motor Cortical Excitability: Evidence From Single and Repeated Sessions.

PubMed

Ho, Kerrie-Anne; Taylor, Janet L; Chew, Taariq; Gálvez, Verònica; Alonzo, Angelo; Bai, Siwei; Dokos, Socrates; Loo, Colleen K

2016-01-01

Current density is considered an important factor in determining the outcomes of tDCS, and is determined by the current intensity and electrode size. Previous studies examining the effect of these parameters on motor cortical excitability with small sample sizes reported mixed results. This study examined the effect of current intensity (1 mA, 2 mA) and electrode size (16 cm(2), 35 cm(2)) on motor cortical excitability over single and repeated tDCS sessions. Data from seven studies in 89 healthy participants were pooled for analysis. Single-session data were analyzed using mixed effects models and repeated-session data were analyzed using mixed design analyses of variance. Computational modeling was used to examine the electric field generated. The magnitude of increases in excitability after anodal tDCS was modest. For single-session tDCS, the 35 cm(2) electrodes produced greater increases in cortical excitability compared to the 16 cm(2) electrodes. There were no differences in the magnitude of cortical excitation produced by 1 mA and 2 mA tDCS. The repeated-sessions data also showed that there were greater increases in excitability with the 35 cm(2) electrodes. Further, repeated sessions of tDCS with the 35 cm(2) electrodes resulted in a cumulative increase in cortical excitability. Computational modeling predicted higher electric field at the motor hotspot for the 35 cm(2) electrodes. 2 mA tDCS does not necessarily produce larger effects than 1 mA tDCS in healthy participants. Careful consideration should be given to the exact positioning, size and orientation of tDCS electrodes relative to cortical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

Mismatch Negativity with Visual-only and Audiovisual Speech

PubMed Central

Ponton, Curtis W.; Bernstein, Lynne E.; Auer, Edward T.

2009-01-01

The functional organization of cortical speech processing is thought to be hierarchical, increasing in complexity and proceeding from primary sensory areas centrifugally. The current study used the mismatch negativity (MMN) obtained with electrophysiology (EEG) to investigate the early latency period of visual speech processing under both visual-only (VO) and audiovisual (AV) conditions. Current density reconstruction (CDR) methods were used to model the cortical MMN generator locations. MMNs were obtained with VO and AV speech stimuli at early latencies (approximately 82-87 ms peak in time waveforms relative to the acoustic onset) and in regions of the right lateral temporal and parietal cortices. Latencies were consistent with bottom-up processing of the visible stimuli. We suggest that a visual pathway extracts phonetic cues from visible speech, and that previously reported effects of AV speech in classical early auditory areas, given later reported latencies, could be attributable to modulatory feedback from visual phonetic processing. PMID:19404730

Striate cortical contribution to the transcorneal electrically evoked response of the visual system.

PubMed

Shimazu, K; Miyake, Y; Fukatsu, Y; Watanabe, S

1996-01-01

Analyses of current-source-density (CSD) and multiple unit activity (MUA) in area 17 of the cat were performed to determine the sources of the cortical transcorneal electrically evoked response. Cortical field potential, CSD and MUA profiles were obtained with multi-electrodes. CSD findings include: current sinks (inward cell membrane current) within 20 ms latency, in layers 4 and 6 of the striate cortex; current sinks corresponding to N3 (negative component of the EER; latency, 35 ms) in layer 4 and lower layer 3 with current sources (outward cell membrane current) for N3 in the supragranular layers; current sinks with latency over 40 ms in the supragranular layers. In the layers 4 and 6, simultaneous MUA was seen. When the stimulus frequency was increased or with dual stimulation, the N3 current sinks were decreased. This indicates that N1 (latency, 9 ms) and N2 (latency, 20 ms) reflect near-field potentials in layers 4 and 6, generated by geniculocortical afferents, and that N3 is a post- and polysynaptic component. It is also suggested that dipoles composed of cell bodies and the apical dendrites of pyramidal cells of layer 3, generated by satellite cells in layer 4, play a major role in generating N3.

HttQ111/+ Huntington’s Disease Knock-in Mice Exhibit Brain Region-Specific Morphological Changes and Synaptic Dysfunction

PubMed Central

Kovalenko, Marina; Milnerwood, Austen; Giordano, James; St. Claire, Jason; Guide, Jolene R.; Stromberg, Mary; Gillis, Tammy; Sapp, Ellen; DiFiglia, Marian; MacDonald, Marcy E.; Carroll, Jeffrey B.; Lee, Jong-Min; Tappan, Susan; Raymond, Lynn; Wheeler, Vanessa C.

2018-01-01

Background: Successful disease-modifying therapy for Huntington’s disease (HD) will require therapeutic intervention early in the pathogenic process. Achieving this goal requires identifying phenotypes that are proximal to the HTT CAG repeat expansion. Objective: To use Htt CAG knock-in mice, precise genetic replicas of the HTT mutation in patients, as models to study proximal disease events. Methods: Using cohorts of B6J.HttQ111/+ mice from 2 to 18 months of age, we analyzed pathological markers, including immunohistochemistry, brain regional volumes and cortical thickness, CAG instability, electron microscopy of striatal synapses, and acute slice electrophysiology to record glutamatergic transmission at striatal synapses. We also incorporated a diet perturbation paradigm for some of these analyses. Results: B6J.HttQ111/+ mice did not exhibit significant neurodegeneration or gliosis but revealed decreased striatal DARPP-32 as well as subtle but regional-specific changes in brain volumes and cortical thickness that parallel those in HD patients. Ultrastructural analyses of the striatum showed reduced synapse density, increased postsynaptic density thickness and increased synaptic cleft width. Acute slice electrophysiology showed alterations in spontaneous AMPA receptor-mediated postsynaptic currents, evoked NMDA receptor-mediated excitatory postsynaptic currents, and elevated extrasynaptic NMDA currents. Diet influenced cortical thickness, but did not impact somatic CAG expansion, nor did it show any significant interaction with genotype on immunohistochemical, brain volume or cortical thickness measures. Conclusions: These data show that a single HttQ111 allele is sufficient to elicit brain region-specific morphological changes and early neuronal dysfunction, highlighting an insidious disease process already apparent in the first few months of life. PMID:29480209

Estimation of skull table thickness with clinical CT and validation with microCT.

PubMed

Lillie, Elizabeth M; Urban, Jillian E; Weaver, Ashley A; Powers, Alexander K; Stitzel, Joel D

2015-01-01

Brain injuries resulting from motor vehicle crashes (MVC) are extremely common yet the details of the mechanism of injury remain to be well characterized. Skull deformation is believed to be a contributing factor to some types of traumatic brain injury (TBI). Understanding biomechanical contributors to skull deformation would provide further insight into the mechanism of head injury resulting from blunt trauma. In particular, skull thickness is thought be a very important factor governing deformation of the skull and its propensity for fracture. Current computed tomography (CT) technology is limited in its ability to accurately measure cortical thickness using standard techniques. A method to evaluate cortical thickness using cortical density measured from CT data has been developed previously. This effort validates this technique for measurement of skull table thickness in clinical head CT scans using two postmortem human specimens. Bone samples were harvested from the skulls of two cadavers and scanned with microCT to evaluate the accuracy of the estimated cortical thickness measured from clinical CT. Clinical scans were collected at 0.488 and 0.625 mm in plane resolution with 0.625 mm thickness. The overall cortical thickness error was determined to be 0.078 ± 0.58 mm for cortical samples thinner than 4 mm. It was determined that 91.3% of these differences fell within the scanner resolution. Color maps of clinical CT thickness estimations are comparable to color maps of microCT thickness measurements, indicating good quantitative agreement. These data confirm that the cortical density algorithm successfully estimates skull table thickness from clinical CT scans. The application of this technique to clinical CT scans enables evaluation of cortical thickness in population-based studies. © 2014 Anatomical Society.

Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study

PubMed Central

Stathopoulos, K.D.; Zoubos, A.B.; Papaioannou, N.A.; Mastrokalos, D.; Galanos, A.; Papagelopoulos, P.J.; Skarantavos, G.

2016-01-01

Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20-79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI). Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID:27282455

Computational modeling of epidural cortical stimulation

NASA Astrophysics Data System (ADS)

Wongsarnpigoon, Amorn; Grill, Warren M.

2008-12-01

Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

Influence of cortical synaptic input on striatal neuronal dendritic arborization and sensitivity to excitotoxicity in corticostriatal coculture.

PubMed

Buren, Caodu; Tu, Gaqi; Parsons, Matthew P; Sepers, Marja D; Raymond, Lynn A

2016-08-01

Corticostriatal cocultures are utilized to recapitulate the cortex-striatum connection in vitro as a convenient model to investigate the development, function, and regulation of synapses formed between cortical and striatal neurons. However, optimization of this dissociated neuronal system to more closely reproduce in vivo circuits has not yet been explored. We studied the effect of varying the plating ratio of cortical to striatal neurons on striatal spiny projection neuron (SPN) characteristics in primary neuronal cocultures. Despite the large difference in cortical-striatal neuron ratio (1:1 vs. 1:3) at day of plating, by 18 days in vitro the difference became modest (∼25% lower cortical-striatal neuron ratio in 1:3 cocultures) and the neuronal density was lower in the 1:3 cocultures, indicating enhanced loss of striatal SPNs. Comparing SPNs in cocultures plated at a 1:1 vs. 1:3 ratio, we found that resting membrane potential, input resistance, current injection-induced action potential firing rates, and input-output curves were similar in the two conditions. However, SPNs in the cocultures plated at the lower cortical ratio exhibited reduced membrane capacitance along with significantly shorter total dendritic length, decreased dendritic complexity, and fewer excitatory synapses, consistent with their trend toward reduced miniature excitatory postsynaptic current frequency. Strikingly, the proportion of NMDA receptors found extrasynaptically in recordings from SPNs was significantly higher in the less cortical coculture. Consistently, SPNs in cocultures with reduced cortical input showed decreased basal pro-survival signaling through cAMP response element binding protein and enhanced sensitivity to NMDA-induced apoptosis. Altogether, our study indicates that abundance of cortical input regulates SPN dendritic arborization and survival/death signaling. Copyright © 2016 the American Physiological Society.

Automated MRI segmentation for individualized modeling of current flow in the human head.

PubMed

Huang, Yu; Dmochowski, Jacek P; Su, Yuzhuo; Datta, Abhishek; Rorden, Christopher; Parra, Lucas C

2013-12-01

High-definition transcranial direct current stimulation (HD-tDCS) and high-density electroencephalography require accurate models of current flow for precise targeting and current source reconstruction. At a minimum, such modeling must capture the idiosyncratic anatomy of the brain, cerebrospinal fluid (CSF) and skull for each individual subject. Currently, the process to build such high-resolution individualized models from structural magnetic resonance images requires labor-intensive manual segmentation, even when utilizing available automated segmentation tools. Also, accurate placement of many high-density electrodes on an individual scalp is a tedious procedure. The goal was to develop fully automated techniques to reduce the manual effort in such a modeling process. A fully automated segmentation technique based on Statical Parametric Mapping 8, including an improved tissue probability map and an automated correction routine for segmentation errors, was developed, along with an automated electrode placement tool for high-density arrays. The performance of these automated routines was evaluated against results from manual segmentation on four healthy subjects and seven stroke patients. The criteria include segmentation accuracy, the difference of current flow distributions in resulting HD-tDCS models and the optimized current flow intensities on cortical targets. The segmentation tool can segment out not just the brain but also provide accurate results for CSF, skull and other soft tissues with a field of view extending to the neck. Compared to manual results, automated segmentation deviates by only 7% and 18% for normal and stroke subjects, respectively. The predicted electric fields in the brain deviate by 12% and 29% respectively, which is well within the variability observed for various modeling choices. Finally, optimized current flow intensities on cortical targets do not differ significantly. Fully automated individualized modeling may now be feasible for large-sample EEG research studies and tDCS clinical trials.

ASSOCIATION BETWEEN NON-ENZYMATIC GLYCATION, RESORPTION, AND MICRODAMAGE IN HUMAN TIBIAL CORTICES

PubMed Central

Karim, Lamya; Diab, Tamim; Vashishth, Deepak

2015-01-01

Purpose/Introduction Changes in the quality of bone material contribute significantly to bone fragility. In order to establish a better understanding of the interaction of the different components of bone quality and their influence on bone fragility we investigated the relationship between non-enzymatic glycation, resorption, and microdamage generated in vivo in cortical bone using bone specimens from the same donors. Methods Total fluorescent advanced glycation end-products (AGEs) were measured in 96 human cortical bone samples from 83 donors. Resorption pit density, average resorption pit area, and percent resorption area were quantified in samples from 48 common donors with AGE measurements. Linear microcrack density and diffuse damage were measured in 21 common donors with AGE and resorption measurements. Correlation analyses were performed between all measured variables to establish the relationships among them and their variation with age. Results We found that average resorption pit area and percent resorption area decreased with increasing AGEs independently of age. Resorption pit density and percent resorption area demonstrated negative age-adjusted correlation with diffuse damage. Furthermore, average resorption pit area, resorption pit density, and percent resorption area were found to decrease significantly with age. Conclusions The current study demonstrated the in vivo interrelationship between the organic constituents, remodeling, and damage formation in cortical bone. In addition to the age-related reduction in resorption, there is a negative correlation between AGEs and resorption independent of age. This inverse relationship indicates that AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties. PMID:25326375

Effect of a growth hormone treatment on bone orthotropic elasticity in dwarf rats

NASA Technical Reports Server (NTRS)

Kohles, S. S.; Martinez, D. A.; Bowers, J. R.; Vailas, A. C.; Vanderby, R. Jr

1997-01-01

A refinement of the current ultrasonic elasticity technique was used to measure the orthotropic elastic properties of rat cortical bone as well as to quantify changes in elastic properties, density, and porosity of the dwarf rat cortex after a treatment with recombinant human growth hormone (rhGH). The ultrasonic elasticity technique was refined via optimized signal management of high-frequency wave propagation through cubic cortical specimens. Twenty dwarf rats (37 days old) were randomly assigned to two groups (10 rats each). The dwarf rat model (5-10% of normal GH) was given subcutaneous injections of either rhGH or saline over a 14-day treatment period. Density was measured using Archimedes technique. Porosity and other microstructural characteristics were also explored via scanning electron microscopy and image analysis. Statistical tests verified significant decreases in cortical orthotropic Young's (-26.7%) and shear (-16.7%) moduli and density (-2.42%) concomitant with an increase in porosity (+125%) after rhGH treatments to the dwarf model (p < 0.05). A change in material symmetry from orthotropy toward planar isotropy within the radial-circumferential plane after GH treatments was also noted. These results demonstrate some alteration in bone properties at this time interval. Structural implications of these changes throughout physiological loading regimens should be explored.

Internal rib structure can be predicted using mathematical models: An anatomic study comparing the chest to a shell dome with application to understanding fractures.

PubMed

Casha, Aaron R; Camilleri, Liberato; Manché, Alexander; Gatt, Ruben; Attard, Daphne; Gauci, Marilyn; Camilleri-Podesta, Marie-Therese; Mcdonald, Stuart; Grima, Joseph N

2015-11-01

The human rib cage resembles a masonry dome in shape. Masonry domes have a particular construction that mimics stress distribution. Rib cortical thickness and bone density were analyzed to determine whether the morphology of the rib cage is sufficiently similar to a shell dome for internal rib structure to be predicted mathematically. A finite element analysis (FEA) simulation was used to measure stresses on the internal and external surfaces of a chest-shaped dome. Inner and outer rib cortical thickness and bone density were measured in the mid-axillary lines of seven cadaveric rib cages using computerized tomography scanning. Paired t tests and Pearson correlation were used to relate cortical thickness and bone density to stress. FEA modeling showed that the stress was 82% higher on the internal than the external surface, with a gradual decrease in internal and external wall stresses from the base to the apex. The inner cortex was more radio-dense, P < 0.001, and thicker, P < 0.001, than the outer cortex. Inner cortical thickness was related to internal stress, r = 0.94, P < 0.001, inner cortical bone density to internal stress, r = 0.87, P = 0.003, and outer cortical thickness to external stress, r = 0.65, P = 0.035. Mathematical models were developed relating internal and external cortical thicknesses and bone densities to rib level. The internal anatomical features of ribs, including the inner and outer cortical thicknesses and bone densities, are similar to the stress distribution in dome-shaped structures modeled using FEA computer simulations of a thick-walled dome pressure vessel. Fixation of rib fractures should include the stronger internal cortex. © 2015 Wiley Periodicals, Inc.

Comparison of spatiotemporal cortical activation pattern during visual perception of Korean, English, Chinese words: an event-related potential study.

PubMed

Kim, Kyung Hwan; Kim, Ja Hyun

2006-02-20

The aim of this study was to compare spatiotemporal cortical activation patterns during the visual perception of Korean, English, and Chinese words. The comparison of these three languages offers an opportunity to study the effect of written forms on cortical processing of visually presented words, because of partial similarity/difference among words of these languages, and the familiarity of native Koreans with these three languages at the word level. Single-character words and pictograms were excluded from the stimuli in order to activate neuronal circuitries that are involved only in word perception. Since a variety of cerebral processes are sequentially evoked during visual word perception, a high-temporal resolution is required and thus we utilized event-related potential (ERP) obtained from high-density electroencephalograms. The differences and similarities observed from statistical analyses of ERP amplitudes, the correlation between ERP amplitudes and response times, and the patterns of current source density, appear to be in line with demands of visual and semantic analysis resulting from the characteristics of each language, and the expected task difficulties for native Korean subjects.

A comparison between block and smooth modeling in finite element simulations of tDCS*

PubMed Central

Indahlastari, Aprinda; Sadleir, Rosalind J.

2018-01-01

Current density distributions in five selected structures, namely, anterior superior temporal gyrus (ASTG), hippocampus (HIP), inferior frontal gyrus (IFG), occipital lobe (OCC) and pre-central gyrus (PRC) were investigated as part of a comparison between electrostatic finite element models constructed directly from MRI-resolution data (block models), and smoothed tetrahedral finite element models (smooth models). Three electrode configurations were applied, mimicking different tDCS therapies. Smooth model simulations were found to require three times longer to complete. The percentage differences between mean and median current densities of each model type in arbitrarily chosen brain structures ranged from −33.33–48.08%. No clear relationship was found between structure volumes and current density differences between the two model types. Tissue regions nearby the electrodes demonstrated the least percentage differences between block and smooth models. Therefore, block models may be adequate to predict current density values in cortical regions presumed targeted by tDCS. PMID:26737023

Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

PubMed Central

Taylor, Sabrina R.; Smith, Colin M.; Keeley, Kristen L.; McGuone, Declan; Dodge, Carter P.; Duhaime, Ann-Christine; Costine, Beth A.

2016-01-01

Cortical contusions are a common type of traumatic brain injury (TBI) in children. Current knowledge of neuroblast response to cortical injury arises primarily from studies utilizing aspiration or cryoinjury in rodents. In infants and children, cortical impact affects both gray and white matter and any neurogenic response may be complicated by the large expanse of white matter between the subventricular zone (SVZ) and the cortex, and the large number of neuroblasts in transit along the major white matter tracts to populate brain regions. Previously, we described an age-dependent increase of neuroblasts in the SVZ in response to cortical impact in the immature gyrencephalic brain. Here, we investigate if neuroblasts target the injury, if white matter injury influences repair efforts, and if postnatal population of brain regions are disrupted. Piglets received a cortical impact to the rostral gyrus cortex or sham surgery at postnatal day (PND) 7, BrdU 2 days prior to (PND 5 and 6) or after injury (PND 7 and 8), and brains were collected at PND 14. Injury did not alter the number of neuroblasts in the white matter between the SVZ and the rostral gyrus. In the gray matter of the injury site, neuroblast density was increased in cavitated lesions, and the number of BrdU+ neuroblasts was increased, but comprised less than 1% of all neuroblasts. In the white matter of the injury site, neuroblasts with differentiating morphology were densely arranged along the cavity edge. In a ventral migratory stream, neuroblast density was greater in subjects with a cavitated lesion, indicating that TBI may alter postnatal development of regions supplied by that stream. Cortical impact in the immature gyrencephalic brain produced complicated and variable lesions, increased neuroblast density in cavitated gray matter, resulted in potentially differentiating neuroblasts in the white matter, and may alter the postnatal population of brain regions utilizing a population of neuroblasts that were born prior to PND 5. This platform may be useful to continue to study potential complications of white matter injury and alterations of postnatal population of brain regions, which may contribute to the chronic effects of TBI in children. PMID:27601978

Comparison of dental implant stabilities by impact response and resonance frequencies using artificial bone.

PubMed

Kim, Dae-Seung; Lee, Woo-Jin; Choi, Soon-Chul; Lee, Sam-Sun; Heo, Min-Suk; Huh, Kyung-Hoe; Kim, Tae-Il; Yi, Won-Jin

2014-06-01

We compared implant stability as determined by the peak frequency from the impact response with the implant stability quotient (ISQ) by resonance frequency analysis (RFA) in various artificial bone conditions. The clinical bone conditions were simulated using an artificial bone material with different cortical thicknesses and trabecular densities. The artificial bone material was solid, rigid polyurethane. The polyurethane foam of 0.8g/cm(3) density was used for the cortical bone layer, and that of 0.08, 0.16, 0.24, 0.32, and 0.48g/cm(3) densities for the trabecular bone layer. The cortical bone material of 4 different thicknesses (1.4, 1.6, 1.8, and 2.0mm) was attached to the trabecular bone with varying density. Two types of dental implants (10 and 13mm lengths of 4.0mm diameter) were placed into the artificial bone blocks. An inductive sensor was used to measure the vibration caused by tapping the adapter-implant assembly. The peak frequency of the power spectrum of the impact response was used as the criterion for implant stability. The ISQ value was also measured for the same conditions. The stability, as measured by peak frequency (SPF) and ISQ value, increased as the trabecular density and the cortical density increased in linear regression analysis. The SPF and ISQ values were highly correlated with each other when the trabecular bone density and cortical bone thickness changed (Pearson correlation=0.90, p<0.01). The linear regression of the SPF with the cortical bone thickness showed higher goodness of fit (R(2) measure) than the ISQ value with the cortical bone thickness. The SPF could differentiate implantation conditions as many as the ISQ value when the trabecular bone density and the cortical density changed. However, the ISQ value was not consistent with the general stability tendency in some conditions. The SPF showed better consistency and differentiability with implant stability than the ISQ value by resonance frequency analysis in the various implantation conditions. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Associations between body composition and bone density and structure in men and women across the adult age spectrum.

PubMed

Baker, Joshua F; Davis, Matthew; Alexander, Ruben; Zemel, Babette S; Mostoufi-Moab, Sogol; Shults, Justine; Sulik, Michael; Schiferl, Daniel J; Leonard, Mary B

2013-03-01

The objective of this study was to identify independent associations between body composition and bone outcomes, including cortical structure and cortical and trabecular volumetric bone mineral density (vBMD) across the adult age spectrum. This cross-sectional study evaluated over 400 healthy adults (48% male, 44% black race), ages 21-78years. Multivariable linear regression models evaluated associations between whole-body DXA measures of lean body mass index (LBMI) and fat mass index (FMI) and tibia peripheral quantitative CT (pQCT) measures of cortical section modulus, cortical and trabecular vBMD and muscle density (as a measure of intramuscular fat), adjusted for age, sex, and race. All associations reported below were statistically significant (p<0.05). Older age and female sex were associated with lower LBMI and muscle strength. Black race was associated with greater LBMI but lower muscle density. Greater FMI was associated with lower muscle density. Cortical section modulus was positively associated with LBMI and muscle strength and negatively associated with FMI. Adjustment for body composition eliminated the greater section modulus observed in black participants and attenuated the lower section modulus in females. Greater LBMI was associated with lower cortical BMD and greater trabecular BMD. FMI was not associated with either BMD outcome. Greater muscle density was associated with greater trabecular and cortical BMD. Associations between body composition and bone outcomes did not vary by sex (no significant tests for interaction). These data highlight age-, sex- and race-specific differences in body composition, muscle strength and muscle density, and demonstrate discrete associations with bone density and structure. These data also show that age-, sex- and race-related patterns of bone density and strength are independent of differences in body composition. Longitudinal studies are needed to examine the temporal relations between changes in bone and body composition. Published by Elsevier Inc.

Associations between Body Composition and Bone Density and Structure in Men and Women across the Adult Age Spectrum

PubMed Central

Baker, Joshua F.; Davis, Matthew; Alexander, Ruben; Zemel, Babette S.; Mostoufi-Moab, Sogol; Shults, Justine; Sulik, Michael; Schiferl, Daniel J.; Leonard, Mary B.

2012-01-01

Background/Purpose The objective of this study was identify independent associations between body composition and bone outcomes, including cortical structure and cortical and trabecular volumetric bone mineral density (vBMD) across the adult age spectrum. Methods This cross-sectional study evaluated over 400 healthy adults (48% male, 44% black race), ages 21–78 years. Multivariable linear regression models evaluated associations between whole-body DXA measures of lean body mass index (LBMI) and fat mass index (FMI) and tibia peripheral quantitative CT (pQCT) measures of cortical section modulus, cortical and trabecular vBMD and muscle density (as a measure of intramuscular fat), adjusted for age, sex, and race. All associations reported below were statistically significant (p < 0.05). Results Older age and female sex were associated with lower LBMI and muscle strength. Black race was associated with greater LBMI but lower muscle density. Greater FMI was associated with lower muscle density. Cortical section modulus was positively associated with LBMI and muscle strength and negatively associated with FMI. Adjustment for body composition eliminated the greater section modulus observed in black participants and attenuated the lower section modulus in females. Greater LBMI was associated with lower cortical BMD and greater trabecular BMD. FMI was not associated with either BMD outcome. Greater muscle density was associated with greater trabecular and cortical BMD. Associations between body composition and bone outcomes did not vary by sex (no significant tests for interaction). Conclusions These data highlight age, sex- and race-specific differences in body composition, muscle strength and muscle density, and demonstrate discrete associations with bone density and structure. These data also show that age, sex- and race- related patterns of bone density and strength are independent of differences in body composition. Longitudinal studies are needed to examine the temporal relations between changes in bone and body composition. PMID:23238122

Precision of pQCT-measured total, trabecular and cortical bone area, content, density and estimated bone strength in children

PubMed Central

Duff, W.R.D.; Björkman, K.M.; Kawalilak, C.E.; Kehrig, A.M.; Wiebe, S.; Kontulainen, S.

2017-01-01

Objectives: To define pQCT precision errors, least-significant-changes, and identify associated factors for bone outcomes at the radius and tibia in children. Methods: We obtained duplicate radius and tibia pQCT scans from 35 children (8-14yrs). We report root-mean-squared coefficient of variation (CV%RMS) and 95% limits-of-agreement to characterize repeatability across scan quality and least-significant-changes for bone outcomes at distal (total and trabecular area, content and density; and compressive bone strength) and shaft sites (total area and content; cortical area content, density and thickness; and torsional bone strength). We used Spearman’s rho to identify associations between CV% and time between measurements, child’s age or anthropometrics. Results: After excluding unanalyzable scans (6-10% of scans per bone site), CV%RMS ranged from 4% (total density) to 19% (trabecular content) at the distal radius, 4% (cortical content) to 8% (cortical thickness) at the radius shaft, 2% (total density) to 14% (trabecular content) at the distal tibia and from 2% (cortical content) to 6% (bone strength) at the tibia shaft. Precision errors were within 95% limits-of-agreement across scan quality. Age was associated (rho -0.4 to -0.5, p <0.05) with CV% at the tibia. Conclusion: Bone density outcomes and cortical bone properties appeared most precise (CV%RMS <5%) in children. PMID:28574412

Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

PubMed Central

Zilles, Karl; Palomero-Gallagher, Nicola

2017-01-01

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area-specific fingerprints of the 44 areas reflect the segregation of the cerebral cortex into functionally and topographically definable groups of cortical areas (visual, auditory, somatosensory, limbic, motor), and reveals their hierarchical position (primary and unimodal (early) sensory to higher sensory and finally to multimodal association areas). Highlights Densities of transmitter receptors vary between areas of human cerebral cortex.Multi-receptor fingerprints segregate cortical layers.The densities of all examined receptor types together reach highest values in the supragranular stratum of all areas.The lowest values are found in the infragranular stratum.Multi-receptor fingerprints of entire areas and their layers segregate functional systemsCortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints. PMID:28970785

Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2008-08-15

To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.

Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in schizophrenia.

PubMed

Park, Hae-Jeong; Kwon, Jun Soo; Youn, Tak; Pae, Ji Soo; Kim, Jae-Jin; Kim, Myung-Sun; Ha, Kyoo-Seob

2002-11-01

We describe a method for the statistical parametric mapping of low resolution electromagnetic tomography (LORETA) using high-density electroencephalography (EEG) and individual magnetic resonance images (MRI) to investigate the characteristics of the mismatch negativity (MMN) generators in schizophrenia. LORETA, using a realistic head model of the boundary element method derived from the individual anatomy, estimated the current density maps from the scalp topography of the 128-channel EEG. From the current density maps that covered the whole cortical gray matter (up to 20,000 points), volumetric current density images were reconstructed. Intensity normalization of the smoothed current density images was used to reduce the confounding effect of subject specific global activity. After transforming each image into a standard stereotaxic space, we carried out statistical parametric mapping of the normalized current density images. We applied this method to the source localization of MMN in schizophrenia. The MMN generators, produced by a deviant tone of 1,200 Hz (5% of 1,600 trials) under the standard tone of 1,000 Hz, 80 dB binaural stimuli with 300 msec of inter-stimulus interval, were measured in 14 right-handed schizophrenic subjects and 14 age-, gender-, and handedness-matched controls. We found that the schizophrenic group exhibited significant current density reductions of MMN in the left superior temporal gyrus and the left inferior parietal gyrus (P < 0. 0005). This study is the first voxel-by-voxel statistical mapping of current density using individual MRI and high-density EEG. Copyright 2002 Wiley-Liss, Inc.

Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

PubMed

Lantoine, Joséphine; Grevesse, Thomas; Villers, Agnès; Delhaye, Geoffrey; Mestdagh, Camille; Versaevel, Marie; Mohammed, Danahe; Bruyère, Céline; Alaimo, Laura; Lacour, Stéphanie P; Ris, Laurence; Gabriele, Sylvain

2016-05-01

The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input.

PubMed

Happel, Max F K; Jeschke, Marcus; Ohl, Frank W

2010-08-18

Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determine how concurrent afferent inputs are integrated. Through separate excitatory horizontal projections, terminating in cortical layers II/III, information about stimulus energy in greater spectral distance is provided even over long cortical distances. These projections effectively broaden spectral tuning width. Based on these data, we suggest a mechanism of spectral integration in primary auditory cortex that is based on temporally precise interactions of afferent thalamocortical inputs and different short- and long-range intracortical networks. The proposed conceptual framework allows integration of different and partly controversial anatomical and physiological models of spectral integration in the literature.

Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), whilemore » trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.« less

PSD-95 uncoupling from NMDA receptors by Tat- N-dimer ameliorates neuronal depolarization in cortical spreading depression.

PubMed

Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders; Strømgaard, Kristian; Lauritzen, Martin

2017-05-01

Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat- N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat- N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat- N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO 2 ) responses were preserved. During cortical spreading depression, the Tat- N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO 2 . We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarization wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke.

Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex

PubMed Central

Keller, Corey J.; Cash, Sydney S.; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A.; Ulbert, Istvan; Halgren, Eric

2009-01-01

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a “laminar optode,” a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans. PMID:19428529

Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex.

PubMed

Keller, Corey J; Cash, Sydney S; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A; Ulbert, Istvan; Halgren, Eric

2009-05-15

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a "laminar optode," a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans.

Tracking the Effect of Cathodal Transcranial Direct Current Stimulation on Cortical Excitability and Connectivity by Means of TMS-EEG

PubMed Central

Varoli, Erica; Pisoni, Alberto; Mattavelli, Giulia C.; Vergallito, Alessandra; Gallucci, Alessia; Mauro, Lilia D.; Rosanova, Mario; Bolognini, Nadia; Vallar, Giuseppe; Romero Lauro, Leonor J.

2018-01-01

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0–50, 50–100, and 100–150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas. PMID:29867330

Distinct Visual Evoked Potential Morphological Patterns for Apparent Motion Processing in School-Aged Children.

PubMed

Campbell, Julia; Sharma, Anu

2016-01-01

Measures of visual cortical development in children demonstrate high variability and inconsistency throughout the literature. This is partly due to the specificity of the visual system in processing certain features. It may then be advantageous to activate multiple cortical pathways in order to observe maturation of coinciding networks. Visual stimuli eliciting the percept of apparent motion and shape change is designed to simultaneously activate both dorsal and ventral visual streams. However, research has shown that such stimuli also elicit variable visual evoked potential (VEP) morphology in children. The aim of this study was to describe developmental changes in VEPs, including morphological patterns, and underlying visual cortical generators, elicited by apparent motion and shape change in school-aged children. Forty-one typically developing children underwent high-density EEG recordings in response to a continuously morphing, radially modulated, circle-star grating. VEPs were then compared across the age groups of 5-7, 8-10, and 11-15 years according to latency and amplitude. Current density reconstructions (CDR) were performed on VEP data in order to observe activated cortical regions. It was found that two distinct VEP morphological patterns occurred in each age group. However, there were no major developmental differences between the age groups according to each pattern. CDR further demonstrated consistent visual generators across age and pattern. These results describe two novel VEP morphological patterns in typically developing children, but with similar underlying cortical sources. The importance of these morphological patterns is discussed in terms of future studies and the investigation of a relationship to visual cognitive performance.

Distinct Visual Evoked Potential Morphological Patterns for Apparent Motion Processing in School-Aged Children

PubMed Central

Campbell, Julia; Sharma, Anu

2016-01-01

Measures of visual cortical development in children demonstrate high variability and inconsistency throughout the literature. This is partly due to the specificity of the visual system in processing certain features. It may then be advantageous to activate multiple cortical pathways in order to observe maturation of coinciding networks. Visual stimuli eliciting the percept of apparent motion and shape change is designed to simultaneously activate both dorsal and ventral visual streams. However, research has shown that such stimuli also elicit variable visual evoked potential (VEP) morphology in children. The aim of this study was to describe developmental changes in VEPs, including morphological patterns, and underlying visual cortical generators, elicited by apparent motion and shape change in school-aged children. Forty-one typically developing children underwent high-density EEG recordings in response to a continuously morphing, radially modulated, circle-star grating. VEPs were then compared across the age groups of 5–7, 8–10, and 11–15 years according to latency and amplitude. Current density reconstructions (CDR) were performed on VEP data in order to observe activated cortical regions. It was found that two distinct VEP morphological patterns occurred in each age group. However, there were no major developmental differences between the age groups according to each pattern. CDR further demonstrated consistent visual generators across age and pattern. These results describe two novel VEP morphological patterns in typically developing children, but with similar underlying cortical sources. The importance of these morphological patterns is discussed in terms of future studies and the investigation of a relationship to visual cognitive performance. PMID:27445738

Intrinsic material property differences in bone tissue from patients suffering low-trauma osteoporotic fractures, compared to matched non-fracturing women.

PubMed

Vennin, S; Desyatova, A; Turner, J A; Watson, P A; Lappe, J M; Recker, R R; Akhter, M P

2017-04-01

Osteoporotic (low-trauma) fractures are a significant public health problem. Over 50% of women over 50yrs. of age will suffer an osteoporotic fracture in their remaining lifetimes. While current therapies reduce skeletal fracture risk by maintaining or increasing bone density, additional information is needed that includes the intrinsic material strength properties of bone tissue to help develop better treatments, since measurements of bone density account for no more than ~50% of fracture risk. The hypothesis tested here is that postmenopausal women who have sustained osteoporotic fractures have reduced bone quality, as indicated with measures of intrinsic material properties compared to those who have not fractured. Transiliac biopsies (N=120) were collected from fracturing (N=60, Cases) and non-fracturing postmenopausal women (N=60, age- and BMD-matched Controls) to measure intrinsic material properties using the nano-indentation technique. Each biopsy specimen was embedded in epoxy resin and then ground, polished and used for the nano-indentation testing. After calibration, multiple indentations were made using quasi-static (hardness, modulus) and dynamic (storage and loss moduli) testing protocols. Multiple indentations allowed the median and variance to be computed for each type of measurement for each specimen. Cases were found to have significantly lower median values for cortical hardness and indentation modulus. In addition, cases showed significantly less within-specimen variability in cortical modulus, cortical hardness, cortical storage modulus and trabecular hardness, and more within-specimen variability in trabecular loss modulus. Multivariate modeling indicated the presence of significant independent mechanical effects of cortical loss modulus, along with variability of cortical storage modulus, cortical loss modulus, and trabecular hardness. These results suggest mechanical heterogeneity of bone tissue may contribute to fracture resistance. Although the magnitudes of differences in the intrinsic properties were not overwhelming, this is the first comprehensive study to investigate, and compare the intrinsic properties of bone tissue in fracturing and non-fracturing postmenopausal women. Copyright © 2017 Elsevier Inc. All rights reserved.

Preventing painful age-related bone fractures: Anti-sclerostin therapy builds cortical bone and increases the proliferation of osteogenic cells in the periosteum of the geriatric mouse femur.

PubMed

Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A; Mantyh, Patrick W

2016-01-01

Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures. © The Author(s) 2016.

Automated MRI Segmentation for Individualized Modeling of Current Flow in the Human Head

PubMed Central

Huang, Yu; Dmochowski, Jacek P.; Su, Yuzhuo; Datta, Abhishek; Rorden, Christopher; Parra, Lucas C.

2013-01-01

Objective High-definition transcranial direct current stimulation (HD-tDCS) and high-density electroencephalography (HD-EEG) require accurate models of current flow for precise targeting and current source reconstruction. At a minimum, such modeling must capture the idiosyncratic anatomy of brain, cerebrospinal fluid (CSF) and skull for each individual subject. Currently, the process to build such high-resolution individualized models from structural magnetic resonance images (MRI) requires labor-intensive manual segmentation, even when leveraging available automated segmentation tools. Also, accurate placement of many high-density electrodes on individual scalp is a tedious procedure. The goal was to develop fully automated techniques to reduce the manual effort in such a modeling process. Approach A fully automated segmentation technique based on Statical Parametric Mapping 8 (SPM8), including an improved tissue probability map (TPM) and an automated correction routine for segmentation errors, was developed, along with an automated electrode placement tool for high-density arrays. The performance of these automated routines was evaluated against results from manual segmentation on 4 healthy subjects and 7 stroke patients. The criteria include segmentation accuracy, the difference of current flow distributions in resulting HD-tDCS models and the optimized current flow intensities on cortical targets. Main results The segmentation tool can segment out not just the brain but also provide accurate results for CSF, skull and other soft tissues with a field of view (FOV) extending to the neck. Compared to manual results, automated segmentation deviates by only 7% and 18% for normal and stroke subjects, respectively. The predicted electric fields in the brain deviate by 12% and 29% respectively, which is well within the variability observed for various modeling choices. Finally, optimized current flow intensities on cortical targets do not differ significantly. Significance Fully automated individualized modeling may now be feasible for large-sample EEG research studies and tDCS clinical trials. PMID:24099977

Automated MRI segmentation for individualized modeling of current flow in the human head

NASA Astrophysics Data System (ADS)

Huang, Yu; Dmochowski, Jacek P.; Su, Yuzhuo; Datta, Abhishek; Rorden, Christopher; Parra, Lucas C.

2013-12-01

Objective. High-definition transcranial direct current stimulation (HD-tDCS) and high-density electroencephalography require accurate models of current flow for precise targeting and current source reconstruction. At a minimum, such modeling must capture the idiosyncratic anatomy of the brain, cerebrospinal fluid (CSF) and skull for each individual subject. Currently, the process to build such high-resolution individualized models from structural magnetic resonance images requires labor-intensive manual segmentation, even when utilizing available automated segmentation tools. Also, accurate placement of many high-density electrodes on an individual scalp is a tedious procedure. The goal was to develop fully automated techniques to reduce the manual effort in such a modeling process. Approach. A fully automated segmentation technique based on Statical Parametric Mapping 8, including an improved tissue probability map and an automated correction routine for segmentation errors, was developed, along with an automated electrode placement tool for high-density arrays. The performance of these automated routines was evaluated against results from manual segmentation on four healthy subjects and seven stroke patients. The criteria include segmentation accuracy, the difference of current flow distributions in resulting HD-tDCS models and the optimized current flow intensities on cortical targets.Main results. The segmentation tool can segment out not just the brain but also provide accurate results for CSF, skull and other soft tissues with a field of view extending to the neck. Compared to manual results, automated segmentation deviates by only 7% and 18% for normal and stroke subjects, respectively. The predicted electric fields in the brain deviate by 12% and 29% respectively, which is well within the variability observed for various modeling choices. Finally, optimized current flow intensities on cortical targets do not differ significantly.Significance. Fully automated individualized modeling may now be feasible for large-sample EEG research studies and tDCS clinical trials.

Effects of methylmercury on muscarinic receptors in the mouse brain: A quantitative autoradiographic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Haesung; Yee, S.; Geddes, J.

1991-03-11

Methylmercury (MeHg) is reported to inhibit several stages of cholinergic neurotransmission in brain tissue in-vitro and in-vivo. To examine whether or not behavioral disturbances and/or selective vulnerability of specific neuronal groups in MeHg poisoning may be related to MeHg effects on cholinergic receptors in specific regions of the brain, the density and distribution of muscarinic receptors in the brains of C57BL/6J mice were determined following repeated injections of 5 mg/kg of methylmercuric chloride (MMC). The receptor densities in six cortical laminae of seven cerebral cortical regions, hippocampus and striatum were quantitated by computer-assisted imaging system following in-vitro labeling with ({supmore » 3}H)-pirenzepine (M1) and ({sup 3}H)N-methyl scopolamine (M2). The results showed heterogeneous distribution of M1 and M2 sites in different regions of the brain, and significant reduction in the density of both receptor subtypes following MeHg poisoning in many cortical and subcortical regions. However, the changes in the density were variable in different laminae even in the same cortical regions. Prominent reductions in M1 densities were noted in the temporal and entorhinal cortices, CA3 and hilar regions of the hippocampus as compared to control, whereas the reduction in M2 receptor density was most prominently noted in the frontal, perirhinal and entorhinal cortices, and CA1 and hilar regions of the hippocampus. Thus, it is apparent that MeHg significantly affects muscarinic receptors in the mouse brain, and that these data when used in conjunction with immunocytochemical and other morphological studies would provide further insights into the mechanisms of neurotoxic effects of MeHg.« less

Bone microarchitecture and estimated bone strength in men with active acromegaly.

PubMed

Silva, Paula P B; Amlashi, Fatemeh G; Yu, Elaine W; Pulaski-Liebert, Karen J; Gerweck, Anu V; Fazeli, Pouneh K; Lawson, Elizabeth; Nachtigall, Lisa B; Biller, Beverly M K; Miller, Karen K; Klibanski, Anne; Bouxsein, Mary; Tritos, Nicholas A

2017-11-01

Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area ( P  < 0.0001), cortical thickness ( P  = 0.0038), cortical pore volume ( P  < 0.0001) and cortical porosity ( P  = 0.0008), but lower trabecular bone density ( P  = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density ( P  = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly. © 2017 European Society of Endocrinology.

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles.

PubMed

Gămănuţ, Răzvan; Kennedy, Henry; Toroczkai, Zoltán; Ercsey-Ravasz, Mária; Van Essen, David C; Knoblauch, Kenneth; Burkhalter, Andreas

2018-02-07

The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of mesh density, cortical thickness and material properties on human rib fracture prediction.

PubMed

Li, Zuoping; Kindig, Matthew W; Subit, Damien; Kent, Richard W

2010-11-01

The purpose of this paper was to investigate the sensitivity of the structural responses and bone fractures of the ribs to mesh density, cortical thickness, and material properties so as to provide guidelines for the development of finite element (FE) thorax models used in impact biomechanics. Subject-specific FE models of the second, fourth, sixth and tenth ribs were developed to reproduce dynamic failure experiments. Sensitivity studies were then conducted to quantify the effects of variations in mesh density, cortical thickness, and material parameters on the model-predicted reaction force-displacement relationship, cortical strains, and bone fracture locations for all four ribs. Overall, it was demonstrated that rib FE models consisting of 2000-3000 trabecular hexahedral elements (weighted element length 2-3mm) and associated quadrilateral cortical shell elements with variable thickness more closely predicted the rib structural responses and bone fracture force-failure displacement relationships observed in the experiments (except the fracture locations), compared to models with constant cortical thickness. Further increases in mesh density increased computational cost but did not markedly improve model predictions. A ±30% change in the major material parameters of cortical bone lead to a -16.7 to 33.3% change in fracture displacement and -22.5 to +19.1% change in the fracture force. The results in this study suggest that human rib structural responses can be modeled in an accurate and computationally efficient way using (a) a coarse mesh of 2000-3000 solid elements, (b) cortical shells elements with variable thickness distribution and (c) a rate-dependent elastic-plastic material model. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Intracranial current density (LORETA) differences in QEEG frequency bands between depressed and non-depressed alcoholic patients.

PubMed

Coutin-Churchman, Pedro; Moreno, Rocío

2008-04-01

To assess possible differences in intracranial source distribution of surface QEEG power between depressed and non-depressed alcoholic patients in order to find any symptom-related topographic features of physiopathologic relevance. Low-Resolution Electromagnetic Tomography (LORETA) for the delta, theta, alpha and beta bands of EEG spectra was estimated from 38 alcoholic patients, 20 with and 18 without clinical depression, in which QEEG showed decreased slow and increased beta activity diffusely. Statistical non-parametric mapping was used to compare depressed and non-depressed groups. Measures of intracranial current density in individual patients at areas of significant differences were correlated with BDI scores. Patients with clinical depression showed areas of significantly lower current density than non-depressed patients in delta band at left anterior temporal, left midtemporal (including amygdala and hippocampus), and both frontopolar cortices mostly on the right; and in theta band at bilateral parietal lobe, anterior cingulate and medial frontal cortex. No differences were found at alpha and beta band. Intracranial current density in delta band at left parahippocampal, left midfrontal cortex and right frontopolar cortex was negatively correlated with BDI score. Theta band also showed negative correlations with BDI at sites of significant differences. Diffusely decreased delta and theta activity in the surface QEEG of alcoholic patients has a different intracranial distribution linked to the presence or not of clinical depression that seems to reveal a dysfunctional neuronal state at several specific limbic and other cortical locations that have been related to a specific clinical disorder such as depression. These results provided further evidence on the effects of depression in the context of alcohol dependence, in this case decreased slow activity as a possible marker of neuronal damage secondary to alcohol toxicity, clinically expressed as depressive symptoms when present in structures that are known to be related to clinical depression.

Abnormalities in cortical gray matter density in borderline personality disorder

PubMed Central

Rossi, Roberta; Lanfredi, Mariangela; Pievani, Michela; Boccardi, Marina; Rasser, Paul E; Thompson, Paul M; Cavedo, Enrica; Cotelli, Maria; Rosini, Sandra; Beneduce, Rossella; Bignotti, Stefano; Magni, Laura R; Rillosi, Luciana; Magnaldi, Silvia; Cobelli, Milena; Rossi, Giuseppe; Frisoni, Giovanni B

2015-01-01

Background Borderline personality disorder (BPD) is a chronic condition with a strong impact on patients‘ affective,cognitive and social functioning. Neuroimaging techniques offer invaluable tools to understand the biological substrate of the disease. We aimed to investigate gray matter alterations over the whole cortex in a group of Borderline Personality Disorder (BPD) patients compared to healthy controls (HC). Methods Magnetic resonance-based cortical pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD patients and in their age- and sex-matched HC (age: 38±11; females: 16, 61%). Results BPD patients showed widespread lower cortical GMD compared to HC (4% difference) with peaks of lower density located in the dorsal frontal cortex, in the orbitofrontal cortex, the anterior and posterior cingulate, the right parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and in the visual cortex (p<0.005). Our BPD subjects displayed a symmetric distribution of anomalies in the dorsal aspect of the cortical mantle, but a wider involvement of the left hemisphere in the mesial aspect in terms of lower density. A few restricted regions of higher density were detected in the right hemisphere. All regions remained significant after correction for multiple comparisons via permutation testing. Conclusions BPD patients feature specific morphology of the cerebral structures involved in cognitive and emotional processing and social cognition/mentalization, consistent with clinical and functional data. PMID:25561291

Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex

NASA Astrophysics Data System (ADS)

Wang, Chun; Brunton, Emma; Haghgooie, Saman; Cassells, Kahli; Lowery, Arthur; Rajan, Ramesh

2013-08-01

Objective. Cortical neural prostheses with implanted electrode arrays have been used to restore compromised brain functions but concerns remain regarding their long-term stability and functional performance. Approach. Here we report changes in electrode impedance and stimulation thresholds for a custom-designed electrode array implanted in rat motor cortex for up to three months. Main Results. The array comprises four 2000 µm long electrodes with a large annular stimulating surface (7860-15700 µm2) displaced from the penetrating insulated tip. Compared to pre-implantation in vitro values there were three phases of impedance change: (1) an immediate large increase of impedance by an average of two-fold on implantation; (2) a period of continued impedance increase, albeit with considerable variability, which reached a peak at approximately four weeks post-implantation and remained high over the next two weeks; (3) finally, a period of 5-6 weeks when impedance stabilized at levels close to those seen immediately post-implantation. Impedance could often be temporarily decreased by applying brief trains of current stimulation, used to evoke motor output. The stimulation threshold to induce observable motor behaviour was generally between 75-100 µA, with charge density varying from 48-128 µC cm-2, consistent with the lower current density generated by electrodes with larger stimulating surface area. No systematic change in thresholds occurred over time, suggesting that device functionality was not compromised by the factors that caused changes in electrode impedance. Significance. The present results provide support for the use of annulus electrodes in future applications in cortical neural prostheses.

Evaluation of local electric fields generated by transcranial direct current stimulation with an extracephalic reference electrode based on realistic 3D body modeling

NASA Astrophysics Data System (ADS)

Im, Chang-Hwan; Park, Ji-Hye; Shim, Miseon; Chang, Won Hyuk; Kim, Yun-Hee

2012-04-01

In this study, local electric field distributions generated by transcranial direct current stimulation (tDCS) with an extracephalic reference electrode were evaluated to address extracephalic tDCS safety issues. To this aim, we generated a numerical model of an adult male human upper body and applied the 3D finite element method to electric current conduction analysis. In our simulations, the active electrode was placed over the left primary motor cortex (M1) and the reference electrode was placed at six different locations: over the right temporal lobe, on the right supraorbital region, on the right deltoid, on the left deltoid, under the chin, and on the right buccinator muscle. The maximum current density and electric field intensity values in the brainstem generated by the extracephalic reference electrodes were comparable to, or even less than, those generated by the cephalic reference electrodes. These results suggest that extracephalic reference electrodes do not lead to unwanted modulation of the brainstem cardio-respiratory and autonomic centers, as indicated by recent experimental studies. The volume energy density was concentrated at the neck area by the use of deltoid reference electrodes, but was still smaller than that around the active electrode locations. In addition, the distributions of elicited cortical electric fields demonstrated that the use of extracephalic reference electrodes might allow for the robust prediction of cortical modulations with little dependence on the reference electrode locations.

Generation of field potentials and modulation of their dynamics through volume integration of cortical activity.

PubMed

Kajikawa, Yoshinao; Schroeder, Charles E

2015-01-01

Field potentials (FPs) recorded within the brain, often called "local field potentials" (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an "LFP" signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs. Copyright © 2015 the American Physiological Society.

Generation of field potentials and modulation of their dynamics through volume integration of cortical activity

PubMed Central

Schroeder, Charles E.

2014-01-01

Field potentials (FPs) recorded within the brain, often called “local field potentials” (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an “LFP” signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs. PMID:25274348

A comparison of bone density and bone morphology between patients presenting with hip fractures, spinal fractures or a combination of the two

PubMed Central

2013-01-01

Background Currently it is uncertain how to define osteoporosis and who to treat after a hip fracture. There is little to support the universal treatment of all such patients but how to select those most in need of treatment is not clear. In this study we have compared cortical and trabecular bone status between patients with spinal fractures and those with hip fracture with or without spinal fracture with the aim to begin to identify, by a simple clinical method (spine x-ray), a group of hip fracture patients likely to be more responsive to treatment with current antiresorptive agents. Methods Comparison of convenience samples of three groups of 50 patients, one with spinal fractures, one with a hip fracture, and one with both. Measurements consist of bone mineral density at the lumbar spine, at the four standard hip sites, number, distribution and severity of spinal fractures by the method of Genant, cortical bone thickness at the infero-medial femoral neck site, femoral neck and axis length and femoral neck width. Results Patients with spinal fractures alone have the most deficient bones at both trabecular and cortical sites: those with hip fracture and no spinal fractures the best at trabecular bone and most cortical bone sites: and those with both hip and spinal fractures intermediate in most measurements. Hip axis length and neck width did not differ between groups. Conclusion The presence of the spinal fracture indicates poor trabecular bone status in hip fracture patients. Hip fracture patients without spinal fractures have a bone mass similar to the reference range for their age and gender. Poor trabecular bone in hip fracture patients may point to a category of patient more likely to benefit from therapy and may be indicated by the presence of spinal fractures. PMID:23432767

Mismatch Negativity in Recent-Onset and Chronic Schizophrenia: A Current Source Density Analysis

PubMed Central

Fulham, W. Ross; Michie, Patricia T.; Ward, Philip B.; Rasser, Paul E.; Todd, Juanita; Johnston, Patrick J.; Thompson, Paul M.; Schall, Ulrich

2014-01-01

Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia. PMID:24949859

Humans and great apes share increased neocortical neuropeptide Y innervation compared to other haplorhine primates.

PubMed

Raghanti, Mary Ann; Edler, Melissa K; Meindl, Richard S; Sudduth, Jessica; Bohush, Tatiana; Erwin, Joseph M; Stimpson, Cheryl D; Hof, Patrick R; Sherwood, Chet C

2014-01-01

Neuropeptide Y (NPY) plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer's disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans). Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv) and NPY-immunoreactive varicosity density to neuron density (Vv/Nv), as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt) of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.

Prediction of low bone mass using a combinational approach of cortical and trabecular bone measures from dental panoramic radiographs.

PubMed

Kathirvelu, D; Anburajan, M

2014-09-01

The aim of this study is to extract cortical and trabecular features of the mandible and to develop a novel combinational model of mandibular cortical thickness, trabecular bone area and age in order to predict low bone mineral density or osteoporosis from a dental panoramic radiograph. The study involved 64 south Indian women (age = 52.5 ± 12.7 years) categorised into two groups (normal and low bone mineral density) based on total femur bone mineral density. The dental panoramic radiographs were obtained by a digital scanner, and measurement of total bone mineral density at the right femur was performed by a dual-energy X-ray absorptiometry scanner. The mandibular cortical thickness and panoramic mandibular index were measured bilaterally, and the mean values were considered. The region of interest of 128 × 128 pixels around the mental foramen region was manually cropped and subjected to pre-processing, normalisation and average threshold-based segmentation to determine trabecular bone area. Multiple linear regression analyses of cortical and trabecular measures along with age were performed to develop a combinational model to classify subjects as normal and low bone mineral density. The proposed approach demonstrated strong correlation (r = 0.76; p < 0.01) against the total bone mineral density and resulted in accuracy, sensitivity and positive predictive values of 0.84, 0.92 and 0.85, respectively; the receiver operating characteristic outcomes disclosed that the area under the curve was 0.89.Our results suggest that the proposed combinational model could be useful to diagnose subjects with low bone mineral density. © IMechE 2014.

An analysis of current source density profiles activated by local stimulation in the mouse auditory cortex in vitro.

PubMed

Yamamura, Daiki; Sano, Ayaka; Tateno, Takashi

2017-03-15

To examine local network properties of the mouse auditory cortex in vitro, we recorded extracellular spatiotemporal laminar profiles driven by short electric local stimulation on a planar multielectrode array substrate. The recorded local field potentials were subsequently evaluated using current source density (CSD) analysis to identify sources and sinks. Current sinks are thought to be an indicator of net synaptic current in the small volume of cortex surrounding the recording site. Thus, CSD analysis combined with multielectrode arrays enabled us to compare mean synaptic activity in response to small current stimuli on a layer-by-layer basis. We also used senescence-accelerated mice (SAM), some strains of which show earlier onset of age-related hearing loss, to examine the characteristic spatiotemporal CSD profiles stimulated by electrodes in specific cortical layers. Thus, the CSD patterns were classified into several clusters based on stimulation sites in the cortical layers. We also found some differences in CSD patterns between the two SAM strains in terms of aging according to principle component analysis with dimension reduction. For simultaneous two-site stimulation, we modeled the obtained CSD profiles as a linear superposition of the CSD profiles to individual single-site stimulation. The model analysis indicated the nonlinearity of spatiotemporal integration over stimulus-driven activity in a layer-specific manner. Finally, on the basis of these results, we discuss the auditory cortex local network properties and the effects of aging on these mouse strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Diffusion spectral imaging modules correlate with EEG LORETA neuroimaging modules.

PubMed

Thatcher, Robert W; North, Duane M; Biver, Carl J

2012-05-01

The purpose of this study was to test the hypothesis that the highest temporal correlations between 3-dimensional EEG current source density corresponds to anatomical Modules of high synaptic connectivity. Eyes closed and eyes open EEG was recorded from 19 scalp locations with a linked ears reference from 71 subjects age 13-42 years. LORETA was computed from 1 to 30 Hz in 2,394 cortical gray matter voxels that were grouped into six anatomical Modules corresponding to the ROIs in the Hagmann et al.'s [2008] diffusion spectral imaging (DSI) study. All possible cross-correlations between voxels within a DSI Module were compared with the correlations between Modules. The Hagmann et al. [ 2008] Module correlation structure was replicated in the correlation structure of EEG three-dimensional current source density. EEG Temporal correlation between brain regions is related to synaptic density as measured by diffusion spectral imaging. Copyright © 2011 Wiley-Liss, Inc.

Cortical compression rapidly trimmed transcallosal projections and altered axonal anterograde transport machinery.

PubMed

Chen, Li-Jin; Wang, Yueh-Jan; Tseng, Guo-Fang

2017-10-24

Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. Using a rat epidural bead implantation model, we studied the effects of unilateral somatosensory cortical compression on its transcallosal projection and the reversibility of the changes following decompression. Compression reduced the density, branching profuseness and boutons of the projection axons in the contralateral homotopic cortex 1week and 1month post-compression. Projection fiber density was higher 1-month than 1-week post-compression, suggesting adaptive temporal changes. Compression reduced contralateral cortical synaptophysin, vesicular glutamate transporter 1 (VGLUT1) and postsynaptic density protein-95 (PSD95) expressions in a week and the first two marker proteins further by 1month. βIII-tubulin and kinesin light chain (KLC) expressions in the corpus callosum (CC) where transcallosal axons traveled were also decreased. Kinesin heavy chain (KHC) level in CC was temporarily increased 1week after compression. Decompression increased transcallosal axon density and branching profuseness to higher than sham while bouton density returned to sham levels. This was accompanied by restoration of synaptophysin, VGLUT1 and PSD95 expressions in the contralateral cortex of the 1-week, but not the 1-month, compression rats. Decompression restored βIII-tubulin, but not KLC and KHC expressions in CC. However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

The biomechanical effect of artificial and human bone density on stopping and stripping torque during screw insertion.

PubMed

Tsuji, Matthew; Crookshank, Meghan; Olsen, Michael; Schemitsch, Emil H; Zdero, Rad

2013-06-01

Orthopedic surgeons apply torque to metal screws manually by "subjective feel" to obtain adequate fracture fixation, i.e. stopping torque, and attempt to avoid accidental over-tightening that leads to screw-bone interface failure, i.e. stripping torque. Few studies have quantified stripping torque in human bone, and only one older study from 1980 reported stopping/ stripping torque ratio. The present aim was to measure stopping and stripping torque of cortical and cancellous screws in artificial and human bone over a wide range of densities. Sawbone blocks were obtained having densities from 0.08 to 0.80g/cm(3). Sixteen fresh-frozen human femurs of known standardized bone mineral density (sBMD) were also used. Using a torque screwdriver, 3.5-mm diameter cortical screws and 6.5-mm diameter cancellous screws were inserted for adequate tightening as determined subjectively by an orthopedic surgeon, i.e. stopping torque, and then further tightened until failure of the screw-bone interface, i.e. stripping torque. There were weak (R=0.25) to strong (R=0.99) linear correlations of absolute and normalized torque vs. density or sBMD. Maximum stopping torques normalized by screw thread area engaged by the host material were 15.2N/mm (cortical screws) and 13.4N/mm (cancellous screws) in sawbone blocks and 20.9N/mm (cortical screws) and 6.1N/mm (cancellous screws) in human femurs. Maximum stripping torques normalized by screw thread area engaged by the host material were 23.4N/mm (cortical screws) and 16.8N/mm (cancellous screws) in sawbone blocks and 29.3N/mm (cortical screws) and 8.3N/mm (cancellous screws) in human femurs. Combined average stopping/ stripping torque ratios were 80.8% (cortical screws) and 76.8% (cancellous screws) in sawbone blocks, as well as 66.6% (cortical screws) and 84.5% (cancellous screws) in human femurs. Surgeons should be aware of stripping torque limits for human femurs and monitor stopping torque during surgery. This is the first study of the effect of sawbone density or human bone sBMD on stopping and stripping torque. Copyright © 2013 Elsevier Ltd. All rights reserved.

Invasive Cortical Stimulation to Promote Recovery of Function After Stroke

PubMed Central

Plow, Ela B.; Carey, James R.; Nudo, Randolph J.; Pascual-Leone, Alvaro

2011-01-01

Background and Purpose Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result. Summary of Review Regarding cortical stimulation, it is important to determine the (1) location of peri-infarct representations by integrating multiple neuroanatomical and physiological techniques; (2) role of other mechanisms of stroke recovery; (3) viability of peri-infarct tissue and descending pathways; (4) lesion geometry to ensure no alteration/displacement of current density; and (5) applicability of lessons generated from noninvasive brain stimulation studies in humans. In terms of combining stimulation with rehabilitation, we should understand (1) the principle of homeostatic plasticity; (2) the effect of ongoing cortical activity and phases of learning; and (3) that subject-specific intervention may be necessary. Conclusions Future cortical stimulation trials should consider the factors that may have contributed to the peculiar results of the Phase III trial and address those in future study designs. PMID:19359643

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Benhamou, Claude-Laurent; Jaffré, Christelle

2012-10-01

While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Dopamine D1 signaling organizes network dynamics underlying working memory.

PubMed

Roffman, Joshua L; Tanner, Alexandra S; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J; Ho, New Fei; Nitenson, Adam Z; Chonde, Daniel B; Greve, Douglas N; Abi-Dargham, Anissa; Buckner, Randy L; Manoach, Dara S; Rosen, Bruce R; Hooker, Jacob M; Catana, Ciprian

2016-06-01

Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.

Dopamine D1 signaling organizes network dynamics underlying working memory

PubMed Central

Roffman, Joshua L.; Tanner, Alexandra S.; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Chonde, Daniel B.; Greve, Douglas N.; Abi-Dargham, Anissa; Buckner, Randy L.; Manoach, Dara S.; Rosen, Bruce R.; Hooker, Jacob M.; Catana, Ciprian

2016-01-01

Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits. PMID:27386561

Reproducibility of Direct Quantitative Measures of Cortical Bone Micro-architecture of the Distal Radius and Tibia by HR-pQCT

PubMed Central

Burghardt, Andrew J.; Buie, Helen R.; Laib, Andres; Majumdar, Sharmila; Boyd, Steven K.

2010-01-01

Quantitative cortical micro-architectural endpoints are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and micro-architecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia, and detect intra-cortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled dataset of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which, the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%; p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23μm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume, but not density nor microarchitecture. This study indicates HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality. PMID:20561906

A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque.

PubMed

Schroeder, C E; Mehta, A D; Givre, S J

1998-01-01

We investigated the spatiotemporal activation pattern, produced by one visual stimulus, across cerebral cortical regions in awake monkeys. Laminar profiles of postsynaptic potentials and action potentials were indexed with current source density (CSD) and multiunit activity profiles respectively. Locally, we found contrasting activation profiles in dorsal and ventral stream areas. The former, like V1 and V2, exhibit a 'feedforward' profile, with excitation beginning at the depth of Lamina 4, followed by activation of the extragranular laminae. The latter often displayed a multilaminar/columnar profile, with initial responses distributed across the laminae and reflecting modulation rather than excitation; CSD components were accompanied by either no changes or by suppression of action potentials. System-wide, response latencies indicated a large dorsal/ventral stream latency advantage, which generalizes across a wide range of methods. This predicts a specific temporal ordering of dorsal and ventral stream components of visual analysis, as well as specific patterns of dorsal-ventral stream interaction. Our findings support a hierarchical model of cortical organization that combines serial and parallel elements. Critical in such a model is the recognition that processing within a location typically entails multiple temporal components or 'waves' of activity, driven by input conveyed over heterogeneous pathways from the retina.

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

PubMed

Ohm, D T; Kim, G; Gefen, T; Rademaker, A; Weintraub, S; Bigio, E H; Mesulam, M-M; Rogalski, E; Geula, C

2018-04-21

Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy. © 2018 British Neuropathological Society.

Low cortical bone density measured by computed tomography in children and adolescents with untreated hyperthyroidism.

PubMed

Numbenjapon, Nawaporn; Costin, Gertrude; Gilsanz, Vicente; Pitukcheewanont, Pisit

2007-05-01

To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P < .001) in children and adolescents with hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

LORETA imaging of P300 in schizophrenia with individual MRI and 128-channel EEG.

PubMed

Pae, Ji Soo; Kwon, Jun Soo; Youn, Tak; Park, Hae-Jeong; Kim, Myung Sun; Lee, Boreom; Park, Kwang Suk

2003-11-01

We investigated the characteristics of P300 generators in schizophrenics by using voxel-based statistical parametric mapping of current density images. P300 generators, produced by a rare target tone of 1500 Hz (15%) under a frequent nontarget tone of 1000 Hz (85%), were measured in 20 right-handed schizophrenics and 21 controls. Low-resolution electromagnetic tomography (LORETA), using a realistic head model of the boundary element method based on individual MRI, was applied to the 128-channel EEG. Three-dimensional current density images were reconstructed from the LORETA intensity maps that covered the whole cortical gray matter. Spatial normalization and intensity normalization of the smoothed current density images were used to reduce anatomical variance and subject-specific global activity and statistical parametric mapping (SPM) was applied for the statistical analysis. We found that the sources of P300 were consistently localized at the left superior parietal area in normal subjects, while those of schizophrenics were diversely distributed. Upon statistical comparison, schizophrenics, with globally reduced current densities, showed a significant P300 current density reduction in the left medial temporal area and in the left inferior parietal area, while both left prefrontal and right orbitofrontal areas were relatively activated. The left parietotemporal area was found to correlate negatively with Positive and Negative Syndrome Scale total scores of schizophrenic patients. In conclusion, the reduced and increased areas of current density in schizophrenic patients suggest that the medial temporal and frontal areas contribute to the pathophysiology of schizophrenia, the frontotemporal circuitry abnormality.

Bone Density and Cortical Structure after Pediatric Renal Transplantation

PubMed Central

Terpstra, Anniek M.; Kalkwarf, Heidi J.; Shults, Justine; Zemel, Babette S.; Wetzsteon, Rachel J.; Foster, Bethany J.; Strife, C. Frederic; Foerster, Debbie L.

2012-01-01

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure. PMID:22282589

Superficial ovarian cortex vascularization is inversely related to the follicle reserve in normal cycling ovaries and is increased in polycystic ovary syndrome.

PubMed

Delgado-Rosas, F; Gaytán, M; Morales, C; Gómez, R; Gaytán, F

2009-05-01

The superficial ovarian cortex constitutes the micro-environment where resting and early growing follicles reside. As small follicles do not possess an independent capillary network, both their survival and early growth depend on their proximity to the cortical vessels. Little is known about the possible changes in superficial ovarian cortex vascularization in normal women throughout reproductive life or in pathological conditions such as polycystic ovary syndrome (PCOS) involving abnormal early follicle growth. We studied the vascularization of the superficial and deep cortical stroma (DCS) in normal cycling ovaries from 21 to 50 years of age and in infertile women with PCOS. We used archival ovarian samples and specific CD34 immunostaining to determine blood vessel density and to analyse correlation with age and with the ovarian follicle reserve. Normal cycling ovaries showed an age-related increase in the superficial cortical stroma vascularization that was inversely correlated with the density of small (primordial and primary) follicles. In contrast, blood vessel density in the DCS significantly decreased in women aged >or=40 years. Ovaries from PCOS showed a 2-fold increase in blood vessel density in both superficial cortical stroma and DCS with respect to age-matched controls. The increased vascularization of the superficial cortical stroma in normal ovaries in relation to age and in ovaries from PCOS could have profound effects on cortical metabolic rate, primordial follicle survival/activation and early follicle growth, and may underline changes in follicle dynamics in mid-aged women and in PCOS.

A method for vibrational assessment of cortical bone

NASA Astrophysics Data System (ADS)

Song, Yan; Gunaratne, Gemunu H.

2006-09-01

Large bones from many anatomical locations of the human skeleton consist of an outer shaft (cortex) surrounding a highly porous internal region (trabecular bone) whose structure is reminiscent of a disordered cubic network. Age related degradation of cortical and trabecular bone takes different forms. Trabecular bone weakens primarily by loss of connectivity of the porous network, and recent studies have shown that vibrational response can be used to obtain reliable estimates for loss of its strength. In contrast, cortical bone degrades via the accumulation of long fractures and changes in the level of mineralization of the bone tissue. In this paper, we model cortical bone by an initially solid specimen with uniform density to which long fractures are introduced; we find that, as in the case of trabecular bone, vibrational assessment provides more reliable estimates of residual strength in cortical bone than is possible using measurements of density or porosity.

Linear distributed source modeling of local field potentials recorded with intra-cortical electrode arrays.

PubMed

Hindriks, Rikkert; Schmiedt, Joscha; Arsiwalla, Xerxes D; Peter, Alina; Verschure, Paul F M J; Fries, Pascal; Schmid, Michael C; Deco, Gustavo

2017-01-01

Planar intra-cortical electrode (Utah) arrays provide a unique window into the spatial organization of cortical activity. Reconstruction of the current source density (CSD) underlying such recordings, however, requires "inverting" Poisson's equation. For inter-laminar recordings, this is commonly done by the CSD method, which consists in taking the second-order spatial derivative of the recorded local field potentials (LFPs). Although the CSD method has been tremendously successful in mapping the current generators underlying inter-laminar LFPs, its application to planar recordings is more challenging. While for inter-laminar recordings the CSD method seems reasonably robust against violations of its assumptions, is it unclear as to what extent this holds for planar recordings. One of the objectives of this study is to characterize the conditions under which the CSD method can be successfully applied to Utah array data. Using forward modeling, we find that for spatially coherent CSDs, the CSD method yields inaccurate reconstructions due to volume-conducted contamination from currents in deeper cortical layers. An alternative approach is to "invert" a constructed forward model. The advantage of this approach is that any a priori knowledge about the geometrical and electrical properties of the tissue can be taken into account. Although several inverse methods have been proposed for LFP data, the applicability of existing electroencephalographic (EEG) and magnetoencephalographic (MEG) inverse methods to LFP data is largely unexplored. Another objective of our study therefore, is to assess the applicability of the most commonly used EEG/MEG inverse methods to Utah array data. Our main conclusion is that these inverse methods provide more accurate CSD reconstructions than the CSD method. We illustrate the inverse methods using event-related potentials recorded from primary visual cortex of a macaque monkey during a motion discrimination task.

Linear distributed source modeling of local field potentials recorded with intra-cortical electrode arrays

PubMed Central

Schmiedt, Joscha; Arsiwalla, Xerxes D.; Peter, Alina; Verschure, Paul F. M. J.; Fries, Pascal; Schmid, Michael C.; Deco, Gustavo

2017-01-01

Planar intra-cortical electrode (Utah) arrays provide a unique window into the spatial organization of cortical activity. Reconstruction of the current source density (CSD) underlying such recordings, however, requires “inverting” Poisson’s equation. For inter-laminar recordings, this is commonly done by the CSD method, which consists in taking the second-order spatial derivative of the recorded local field potentials (LFPs). Although the CSD method has been tremendously successful in mapping the current generators underlying inter-laminar LFPs, its application to planar recordings is more challenging. While for inter-laminar recordings the CSD method seems reasonably robust against violations of its assumptions, is it unclear as to what extent this holds for planar recordings. One of the objectives of this study is to characterize the conditions under which the CSD method can be successfully applied to Utah array data. Using forward modeling, we find that for spatially coherent CSDs, the CSD method yields inaccurate reconstructions due to volume-conducted contamination from currents in deeper cortical layers. An alternative approach is to “invert” a constructed forward model. The advantage of this approach is that any a priori knowledge about the geometrical and electrical properties of the tissue can be taken into account. Although several inverse methods have been proposed for LFP data, the applicability of existing electroencephalographic (EEG) and magnetoencephalographic (MEG) inverse methods to LFP data is largely unexplored. Another objective of our study therefore, is to assess the applicability of the most commonly used EEG/MEG inverse methods to Utah array data. Our main conclusion is that these inverse methods provide more accurate CSD reconstructions than the CSD method. We illustrate the inverse methods using event-related potentials recorded from primary visual cortex of a macaque monkey during a motion discrimination task. PMID:29253006

Effects of Habitual Physical Activity and Fitness on Tibial Cortical Bone Mass, Structure and Mass Distribution in Pre-pubertal Boys and Girls: The Look Study.

PubMed

Duckham, Rachel L; Rantalainen, Timo; Ducher, Gaele; Hill, Briony; Telford, Richard D; Telford, Rohan M; Daly, Robin M

2016-07-01

Targeted weight-bearing activities during the pre-pubertal years can improve cortical bone mass, structure and distribution, but less is known about the influence of habitual physical activity (PA) and fitness. This study examined the effects of contrasting habitual PA and fitness levels on cortical bone density, geometry and mass distribution in pre-pubertal children. Boys (n = 241) and girls (n = 245) aged 7-9 years had a pQCT scan to measure tibial mid-shaft total, cortical and medullary area, cortical thickness, density, polar strength strain index (SSIpolar) and the mass/density distribution through the bone cortex (radial distribution divided into endo-, mid- and pericortical regions) and around the centre of mass (polar distribution). Four contrasting PA and fitness groups (inactive-unfit, inactive-fit, active-unfit, active-fit) were generated based on daily step counts (pedometer, 7-days) and fitness levels (20-m shuttle test and vertical jump) for boys and girls separately. Active-fit boys had 7.3-7.7 % greater cortical area and thickness compared to inactive-unfit boys (P < 0.05), which was largely due to a 6.4-7.8 % (P < 0.05) greater cortical mass in the posterior-lateral, medial and posterior-medial 66 % tibial regions. Cortical area was not significantly different across PA-fitness categories in girls, but active-fit girls had 6.1 % (P < 0.05) greater SSIpolar compared to inactive-fit girls, which was likely due to their 6.7 % (P < 0.05) greater total bone area. There was also a small region-specific cortical mass benefit in the posterior-medial 66 % tibia cortex in active-fit girls. Higher levels of habitual PA-fitness were associated with small regional-specific gains in 66 % tibial cortical bone mass in pre-pubertal children, particularly boys.

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case.

PubMed

Phielipp, Nicolás M; Saha, Utpal; Sankar, Tejas; Yugeta, Akihiro; Chen, Robert

2017-06-01

To evaluate the safety of repetitive transcranial magnetic stimulation (rTMS) in patients with implanted subdural cortical electrodes. We performed ex-vivo experiments to test the temperature, displacement and current induced in the electrodes with single pulse transcranial magnetic stimulation (TMS) from 10 to 100% of stimulator output and tested a typical rTMS protocol used in a clinical setting. We then used rTMS to the motor cortex to treat a patient with refractory post-herpetic neuralgia who had previously been implanted with a subdural motor cortical electrode for pain management. The rTMS protocol consisted of ten sessions of 2000 stimuli at 20Hz and 90% of resting motor threshold. The ex-vivo study showed an increase in the coil temperature of 2°C, a maximum induced charge density of 30.4μC/cm 2 /phase, and no electrode displacement with TMS. There was no serious adverse effect associated with rTMS treatment of the patient. Cortical tremor was observed in the intervals between trains of stimuli during one treatment session. TMS was safe in a patient with implanted Medtronic Resume II electrode (model 3587A) subdural cortical electrode. TMS may be used as a therapeutic, diagnostic or research tool in patients this type of with implanted cortical electrodes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Object-based attentional modulation of biological motion processing: spatiotemporal dynamics using functional magnetic resonance imaging and electroencephalography.

PubMed

Safford, Ashley S; Hussey, Elizabeth A; Parasuraman, Raja; Thompson, James C

2010-07-07

Although it is well documented that the ability to perceive biological motion is mediated by the lateral temporal cortex, whether and when neural activity in this brain region is modulated by attention is unknown. In particular, it is unclear whether the processing of biological motion requires attention or whether such stimuli are processed preattentively. Here, we used functional magnetic resonance imaging, high-density electroencephalography, and cortically constrained source estimation methods to investigate the spatiotemporal effects of attention on the processing of biological motion. Directing attention to tool motion in overlapping movies of biological motion and tool motion suppressed the blood oxygenation level-dependent (BOLD) response of the right superior temporal sulcus (STS)/middle temporal gyrus (MTG), while directing attention to biological motion suppressed the BOLD response of the left inferior temporal sulcus (ITS)/MTG. Similarly, category-based modulation of the cortical current source density estimates from the right STS/MTG and left ITS was observed beginning at approximately 450 ms following stimulus onset. Our results indicate that the cortical processing of biological motion is strongly modulated by attention. These findings argue against preattentive processing of biological motion in the presence of stimuli that compete for attention. Our findings also suggest that the attention-based segregation of motion category-specific responses only emerges relatively late (several hundred milliseconds) in processing.

Correlation between ultrasound velocity and densitometry in fresh and demineralized cortical bone

PubMed Central

de Mesquita, Alessandro Queiroz; Barbieri, Giuliano; Barbieri, Claudio Henrique

2016-01-01

OBJECTIVE: To compare ultrasound propagation velocity with densitometry in the diaphyseal compact cortical bone of whole sheep metatarsals. METHODS: The transverse ultrasound velocity and bone mineral density of 5-cm-long diaphyseal bone segments were first measured. The bone segments were then divided into four groups of 15 segments each and demineralized in an aqueous 0.5 N hydrochloric acid solution for 6, 12, 24 or 36 hours. All measurements were repeated after demineralization for each time duration and the values measured before and after demineralization were compared. RESULTS: Ultrasound velocity and bone mineral density decreased with demineralization time, and most differences in the pre- and post-demineralization values within each group and between groups were significant: A moderate correlation coefficient (r=0.75956) together with a moderate agreement was determined between both post-demineralization parameters, detected by the Bland-Altman method. CONCLUSION: We conclude that both ultrasound velocity and bone mineral density decrease as a result of demineralization, thus indicating that bone mineral content is of great importance for maintaining the acoustic parameters of cortical bone, as observed for cancellous bone. Ultrasound velocity can be used to evaluate both compact cortical bone quality and bone mineral density. PMID:27982167

Correlation between ultrasound velocity and densitometry in fresh and demineralized cortical bone.

PubMed

Mesquita, Alessandro Queiroz de; Barbieri, Giuliano; Barbieri, Claudio Henrique

2016-11-01

To compare ultrasound propagation velocity with densitometry in the diaphyseal compact cortical bone of whole sheep metatarsals. The transverse ultrasound velocity and bone mineral density of 5-cm-long diaphyseal bone segments were first measured. The bone segments were then divided into four groups of 15 segments each and demineralized in an aqueous 0.5 N hydrochloric acid solution for 6, 12, 24 or 36 hours. All measurements were repeated after demineralization for each time duration and the values measured before and after demineralization were compared. Ultrasound velocity and bone mineral density decreased with demineralization time, and most differences in the pre- and post-demineralization values within each group and between groups were significant: A moderate correlation coefficient (r=0.75956) together with a moderate agreement was determined between both post-demineralization parameters, detected by the Bland-Altman method. We conclude that both ultrasound velocity and bone mineral density decrease as a result of demineralization, thus indicating that bone mineral content is of great importance for maintaining the acoustic parameters of cortical bone, as observed for cancellous bone. Ultrasound velocity can be used to evaluate both compact cortical bone quality and bone mineral density.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PubMed

Laouchedi, M; Galanaud, D; Delmaire, C; Fernandez-Vidal, S; Messé, A; Mesmoudi, S; Oulebsir Boumghar, F; Pélégrini-Issac, M; Puybasset, L; Benali, H; Perlbarg, V

2015-07-01

Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Bedside functional brain imaging in critically-ill children using high-density EEG source modeling and multi-modal sensory stimulation.

PubMed

Eytan, Danny; Pang, Elizabeth W; Doesburg, Sam M; Nenadovic, Vera; Gavrilovic, Bojan; Laussen, Peter; Guerguerian, Anne-Marie

2016-01-01

Acute brain injury is a common cause of death and critical illness in children and young adults. Fundamental management focuses on early characterization of the extent of injury and optimizing recovery by preventing secondary damage during the days following the primary injury. Currently, bedside technology for measuring neurological function is mainly limited to using electroencephalography (EEG) for detection of seizures and encephalopathic features, and evoked potentials. We present a proof of concept study in patients with acute brain injury in the intensive care setting, featuring a bedside functional imaging set-up designed to map cortical brain activation patterns by combining high density EEG recordings, multi-modal sensory stimulation (auditory, visual, and somatosensory), and EEG source modeling. Use of source-modeling allows for examination of spatiotemporal activation patterns at the cortical region level as opposed to the traditional scalp potential maps. The application of this system in both healthy and brain-injured participants is demonstrated with modality-specific source-reconstructed cortical activation patterns. By combining stimulation obtained with different modalities, most of the cortical surface can be monitored for changes in functional activation without having to physically transport the subject to an imaging suite. The results in patients in an intensive care setting with anatomically well-defined brain lesions suggest a topographic association between their injuries and activation patterns. Moreover, we report the reproducible application of a protocol examining a higher-level cortical processing with an auditory oddball paradigm involving presentation of the patient's own name. This study reports the first successful application of a bedside functional brain mapping tool in the intensive care setting. This application has the potential to provide clinicians with an additional dimension of information to manage critically-ill children and adults, and potentially patients not suited for magnetic resonance imaging technologies.

Increased gray matter density in the parietal cortex of mathematicians: a voxel-based morphometry study.

PubMed

Aydin, K; Ucar, A; Oguz, K K; Okur, O O; Agayev, A; Unal, Z; Yilmaz, S; Ozturk, C

2007-01-01

The training to acquire or practicing to perform a skill, which may lead to structural changes in the brain, is called experience-dependent structural plasticity. The main purpose of this cross-sectional study was to investigate the presence of experience-dependent structural plasticity in mathematicians' brains, which may develop after long-term practice of mathematic thinking. Twenty-six volunteer mathematicians, who have been working as academicians, were enrolled in the study. We applied an optimized method of voxel-based morphometry in the mathematicians and the age- and sex-matched control subjects. We assessed the gray and white matter density differences in mathematicians and the control subjects. Moreover, the correlation between the cortical density and the time spent as an academician was investigated. We found that cortical gray matter density in the left inferior frontal and bilateral inferior parietal lobules of the mathematicians were significantly increased compared with the control subjects. Furthermore, increase in gray matter density in the right inferior parietal lobule of the mathematicians was strongly correlated with the time spent as an academician (r = 0.84; P < .01). Left-inferior frontal and bilateral parietal regions are involved in arithmetic processing. Inferior parietal regions are also involved in high-level mathematic thinking, which requires visuospatial imagery, such as mental creation and manipulation of 3D objects. The voxel-based morphometric analysis of mathematicians' brains revealed increased gray matter density in the cortical regions related to mathematic thinking. The correlation between cortical density increase and the time spent as an academician suggests experience-dependent structural plasticity in mathematicians' brains.

Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fractures: Analysis of Risk Factors.

PubMed

Xie, Weixing; Jin, Daxiang; Ma, Hui; Ding, Jinyong; Xu, Jixi; Zhang, Shuncong; Liang, De

2016-05-01

The risk factors for cement leakage were retrospectively reviewed in 192 patients who underwent percutaneous vertebral augmentation (PVA). To discuss the factors related to the cement leakage in PVA procedure for the treatment of osteoporotic vertebral compression fractures. PVA is widely applied for the treatment of osteoporotic vertebral fractures. Cement leakage is a major complication of this procedure. The risk factors for cement leakage were controversial. A retrospective review of 192 patients who underwent PVA was conducted. The following data were recorded: age, sex, bone density, number of fractured vertebrae before surgery, number of treated vertebrae, severity of the treated vertebrae, operative approach, volume of injected bone cement, preoperative vertebral compression ratio, preoperative local kyphosis angle, intraosseous clefts, preoperative vertebral cortical bone defect, and ratio and type of cement leakage. To study the correlation between each factor and cement leakage ratio, bivariate regression analysis was employed to perform univariate analysis, whereas multivariate linear regression analysis was employed to perform multivariate analysis. The study included 192 patients (282 treated vertebrae), and cement leakage occurred in 100 vertebrae (35.46%). The vertebrae with preoperative cortical bone defects generally exhibited higher cement leakage ratio, and the leakage is typically type C. Vertebrae with intact cortical bones before the procedure tend to experience type S leakage. Univariate analysis showed that patient age, bone density, number of fractured vertebrae before surgery, and vertebral cortical bone were associated with cement leakage ratio (P<0.05). Multivariate analysis showed that the main factors influencing bone cement leakage are bone density and vertebral cortical bone defect, with standardized partial regression coefficients of -0.085 and 0.144, respectively. High bone density and vertebral cortical bone defect are independent risk factors associated with bone cement leakage.

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

PubMed

Tournis, S; Michopoulou, E; Fatouros, I G; Paspati, I; Michalopoulou, M; Raptou, P; Leontsini, D; Avloniti, A; Krekoukia, M; Zouvelou, V; Galanos, A; Aggelousis, N; Kambas, A; Douroudos, I; Lyritis, G P; Taxildaris, K; Pappaioannou, N

2010-06-01

Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. We conducted a cross-sectional study at a tertiary center. We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

PubMed

Nishiyama, Yuichi; Kanayama, Hidekazu; Mori, Hiroshi; Tada, Keiji; Yamamoto, Yasushi; Katsube, Takashi; Takeshita, Haruo; Kawakami, Kazunori; Kitagaki, Hajime

2017-06-01

This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

Normalization of cortical bone density in children and adolescents with hyperthyroidism treated with antithyroid medication.

PubMed

Numbenjapon, N; Costin, G; Pitukcheewanont, P

2012-09-01

We assessed bone size and bone density (BD) measurements using computed tomography (CT) in children and adolescents with hyperthyroidism treated with antithyroid medication. We found that cortical BD appeared to improve at 1 year and normalize at 2 years in all tested patients. Our previous study demonstrated that cortical BD in children and adolescents with untreated hyperthyroidism was significantly decreased as compared to age-, sex- and ethnicity-matched healthy controls. The present report evaluated whether attainment of euthyroidism by medical antithyroid treatment was able to improve or normalize cortical BD in these patients. Anthropometrics and three-dimensional CT bone measurements including cross-sectional area (CSA), cortical bone area (CBA) and cortical BD at midshaft of the femur (cortical bone), and CSA and BD of L(1) to L(3) vertebrae (cancellous bone) in 15 children and adolescents after 1- and 2-year treatments with antithyroid medication were reviewed and compared to their pretreatment results. All patients were euthyroid at 1 and 2 years after medical antithyroid treatment. After adjusting for age, height, weight and Tanner stage, a significant increase in cortical BD in all patients (15/15) was found after 1 year of treatment (P < 0.001). Normalization of cortical BD was demonstrated in all tested patients (10/15) after 2 years. There were no significant changes in the other cancellous or cortical bone parameters. Cortical BD was improved at 1 year and normalized at 2 years in hyperthyroid patients rendered euthyroid with antithyroid medication.

Hemispheric comparisons of neuron density in the planum temporale of schizophrenia and nonpsychiatric brains

PubMed Central

Smiley, John F.; Rosoklija, Gorazd; Mancevski, Branislav; Pergolizzi, Denise; Figarsky, Khadija; Bleiwas, Cynthia; Duma, Aleksej; Mann, J. John; Javitt, Daniel C.; Dwork, Andrew J.

2010-01-01

Postmortem and in vivo studies of schizophrenia frequently reveal reduced cortical volume, but the underlying cellular abnormalities are incompletely defined. One influential hypothesis, especially investigated in Brodmann’s area 9 of prefrontal cortex, is that the number of neurons is normal, and the volume change is caused by reduction of the surrounding neuropil. However, studies have differed on whether the cortex has the increased neuron density that is predicted by this hypothesis. In a recent study of bilateral planum temporale (PT), we reported smaller volume and width of the outer cortex (layers I-III), especially in the left hemisphere, among subjects with schizophrenia. In the present study, we measured neuron density and size in the same PT samples, and also in prefrontal area 9 of the same brains. In the PT, separate stereological measurements were made in layers II, IIIc, and VI, whereas area 9 was sampled in layer IIIb-c. In both cortical regions, there was no significant effect of schizophrenia on neuronal density or size. There was, nevertheless, a trend-level right>left hemispheric asymmetry of neuron density in the PT, which may partially explain the previously reported left>right asymmetry of cortical width. In schizophrenia, our findings suggest that closer packing of neurons may not always explain reduced cortical volume, and subtly decreased neuron number may be a contributing factor. PMID:21377842

Synaptic activation patterns of the perirhinal-entorhinal inter-connections.

PubMed

de Villers-Sidani, E; Tahvildari, B; Alonso, A

2004-01-01

Ample neuropsychological evidence supports the role of rhinal cortices in memory. The perirhinal cortex (PRC) represents one of the main conduits for the bi-directional flow of information between the entorhinal-hippocampal network and the cortical mantle, a process essential in memory formation. However, despite anatomical evidence for a robust reciprocal connectivity between the perirhinal and entorhinal cortices, neurophysiological understanding of this circuitry is lacking. We now present the results of a series of electrophysiological experiments in rats that demonstrate robust synaptic activation patterns of the perirhinal-entorhinal inter-connections. First, using silicon multi-electrode arrays placed under visual guidance in vivo we performed current source density (CSD) analysis of lateral entorhinal cortex (LEC) responses to PRC stimulation, which demonstrated a current sink in layers II-III of the LEC with a latency consistent with monosynaptic activation. To further substantiate and extend this conclusion, we developed a PRC-LEC slice preparation where CSD analysis also revealed a current sink in superficial LEC layers in response to PRC stimulation. Importantly, intracellular recording of superficial LEC layer neurons confirmed that they receive a major monosynaptic excitatory input from the PRC. Finally, CSD analysis of the LEC to PRC projection in vivo also allowed us to document robust feedback synaptic activation of PRC neurons to deep LEC layer activation. We conclude that a clear bidirectional pattern of synaptic interactions exists between the PRC and LEC that would support a dynamic flow of information subserving memory function in the temporal lobe.

Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models.

PubMed

Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L; Snyder, Brian D; Rosenberg, Andrew E; Nazarian, Rosalynn M; Hrovat, Mirko I; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang

2010-06-01

In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization. Copyright 2010 Elsevier Inc. All rights reserved.

Dopamine-Modulated Recurrent Corticoefferent Feedback in Primary Sensory Cortex Promotes Detection of Behaviorally Relevant Stimuli

PubMed Central

Handschuh, Juliane

2014-01-01

Dopaminergic neurotransmission in primary auditory cortex (AI) has been shown to be involved in learning and memory functions. Moreover, dopaminergic projections and D1/D5 receptor distributions display a layer-dependent organization, suggesting specific functions in the cortical circuitry. However, the circuit effects of dopaminergic neurotransmission in sensory cortex and their possible roles in perception, learning, and memory are largely unknown. Here, we investigated layer-specific circuit effects of dopaminergic neuromodulation using current source density (CSD) analysis in AI of Mongolian gerbils. Pharmacological stimulation of D1/D5 receptors increased auditory-evoked synaptic currents in infragranular layers, prolonging local thalamocortical input via positive feedback between infragranular output and granular input. Subsequently, dopamine promoted sustained cortical activation by prolonged recruitment of long-range corticocortical networks. A detailed circuit analysis combining layer-specific intracortical microstimulation (ICMS), CSD analysis, and pharmacological cortical silencing revealed that cross-laminar feedback enhanced by dopamine relied on a positive, fast-acting recurrent corticoefferent loop, most likely relayed via local thalamic circuits. Behavioral signal detection analysis further showed that activation of corticoefferent output by infragranular ICMS, which mimicked auditory activation under dopaminergic influence, was most effective in eliciting a behaviorally detectable signal. Our results show that D1/D5-mediated dopaminergic modulation in sensory cortex regulates positive recurrent corticoefferent feedback, which enhances states of high, persistent activity in sensory cortex evoked by behaviorally relevant stimuli. In boosting horizontal network interactions, this potentially promotes the readout of task-related information from cortical synapses and improves behavioral stimulus detection. PMID:24453315

Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.

PubMed

Sanada, Luciana Sayuri; Sato, Karina Laurenti; Machado, Nathalia Leilane Berto; Carmo, Elisabete de Cássia do; Sluka, Kathleen A; Fazan, Valeria Paula Sassoli

2014-06-01

We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Femoral Neck X-Ray Absorptiometry Parameters and Peripheral Quantitative Computer Tomography Tibial Cortical Density Predict Survival in Dialysis Patients.

PubMed

Yap, Natalie; Wong, Phillip; McGinn, Stella; Nery, Maria-Liza; Doyle, Jean; Wells, Lynda; Clifton-Bligh, Phillip; Clifton-Bligh, Roderick J

2017-01-01

Low bone mineral density (BMD) is a known independent predictor of mortality in the general elderly population. However, studies in patients with end-stage renal disease (ESRD) are limited. The present study evaluated mortality during long-term follow-up in a population of patients having dialysis for ESRD, in whom BMD was also measured. Fifty-eight patients with ESRD were recruited consecutively from a dialysis clinic and followed prospectively for 6 years. Baseline BMD of the lumbar spine and femoral neck (FN) were measured by X-ray absorptiometry and by peripheral quantitative CT at the radius and tibia. Serum calcium, phosphate, parathyroid hormone (PTH), and albumin were measured at baseline. During follow-up, 25 patients died. Univariate analysis showed that mortality was significantly associated with FN-BMD: hazards ratio (HR) per 0.1 g/cm2 decrease 1.50 (95% CI 1.07-2.10), p = 0.019; FN-T score: HR per 1-SD decrease 1.84 (95% CI 1.16-2.92), p = 0.009; and tibial cortical density: HR per 10 mg/cm3 decrease 1.08 (95% CI 1.02-1.14), p = 0.010. In multivariate analysis with stepwise adjustment for age, sex, transplant status, albumin, PTH, phosphate, dialysis duration, diabetes, and smoking, FN-T score remained significantly associated with mortality: HR per 1-SD decrease 1.82 (95% CI 1.02-3.24), p = 0.044, whereas the HR for FN-BMD and tibial cortical density were no longer significant. When 4 patients who had peritoneal dialysis were excluded, the HR relating FN-BMD, FN-T score, and tibial cortical density to mortality remained significant but became insignificant when albumin was included in the multivariate analysis. Reduced FN-BMD, FN-T score, and tibial cortical density were significantly associated with an increased risk of death in patients with ESRD. © 2017 S. Karger AG, Basel.

sLORETA current source density analysis of evoked potentials for spatial updating in a virtual navigation task

PubMed Central

Nguyen, Hai M.; Matsumoto, Jumpei; Tran, Anh H.; Ono, Taketoshi; Nishijo, Hisao

2014-01-01

Previous studies have reported that multiple brain regions are activated during spatial navigation. However, it is unclear whether these activated brain regions are specifically associated with spatial updating or whether some regions are recruited for parallel cognitive processes. The present study aimed to localize current sources of event related potentials (ERPs) associated with spatial updating specifically. In the control phase of the experiment, electroencephalograms (EEGs) were recorded while subjects sequentially traced 10 blue checkpoints on the streets of a virtual town, which were sequentially connected by a green line, by manipulating a joystick. In the test phase of the experiment, the checkpoints and green line were not indicated. Instead, a tone was presented when the subjects entered the reference points where they were then required to trace the 10 invisible spatial reference points corresponding to the checkpoints. The vertex-positive ERPs with latencies of approximately 340 ms from the moment when the subjects entered the unmarked reference points were significantly larger in the test than in the control phases. Current source density analysis of the ERPs by standardized low-resolution brain electromagnetic tomography (sLORETA) indicated activation of brain regions in the test phase that are associated with place and landmark recognition (entorhinal cortex/hippocampus, parahippocampal and retrosplenial cortices, fusiform, and lingual gyri), detecting self-motion (posterior cingulate and posterior insular cortices), motor planning (superior frontal gyrus, including the medial frontal cortex), and regions that process spatial attention (inferior parietal lobule). The present results provide the first identification of the current sources of ERPs associated with spatial updating, and suggest that multiple systems are active in parallel during spatial updating. PMID:24624067

Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

PubMed

Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

2016-05-01

Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

Change in cortical bone density and its distribution differs between boys and girls during puberty.

PubMed

Kontulainen, Saija A; Macdonald, Heather M; McKay, Heather A

2006-07-01

Postmenarchal girls and premenopausal women have 3-4% higher cortical bone density (CoD, milligrams per cubic centimeter), compared with postpubertal boys and men, respectively. Females' denser cortical bone is thought to serve as a calcium reservoir for reproductive needs. However, prospective data are lacking that describe CoD development and bone mineral density distribution during puberty in both sexes. Thus, our objectives were to assess maturity and sex differences in the 20-month change of CoD and radial distribution of bone mineral density (RDBMD, milligrams per cubic centimeter) in early-, peri-, and postpubertal girls and boys. Maturity groups were based on change in menarcheal status (girls, n = 68) and pubic hair stage (Tanner) (boys, n = 59). Peripheral quantitative computed tomography was used to measure CoD and RDBMD at the tibial middiaphysis. The increase in average CoD was 1.9% [22.8 mg/cm(3); 95% confidence interval (CI), 10-36], 2.8% (33.8 mg/cm(3); 95% CI, 21-47), and 1.5% (55.0 mg/cm(3); 95% CI, 17-93) greater in early, peri-, and postpubertal girls, compared with boys, respectively. Analysis of RDBMD revealed that the change in density distribution varied across pubertal groups in girls. Across puberty, all girls showed an increase in the high density midcortical region, whereas only peripubertal girls showed an increase in the lower density subcortical region. A sex-difference in RDBMD change was noted within early and peripubertal groups. Our findings of sexual dimorphism in CoD development give support to the hypothesis that female bone deposits calcium for reproductive needs by consolidation of cortical bone during puberty.

Neural signatures of second language learning and control.

PubMed

Bartolotti, James; Bradley, Kailyn; Hernandez, Arturo E; Marian, Viorica

2017-04-01

Experience with multiple languages has unique effects on cortical structure and information processing. Differences in gray matter density and patterns of cortical activation are observed in lifelong bilinguals compared to monolinguals as a result of their experience managing interference across languages. Monolinguals who acquire a second language later in life begin to encounter the same type of linguistic interference as bilinguals, but with a different pre-existing language architecture. The current study used functional magnetic resonance imaging to explore the beginning stages of second language acquisition and cross-linguistic interference in monolingual adults. We found that after English monolinguals learned novel Spanish vocabulary, English and Spanish auditory words led to distinct patterns of cortical activation, with greater recruitment of posterior parietal regions in response to English words and of left hippocampus in response to Spanish words. In addition, cross-linguistic interference from English influenced processing of newly-learned Spanish words, decreasing hippocampus activity. Results suggest that monolinguals may rely on different memory systems to process a newly-learned second language, and that the second language system is sensitive to native language interference. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transmitter receptors reveal segregation of cortical areas in the human superior parietal cortex: relations to visual and somatosensory regions.

PubMed

Scheperjans, Filip; Palomero-Gallagher, Nicola; Grefkes, Christian; Schleicher, Axel; Zilles, Karl

2005-11-01

Regional distributions of ligand binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABA(A), GABA(B); cholinergic: muscarinic M2, nicotinic; adrenergic: alpha1, alpha2; serotonergic: 5-HT1A, 5-HT2; dopaminergic: D1) were studied in human postmortem brains by means of quantitative receptor autoradiography. Binding site densities were measured in the superior parietal lobule (SPL) (areas 5L, 5M, 5Ci, and different locations within Brodmann's area (BA) 7), somatosensory (BA 2), and visual cortical areas (BA 17, and different locations within BAs 18 and 19). Similarities of receptor distribution between cortical areas were analyzed by cluster analysis, uni- and multivariate statistics of mean receptor densities (averaged over all cortical layers), and profiles representing the laminar distribution patterns of receptors. A considerable heterogeneity of regional receptor densities and laminar patterns between the sites was found in the SPL and the visual cortex. The most prominent regional differences were found for M2 receptors. In the SPL, rostrocaudally oriented changes of receptor densities were more pronounced than those in mediolateral direction. The receptor distribution in the rostral SPL was more similar to that of the somatosensory cortex, whereas caudal SPL resembled the receptor patterns of the dorsolateral extrastriate visual areas. These results suggest a segregation of the different SPL areas based on receptor distribution features typical for somatosensory or visual areas, which fits to the dual functional role of this cortical region, i.e., the involvement of the human SPL in visuomotor and somatosensory motor transformations.

Comparison of amyloid plaque contrast generated by T2-, T2*-, and susceptibility-weighted imaging methods in transgenic mouse models of Alzheimer’s disease

PubMed Central

Chamberlain, Ryan; Reyes, Denise; Curran, Geoffrey L.; Marjanska, Malgorzata; Wengenack, Thomas M.; Poduslo, Joseph F.; Garwood, Michael; Jack, Clifford R.

2009-01-01

One of the hallmark pathologies of Alzheimer’s disease (AD) is amyloid plaque deposition. Plaques appear hypointense on T2- and T2*-weighted MR images probably due to the presence of endogenous iron, but no quantitative comparison of various imaging techniques has been reported. We estimated the T1, T2, T2*, and proton density values of cortical plaques and normal cortical tissue and analyzed the plaque contrast generated by a collection of T2-, T2*-, and susceptibility-weighted imaging (SWI) methods in ex vivo transgenic mouse specimens. The proton density and T1 values were similar for both cortical plaques and normal cortical tissue. The T2 and T2* values were similar in cortical plaques, which indicates that the iron content of cortical plaques may not be as large as previously thought. Ex vivo plaque contrast was increased compared to a previously reported spin echo sequence by summing multiple echoes and by performing SWI; however, gradient echo and susceptibility weighted imaging was found to be impractical for in vivo imaging due to susceptibility interface-related signal loss in the cortex. PMID:19253386

Estimation of hyper-parameters for a hierarchical model of combined cortical and extra-brain current sources in the MEG inverse problem.

PubMed

Morishige, Ken-ichi; Yoshioka, Taku; Kawawaki, Dai; Hiroe, Nobuo; Sato, Masa-aki; Kawato, Mitsuo

2014-11-01

One of the major obstacles in estimating cortical currents from MEG signals is the disturbance caused by magnetic artifacts derived from extra-cortical current sources such as heartbeats and eye movements. To remove the effect of such extra-brain sources, we improved the hybrid hierarchical variational Bayesian method (hyVBED) proposed by Fujiwara et al. (NeuroImage, 2009). hyVBED simultaneously estimates cortical and extra-brain source currents by placing dipoles on cortical surfaces as well as extra-brain sources. This method requires EOG data for an EOG forward model that describes the relationship between eye dipoles and electric potentials. In contrast, our improved approach requires no EOG and less a priori knowledge about the current variance of extra-brain sources. We propose a new method, "extra-dipole," that optimally selects hyper-parameter values regarding current variances of the cortical surface and extra-brain source dipoles. With the selected parameter values, the cortical and extra-brain dipole currents were accurately estimated from the simulated MEG data. The performance of this method was demonstrated to be better than conventional approaches, such as principal component analysis and independent component analysis, which use only statistical properties of MEG signals. Furthermore, we applied our proposed method to measured MEG data during covert pursuit of a smoothly moving target and confirmed its effectiveness. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations of bone microstructure and strength in end-stage renal failure.

PubMed

Trombetti, A; Stoermann, C; Chevalley, T; Van Rietbergen, B; Herrmann, F R; Martin, P-Y; Rizzoli, R

2013-05-01

End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients. Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density. We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0 ± 12.6 years) and 33 age-matched healthy controls. Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with "Kidney Disease: Improving Global Outcomes" working group PTH level categories (r = 0.36, p < 0.04). BMI correlated positively with trabecular number (r = 0.4, p < 0.02) and negatively with trabecular spacing (r = -0.37, p < 0.03) and trabecular network heterogeneity (r = -0.4, p < 0.02). Biomechanics positively correlated with BMI and negatively with BALP. Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone fragility in ESRD patients.

Effect of rotopositioning on the growth and maturation of mandibular bone in immobilized Rhesus monkeys

NASA Technical Reports Server (NTRS)

Simmons, D. J.; Parvin, C.; Smith, K. C.; France, P.; Kazarian, L.

1986-01-01

The rates of bone formation and mineralization in the mandibular cortex of juvenile Rhesus monkeys exposed to immobilization/rotopositioning are evaluated. The monkeys were restrained in a supine position and rotated 90 deg every 30 minutes through a full 360 deg for 14 days. The microscopic distribution of mineral densities in osteonal bone and the porosity of cortical bone are studied using microradiographs, and osteon closure rates are assessed using tetracycline labeling; normal distributions of osteons of different mineral density and cortical bone porosity values are observed. It is concluded that 14 days of immobilization/rotopositioning did not cause abnormal changes in osteon mineralization, cortical porosity, and osteon closure rates.

Ultrasonic wave velocity measurement in small polymeric and cortical bone specimens

NASA Technical Reports Server (NTRS)

Kohles, S. S.; Bowers, J. R.; Vailas, A. C.; Vanderby, R. Jr

1997-01-01

A system was refined for the determination of the bulk ultrasonic wave propagation velocity in small cortical bone specimens. Longitudinal and shear wave propagations were measured using ceramic, piezoelectric 20 and 5 MHz transducers, respectively. Results of the pulse transmission technique were refined via the measurement of the system delay time. The precision and accuracy of the system were quantified using small specimens of polyoxymethylene, polystyrene-butadiene, and high-density polyethylene. These polymeric materials had known acoustic properties, similarity of propagation velocities to cortical bone, and minimal sample inhomogeneity. Dependence of longitudinal and transverse specimen dimensions upon propagation times was quantified. To confirm the consistency of longitudinal wave propagation in small cortical bone specimens (< 1.0 mm), cut-down specimens were prepared from a normal rat femur. Finally, cortical samples were prepared from each of ten normal rat femora, and Young's moduli (Eii), shear moduli (Gij), and Poisson ratios (Vij) were measured. For all specimens (bone, polyoxymethylene, polystyrene-butadiene, and high-density polyethylene), strong linear correlations (R2 > 0.997) were maintained between propagation time and distance throughout the size ranges down to less than 0.4 mm. Results for polyoxymethylene, polystyrene-butadiene, and high-density polyethylene were accurate to within 5 percent of reported literature values. Measurement repeatability (precision) improved with an increase in the wave transmission distance (propagating dimension). No statistically significant effect due to the transverse dimension was detected.

Impact of the material composition on proton range variation - A Monte Carlo study

NASA Astrophysics Data System (ADS)

Wu, S. W.; Tung, C. J.; Lee, C. C.; Fan, K. H.; Huang, H. C.; Chao, T. C.

2015-11-01

In this study, we used the Geant4 toolkit to demonstrate the impacts of the material composition of tissues on proton range variation. Bragg curves of different materials subjected to a 250 MeV mono-energy proton beam were simulated and compared. These simulated materials included adipose, heart, brain, cartilage, cortical bone and water. The results showed that there was significant proton range deviation between Bragg curves, especially for cortical bone. The R50 values for a 250 MeV proton beam were approximately 39.55 cm, 35.52 cm, 37.00 cm, 36.51 cm, 36.72 cm, 22.53 cm, and 38.52 cm in the phantoms that were composed completely of adipose, cartilage, tissue, heart, brain, cortical bone, and water, respectively. Mass density and electron density were used to scale the proton range for each material; electron density provided better range scaling. In addition, a similar comparison was performed by artificially setting all material density to 1.0 g/cm3 to evaluate the range deviation due to chemical components alone. Tissue heterogeneity effects due to density variation were more significant, and less significant for chemical composition variation unless the Z/A was very different.

The basic nonuniformity of the cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.; Lent, Roberto

2008-01-01

Evolutionary changes in the size of the cerebral cortex, a columnar structure, often occur through the addition or subtraction of columnar modules with the same number of neurons underneath a unit area of cortical surface. This view is based on the work of Rockel et al. [Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221–244], who found a steady number of approximately 110 neurons underneath a surface area of 750 μm2 (147,000 underneath 1 mm2) of the cerebral cortex of five species from different mammalian orders. These results have since been either corroborated or disputed by different groups. Here, we show that the number of neurons underneath 1 mm2 of the cerebral cortical surface of nine primate species and the closely related Tupaia sp. is not constant and varies by three times across species. We found that cortical thickness is not inversely proportional to neuronal density across species and that total cortical surface area increases more slowly than, rather than linearly with, the number of neurons underneath it. The number of neurons beneath a unit area of cortical surface varies linearly with neuronal density, a parameter that is neither related to cortical size nor total number of neurons. Our finding of a variable number of neurons underneath a unit area of the cerebral cortex across primate species indicates that models of cortical organization cannot assume that cortical columns in different primates consist of invariant numbers of neurons. PMID:18689685

The basic nonuniformity of the cerebral cortex.

PubMed

Herculano-Houzel, Suzana; Collins, Christine E; Wong, Peiyan; Kaas, Jon H; Lent, Roberto

2008-08-26

Evolutionary changes in the size of the cerebral cortex, a columnar structure, often occur through the addition or subtraction of columnar modules with the same number of neurons underneath a unit area of cortical surface. This view is based on the work of Rockel et al. [Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221-244], who found a steady number of approximately 110 neurons underneath a surface area of 750 microm(2) (147,000 underneath 1 mm(2)) of the cerebral cortex of five species from different mammalian orders. These results have since been either corroborated or disputed by different groups. Here, we show that the number of neurons underneath 1 mm(2) of the cerebral cortical surface of nine primate species and the closely related Tupaia sp. is not constant and varies by three times across species. We found that cortical thickness is not inversely proportional to neuronal density across species and that total cortical surface area increases more slowly than, rather than linearly with, the number of neurons underneath it. The number of neurons beneath a unit area of cortical surface varies linearly with neuronal density, a parameter that is neither related to cortical size nor total number of neurons. Our finding of a variable number of neurons underneath a unit area of the cerebral cortex across primate species indicates that models of cortical organization cannot assume that cortical columns in different primates consist of invariant numbers of neurons.

High Density Polyetherurethane Foam as a Fragmentation and Radiographic Surrogate for Cortical Bone

PubMed Central

Beardsley, Christina L; Heiner, Anneliese D; Brandser, Eric A; Marsh, J Lawrence; Brown, Thomas D

2000-01-01

Background Although one of the most important factors in predicting outcome of articular fracture, the comminution of the fracture is only subjectively assessed. To facilitate development of objective, quantitative measures of comminution phenomena, there is need for a bone fragmentation surrogate. Methods Laboratory investigation was undertaken to develop and characterize a novel synthetic material capable of emulating the fragmentation and radiographic behavior of human cortical bone. Result Screening tests performed with a drop tower apparatus identified high-density polyetherurethane foam as having suitable fragmentation properties. The material's impact behavior and its quasi-static mechanical properties are here described. Dispersal of barium sulfate (BaSO4) in the resin achieved radio-density closely resembling that of bone, without detectably altering mechanical behavior. The surrogate material's ultimate strength, elastic modulus, and quasi-static toughness are within an order of magnitude of those of mammalian cortical bone. The spectrum of comminution patterns produced by this material when impacted with varying amounts of energy is very comparable to the spectrum of bone fragment comminution seen clinically. Conclusions A novel high-density polyetherurethane foam, when subjected to impact loading, sustains comminuted fracture in a manner strikingly similar to cortical bone. Moreover, since the material also can be doped with radio-opacifier so as to closely emulate bone's radiographic signature, it opens many new possibilities for CT-based systematic study of comminution phenomena. PMID:10934621

Slow-Frequency Pulsed Transcranial Electrical Stimulation for Modulation of Cortical Plasticity Based on Reciprocity Targeting with Precision Electrical Head Modeling

PubMed Central

Luu, Phan; Essaki Arumugam, Easwara Moorthy; Anderson, Erik; Gunn, Amanda; Rech, Dennis; Turovets, Sergei; Tucker, Don M.

2016-01-01

In pain management as well as other clinical applications of neuromodulation, it is important to consider the timing parameters influencing activity-dependent plasticity, including pulsed versus sustained currents, as well as the spatial action of electrical currents as they polarize the complex convolutions of the cortical mantle. These factors are of course related; studying temporal factors is not possible when the spatial resolution of current delivery to the cortex is so uncertain to make it unclear whether excitability is increased or decreased with anodal vs. cathodal current flow. In the present study we attempted to improve the targeting of specific cortical locations by applying current through flexible source-sink configurations of 256 electrodes in a geodesic array. We constructed a precision electric head model for 12 healthy individuals. Extraction of the individual’s cortical surface allowed computation of the component of the induced current that is normal to the target cortical surface. In an effort to replicate the long-term depression (LTD) induced with pulsed protocols in invasive animal research and transcranial magnetic stimulation studies, we applied 100 ms pulses at 1.9 s intervals either in cortical-surface-anodal or cortical-surface-cathodal directions, with a placebo (sham) control. The results showed significant LTD of the motor evoked potential as a result of the cortical-surface-cathodal pulses in contrast to the placebo control, with a smaller but similar LTD effect for anodal pulses. The cathodal LTD after-effect was sustained over 90 min following current injection. These results support the feasibility of pulsed protocols with low total charge in non-invasive neuromodulation when the precision of targeting is improved with a dense electrode array and accurate head modeling. PMID:27531976

P300 and LORETA: comparison of normal subjects and schizophrenic patients.

PubMed

Winterer, G; Mulert, C; Mientus, S; Gallinat, J; Schlattmann, P; Dorn, H; Herrmann, W M

2001-01-01

It was the aim of the present study 1) to investigate how many cortical activity maxima of scalp-recorded P300 are detected by Low Resolution Electromagentic Tomography (LORETA) when analyses are performed with high time-resolution, 2) to see if the resulting LORETA-solution is in accordance with intracortical recordings as reported by others and 3) to compare the given pattern of cortical activation maxima in the P300-timeframe between schizophrenic patients and normal controls. Current density analysis was performed in 3-D Talairach space with high time resolution i.e. in 6 ms steps. This was done during an auditory choice reaction paradigm separately for normal subjects and schizophrenic patients with subsequent group comparisons. In normal subjects, a sequence of at least seven cortical activation maxima was found between 240-420ms poststimulus: the prefrontal cortex, anterior or medial cingulum, posterior cingulum, parietal cortex, temporal lobe, prefrontal cortex, medial or anterior cingulum. Within the given limits of spatial resolution, this sequential maxima distribution largely met the expectations from reports on intracranial recordings and functional neuroimaging studies. However, localization accuracy was higher near the central midline than at lateral aspects of the brain. Schizophrenic patients less activated their cortex in a widespread area mainly in the left hemisphere including the prefrontal cortex, posterior cingulum and the temporal lobe. From these analyses and comparsions with intracranial recordings as reported by others, it is concluded that LORETA correctly localizes P300-related cortical activity maxima on the basis of 19 electrodes except for lateral cortical aspects which is most likely an edge-phenomenon. The data further suggest that the P300-deficit in schizophrenics involves an extended cortical network of the left hemisphere at several steps in time during the information processing stream.

Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex.

PubMed

Pinto, Joshua G A; Jones, David G; Murphy, Kathryn M

2013-01-01

Two theories have influenced our understanding of cortical development: the integrated network theory, where synaptic development is coordinated across areas; and the cascade theory, where the cortex develops in a wave-like manner from sensory to non-sensory areas. These different views on cortical development raise challenges for current studies aimed at comparing detailed maturation of the connectome among cortical areas. We have taken a different approach to compare synaptic development in rat visual, somatosensory, and frontal cortex by measuring expression of pre-synaptic (synapsin and synaptophysin) proteins that regulate vesicle cycling, and post-synaptic density (PSD-95 and Gephyrin) proteins that anchor excitatory or inhibitory (E-I) receptors. We also compared development of the balances between the pairs of pre- or post-synaptic proteins, and the overall pre- to post-synaptic balance, to address functional maturation and emergence of the E-I balance. We found that development of the individual proteins and the post-synaptic index overlapped among the three cortical areas, but the pre-synaptic index matured later in frontal cortex. Finally, we applied a neuroinformatics approach using principal component analysis and found that three components captured development of the synaptic proteins. The first component accounted for 64% of the variance in protein expression and reflected total protein expression, which overlapped among the three cortical areas. The second component was gephyrin and the E-I balance, it emerged as sequential waves starting in somatosensory, then frontal, and finally visual cortex. The third component was the balance between pre- and post-synaptic proteins, and this followed a different developmental trajectory in somatosensory cortex. Together, these results give the most support to an integrated network of synaptic development, but also highlight more complex patterns of development that vary in timing and end point among the cortical areas.

Mouse auditory cortex differs from visual and somatosensory cortices in the laminar distribution of cytochrome oxidase and acetylcholinesterase.

PubMed

Anderson, L A; Christianson, G B; Linden, J F

2009-02-03

Cytochrome oxidase (CYO) and acetylcholinesterase (AChE) staining density varies across the cortical layers in many sensory areas. The laminar variations likely reflect differences between the layers in levels of metabolic activity and cholinergic modulation. The question of whether these laminar variations differ between primary sensory cortices has never been systematically addressed in the same set of animals, since most studies of sensory cortex focus on a single sensory modality. Here, we compared the laminar distribution of CYO and AChE activity in the primary auditory, visual, and somatosensory cortices of the mouse, using Nissl-stained sections to define laminar boundaries. Interestingly, for both CYO and AChE, laminar patterns of enzyme activity were similar in the visual and somatosensory cortices, but differed in the auditory cortex. In the visual and somatosensory areas, staining densities for both enzymes were highest in layers III/IV or IV and in lower layer V. In the auditory cortex, CYO activity showed a reliable peak only at the layer III/IV border, while AChE distribution was relatively homogeneous across layers. These results suggest that laminar patterns of metabolic activity and cholinergic influence are similar in the mouse visual and somatosensory cortices, but differ in the auditory cortex.

Enhanced Androgen Signaling with Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality, and Bone Architecture

DTIC Science & Technology

2005-12-01

the BMD of female-to-male transsexuals treated with ‘male’ levels of testosterone increased to normal male levels at cortical sites [35]. Finally, men...Testosterone increases bone mineral density in female-to- male transsexuals : a case series of 15 subjects.Clin Endocrinol (Oxf) 2004, 61:560-566. 35...Ruetsche A, Kneubuehl R, Birkhaeuser M, Lippuner K: Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment

Nano-structural, compositional and micro-architectural signs of cortical bone fragility at the superolateral femoral neck in elderly hip fracture patients vs. healthy aged controls.

PubMed

Milovanovic, Petar; Rakocevic, Zlatko; Djonic, Danijela; Zivkovic, Vladimir; Hahn, Michael; Nikolic, Slobodan; Amling, Michael; Busse, Bjoern; Djuric, Marija

2014-07-01

To unravel the origins of decreased bone strength in the superolateral femoral neck, we assessed bone structural features across multiple length scales at this cortical fracture initiating region in postmenopausal women with hip fracture and in aged-matched controls. Our combined methodological approach encompassed atomic force microscopy (AFM) characterization of cortical bone nano-structure, assessment of mineral content/distribution via quantitative backscattered electron imaging (qBEI), measurement of bone material properties by reference point indentation, as well as evaluation of cortical micro-architecture and osteocyte lacunar density. Our findings revealed a wide range of differences between the fracture group and the controls, suggesting a number of detrimental changes at various levels of cortical bone hierarchical organization that may render bone fragile. Namely, mineral crystals at external cortical bone surfaces of the fracture group were larger (65.22nm±41.21nm vs. 36.75nm±18.49nm, p<0.001), and a shift to a higher mineral content and more homogenous mineralization profile as revealed via qBEI were found in the bone matrix of the fracture group. Fracture cases showed nearly 35% higher cortical porosity and showed significantly reduced osteocyte lacunar density compared to controls (226±27 vs. 247±32#/mm(2), p=0.05). Along with increased crystal size, a shift towards higher mineralization and a tendency to increased cortical porosity and reduced osteocyte lacunar number delineate that cortical bone of the superolateral femoral neck bears distinct signs of fragility at various levels of its structural organization. These results contribute to the understanding of hierarchical bone structure changes in age-related fragility. Copyright © 2014 Elsevier Inc. All rights reserved.

A comparison of auditory evoked potentials to acoustic beats and to binaural beats.

PubMed

Pratt, Hillel; Starr, Arnold; Michalewski, Henry J; Dimitrijevic, Andrew; Bleich, Naomi; Mittelman, Nomi

2010-04-01

The purpose of this study was to compare cortical brain responses evoked by amplitude modulated acoustic beats of 3 and 6 Hz in tones of 250 and 1000 Hz with those evoked by their binaural beats counterparts in unmodulated tones to indicate whether the cortical processes involved differ. Event-related potentials (ERPs) were recorded to 3- and 6-Hz acoustic and binaural beats in 2000 ms duration 250 and 1000 Hz tones presented with approximately 1 s intervals. Latency, amplitude and source current density estimates of ERP components to beats-evoked oscillations were determined and compared across beat types, beat frequencies and base (carrier) frequencies. All stimuli evoked tone-onset components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude in response to acoustic than to binaural beats, to 250 than to 1000 Hz base frequency and to 3 Hz than to 6 Hz beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left temporal lobe areas. Differences between estimated sources of potentials to acoustic and binaural beats were not significant. The perceptions of binaural beats involve cortical activity that is not different than acoustic beats in distribution and in the effects of beat- and base frequency, indicating similar cortical processing. Copyright 2010 Elsevier B.V. All rights reserved.

Differential distribution of neurons in the gyral white matter of the human cerebral cortex.

PubMed

García-Marín, V; Blazquez-Llorca, L; Rodriguez, J R; Gonzalez-Soriano, J; DeFelipe, J

2010-12-01

The neurons in the cortical white matter (WM neurons) originate from the first set of postmitotic neurons that migrates from the ventricular zone. In particular, they arise in the subplate that contains the earliest cells generated in the telencephalon, prior to the appearance of neurons in gray matter cortical layers. These cortical WM neurons are very numerous during development, when they are thought to participate in transient synaptic networks, although many of these cells later die, and relatively few cells survive as WM neurons in the adult. We used light and electron microscopy to analyze the distribution and density of WM neurons in various areas of the adult human cerebral cortex. Furthermore, we examined the perisomatic innervation of these neurons and estimated the density of synapses in the white matter. Finally, we examined the distribution and neurochemical nature of interneurons that putatively innervate the somata of WM neurons. From the data obtained, we can draw three main conclusions: first, the density of WM neurons varies depending on the cortical areas; second, calretinin-immunoreactive neurons represent the major subpopulation of GABAergic WM neurons; and, third, the somata of WM neurons are surrounded by both glutamatergic and GABAergic axon terminals, although only symmetric axosomatic synapses were found. By contrast, both symmetric and asymmetric axodendritic synapses were observed in the neuropil. We discuss the possible functional implications of these findings in terms of cortical circuits. © 2010 Wiley-Liss, Inc.

Evaluating differential nuclear DNA yield rates and osteocyte numbers among human bone tissue types: A synchrotron radiation micro-CT approach.

PubMed

Andronowski, Janna M; Mundorff, Amy Z; Pratt, Isaac V; Davoren, Jon M; Cooper, David M L

2017-05-01

Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren's (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for a scale of analysis that revealed a high range of variation in lacunar abundance in both tissue types. Moreover, high-resolution SR micro-CT imaging revealed potential soft tissue remnants within marrow spaces not visible macroscopically. It is hypothesized that soft tissue remnants observed among the trabeculae of skeletal elements with high quantities of cancellous bone tissue are responsible for the high nuclear DNA yields. These findings have significant implications for bone-sample selection for nuclear DNA analysis in a forensic context when skeletal remains are recovered from the ground surface. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in tibial bone microarchitecture in female recruits in response to 8 weeks of U.S. Army Basic Combat Training.

PubMed

Hughes, Julie M; Gaffney-Stomberg, Erin; Guerriere, Katelyn I; Taylor, Kathryn M; Popp, Kristin L; Xu, Chun; Unnikrishnan, Ginu; Staab, Jeffery S; Matheny, Ronald W; McClung, James P; Reifman, Jaques; Bouxsein, Mary L

2018-08-01

U.S. Army Basic Combat Training (BCT) is a physically-demanding program at the start of military service. Whereas animal studies have shown that increased mechanical loading rapidly alters bone structure, there is limited evidence of changes in bone density and structure in humans exposed to a brief period of unaccustomed physical activity. We aimed to characterize changes in tibial bone density and microarchitecture and serum-based biochemical markers of bone metabolism in female recruits as a result of 8 weeks of BCT. We collected high-resolution peripheral quantitative computed tomographic images of the distal tibial metaphysis and diaphysis (4% and 30% of tibia length from the distal growth plate, respectively) and serum markers of bone metabolism before and after BCT. Linear mixed models were used to estimate the mean difference for each outcome from pre- to post-BCT, while controlling for race/ethnicity, age, and body mass index. 91 female BCT recruits volunteered and completed this observational study (age = 21.5 ± 3.3 yrs). At the distal tibial metaphysis, cortical thickness, trabecular thickness, trabecular number, bone volume/total volume, and total and trabecular volumetric bone density (vBMD) increased significantly by 1-2% (all p < 0.05) over the BCT period, whereas trabecular separation, cortical tissue mineral density (TMD), and cortical vBMD decreased significantly by 0.3-1.0% (all p < 0.05). At the tibial diaphysis, cortical vBMD and cortical TMD decreased significantly (both -0.7%, p < 0.001). Bone strength, estimated by micro finite element analysis, increased by 2.5% and 0.7% at the distal tibial metaphysis and diaphysis, respectively (both p < 0.05). Among the biochemical markers of bone metabolism, sclerostin decreased (-5.7%), whereas bone alkaline phosphatase, C-telopeptide cross-links of type 1 collagen, tartrate-resistance acid phosphatase, and 25(OH)D increased by 10-28% (all p < 0.05). BCT leads to improvements in trabecular bone microarchitecture and increases in serum bone formation markers indicative of new bone formation, as well as increases in serum bone resorption markers and decreases in cortical vBMD consistent with intracortical remodeling. Together, these results demonstrate specific changes in trabecular and cortical bone density and microarchitecture following 8 weeks of unaccustomed physical activity in women. Copyright © 2018 Elsevier Inc. All rights reserved.

Change in Mean Frequency of Resting-State Electroencephalography after Transcranial Direct Current Stimulation

PubMed Central

Boonstra, Tjeerd W.; Nikolin, Stevan; Meisener, Ann-Christin; Martin, Donel M.; Loo, Colleen K.

2016-01-01

Transcranial direct current stimulation (tDCS) is proposed as a tool to investigate cognitive functioning in healthy people and as a treatment for various neuropathological disorders. However, the underlying cortical mechanisms remain poorly understood. We aim to investigate whether resting-state electroencephalography (EEG) can be used to monitor the effects of tDCS on cortical activity. To this end we tested whether the spectral content of ongoing EEG activity is significantly different after a single session of active tDCS compared to sham stimulation. Twenty participants were tested in a sham-controlled, randomized, crossover design. Resting-state EEG was acquired before, during and after active tDCS to the left dorsolateral prefrontal cortex (15 min of 2 mA tDCS) and sham stimulation. Electrodes with a diameter of 3.14 cm2 were used for EEG and tDCS. Partial least squares (PLS) analysis was used to examine differences in power spectral density (PSD) and the EEG mean frequency to quantify the slowing of EEG activity after stimulation. PLS revealed a significant increase in spectral power at frequencies below 15 Hz and a decrease at frequencies above 15 Hz after active tDCS (P = 0.001). The EEG mean frequency was significantly reduced after both active tDCS (P < 0.0005) and sham tDCS (P = 0.001), though the decrease in mean frequency was smaller after sham tDCS than after active tDCS (P = 0.073). Anodal tDCS of the left DLPFC using a high current density bi-frontal electrode montage resulted in general slowing of resting-state EEG. The similar findings observed following sham stimulation question whether the standard sham protocol is an appropriate control condition for tDCS. PMID:27375462

Dissipation of ‘dark energy’ by cortex in knowledge retrieval

NASA Astrophysics Data System (ADS)

Capolupo, Antonio; Freeman, Walter J.; Vitiello, Giuseppe

2013-03-01

We have devised a thermodynamic model of cortical neurodynamics expressed at the classical level by neural networks and at the quantum level by dissipative quantum field theory. Our model is based on features in the spatial images of cortical activity newly revealed by high-density electrode arrays. We have incorporated the mechanism and necessity for so-called dark energy in knowledge retrieval. We have extended the model first using the Carnot cycle to define our measures for energy, entropy and temperature, and then using the Rankine cycle to incorporate criticality and phase transitions. We describe the dynamics of two interactive fields of neural activity that express knowledge, one at high and the other at low energy density, and the two operators that create and annihilate the fields. We postulate that the extremely high density of energy sequestered briefly in cortical activity patterns can account for the vividness, richness of associations, and emotional intensity of memories recalled by stimuli.

Dissipation of 'dark energy' by cortex in knowledge retrieval.

PubMed

Capolupo, Antonio; Freeman, Walter J; Vitiello, Giuseppe

2013-03-01

We have devised a thermodynamic model of cortical neurodynamics expressed at the classical level by neural networks and at the quantum level by dissipative quantum field theory. Our model is based on features in the spatial images of cortical activity newly revealed by high-density electrode arrays. We have incorporated the mechanism and necessity for so-called dark energy in knowledge retrieval. We have extended the model first using the Carnot cycle to define our measures for energy, entropy and temperature, and then using the Rankine cycle to incorporate criticality and phase transitions. We describe the dynamics of two interactive fields of neural activity that express knowledge, one at high and the other at low energy density, and the two operators that create and annihilate the fields. We postulate that the extremely high density of energy sequestered briefly in cortical activity patterns can account for the vividness, richness of associations, and emotional intensity of memories recalled by stimuli. Copyright © 2013 Elsevier B.V. All rights reserved.

Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1).

PubMed

Krøigård, Anne Bruun; Frost, Morten; Larsen, Martin Jakob; Ousager, Lilian Bomme; Frederiksen, Anja Lisbeth

2016-11-01

Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), or Taybi-Linder syndrome is characterized by distinctive skeletal dysplasia, severe intrauterine and postnatal growth retardation, microcephaly, dysmorphic features, and neurological malformations. It is an autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the RNU4ATAC gene resulting in impaired function of the minor spliceosome. Here, we present the first report on bone morphology, bone density and bone microstructure in two adult MOPD1 patients and applied radiographs, dual energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography and biochemical evaluation. The MOPD1 patients presented with short stature, low BMI but normal macroscopic bone configuration. Bone mineral density was low. Compared to Danish reference data, total bone area, cortical bone area, cortical thickness, total bone density, cortical bone density, trabecular bone density and trabecular bone volume per tissue volume (BV/TV) were all low. These findings may correlate to the short stature and low body weight of the MOPD1 patients. Our findings suggest that minor spliceosome malfunction may be associated with altered bone modelling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Long-range synchrony of gamma oscillations and auditory hallucination symptoms in schizophrenia

PubMed Central

Mulert, C.; Kirsch; Pascual-Marqui, Roberto; McCarley, Robert W.; Spencer, Kevin M.

2010-01-01

Phase locking in the gamma-band range has been shown to be diminished in patients with schizophrenia. Moreover, there have been reports of positive correlations between phase locking in the gamma-band range and positive symptoms, especially hallucinations. The aim of the present study was to use a new methodological approach in order to investigate gamma-band phase synchronization between the left and right auditory cortex in patients with schizophrenia and its relationship to auditory hallucinations. Subjects were 18 patients with chronic schizophrenia (SZ) and 16 healthy control (HC) subjects. Auditory hallucination symptom scores were obtained using the Scale for the Assessment of Positive Symptoms. Stimuli were 40-Hz binaural click trains. The generators of the 40 Hz-ASSR were localized using eLORETA and based on the computed intracranial signals lagged interhemispheric phase locking between primary and secondary auditory cortices was analyzed. Current source density of the 40 ASSR response was significantly diminished in SZ in comparison to HC in the right superior and middle temporal gyrus (p<0.05). Interhemispheric phase locking was reduced in SZ in comparison to HC for the primary auditory cortices (p<0.05) but not in the secondary auditory cortices. A significant positive correlation was found between auditory hallucination symptom scores and phase synchronization between the primary auditory cortices (p<0.05, corrected for multiple testing) but not for the secondary auditory cortices. These results suggest that long-range synchrony of gamma oscillations is disturbed in schizophrenia and that this deficit is related to clinical symptoms such as auditory hallucinations. PMID:20713096

Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency.

PubMed

Bakalov, Vladimir K; Axelrod, Lauren; Baron, Jeffrey; Hanton, Lori; Nelson, Lawrence M; Reynolds, James C; Hill, Suvimol; Troendle, James; Bondy, Carolyn A

2003-12-01

Women with Turner syndrome (TS) are at risk for osteoporosis from ovarian failure and possibly from haploinsufficiency for bone-related X-chromosome genes. To establish whether cortical or trabecular bone is predominantly affected, and to control for the ovarian failure, we studied forearm bone mineral density (BMD) in 41 women with TS ages 18-45 yr and in 35 age-matched women with karyotypically normal premature ovarian failure (POF). We measured BMD at the 1/3 distal radius (D-Rad(1/3); predominantly cortical bone) and at the ultradistal radius (UD-Rad; predominantly trabecular bone) by dual x-ray absorptiometry. Women with TS had lower cortical BMD compared with POF (D-Rad(1/3) Z-score = -1.5 +/- 0.8 for TS and 0.08 +/- 0.7 for POF; P < 0.0001). In contrast, the primarily trabecular UD-Rad BMD was normal in TS and not significantly different from POF (Z-score = -0.62 +/- 1.1 for TS and -0.34 +/- 1.0 for POF; P = 0.26). The difference in cortical BMD remained after adjustment for height, age of puberty, lifetime estrogen exposure, and serum 25-hydroxyvitamin D (P = 0.0013). Cortical BMD was independent of serum IGF-I and -II, PTH, and testosterone in TS. We conclude that there is a selective deficiency in forearm cortical bone in TS that appears independent of ovarian hormone exposure and is probably related to X-chromosome gene(s) haploinsufficiency.

Lewy body dementia--clinical, pathological and neurochemical interconnections.

PubMed

Perry, R; McKeith, I; Perry, E

1997-01-01

Senile dementia of Lewy body type or Lewy body dementia (SDLT or LBD) is defined as a Lewy body associated disease presenting in the elderly primarily with dementia with variable extrapyramidal disorder. Characteristic clinical symptoms include fluctuating cognitive impairment, psychotic features such as hallucinations and a particular sensitivity to neuroleptic medication. Although apolipoprotein e4 allele is increased 2-3 fold in SDLT (as in Alzheimer's disease) and beta-amyloidosis occurs in most cases, the most robust neurobiological correlate of the dementia so far identified appears to be extensive cholinergic deficits in the neocortex. This is consistent with previously reported correlations between cortical cholinergic activity and dementia in Parkinson's disease (PD) and Alzheimer's disease. There is also a significant interaction between the density of limbic cortical Lewy bodies and dementia in both SDLT and PD, although the cortical neuronal population affected remains to be identified. Cortical Lewy body density is positively correlated with the age of disease onset in PD and SDLT. This may account for the increased incidence of psychiatric syndromes, as opposed to extrapyramidal disorder in Lewy body disease with advancing age as may age-related loss of cholinergic activity in cortical areas such as the hippocampus.

Modelling the effect of electrode displacement on transcranial direct current stimulation (tDCS)

NASA Astrophysics Data System (ADS)

Ramaraju, Sriharsha; Roula, Mohammed A.; McCarthy, Peter W.

2018-02-01

Objective. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers a low-intensity, direct current to cortical areas with the purpose of modulating underlying brain activity. Recent studies have reported inconsistencies in tDCS outcomes. The underlying assumption of many tDCS studies has been that replication of electrode montage equates to replicating stimulation conditions. It is possible however that anatomical difference between subjects, as well as inherent inaccuracies in montage placement, could affect current flow to targeted areas. The hypothesis that stimulation of a defined brain region will be stable under small displacements was tested. Approach. Initially, we compared the total simulated current flowing through ten specific brain areas for four commonly used tDCS montages: F3-Fp2, C3-Fp2, Fp1-F4, and P3-P4 using the software tool COMETS. The effect of a slight (~1 cm in each of four directions) anode displacement on the simulated regional current density for each of the four tDCS montages was then determined. Current flow was calculated and compared through ten segmented brain areas to determine the effect of montage type and displacement. The regional currents, as well as the localised current densities, were compared with the original electrode location, for each of these new positions. Main results. Recommendations for montages that maximise stimulation current for the ten brain regions are considered. We noted that the extent to which stimulation is affected by electrode displacement varies depending on both area and montage type. The F3-Fp2 montage was found to be the least stable with up to 38% change in average current density in the left frontal lobe while the Fp1-F4 montage was found to the most stable exhibiting only 1% change when electrodes were displaced. Significance. These results indicate that even relatively small changes in stimulation electrode placement appear to result in surprisingly large changes in current densities and distribution.

Genetic and epigenetic contributions to the cortical phenotype in mammals☆

PubMed Central

Larsen, DeLaine D.; Krubitzer, Leah

2008-01-01

One aspect of cortical organization, cortical field size, is variable both within and across species. The observed variability arises from a variety of sources, including genes intrinsic to the neocortex and a number of extrinsic and epigenetic factors. Genes intrinsic to the cortex are directly involved in the development and specification of cortical fields and are regulated from both signaling centers located outside of the neocortex, which secrete diffusible molecules, and the expression of transcription factors within the neocortex. In addition, extrinsic factors such as the type, location and density of sensory receptor arrays and how these receptor arrays are utilized, are also strongly related to cortical field size. Epigenetic factors including the relative activity patterns generated by the different types of physical stimuli in a given environment also contribute to differences in cortical organization, including cortical field size. Since both genetic and epigenetic factors contribute to cortical organization, some aspects of the cortical phenotype evolve, while other aspects of the cortical phenotype persist only if the environment in which an individual develops is relatively stable. PMID:18331904

Estimation of in vivo cortical bone thickness using ultrasonic waves.

PubMed

Mano, Isao; Horii, Kaoru; Hagino, Hiroshi; Miki, Takami; Matsukawa, Mami; Otani, Takahiko

2015-07-01

To verify the measurement of cortical bone thickness at the distal radius in vivo using an ultrasonic method. The method for estimating cortical bone thickness was derived from experiments with in vitro bovine specimens. Propagation time of echo waves and propagation time of slow waves were used for the estimation. The outside diameter of cortical bone and the cortical bone thickness at the distal 5.5 % site of radius were measured with the new ultrasonic bone measurement system, and the results were compared with X-ray pQCT clinical measurements. There was a high positive correlation (r: 0.76) between the cortical bone thickness measured by the new ultrasonic system and the X-ray pQCT results. We will be able to measure not only cancellous bone density but also cortical bone thickness in vivo using ultrasonic waves (without X-ray) safely and repeatedly.

Detection of changes in bone quality of osteoporotic model induced by sciatic nerve resection by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

2018-02-01

To detect the bone quality loss in osteoporosis, we performed Raman spectroscopic analysis of sciatic nerve resection (NX) mice. Eight months after surgery, lower limbs were collected from the mice and fixed with 70% ethanol. Raman spectra of anterior cortical surface of the proximal tibia at 5 points in each bone were measured by RENISHAW inVia Raman Microscope. Excitation wave length was 785 nm. We also performed DXA and micro CT measurement to confirm the bone mineral density and bone microstructure in the osteoporotic model induced by sciatic nerve resection. In the result of Raman spectroscopy, we detected changes of Raman peak intensity ratio in carbonate/phosphate, mineral/combined proline and hydroxyproline and mineral/phenylalanine. In addition, in the result of micro CT, we found significant changes in VOX BV/TV, Trabecular number, thickness, cancellous bone mineral density, cortical thickness and cortical bone mineral density. The results suggest that not only the bone mineral density but also bone quality reduced in the NX mice. We conclude that Raman spectroscopy is a useful for bone quality assessment as a complementary technique for conventional diagnostics.

Radiographic morphometry and densitometry predict strength of cadaveric proximal humeri more reliably than age and DXA scan density.

PubMed

Skedros, John G; Knight, Alex N; Pitts, Todd C; O'Rourke, Peter J; Burkhead, Wayne Z

2016-02-01

Methods are needed for identifying poorer quality cadaver proximal humeri to ensure that they are not disproportionately segregated into experimental groups for fracture studies. We hypothesized that measurements made from radiographs of cadaveric proximal humeri are stronger predictors of fracture strength than chronological age or bone density values derived from dual-energy x-ray absorptiometry (DXA) scans. Thirty-three proximal humeri (range: 39-78 years) were analyzed for: (1) bone mineral density (BMD, g/cm(2)) using DXA, (2) bulk density (g/cm(3)) using DXA and volume displacement, (3) regional bone density in millimeters of aluminum (mmAl) using radiographs, and (4) regional mean (medial+lateral) cortical thickness and cortical index (CI) using radiographs. The bones were then fractured simulating a fall. Strongest correlations with ultimate fracture load (UFL) were: mean cortical thickness at two diaphyseal locations (r = 0.71; p < 0.001), and mean mmAl in the humeral head (r = 0.70; p < 0.001). Weaker correlations were found between UFL and DXA-BMD (r = 0.60), bulk density (r = 0.43), CI (r = 0.61), and age (r = -0.65) (p values <0.01). Analyses between UFL and the product of any two characteristics showed six combinations with r-values >0.80, but none included DXA-derived density, CI, or age. Radiographic morphometric and densitometric measurements from radiographs are therefore stronger predictors of UFL than age, CI, or DXA-derived density measurements. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool.

PubMed

Del Felice, Alessandra; Magalini, Alessandra; Masiero, Stefano

2015-01-01

Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Alterations of bone density, microstructure, and strength of the distal radius in male patients with rheumatoid arthritis: a case-control study with HR-pQCT.

PubMed

Zhu, Tracy Y; Griffith, James F; Qin, Ling; Hung, Vivian W; Fong, Tsz-Ning; Au, Sze-Ki; Li, Martin; Lam, Yvonne Yi-On; Wong, Chun-Kwok; Kwok, Anthony W; Leung, Ping-Chung; Li, Edmund K; Tam, Lai-Shan

2014-09-01

In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation. © 2014 American Society for Bone and Mineral Research.

Laminar Profile and Physiology of the α Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex.

PubMed

Haegens, Saskia; Barczak, Annamaria; Musacchia, Gabriella; Lipton, Michael L; Mehta, Ashesh D; Lakatos, Peter; Schroeder, Charles E

2015-10-21

The functional significance of the α rhythm is widely debated. It has been proposed that α reflects sensory inhibition and/or a temporal sampling or "parsing" mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate α rhythms and whether the generation of α is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed α current generators in the supragranular, granular, and infragranular layers. MUA phase-locked to local current source/sink configurations confirmed that α rhythms index local neuronal excitability fluctuations. CSD-defined α generators were strongest in the supragranular layers, whereas LFP α power was greatest in the infragranular layers, consistent with some of the previous reports. The discrepancy between LFP and CSD findings appears to be attributable to contamination of the infragranular LFP signal by activity that is volume-conducted from the stronger supragranular α generators. The presence of α generators across cortical depth in V1, S1, and A1 suggests the involvement of α in feedforward as well as feedback processes and is consistent with the view that α rhythms, perhaps in addition to a role in sensory inhibition, may parse sensory input streams in a way that facilitates communication across cortical areas. The α rhythm is thought to reflect sensory inhibition and/or a temporal parsing mechanism. Here, we address two outstanding issues: (1) whether α is a general mechanism across sensory systems and (2) which cortical layers generate α oscillations. Using intracranial recordings from macaque V1, S1, and A1, we show α band activity with a similar spectral and laminar profile in each of these sensory areas. Furthermore, α generators were present in each of the cortical layers, with a strong source in superficial layers. We argue that previous findings, locating α generators exclusively in the deeper layers, were biased because of use of less locally specific local field potential measurements. The laminar distribution of α band activity appears more complex than generally assumed. Copyright © 2015 the authors 0270-6474/15/3514341-12$15.00/0.

Laminar Profile and Physiology of the α Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex

PubMed Central

Barczak, Annamaria; Musacchia, Gabriella; Lipton, Michael L.; Mehta, Ashesh D.; Lakatos, Peter; Schroeder, Charles E.

2015-01-01

The functional significance of the α rhythm is widely debated. It has been proposed that α reflects sensory inhibition and/or a temporal sampling or “parsing” mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate α rhythms and whether the generation of α is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed α current generators in the supragranular, granular, and infragranular layers. MUA phase-locked to local current source/sink configurations confirmed that α rhythms index local neuronal excitability fluctuations. CSD-defined α generators were strongest in the supragranular layers, whereas LFP α power was greatest in the infragranular layers, consistent with some of the previous reports. The discrepancy between LFP and CSD findings appears to be attributable to contamination of the infragranular LFP signal by activity that is volume-conducted from the stronger supragranular α generators. The presence of α generators across cortical depth in V1, S1, and A1 suggests the involvement of α in feedforward as well as feedback processes and is consistent with the view that α rhythms, perhaps in addition to a role in sensory inhibition, may parse sensory input streams in a way that facilitates communication across cortical areas. SIGNIFICANCE STATEMENT The α rhythm is thought to reflect sensory inhibition and/or a temporal parsing mechanism. Here, we address two outstanding issues: (1) whether α is a general mechanism across sensory systems and (2) which cortical layers generate α oscillations. Using intracranial recordings from macaque V1, S1, and A1, we show α band activity with a similar spectral and laminar profile in each of these sensory areas. Furthermore, α generators were present in each of the cortical layers, with a strong source in superficial layers. We argue that previous findings, locating α generators exclusively in the deeper layers, were biased because of use of less locally specific local field potential measurements. The laminar distribution of α band activity appears more complex than generally assumed. PMID:26490871

Correlates of Trabecular and Cortical Volumetric Bone Mineral Density of the Radius and Tibia in Older Men: The Osteoporotic Fractures in Men Study

PubMed Central

Barbour, Kamil E; Zmuda, Joseph M; Strotmeyer, Elsa S; Horwitz, Mara J; Boudreau, Robert; Evans, Rhobert W; Ensrud, Kristine E; Petit, Moira A; Gordon, Christopher L; Cauley, Jane A

2010-01-01

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (−), caffeine intake (−), total calcium intake (+), nontrauma fracture (−), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (−), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (−), and antiandrogen use (−) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (−), androgen use (+), grip strength (+), past smoker (−), and time to complete five chair stands (−). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research. PMID:20200975

Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment.

PubMed

Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Chakravarty, M Mallar; Caravaggio, Fernando; Gerretsen, Philip; Iwata, Yusuke; Graff-Guerrero, Ariel

2016-05-01

Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia. © The Author(s) 2015.

Probing phase- and frequency-dependent characteristics of cortical interneurons using combined transcranial alternating current stimulation and transcranial magnetic stimulation.

PubMed

Hussain, Sara J; Thirugnanasambandam, Nivethida

2017-06-01

Paired-pulse transcranial magnetic stimulation (TMS) and peripheral stimulation combined with TMS can be used to study cortical interneuronal circuitry. By combining these procedures with concurrent transcranial alternating current stimulation (tACS), Guerra and colleagues recently showed that different cortical interneuronal populations are differentially modulated by the phase and frequency of tACS-imposed oscillations (Guerra A, Pogosyan A, Nowak M, Tan H, Ferreri F, Di Lazzaro V, Brown P. Cerebral Cortex 26: 3977-2990, 2016). This work suggests that different cortical interneuronal populations can be characterized by their phase and frequency dependency. Here we discuss how combining TMS and tACS can reveal the frequency at which cortical interneuronal populations oscillate, the neuronal origins of behaviorally relevant cortical oscillations, and how entraining cortical oscillations could potentially treat brain disorders. Copyright © 2017 the American Physiological Society.

Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

PubMed Central

Yang, Chun; McKenna, James T.; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika

2014-01-01

The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+ and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically projecting GABAergic/PV neurons. PMID:24553925

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats

NASA Technical Reports Server (NTRS)

Allen, Matthew R.; Bloomfield, Susan A.

2003-01-01

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

Improved selection of cortical ovarian strips for autotransplantation of ovarian tissue using full-field optical coherence tomography (FFOCT)

NASA Astrophysics Data System (ADS)

Stegehuis, Paulien L.; Peters, Inge T. A.; Eggermont, Jeroen; Kuppen, Peter J. K.; Trimbos, J. Baptist; Lelieveldt, Boudewijn P. F.; van de Velde, Cornelis J. H.; Bosse, Tjalling; Dijkstra, Jouke; Vahrmeijer, Alexander L.

2016-02-01

Premature ovarian failure is a major concern in women of reproductive age who undergo gonadotoxic cancer treatment. Autotransplantation of frozen-thawed cortical ovarian tissue allows the immediate start of cancer treatment, but risks reintroduction of cancer. Current tumor detection methods compromise the ovarian tissue's viability and can therefore only be used to exclude the presence of metastases in the cortical ovarian strips that are not transplanted. A non-invasive method is needed that can be used to exclude metastases in the actual ovarian autografts without affecting the tissue's viability. In this study we applied FFOCT - a non-fixative technique that uses white light interferometry to make highresolution images (1μm isotropic) of fresh tissue - to study healthy and malignant ovarian tissue. We created an image atlas of healthy ovarian tissues from premenopausal patients and ovarian tissues with breast cancer metastases. To get the best possible match between hematoxylin-and-eosin stained slides and FFOCT images formalinfixed paraffin-embedded tissue samples were deparaffinized and FFOCT images were acquired within a few minutes. FFOCT images were compared with histology images. All normal structures such as follicles in all phases, inclusion cysts, blood vessels, corpora lutea, and corpora albicantia were clearly recognizable. Ovarian metastases could be well distinguished from normal ovarian tissue. FFOCT is a promising technique in the field of fertility preservation: metastases can be detected and additionally cortical ovarian strips can be selected on the basis of high follicle density.

Gradients in cytoarchitectural landscapes of the isocortex: Diprotodont marsupials in comparison to eutherian mammals.

PubMed

Charvet, Christine J; Stimpson, Cheryl D; Kim, Young Do; Raghanti, Mary Ann; Lewandowski, Albert H; Hof, Patrick R; Gómez-Robles, Aida; Krienen, Fenna M; Sherwood, Chet C

2017-06-01

Although it has been claimed that marsupials possess a lower density of isocortical neurons compared with other mammals, little is known about cross-cortical variation in neuron distributions in this diverse taxonomic group. We quantified upper-layer (layers II-IV) and lower-layer (layers V-VI) neuron numbers per unit of cortical surface area in three diprotodont marsupial species (two macropodiformes, the red kangaroo and the parma wallaby, and a vombatiform, the koala) and compared these results to eutherian mammals (e.g., xenarthrans, rodents, primates). In contrast to the notion that the marsupial isocortex contains a low density of neurons, we found that neuron numbers per unit of cortical surface area in several marsupial species overlap with those found in eutherian mammals. Furthermore, neuron numbers vary systematically across the isocortex of the marsupial mammals examined. Neuron numbers under a unit of cortical surface area are low toward the frontal cortex and high toward the caudo-medial (occipital) pole. Upper-layer neurons (i.e., layers II-IV) account for most of the variation in neuron numbers across the isocortex. The variation in neuron numbers across the rostral to the caudal pole resembles primates. These findings suggest that diprotodont marsupials and eutherian mammals share a similar cortical architecture despite their distant evolutionary divergence. © 2017 Wiley Periodicals, Inc.

Skeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning.

PubMed

Stein, Emily M; Kepley, Anna; Walker, Marcella; Nickolas, Thomas L; Nishiyama, Kyle; Zhou, Bin; Liu, X Sherry; McMahon, Donald J; Zhang, Chiyuan; Boutroy, Stephanie; Cosman, Felicia; Nieves, Jeri; Guo, X Edward; Shane, Elizabeth

2014-01-01

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity.Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius.In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls,despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia.

Imaging the cortical effect of lamotrigine in patients with idiopathic generalized epilepsy: a low-resolution electromagnetic tomography (LORETA) study.

PubMed

Clemens, Béla; Piros, Pálma; Bessenyei, Mónika; Tóth, Márton; Hollódy, Katalin; Kondákor, István

2008-10-01

Anatomical localization of the cortical effect of lamotrigine (LTG) in patients with idiopathic generalized epilepsy (IGE). 19 patients with untreated IGE were investigated. EEG was recorded in the untreated condition and 3 months later when LTG treatment abolished the seizures. 19-channel EEG was recorded, and a total of 2min artifact-free, waking EEG was processed to low-resolution electromagnetic tomography (LORETA) analysis. Activity (that is, current source density, A/m(2)) was computed in four frequency bands (delta, theta, alpha, and beta), for 2394 voxels that represented the cortical gray matter and the hippocampi. Group differences between the untreated and treated conditions were computed for the four bands and all voxels by multiple t-tests for interdependent datasets. The results were presented in terms of anatomical distribution and statistical significance. p<0.01 (uncorrected) changes (decrease of activity) emerged in the theta and the alpha bands. Theta activity decreased in a large cluster of voxels including parts of the temporal, parietal, occipital cortex bilaterally, and in the transverse temporal gyri, insula, hippocampus, and uncus on the right side. Alpha activity decreased in a relatively smaller cortical area involving the right temporo-parietal junction and surrounding parts of the cortex, and part of the insula on the right side. LTG decreased theta activity in several cortical areas where abnormally increased theta activity had been found in a prior study in another cohort of untreated IGE patients [Clemens, B., Bessenyei, M., Piros, P., Tóth, M., Seress, L., Kondákor, I., 2007b. Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy. Epilepsia 48, 941-949]. These LTG-related changes might be related to the decrease of seizure propensity in IGE.

Biomechanical implications of cortical elastic properties of the macaque mandible.

PubMed

Dechow, Paul C; Panagiotopoulou, Olga; Gharpure, Poorva

2017-10-01

Knowledge of the variation in the elastic properties of mandibular cortical bone is essential for modeling bone function. Our aim was to characterize the elastic properties of rhesus macaque mandibular cortical bone and compare these to the elastic properties from mandibles of dentate humans and baboons. Thirty cylindrical samples were harvested from each of six adult female rhesus monkey mandibles. Assuming orthotropy, axes of maximum stiffness in the plane of the cortical plate were derived from ultrasound velocity measurements. Further velocity measurements with longitudinal and transverse ultrasonic transducers along with measurements of bone density were used to compute three-dimensional cortical elastic properties using equations based on Hooke's law. Results showed regional variations in the elastic properties of macaque mandibular cortical bone that have both similarities and differences with that of humans and baboons. So far, the biological and structural basis of these differences is poorly understood. Copyright © 2017 Elsevier GmbH. All rights reserved.

Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

PubMed Central

Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

2013-01-01

How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later. PMID:24155697

SU-F-J-213: Feasibility Study of Using a Dual-Energy Cone Beam CT (DECBCT) in Proton Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, H; Xing, L; Kanehira, T

2016-06-15

Purpose: The aim of this study is to evaluate the feasibility of using a dual-energy CBCT (DECBCT) in proton therapy treatment planning to allow for accurate electron density estimation. Methods: For direct comparison, two scenarios were selected: a dual-energy fan-beam CT (high: 140 kVp, low: 80 kVp) and a DECBCT (high: 125 kVp, low: 80 kVp). A Gammex 467 tissue characterization phantom was used, including the rods of air, water, bone (B2–30% mineral), cortical bone (SB3), lung (LN-300), brain, liver and adipose. For the CBCT, Hounsfield Unit (HU) numbers were first obtained from the reconstructed images after a calibration wasmore » made based on water (=0) and air materials (=−1000). For each tissue surrogate, region-of-interest (ROI) analyses were made to derive high-energy and low-energy HU values (HUhigh and HUlow), which were subsequently used to estimate electron density based on the algorithm as previously described by Hunemohr N., et al. Parameters k1 and k2 are energy dependent and can be derived from calibration materials. Results: While for the dual-energy FBCT, the electron density is found be within +/−3% error relative to the values provided by the phantom vendor: −1.8% (water), 0.03% (lung), 1.1% (brain), −2.82% (adipose), −0.49% (liver) and −1.89% (cortical bones). While for the DECBCT, the estimation of electron density exhibits a relatively larger variation: −1.76% (water), −36.7% (lung), −1.92% (brain), −3.43% (adipose), 8.1% (liver) and 9.5% (cortical bones). Conclusion: For DECBCT, the accuracy of electron density estimation is inferior to that of a FBCT, especially for materials of either low-density (lung) or high density (cortical bone) compared to water. Such limitation arises from inaccurate HU number derivation in a CBCT. Advanced scatter-correction and HU calibration routines, as well as the deployment of photon counting CT detectors need be investigated to minimize the difference between FBCT and CBCT.« less

Mild prenatal protein malnutrition increases alpha2C-adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long-term potentiation and visuo-spatial performance in rats.

PubMed

Soto-Moyano, Rubén; Valladares, Luis; Sierralta, Walter; Pérez, Hernán; Mondaca, Mauricio; Fernández, Victor; Burgos, Héctor; Hernández, Alejandro

2005-06-01

Mild reduction in the protein content of the mother's diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long-term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the alpha2C-adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo-spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical alpha2C-adrenoceptor density. At 60 days-of-age, alpha2C-adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo-spatial memory performance. Results suggest that overexpression of neocortical alpha2C-adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo-spatial memory formation.

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle

PubMed Central

Fernández-Corazza, Mariano; Turovets, Sergei; Luu, Phan; Anderson, Erik; Tucker, Don

2016-01-01

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints. PMID:27303311

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle.

PubMed

Fernández-Corazza, Mariano; Turovets, Sergei; Luu, Phan; Anderson, Erik; Tucker, Don

2016-01-01

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints.

A biomechanical study comparing a raft of 3.5 mm cortical screws with 6.5 mm cancellous screws in depressed tibial plateau fractures.

PubMed

Patil, Sunit; Mahon, Andrew; Green, Sarah; McMurtry, Ian; Port, Andrew

2006-06-01

There has been a recent trend towards using a raft of small diameter 3.5mm cortical screws for supporting depressed tibial plateau fractures (Schatzker type III). Our aim was to compare the biomechanical properties of a raft of 3.5 mm cortical screws with that of 6.5 mm cancellous screws in a synthetic bone model. Ten rigid polyurethane foam (sawbone) blocks, with a density simulating osteoporotic bone and ten blocks with a density simulating normal density bone were obtained. A Schatzker type III fracture was created in each block. The fracture fragments were then elevated and supported using two 6.5 mm cancellous screws in ten blocks and four 3.5 mm cortical screws in the remaining. The fractures were loaded using a Lloyd testing machine. The mean force needed to produce a depression of 5 mm was 700.8 N with the four-screw construct and 512.4 N with the two-screw construct in the osteoporotic model. This difference was highly statistically significant (p = 0.009). The mean force required to produce the same depression was 1878.2 N with the two-screw construct and 1938.2 N with the four-screw construct in the non-osteoporotic model. Though the difference was not statistically significant (p = 0.42), an increased fragmentation of the synthetic bone fragments was noticed with the two-screw construct but not with the four-screw construct. A raft of four 3.5 mm cortical screws is biomechanically stronger than two 6.5 mm cancellous screws in resisting axial compression in osteoporotic bone.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields

PubMed Central

Ruffini, Giulio; Fox, Michael D.; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-01-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint of the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). PMID:24345389

Macroscopic neural mass model constructed from a current-based network model of spiking neurons.

PubMed

Umehara, Hiroaki; Okada, Masato; Teramae, Jun-Nosuke; Naruse, Yasushi

2017-02-01

Neural mass models (NMMs) are efficient frameworks for describing macroscopic cortical dynamics including electroencephalogram and magnetoencephalogram signals. Originally, these models were formulated on an empirical basis of synaptic dynamics with relatively long time constants. By clarifying the relations between NMMs and the dynamics of microscopic structures such as neurons and synapses, we can better understand cortical and neural mechanisms from a multi-scale perspective. In a previous study, the NMMs were analytically derived by averaging the equations of synaptic dynamics over the neurons in the population and further averaging the equations of the membrane-potential dynamics. However, the averaging of synaptic current assumes that the neuron membrane potentials are nearly time invariant and that they remain at sub-threshold levels to retain the conductance-based model. This approximation limits the NMM to the non-firing state. In the present study, we newly propose a derivation of a NMM by alternatively approximating the synaptic current which is assumed to be independent of the membrane potential, thus adopting a current-based model. Our proposed model releases the constraint of the nearly constant membrane potential. We confirm that the obtained model is reducible to the previous model in the non-firing situation and that it reproduces the temporal mean values and relative power spectrum densities of the average membrane potentials for the spiking neurons. It is further ensured that the existing NMM properly models the averaged dynamics over individual neurons even if they are spiking in the populations.

Low serum vitamin D is associated with higher cortical porosity in elderly men.

PubMed

Sundh, D; Mellström, D; Ljunggren, Ö; Karlsson, M K; Ohlsson, C; Nilsson, M; Nilsson, A G; Lorentzon, M

2016-11-01

Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L -1 ) or insufficiency [25-49 nmol L -1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04). Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

[Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

PubMed

Furong, Liu; Shengtian, L I

2016-05-25

To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

Defects in cortical microarchitecture among African-American women with type 2 diabetes

PubMed Central

Yu, Elaine W.; Putman, Melissa S.; Derrico, Nicolas; Abrishamanian-Garcia, Gabriela; Finkelstein, Joel S.; Bouxsein, Mary L.

2015-01-01

Introduction/Purpose Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure. Methods We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR. Results Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r=−0.54, p=0.018). Conclusions DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2. PMID:25398431

Jealousy increased by induced relative left frontal cortical activity.

PubMed

Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

2015-10-01

Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance.

PubMed

Kim, Garam; Vahedi, Shahrooz; Gefen, Tamar; Weintraub, Sandra; Bigio, Eileen H; Mesulam, Marek-Marsel; Geula, Changiz

2018-01-30

To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language- and memory-related cortical regions. Clinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere. The distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology. © 2018 American Academy of Neurology.

MDMA ("Ecstasy") and its association with cerebrovascular accidents: preliminary findings.

PubMed

Reneman, L; Habraken, J B; Majoie, C B; Booij, J; den Heeten, G J

2000-01-01

Abuse of the popular recreational drug "Ecstasy" (MDMA) has been linked to the occurrence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT(2) receptors play a role in the regulation of brain microvasculature. Therefore, we used brain imaging to find out whether MDMA use predisposes one to cerebrovascular accidents by altering brain 5-HT neurotransmission. The effects of MDMA use on brain cortical 5-HT(2A) receptor densities were studied using [(123)I]R91150 single-photon emission CT in 10 abstinent recent MDMA users, five former MDMA users, and 10 healthy control subjects. Furthermore, to examine whether changes in brain 5-HT(2A) receptor densities are associated with alterations in blood vessel volumes, we calculated relative cerebral blood volume maps from dynamic MR imaging sets in five MDMA users and six healthy control subjects. An analysis of variance revealed that mean cortical [(123)I]R91150 binding ratios were significantly lower in recent MDMA users than in former MDMA users and control subjects. This finding suggests down-regulation of 5-HT(2) receptors caused by MDMA-induced 5-HT release. Furthermore, in MDMA users, low cortical 5-HT(2) receptor densities were significantly associated with low cerebral blood vessel volumes (implicating vasoconstriction) and high cortical 5-HT(2) receptor densities with high cerebral blood vessel volumes (implicating vasodilatation) in specific brain regions. These findings suggest a relationship between the serotonergic system and an altered regulation of 5-HT(2) receptors in human MDMA users. MDMA users may therefore be at risk for cerebrovascular accidents resulting from alterations in the 5-HT neurotransmission system.

Markedly Lower Glutamic Acid Decarboxylase 67 Protein Levels in a Subset of Boutons in Schizophrenia.

PubMed

Rocco, Brad R; Lewis, David A; Fish, Kenneth N

2016-06-15

Convergent findings indicate that cortical gamma-aminobutyric acid (GABA)ergic circuitry is altered in schizophrenia. Postmortem studies have consistently found lower levels of glutamic acid decarboxylase 67 (GAD67) messenger RNA (mRNA) in the prefrontal cortex (PFC) of subjects with schizophrenia. At the cellular level, the density of GABA neurons with detectable levels of GAD67 mRNA is ~30% lower across cortical layers. Knowing how this transcript deficit translates to GAD67 protein levels in axonal boutons is important for understanding the impact it might have on GABA synthesis. In addition, because reductions in GAD67 expression before, but not after, the maturation of GABAergic boutons results in a lower density of GABAergic boutons in mouse cortical cultures, knowing if GABAergic bouton density is altered in schizophrenia would provide insight into the timing of the GAD67 deficit. PFC tissue sections from 20 matched pairs of schizophrenia and comparison subjects were immunolabeled for the vesicular GABA transporter (vGAT) and GAD67. vGAT+ bouton density did not differ between subject groups, consistent with findings that vGAT mRNA levels are unaltered in the illness and confirming that the number of cortical GABAergic boutons is not lower in schizophrenia. In contrast, in schizophrenia subjects, the proportion of vGAT+ boutons with detectable GAD67 levels (vGAT+/GAD67+ boutons) was 16% lower and mean GAD67 levels were 14% lower in the remaining vGAT+/GAD67+ boutons. Our findings suggest that GABA production is markedly reduced in a subset of boutons in the PFC of schizophrenia subjects and that this reduction likely occurs after the maturation of GABAergic boutons. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Pulse Wave Amplitude Drops during Sleep are Reliable Surrogate Markers of Changes in Cortical Activity

PubMed Central

Delessert, Alexandre; Espa, Fabrice; Rossetti, Andrea; Lavigne, Gilles; Tafti, Mehdi; Heinzer, Raphael

2010-01-01

Background: During sleep, sudden drops in pulse wave amplitude (PWA) measured by pulse oximetry are commonly associated with simultaneous arousals and are thought to result from autonomic vasoconstriction. In the present study, we determine whether PWA drops were associated with changes in cortical activity as determined by EEG spectral analysis. Methods: A 20% decrease in PWA was chosen as a minimum for a drop. A total of 1085 PWA drops from 10 consecutive sleep recordings were analyzed. EEG spectral analysis was performed over 5 consecutive epochs of 5 seconds: 2 before, 1 during, and 2 after the PWA drop. EEG spectral analysis was performed over delta, theta, alpha, sigma, and beta frequency bands. Within each frequency band, power density was compared across the five 5-sec epochs. Presence or absence of visually scored EEG arousals were adjudicated by an investigator blinded to the PWA signal and considered associated with PWA drop if concomitant. Results: A significant increase in EEG power density in all EEG frequency bands was found during PWA drops (P < 0.001) compared to before and after drop. Even in the absence of visually scored arousals, PWA drops were associated with a significant increase in EEG power density (P < 0.001) in most frequency bands. Conclusions: Drops in PWA are associated with a significant increase in EEG power density, suggesting that these events can be used as a surrogate for changes in cortical activity during sleep. This approach may prove of value in scoring respiratory events on limited-channel (type III) portable monitors. Citation: Delessert A; Espa F; Rossetti A; Lavigne G; Tafti M; Heinzer R. Pulse wave amplitude drops during sleep are reliable surrogate markers of changes in cortical activity. SLEEP 2010;33(12):1687-1692. PMID:21120131

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

PubMed

Duff, Whitney R D; Chilibeck, Philip D; Candow, Darren G; Gordon, Julianne J; Mason, Riley S; Taylor-Gjevre, Regina; Nair, Bindu; Szafron, Michael; Baxter-Jones, Adam; Zello, Gordon A; Kontulainen, Saija A

2017-04-01

Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

Optimizing finite element predictions of local subchondral bone structural stiffness using neural network-derived density-modulus relationships for proximal tibial subchondral cortical and trabecular bone.

PubMed

Nazemi, S Majid; Amini, Morteza; Kontulainen, Saija A; Milner, Jaques S; Holdsworth, David W; Masri, Bassam A; Wilson, David R; Johnston, James D

2017-01-01

Quantitative computed tomography based subject-specific finite element modeling has potential to clarify the role of subchondral bone alterations in knee osteoarthritis initiation, progression, and pain. However, it is unclear what density-modulus equation(s) should be applied with subchondral cortical and subchondral trabecular bone when constructing finite element models of the tibia. Using a novel approach applying neural networks, optimization, and back-calculation against in situ experimental testing results, the objective of this study was to identify subchondral-specific equations that optimized finite element predictions of local structural stiffness at the proximal tibial subchondral surface. Thirteen proximal tibial compartments were imaged via quantitative computed tomography. Imaged bone mineral density was converted to elastic moduli using multiple density-modulus equations (93 total variations) then mapped to corresponding finite element models. For each variation, root mean squared error was calculated between finite element prediction and in situ measured stiffness at 47 indentation sites. Resulting errors were used to train an artificial neural network, which provided an unlimited number of model variations, with corresponding error, for predicting stiffness at the subchondral bone surface. Nelder-Mead optimization was used to identify optimum density-modulus equations for predicting stiffness. Finite element modeling predicted 81% of experimental stiffness variance (with 10.5% error) using optimized equations for subchondral cortical and trabecular bone differentiated with a 0.5g/cm 3 density. In comparison with published density-modulus relationships, optimized equations offered improved predictions of local subchondral structural stiffness. Further research is needed with anisotropy inclusion, a smaller voxel size and de-blurring algorithms to improve predictions. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-resolution EEG techniques for brain-computer interface applications.

PubMed

Cincotti, Febo; Mattia, Donatella; Aloise, Fabio; Bufalari, Simona; Astolfi, Laura; De Vico Fallani, Fabrizio; Tocci, Andrea; Bianchi, Luigi; Marciani, Maria Grazia; Gao, Shangkai; Millan, Jose; Babiloni, Fabio

2008-01-15

High-resolution electroencephalographic (HREEG) techniques allow estimation of cortical activity based on non-invasive scalp potential measurements, using appropriate models of volume conduction and of neuroelectrical sources. In this study we propose an application of this body of technologies, originally developed to obtain functional images of the brain's electrical activity, in the context of brain-computer interfaces (BCI). Our working hypothesis predicted that, since HREEG pre-processing removes spatial correlation introduced by current conduction in the head structures, by providing the BCI with waveforms that are mostly due to the unmixed activity of a small cortical region, a more reliable classification would be obtained, at least when the activity to detect has a limited generator, which is the case in motor related tasks. HREEG techniques employed in this study rely on (i) individual head models derived from anatomical magnetic resonance images, (ii) distributed source model, composed of a layer of current dipoles, geometrically constrained to the cortical mantle, (iii) depth-weighted minimum L(2)-norm constraint and Tikhonov regularization for linear inverse problem solution and (iv) estimation of electrical activity in cortical regions of interest corresponding to relevant Brodmann areas. Six subjects were trained to learn self modulation of sensorimotor EEG rhythms, related to the imagination of limb movements. Off-line EEG data was used to estimate waveforms of cortical activity (cortical current density, CCD) on selected regions of interest. CCD waveforms were fed into the BCI computational pipeline as an alternative to raw EEG signals; spectral features are evaluated through statistical tests (r(2) analysis), to quantify their reliability for BCI control. These results are compared, within subjects, to analogous results obtained without HREEG techniques. The processing procedure was designed in such a way that computations could be split into a setup phase (which includes most of the computational burden) and the actual EEG processing phase, which was limited to a single matrix multiplication. This separation allowed to make the procedure suitable for on-line utilization, and a pilot experiment was performed. Results show that lateralization of electrical activity, which is expected to be contralateral to the imagined movement, is more evident on the estimated CCDs than in the scalp potentials. CCDs produce a pattern of relevant spectral features that is more spatially focused, and has a higher statistical significance (EEG: 0.20+/-0.114 S.D.; CCD: 0.55+/-0.16 S.D.; p=10(-5)). A pilot experiment showed that a trained subject could utilize voluntary modulation of estimated CCDs for accurate (eight targets) on-line control of a cursor. This study showed that it is practically feasible to utilize HREEG techniques for on-line operation of a BCI system; off-line analysis suggests that accuracy of BCI control is enhanced by the proposed method.

Adaptations in tibial cortical thickness and total volumetric bone density in postmenopausal South Asian women with small bone size.

PubMed

Darling, Andrea L; Hakim, Ohood A; Horton, Khim; Gibbs, Michelle A; Cui, Liang; Berry, Jacqueline L; Lanham-New, Susan A; Hart, Kathryn H

2013-07-01

There is some evidence that South Asian women may have an increased risk of osteoporosis compared with Caucasian women, although whether South Asians are at increased risk of fracture is not clear. It is unknown whether older South Asian women differ from Caucasian women in bone geometry. This is the first study, to the authors' knowledge, to use peripheral Quantitative Computed Tomography (pQCT) to measure radial and tibial bone geometry in postmenopausal South Asian women. In comparison to Caucasian women, Asian women had smaller bone size at the 4% (-18% p<0.001) and 66% radius (-15% p=0.04) as well as increased total density at the 4% (+13% p=0.01) radius. For the tibia, they had a smaller bone size at the 4% (-16% p=0.005) and 14% (-38% p=0.002) sites. Also, Asians had increased cortical thickness (-17% p=0.04) at the 38% tibia, (in proportion to bone size (-30% p=0.003)). Furthermore, at the 4% and 14% tibia there were increased total densities (+12% to +29% p<0.01) and at the 14% tibia there was increased cortical density (+5% p=0.005) in Asians. These differences at the 14% and 38% (but not 4%) remained statistically significant after adjustment for Body Mass Index (BMI). These adaptations are similar to those seen previously in Chinese women. Asian women had reduced strength at the radius and tibia, evidenced by the 20-40% reduction in both polar Strength Strain Index (SSIp) and fracture load (under bending). Overall, the smaller bone size in South Asians is likely to be detrimental to bone strength, despite some adaptations in tibial cortical thickness and tibial and radial density which may partially compensate for this. Copyright © 2013 Elsevier Inc. All rights reserved.

Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease

PubMed Central

Lax, Nichola Z.; Grady, John; Laude, Alex; Chan, Felix; Hepplewhite, Philippa D.; Gorman, Grainne; Whittaker, Roger G.; Ng, Yi; Cunningham, Mark O.

2015-01-01

Aims Mitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ‐aminobutyric acid (GABA)‐ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease. Methods Histochemical, immunohistochemical and immunofluorescent assays were performed on post‐mortem brain tissue from 10 patients and 10 age‐matched control individuals. We applied a quantitative immunofluorescent method to interrogate complex I and IV protein expression in mitochondria within GABAergic interneurone populations in the frontal, temporal and occipital cortices. We also evaluated the density of inhibitory interneurones in serial sections to determine if cell loss was occurring. Results We observed significant, global reductions in complex I expression within GABAergic interneurones in frontal, temporal and occipital cortices in the majority of patients. While complex IV expression is more variable, there is reduced expression in patients harbouring m.8344A>G point mutations and POLG mutations. In addition to the severe respiratory chain deficiencies observed in remaining interneurones, quantification of GABAergic cell density showed a dramatic reduction in cell density suggesting interneurone loss. Conclusions We propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease. PMID:25786813

Use of functional near-infrared spectroscopy to monitor cortical plasticity induced by transcranial direct current stimulation

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hervey, Nathan; Stowe, Ann; Hodics, Timea; Alexandrakis, George

2013-03-01

Electrical stimulation of the human cortex in conjunction with physical rehabilitation has been a valuable approach in facilitating the plasticity of the injured brain. One such method is transcranial direct current stimulation (tDCS) which is a non-invasive method to elicit neural stimulation by delivering current through electrodes placed on the scalp. In order to better understand the effects tDCS has on cortical plasticity, neuroimaging techniques have been used pre and post tDCS stimulation. Recently, neuroimaging methods have discovered changes in resting state cortical hemodynamics after the application of tDCS on human subjects. However, analysis of the cortical hemodynamic activity for a physical task during and post tDCS stimulation has not been studied to our knowledge. A viable and sensitive neuroimaging method to map changes in cortical hemodynamics during activation is functional near-infrared spectroscopy (fNIRS). In this study, the cortical activity during an event-related, left wrist curl task was mapped with fNIRS before, during, and after tDCS stimulation on eight healthy adults. Along with the fNIRS optodes, two electrodes were placed over the sensorimotor hand areas of both brain hemispheres to apply tDCS. Changes were found in both resting state cortical connectivity and cortical activation patterns that occurred during and after tDCS. Additionally, changes to surface electromyography (sEMG) measurements of the wrist flexor and extensor of both arms during the wrist curl movement, acquired concurrently with fNIRS, were analyzed and related to the transient cortical plastic changes induced by tDCS.

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

PubMed Central

Ballesteros-Yáñez, Inmaculada; Benavides-Piccione, Ruth; Bourgeois, Jean-Pierre; Changeux, Jean-Pierre; DeFelipe, Javier

2010-01-01

The neuronal nicotinic acetylcholine receptors (nAChRs) are allosteric membrane proteins involved in multiple cognitive processes, including attention, learning, and memory. The most abundant form of heterooligomeric nAChRs in the brain contains the β2- and α4- subunits and binds nicotinic agonists with high affinity. In the present study, we investigated in the mouse the consequences of the deletion of one of the nAChR components: the β2-subunit (β2−/−) on the microanatomy of cortical pyramidal cells. Using an intracellular injection method, complete basal dendritic arbors of 650 layer III pyramidal neurons were sampled from seven cortical fields, including primary sensory, motor, and associational areas, in both β2−/− and WT animals. We observed that the pyramidal cell phenotype shows significant quantitative differences among different cortical areas in mutant and WT mice. In WT mice, the density of dendritic spines was rather similar in all cortical fields, except in the prelimbic/infralimbic cortex, where it was significantly higher. In the absence of the β2-subunit, the most significant reduction in the density of spines took place in this high-order associational field. Our data suggest that the β2-subunit is involved in the dendritic morphogenesis of pyramidal neurons and, in particular, in the circuits that contribute to the high-order functional connectivity of the cerebral cortex. PMID:20534523

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

PubMed

Li, Chuanming; Wang, Jian; Gui, Li; Zheng, Jian; Liu, Chen; Du, Hanjian

2011-01-01

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

Cortical Serotonin Type-2 Receptor Density in Parents of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Goldberg, Jeremy; Anderson, George M.; Zwaigenbaum, Lonnie; Hall, Geoffrey B. C.; Nahmias, Claude; Thompson, Ann; Szatmari, Peter

2009-01-01

Parents (N = 19) of children with autism spectrum disorders (ASD) and adult controls (N = 17) underwent positron emission tomography (PET) using [[superscript 18]F]setoperone to image cortical serotonin type-2 (5-HT2) receptors. The 5-HT2 binding potentials (BPs) were calculated by ratioing [[superscript 18]F]setoperone intensity in regions of…

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes

PubMed Central

Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M.; Batista, Claudia Maria de Castro; Mattson, Mark P.; de Mello Coelho, Valeria

2016-01-01

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN+ LLC. Some cortical NeuN+ neurons, GFAP+ glia limitans astrocytes, Iba-1+ microglia and S100β+ ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

PubMed

Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

2016-03-31

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes.

Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

PubMed

Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

2018-06-01

Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

Histomorphometry and cortical robusticity of the adult human femur.

PubMed

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

Abnormal functional connectivity density in children with anisometropic amblyopia at resting-state.

PubMed

Wang, Tianyue; Li, Qian; Guo, Mingxia; Peng, Yanmin; Li, Qingji; Qin, Wen; Yu, Chunshui

2014-05-14

Amblyopia is a developmental disorder resulting from anomalous binocular visual input in early life. Task-based neuroimaging studies have widely investigated cortical functional impairments in amblyopia, but changes in spontaneous neuronal functional activities in amblyopia remain largely unknown. In the present study, functional connectivity density (FCD) mapping, an ultrafast data-driven method based on fMRI, was applied for the first time to investigate changes in cortical functional connectivities in amblyopia during the resting-state. We quantified and compared both short- and long-range FCD in both the brains of children with anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to the NSC, the AAC showed significantly decreased short-range FCD in the inferior temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices, as well as decreased long-range FCD in the premotor cortex, dorsal inferior parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore, most regions with reduced long-range FCD in the AAC showed decreased functional connectivity with occipital and posterior parietal cortices in the AAC. The results suggest that chronically poor visual input in amblyopia not only impairs the brain's short-range functional connections in visual pathways and in the frontal cortex, which is important for cognitive control, but also affects long-range functional connections among the visual areas, posterior parietal and frontal cortices that subserve visuomotor and visual-guided actions, visuospatial attention modulation and the integration of salient information. This study provides evidence for abnormal spontaneous brain activities in amblyopia. Copyright © 2014 Elsevier B.V. All rights reserved.

The auditory P50 component to onset and offset of sound

PubMed Central

Pratt, Hillel; Starr, Arnold; Michalewski, Henry J.; Bleich, Naomi; Mittelman, Nomi

2008-01-01

Objective: The auditory Event-Related Potentials (ERP) component P50 to sound onset and offset have been reported to be similar, but their magnetic homologue has been reported absent to sound offset. We compared the spatio-temporal distribution of cortical activity during P50 to sound onset and offset, without confounds of spectral change. Methods: ERPs were recorded in response to onsets and offsets of silent intervals of 0.5 s (gaps) appearing randomly in otherwise continuous white noise and compared to ERPs to randomly distributed click pairs with half second separation presented in silence. Subjects were awake and distracted from the stimuli by reading a complicated text. Measures of P50 included peak latency and amplitude, as well as source current density estimates to the clicks and sound onsets and offsets. Results P50 occurred in response to noise onsets and to clicks, while to noise offset it was absent. Latency of P50 was similar to noise onset (56 msec) and to clicks (53 msec). Sources of P50 to noise onsets and clicks included bilateral superior parietal areas. In contrast, noise offsets activated left inferior temporal and occipital areas at the time of P50. Source current density was significantly higher to noise onset than offset in the vicinity of the temporo-parietal junction. Conclusions: P50 to sound offset is absent compared to the distinct P50 to sound onset and to clicks, at different intracranial sources. P50 to stimulus onset and to clicks appears to reflect preattentive arousal by a new sound in the scene. Sound offset does not involve a new sound and hence the absent P50. Significance: Stimulus onset activates distinct early cortical processes that are absent to offset. PMID:18055255

Psychogenic seizures and frontal disconnection: EEG synchronisation study.

PubMed

Knyazeva, Maria G; Jalili, Mahdi; Frackowiak, Richard S; Rossetti, Andrea O

2011-05-01

Psychogenic non-epileptic seizures (PNES) are paroxysmal events that, in contrast to epileptic seizures, are related to psychological causes without the presence of epileptiform EEG changes. Recent models suggest a multifactorial basis for PNES. A potentially paramount, but currently poorly understood factor is the interplay between psychiatric features and a specific vulnerability of the brain leading to a clinical picture that resembles epilepsy. Hypothesising that functional cerebral network abnormalities may predispose to the clinical phenotype, the authors undertook a characterisation of the functional connectivity in PNES patients. The authors analysed the whole-head surface topography of multivariate phase synchronisation (MPS) in interictal high-density EEG of 13 PNES patients as compared with 13 age- and sex-matched controls. MPS mapping reduces the wealth of dynamic data obtained from high-density EEG to easily readable synchronisation maps, which provide an unbiased overview of any changes in functional connectivity associated with distributed cortical abnormalities. The authors computed MPS maps for both Laplacian and common-average-reference EEGs. In a between-group comparison, only patchy, non-uniform changes in MPS survived conservative statistical testing. However, against the background of these unimpressive group results, the authors found widespread inverse correlations between individual PNES frequency and MPS within the prefrontal and parietal cortices. PNES appears to be associated with decreased prefrontal and parietal synchronisation, possibly reflecting dysfunction of networks within these regions.

Cortical thickness abnormalities in trichotillomania: international multi-site analysis.

PubMed

Chamberlain, Samuel R; Harries, Michael; Redden, Sarah A; Keuthen, Nancy J; Stein, Dan J; Lochner, Christine; Grant, Jon E

2018-06-01

Trichotillomania is a prevalent but often hidden psychiatric condition, characterized by repetitive hair pulling. The aim of this study was to confirm or refute structural brain abnormalities in trichotillomania by pooling all available global data. De-identified MRI scans were pooled by contacting authors of previous studies. Cortical thickness and sub-cortical volumes were compared between patients and controls. Patients (n = 76) and controls (n = 41) were well-matched in terms of demographic characteristics. Trichotillomania patients showed excess cortical thickness in a cluster maximal at right inferior frontal gyrus, unrelated to symptom severity. No significant sub-cortical volume differences were detected in the regions of interest. Morphometric changes in the right inferior frontal gyrus appear to play a central role in the pathophysiology of trichotillomania, and to be trait in nature. The findings are distinct from other impulsive-compulsive disorders (OCD, ADHD, gambling disorder), which have typically been associated with reduced, rather than increased, cortical thickness. Future work should examine sub-cortical and cerebellar morphology using analytic approaches designed for this purpose, and should also characterize grey matter densities/volumes.

Elastic Properties of Chimpanzee Craniofacial Cortical Bone

PubMed Central

Gharpure, Poorva; Kontogiorgos, Elias D.; Opperman, Lynne A.; Ross, Callum F.; Strait, David S.; Smith, Amanda; Pryor, Leslie C.; Wang, Qian; Dechow, Paul C.

2017-01-01

Relatively few assessments of cranial biomechanics formally take into account variation in the material properties of cranial cortical bone. Our aim was to characterize the elastic properties of chimpanzee craniofacial cortical bone and compare these to the elastic properties of dentate human craniofacial cortical bone. From seven cranial regions, 27 cylindrical samples were harvested from each of five chimpanzee crania. Assuming orthotropy, axes of maximum stiffness in the plane of the cortical plate were derived using modified equations of Hooke’s law in a Mathcad program. Consistent orientations among individuals were observed in the zygomatic arch and alveolus. The density of cortical bone showed significant regional variation (P<0.001). The elastic moduli demonstrated significant differences between sites, and a distinct pattern where E3 >E2 > E1. Shear moduli were significantly different among regions (P<0.001). The pattern by which chimpanzee cranial cortical bone varies in elastic properties resembled that seen in humans, perhaps suggesting that the elastic properties of craniofacial bone in fossil hominins can be estimated with at least some degree of confidence. PMID:27870344

No differences in calcium-binding protein immunoreactivity in the posterior cingulate and visual cortex: schizophrenia and controls.

PubMed

Wheeler, David G; Dixon, Gavin; Harper, Clive G

2006-06-01

Schizophrenia-specific alterations in the densities of interneurons immunoreactive (ir) to the calcium binding proteins are reported for several cortical regions. However, no reported studies have searched for such differences within the posterior cingulate cortex using antibodies to a specific calcium binding protein, calbindin (Cb). Compare the (a) relative density of Cb-ir neurons (ratio of labeled neurons to total neurons), (b) relative width of cortical layers II/III and (c) somal areas of Cb-ir neurons in people with schizophrenia and non-psychiatric age-, gender- and postmortem index-matched controls (9 per group). Tissue from Brodmann's area (BA) 30 and 23 and an internal control region, the visual cortex (BA 18) were labeled with polyclonal Cb antibodies then Nissl counter-stained. Cb-ir neurons as well as counter-stained neurons with clearly visible nucleoli were plotted and counted within their area 1 and laminar boundaries. No qualitative or statistical differences in the relative density of Cb-ir neurons were observed. A trend towards a significant effect was detected in BA 30, the relative density of Cb-ir neurons for controls was greater than for schizophrenics (P=0.0518). There were no significant differences in the relative cortical widths or somal areas. The data from this study suggest that the posterior cingulate cortex may not be involved in schizophrenia, at least not as far as Cb-ir neurons are concerned.

Spatiotemporal relationships between the cell shape and the actomyosin cortex of periodically protruding cells

PubMed Central

Driscoll, Meghan K.; Losert, Wolfgang; Jacobson, Ken

2015-01-01

We investigate the dynamics of cell shape and analyze the actin and myosin distributions of cells exhibiting cortical density traveling waves. These waves propagate by repeated cycles of cortical compression (folding) and dilation (unfolding) that lead to periodic protrusions (oscillations) of the cell boundary. The focus of our detailed analysis is the remarkable periodicity of this phenotype, in which both the overall shape transformation and distribution of actomyosin density are repeated from cycle to cycle even though the characteristics of the shape transformation vary significantly for different regions of the cell. We show, using correlation analysis, that during traveling wave propagation cortical actin and plasma membrane densities are tightly coupled at each point along the cell periphery. We also demonstrate that the major protrusion appears at the wave trailing edge just after the actin cortex density has reached a maximum. Making use of the extraordinary periodicity, we employ latrunculin to demonstrate that sequestering actin monomers can have two distinct effects: low latrunculin concentrations can trigger and enhance traveling waves but higher concentrations of this drug retard the waves. The fundamental mechanism underlying this periodically protruding phenotype, involving folding and unfolding of the cortex‐membrane couple, is likely to hold important clues for diverse phenomena including cell division and amoeboid‐type migration. © 2015 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc. PMID:26147497

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions

PubMed Central

Intskirveli, Irakli

2017-01-01

Abstract Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral “notch” of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing. PMID:28660244

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions.

PubMed

Askew, Caitlin; Intskirveli, Irakli; Metherate, Raju

2017-01-01

Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral "notch" of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing.

Simultaneous EEG and MEG source reconstruction in sparse electromagnetic source imaging.

PubMed

Ding, Lei; Yuan, Han

2013-04-01

Electroencephalography (EEG) and magnetoencephalography (MEG) have different sensitivities to differently configured brain activations, making them complimentary in providing independent information for better detection and inverse reconstruction of brain sources. In the present study, we developed an integrative approach, which integrates a novel sparse electromagnetic source imaging method, i.e., variation-based cortical current density (VB-SCCD), together with the combined use of EEG and MEG data in reconstructing complex brain activity. To perform simultaneous analysis of multimodal data, we proposed to normalize EEG and MEG signals according to their individual noise levels to create unit-free measures. Our Monte Carlo simulations demonstrated that this integrative approach is capable of reconstructing complex cortical brain activations (up to 10 simultaneously activated and randomly located sources). Results from experimental data showed that complex brain activations evoked in a face recognition task were successfully reconstructed using the integrative approach, which were consistent with other research findings and validated by independent data from functional magnetic resonance imaging using the same stimulus protocol. Reconstructed cortical brain activations from both simulations and experimental data provided precise source localizations as well as accurate spatial extents of localized sources. In comparison with studies using EEG or MEG alone, the performance of cortical source reconstructions using combined EEG and MEG was significantly improved. We demonstrated that this new sparse ESI methodology with integrated analysis of EEG and MEG data could accurately probe spatiotemporal processes of complex human brain activations. This is promising for noninvasively studying large-scale brain networks of high clinical and scientific significance. Copyright © 2011 Wiley Periodicals, Inc.

The peak bone mass concept: is it still relevant?

PubMed

Schönau, Eckhard

2004-08-01

The peak bone mass concept implies that optimal skeletal development during childhood and adolescence will prevent fractures in late adulthood. This concept is based on the observation that areal bone density increases with growth during childhood, is highest around 20 years of age and declines thereafter. However, it is now clear that strong bones in the youngster do not necessarily lead to a fracture-free old age. In the recent bone densitometric literature, the terms bone mass and bone density are typically used synonymously. In physics, density has been defined as the mass of a body divided by its volume. In clinical practice and science, "bone density" usually has a different meaning-the degree to which a radiation beam is attenuated by a bone, as judged from a two-dimensional projection image (areal bone density). The attenuation of a radiation beam does not only depend on physical density, but also on bone size. A small bone therefore has a lower areal bone density than a larger bone, even if the physical density is the same. Consequently, a low areal bone density value can simply reflect the small size of an otherwise normal bone. At present, bone mass analysis is very useful for epidemiological studies on factors that may have an impact on bone development. There is an ongoing discussion about whether the World Health Organization (WHO) definition of osteoporosis is over-simplistic and requires upgrading to include indices representing the distribution of bone and mineral (bone strength indices). The following suggestions and recommendations outline a new concept: bone mass should not be related to age. There is now more and more evidence that bone mass should be related to bone size or muscle function. Thus analyzed, there is no such entity as a "peak bone mass". Many studies are currently under way to evaluate whether these novel approaches increase sensitivity and specificity of fracture prediction in an individual. Furthermore, the focus of many bone researchers is shifting away from bone mass to bone geometry or bone strength. Bone mass is one surrogate marker of bone strength. Widely available techniques for measurement of bone mass, such as dual-energy X-ray absorptiometry, radiogrammetry, and computed tomography, can also be used to measure variables of bone geometry such as cortical thickness, cortical area, and moment of inertia.

Fatigue of immature baboon cortical bone.

PubMed

Keller, T S; Lovin, J D; Spengler, D M; Carter, D R

1985-01-01

Strain-controlled uniaxial fatigue and monotonic tensile tests were conducted on turned femoral cortical bone specimens obtained from baboons at various ages of maturity. Fatigue loading produced a progressive loss in stiffness and an increase in hysteresis prior to failure, indicating that immature primate cortical bone responds to repeated loading in a fashion similar to that previously observed for adult human cortical bone. Bone fatigue resistance under this strain controlled testing decreased during maturation. Maturation was also associated with an increase in bone dry density, ash fraction and elastic modulus. The higher elastic modulus of more mature bone meant that these specimens were subjected to higher stress levels during testing than more immature bone specimens. Anatomical regions along the femoral shaft exhibited differences in strength and fatigue resistance.

Characterization of focal cortical dysplasia with balloon cells by layer-specific markers: Evidence for differential vulnerability of interneurons.

PubMed

Nakagawa, Julia M; Donkels, Catharina; Fauser, Susanne; Schulze-Bonhage, Andreas; Prinz, Marco; Zentner, Josef; Haas, Carola A

2017-04-01

Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer-specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region. We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer-specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32-positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin- and Calretinin-positive interneurons in layers II and III were not different from controls, whereas Parvalbumin-expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4-positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b. The application of a broad panel of markers defining layer-specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin-positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Cortical excitability and neurology: insights into the pathophysiology

PubMed Central

Badawy, Radwa A.B.; Loetscher, Tobias; Macdonell, Richard A.L.; Brodtmann, Amy

2012-01-01

Summary Transcranial magnetic stimulation (TMS) is a technique developed to non-invasively investigate the integrity of human motor corticospinal tracts. Over the last three decades, the use of stimulation paradigms including single-pulse TMS, paired-pulse TMS, repetitive TMS, and integration with EEG and functional imaging have been developed to facilitate measurement of cortical excitability. Through the use of these protocols, TMS has evolved into an excellent tool for measuring cortical excitability. TMS has high sensitivity in detecting subtle changes in cortical excitability, and therefore it is also a good measure of disturbances associated with brain disorders. In this review, we appraise the current literature on cortical excitability studies using TMS in neurological disorders. We begin with a brief overview of current TMS measures and then show how these have added to our understanding of the underlying mechanisms of brain disorders. PMID:23402674

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

PubMed

Ruffini, Giulio; Fox, Michael D; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-04-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). Copyright © 2013 Elsevier Inc. All rights reserved.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia

PubMed Central

Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-01-01

Abstract Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. PMID:27729486

Reciprocal Relation between Marrow Adiposity and the Amount of Bone in the Axial and Appendicular Skeleton of Young Adults

PubMed Central

Di Iorgi, Natascia; Rosol, Michael; Mittelman, Steven D.; Gilsanz, Vicente

2008-01-01

Background: Studies in the elderly suggest a reciprocal relation between increased marrow adiposity and bone loss, supporting basic research data indicating that osteoblasts and adipocytes share a common progenitor cell. However, whether this relation represents a preferential differentiation of stromal cells from osteoblasts to adipocytes or whether a passive accumulation of fat as bone is lost and marrow space increases with aging is unknown. To address this question and avoid the confounding effect of bone loss, we examined teenagers and young adults. Methods: Using computed tomography, we obtained measurements of bone density and cross-sectional area of the lumbar vertebral bodies and cortical bone area, cross-sectional area, marrow canal area, and fat density in the marrow of the femurs in 255 sexually mature subjects (126 females, 129 males; 15–24.9 yr of age). Additionally, values for total body fat were obtained with dual-energy x-ray absorptiometry. Results: Regardless of gender, reciprocal relations were found between fat density and measures of vertebral bone density and femoral cortical bone area (r = 0.19–0.39; all P values ≤ .03). In contrast, there was no relation between marrow canal area and cortical bone area in the femurs, neither between fat density and the cross-sectional dimensions of the bones. We also found no relation between anthropometric or dual-energy x-ray absorptiometry fat values and measures for marrow fat density. Conclusions: Our results indicate an inverse relation between bone marrow adiposity and the amount of bone in the axial and appendicular skeleton and support the notion of a common progenitor cell capable of mutually exclusive differentiation into the cell lineages responsible for bone and fat formation. PMID:18381577

Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).

PubMed

Krupski, W; Tatara, M R; Charuta, A; Brodzki, A; Szpetnar, M; Jóźwik, A; Strzałkowska, N; Poławska, E; Łuszczewska-Sierakowska, I

2018-06-01

1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.

Cortical characterization of the perception of intelligible and unintelligible speech measured via high-density electroencephalography.

PubMed

Utianski, Rene L; Caviness, John N; Liss, Julie M

2015-01-01

High-density electroencephalography was used to evaluate cortical activity during speech comprehension via a sentence verification task. Twenty-four participants assigned true or false to sentences produced with 3 noise-vocoded channel levels (1--unintelligible, 6--decipherable, 16--intelligible), during simultaneous EEG recording. Participant data were sorted into higher- (HP) and lower-performing (LP) groups. The identification of a late-event related potential for LP listeners in the intelligible condition and in all listeners when challenged with a 6-Ch signal supports the notion that this induced potential may be related to either processing degraded speech, or degraded processing of intelligible speech. Different cortical locations are identified as neural generators responsible for this activity; HP listeners are engaging motor aspects of their language system, utilizing an acoustic-phonetic based strategy to help resolve the sentence, while LP listeners do not. This study presents evidence for neurophysiological indices associated with more or less successful speech comprehension performance across listening conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow.

PubMed

Hannah, Rachael M; Dunn, Kathryn M; Bonev, Adrian D; Nelson, Mark T

2011-05-01

Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK(Ca)) and intermediate-conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and IK(Ca) channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents were not detected in PA SMCs. In contrast, BK(Ca) currents were prominent in PA SMCs (~154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK(Ca) (~16%) and IK(Ca) (~16%) channels, but were only modestly affected by inhibition of BK(Ca) channels (~5%). Blockade of SK(Ca) and IK(Ca) channels decreased resting cortical cerebral blood flow (CBF) by ~15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SK(Ca)/IK(Ca) channel opener, hyperpolarized PA SMCs by ~27 mV, maximally dilated pressurized PAs, and increased CBF by ~40%. In conclusion, these data show that SK(Ca) and IK(Ca) channels in ECs profoundly modulate PA tone and CBF, whereas BK(Ca) channels in SMCs only modestly influence PA diameter.

What can volumes reveal about human brain evolution? A framework for bridging behavioral, histometric, and volumetric perspectives

PubMed Central

de Sousa, Alexandra A.; Proulx, Michael J.

2014-01-01

An overall relationship between brain size and cognitive ability exists across primates. Can more specific information about neural function be gleaned from cortical area volumes? Numerous studies have found significant relationships between brain structures and behaviors. However, few studies have speculated about brain structure-function relationships from the microanatomical to the macroanatomical level. Here we address this problem in comparative neuroanatomy, where the functional relevance of overall brain size and the sizes of cortical regions have been poorly understood, by considering comparative psychology, with measures of visual acuity and the perception of visual illusions. We outline a model where the macroscopic size (volume or surface area) of a cortical region (such as the primary visual cortex, V1) is related to the microstructure of discrete brain regions. The hypothesis developed here is that an absolutely larger V1 can process more information with greater fidelity due to having more neurons to represent a field of space. This is the first time that the necessary comparative neuroanatomical research at the microstructural level has been brought to bear on the issue. The evidence suggests that as the size of V1 increases: the number of neurons increases, the neuron density decreases, and the density of neuronal connections increases. Thus, we describe how information about gross neuromorphology, using V1 as a model for the study of other cortical areas, may permit interpretations of cortical function. PMID:25009469

Differential polarization of cortical pyramidal neuron dendrites through weak extracellular fields

PubMed Central

Obermayer, Klaus

2018-01-01

The rise of transcranial current stimulation (tCS) techniques have sparked an increasing interest in the effects of weak extracellular electric fields on neural activity. These fields modulate ongoing neural activity through polarization of the neuronal membrane. While the somatic polarization has been investigated experimentally, the frequency-dependent polarization of the dendritic trees in the presence of alternating (AC) fields has received little attention yet. Using a biophysically detailed model with experimentally constrained active conductances, we analyze the subthreshold response of cortical pyramidal cells to weak AC fields, as induced during tCS. We observe a strong frequency resonance around 10-20 Hz in the apical dendrites sensitivity to polarize in response to electric fields but not in the basal dendrites nor the soma. To disentangle the relative roles of the cell morphology and active and passive membrane properties in this resonance, we perform a thorough analysis using simplified models, e.g. a passive pyramidal neuron model, simple passive cables and reconstructed cell model with simplified ion channels. We attribute the origin of the resonance in the apical dendrites to (i) a locally increased sensitivity due to the morphology and to (ii) the high density of h-type channels. Our systematic study provides an improved understanding of the subthreshold response of cortical cells to weak electric fields and, importantly, allows for an improved design of tCS stimuli. PMID:29727454

Thalamic modulation of cingulate seizure activity via the regulation of gap junctions in mice thalamocingulate slice.

PubMed

Chang, Wei-Pang; Wu, José Jiun-Shian; Shyu, Bai-Chuang

2013-01-01

The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5-50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions.

Thalamic Modulation of Cingulate Seizure Activity Via the Regulation of Gap Junctions in Mice Thalamocingulate Slice

PubMed Central

Chang, Wei-Pang; Wu, José Jiun-Shian; Shyu, Bai-Chuang

2013-01-01

The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5–50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions. PMID:23690968

Correlates of bone quality in older persons

PubMed Central

Lauretani, F.; Bandinelli, S.; Russo, C.R.; Maggio, M.; Di Iorio, A.; Cherubini, A.; Maggio, D.; Ceda, G.P.; Valenti, G.; Guralnik, J.M.; Ferrucci, L.

2009-01-01

Purpose of the study In a population-based sample of older persons, we studied the relationship between tibial bone density and geometry and factors potentially affecting osteoporosis. Methods Of the 1260 participants aged 65 years or older eligible for the InCHIANTI study, 1155 received an interview and 915 (79.2%) had complete data on tibial QCTscans and other variables used in the analysis presented here. The final study population included 807 persons (372 men and 435 women, age range 65–96 years) after exclusion of participants affected by bone diseases or treated with drugs that interfere with bone metabolism. Results In both sexes, calf cross-sectional muscle area (CSMA) was significantly and independently associated with total bone cross-sectional area (tCSA) and cortical bone cross-sectional area (cCSA) but not with trabecular or cortical volumetric bone mineral density (vBMD). Bioavailable testosterone (Bio-T) was independently associated with both trabecular and cortical vBMD in both sexes. In women, independently of confounders, 25(OH)-vitamin D was positively associated with tCSA and cortical vBMD, while PTH was negatively associated with cortical vBMD. IL-1 beta was negatively correlated with cortical vBMD in women, while TNF-alpha was associated with enhanced bone geometrical adaptation in men. Conclusions Physiological parameters that are generically considered risk factors for osteoporosis were associated with specific bone parameters assessed by tibial QCT. Factors known to be associated with increased bone reabsorption, such as 25(OH)-vitamin D, PTH and Bio-T, affected mainly volumetric BMD, while factors associated with bone mechanical stimulation, such as CSMA, affected primarily bone geometry. Our results also suggested that pro-inflammatory cytokines might be considered as markers of bone resorption. PMID:16709469

A transition in brain state during propofol-induced unconsciousness.

PubMed

Mukamel, Eran A; Pirondini, Elvira; Babadi, Behtash; Wong, Kin Foon Kevin; Pierce, Eric T; Harrell, P Grace; Walsh, John L; Salazar-Gomez, Andres F; Cash, Sydney S; Eskandar, Emad N; Weiner, Veronica S; Brown, Emery N; Purdon, Patrick L

2014-01-15

Rhythmic oscillations shape cortical dynamics during active behavior, sleep, and general anesthesia. Cross-frequency phase-amplitude coupling is a prominent feature of cortical oscillations, but its role in organizing conscious and unconscious brain states is poorly understood. Using high-density EEG and intracranial electrocorticography during gradual induction of propofol general anesthesia in humans, we discovered a rapid drug-induced transition between distinct states with opposite phase-amplitude coupling and different cortical source distributions. One state occurs during unconsciousness and may be similar to sleep slow oscillations. A second state occurs at the loss or recovery of consciousness and resembles an enhanced slow cortical potential. These results provide objective electrophysiological landmarks of distinct unconscious brain states, and could be used to help improve EEG-based monitoring for general anesthesia.

Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

NASA Astrophysics Data System (ADS)

Xia, Yi

Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in clinical applications. It has been demonstrated that the QUS has similar performance for in vivo bone density measurement compared to current gold-standard method, i.e., DXA, while additional information are obtained by the QUS for predicting fracture risk by monitoring of bone's quality. The developed QUS imaging technique can be used to assess bone's quantity and quality with improved accuracy and precision.

Scalp and Source Power Topography in Sleepwalking and Sleep Terrors: A High-Density EEG Study

PubMed Central

Castelnovo, Anna; Riedner, Brady A.; Smith, Richard F.; Tononi, Giulio; Boly, Melanie; Benca, Ruth M.

2016-01-01

Study Objectives: To examine scalp and source power topography in sleep arousals disorders (SADs) using high-density EEG (hdEEG). Methods: Fifteen adult subjects with sleep arousal disorders (SADs) and 15 age- and gender-matched good sleeping healthy controls were recorded in a sleep laboratory setting using a 256 channel EEG system. Results: Scalp EEG analysis of all night NREM sleep revealed a localized decrease in slow wave activity (SWA) power (1–4 Hz) over centro-parietal regions relative to the rest of the brain in SADs compared to good sleeping healthy controls. Source modelling analysis of 5-minute segments taken from N3 during the first half of the night revealed that the local decrease in SWA power was prominent at the level of the cingulate, motor, and sensori-motor associative cortices. Similar patterns were also evident during REM sleep and wake. These differences in local sleep were present in the absence of any detectable clinical or electrophysiological sign of arousal. Conclusions: Overall, results suggest the presence of local sleep differences in the brain of SADs patients during nights without clinical episodes. The persistence of similar topographical changes in local EEG power during REM sleep and wakefulness points to trait-like functional changes that cross the boundaries of NREM sleep. The regions identified by source imaging are consistent with the current neurophysiological understanding of SADs as a disorder caused by local arousals in motor and cingulate cortices. Persistent localized changes in neuronal excitability may predispose affected subjects to clinical episodes. Citation: Castelnovo A, Riedner BA, Smith RF, Tononi G, Boly M, Benca RM. Scalp and source power topography in sleepwalking and sleep terrors: a high-density EEG study. SLEEP 2016;39(10):1815–1825. PMID:27568805

Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease.

PubMed

Lax, Nichola Z; Grady, John; Laude, Alex; Chan, Felix; Hepplewhite, Philippa D; Gorman, Grainne; Whittaker, Roger G; Ng, Yi; Cunningham, Mark O; Turnbull, Doug M

2016-02-01

Mitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ-aminobutyric acid (GABA)-ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease. Histochemical, immunohistochemical and immunofluorescent assays were performed on post-mortem brain tissue from 10 patients and 10 age-matched control individuals. We applied a quantitative immunofluorescent method to interrogate complex I and IV protein expression in mitochondria within GABAergic interneurone populations in the frontal, temporal and occipital cortices. We also evaluated the density of inhibitory interneurones in serial sections to determine if cell loss was occurring. We observed significant, global reductions in complex I expression within GABAergic interneurones in frontal, temporal and occipital cortices in the majority of patients. While complex IV expression is more variable, there is reduced expression in patients harbouring m.8344A>G point mutations and POLG mutations. In addition to the severe respiratory chain deficiencies observed in remaining interneurones, quantification of GABAergic cell density showed a dramatic reduction in cell density suggesting interneurone loss. We propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Primary Hyperparathyroidism is Associated with Abnormal Cortical and Trabecular Microstructure and Reduced Bone Stiffness in Postmenopausal Women

PubMed Central

Stein, Emily M; Silva, Barbara C; Boutroy, Stephanie; Zhou, Bin; Wang, Ji; Udesky, Julia; Zhang, Chiyuan; McMahon, Donald J; Romano, Megan; Dworakowski, Elzbieta; Costa, Aline G.; Cusano, Natalie; Irani, Dinaz; Cremers, Serge; Shane, Elizabeth; Guo, X Edward; Bilezikian, John P

2013-01-01

Typically, in the milder form of primary hyperparathyroidism (PHPT), seen in most countries now, bone density by DXA and detailed analyses of iliac crest bone biopsies by histomorphometry and µCT show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and non-vertebral sites is increased in PHPT. Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate-like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate-rod and plate-plate junctions at the radius and tibia, and rod-rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment. They may help to account for increased global fracture risk in PHPT. PMID:23225022

Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

PubMed Central

Dechow, Paul C.; Wang, Qian; Peterson, Jill

2011-01-01

Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which have been thought to be little affected by function, because of low in vivo strains found there in several primate studies. PMID:20235319

Comparison of cyclic and impact-based reference point indentation measurements in human cadaveric tibia.

PubMed

Karim, Lamya; Van Vliet, Miranda; Bouxsein, Mary L

2018-01-01

Although low bone mineral density (BMD) is strongly associated with increased fracture risk, up to 50% of those who suffer fractures are not detected as high-risk patients by BMD testing. Thus, new approaches may improve identification of those at increased risk for fracture by in vivo assessment of altered bone tissue properties, which may contribute to skeletal fragility. Recently developed reference point indentation (RPI) allows for assessment of cortical bone indentation properties in vivo using devices that apply cyclic loading or impact loading, but there is little information available to assist with interpretation of RPI measurements. Our goals were to use human cadaveric tibia to determine: 1) the associations between RPI variables, cortical bone density, and morphology; 2) the association between variables obtained from RPI systems using cyclic, slow loading versus a single impact load; and 3) age-related differences in RPI variables. We obtained 20 human tibia and femur pairs from female donors (53-97years), measured total hip BMD using dual-energy X-ray absorptiometry, assessed tibial cortical microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT), and assessed cortical bone indentation properties at the mid-tibial diaphysis using both the cyclic and impact-based RPI systems (Biodent and Osteoprobe, respectively, Active Life Scientific, Santa Barbara, CA). We found a few weak associations between RPI variables, BMD, and cortical geometry; a few weak associations between measurements obtained by the two RPI systems; and no age-related differences in RPI variables. Our findings indicate that in cadaveric tibia from older women RPI measurements are largely independent of age, femoral BMD, and cortical geometry. Furthermore, measurements from the cyclic and impact loading RPI devices are weakly related to each other, indicating that each device reflects different aspects of cortical bone indentation properties. Copyright © 2016. Published by Elsevier Inc.

Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis.

PubMed Central

Ferrer, I; Tuñón, T; Serrano, M T; Casas, R; Alcántara, S; Zújar, M J; Rivera, R M

1993-01-01

The morphology and distribution of local-circuit neurons (interneurons) were examined, by calbindin D-28k and parvalbumin immunocytochemistry, in the frontal cortex (area 8) in two patients with frontal lobe dementia of non-Alzheimer type associated with classical amyotrophic lateral sclerosis (ALS), and in seven normal cases. The density of calbindin D-28k immunoreactive cells was dramatically reduced in ALS patients, but the density of parvalbumin-immunoreactive neurons was preserved. Decreased density of calbindin D-28k-immunoreactive neurons, which are mainly located in the upper cortical layers, may interfere with the normal processing of cortico-cortical connections, whereas integrity of parvalbumin-immunoreactive cells may be associated with the preservation of the major inhibitory intracortical circuits in patients with frontal lobe dementia. Images PMID:8459241

How well can an amoeba climb?

PubMed Central

Fukui, Yoshio; Uyeda, Taro Q. P.; Kitayama, Chikako; Inoué, Shinya

2000-01-01

We report here our efforts to measure the crawling force generated by cells undergoing amoeboid locomotion. In a centrifuge microscope, acceleration was increased until amoebae of Dictyostelium discoideum were “stalled” or no longer able to “climb up.” The “apparent weight” of the amoebae at stalling rpm in myosin mutants depended on the presence of myosin II (but not myosins IA and IB) and paralleled the cortical strength of the cells. Surprisingly, however, the cell stalled not only in low-density media as expected but also in media with densities greater than the cell density where the buoyant force should push the amoeba upward. We find that the leading pseudopod is bent under centrifugal force in all stalled amoebae, suggesting that this pseudopod is very dense indeed. This finding also suggests that directional cell locomotion against resistive forces requires a turgid forward-pointing pseudopod, most likely sustained by cortical actomyosin II. PMID:10963666

Elastic Properties of Chimpanzee Craniofacial Cortical Bone.

PubMed

Gharpure, Poorva; Kontogiorgos, Elias D; Opperman, Lynne A; Ross, Callum F; Strait, David S; Smith, Amanda; Pryor, Leslie C; Wang, Qian; Dechow, Paul C

2016-12-01

Relatively few assessments of cranial biomechanics formally take into account variation in the material properties of cranial cortical bone. Our aim was to characterize the elastic properties of chimpanzee craniofacial cortical bone and compare these to the elastic properties of dentate human craniofacial cortical bone. From seven cranial regions, 27 cylindrical samples were harvested from each of five chimpanzee crania. Assuming orthotropy, axes of maximum stiffness in the plane of the cortical plate were derived using modified equations of Hooke's law in a Mathcad program. Consistent orientations among individuals were observed in the zygomatic arch and alveolus. The density of cortical bone showed significant regional variation (P < 0.001). The elastic moduli demonstrated significant differences between sites, and a distinct pattern where E 3  > E 2  > E 1 . Shear moduli were significantly different among regions (P < 0.001). The pattern by which chimpanzee cranial cortical bone varies in elastic properties resembled that seen in humans, perhaps suggesting that the elastic properties of craniofacial bone in fossil hominins can be estimated with at least some degree of confidence. Anat Rec, 299:1718-1733, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Advances in Imaging Approaches to Fracture Risk Evaluation

PubMed Central

Manhard, Mary Kate; Nyman, Jeffry S.; Does, Mark D.

2016-01-01

Fragility fractures are a growing problem worldwide, and current methods for diagnosing osteoporosis do not always identify individuals who require treatment to prevent a fracture and may misidentify those not a risk. Traditionally, fracture risk is assessed using dual-energy X-ray absorptiometry, which provides measurements of areal bone mineral density (BMD) at sites prone to fracture. Recent advances in imaging show promise in adding new information that could improve the prediction of fracture risk in the clinic. As reviewed herein, advances in quantitative computed tomography (QCT) predict hip and vertebral body strength; high resolution HR-peripheral QCT (HR-pQCT) and micro-magnetic resonance imaging (μMRI) assess the micro-architecture of trabecular bone; quantitative ultrasound (QUS) measures the modulus or tissue stiffness of cortical bone; and quantitative ultra-short echo time MRI methods quantify the concentrations of bound water and pore water in cortical bone, which reflect a variety of mechanical properties of bone. Each of these technologies provides unique characteristics of bone and may improve fracture risk diagnoses and reduce prevalence of fractures by helping to guide treatment decisions. PMID:27816505

No Evidence of Association between Childhood Urban Environment and Cortical Thinning in Psychotic Disorder.

PubMed

Frissen, Aleida; van Os, Jim; Habets, Petra; Gronenschild, Ed; Marcelis, Machteld

2017-01-01

The alterations in cortical morphology, such as cortical thinning, observed in psychotic disorder, may be the outcome of interacting genetic and environmental effects. It has been suggested that urban upbringing may represent a proxy environmental effect impacting cortical thickness (CT). Therefore, the current study examined whether the association between group as a proxy genetic variable (patients with psychotic disorder [high genetic risk], healthy siblings of patients [intermediate risk] and healthy control subjects [average risk]) and CT was conditional on different levels of the childhood urban environment and whether this was sex-dependent. T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 non-psychotic siblings of patients with psychotic disorder and 87 healthy control subjects. Freesurfer software was used to measure CT. Developmental urban exposure was classified as low, medium, and high, reflecting the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. Multilevel regression analyses were used to examine the association between group, sex, and urban upbringing (as well as their interactions) and cortical CT as the dependent variable. CT was significantly smaller in the patient group compared to the controls (B = -0.043, p <0.001), but not in the siblings compared to the controls (B = -0.013, p = 0.31). There was no main effect of developmental urbanicity on CT (B = 0.001, p = 0.91). Neither the three-way group × urbanicity × sex interaction (χ2 = 3.73, p = 0.16), nor the two-way group × urbanicity interaction was significant (χ2 = 0.51, p = 0.77). The negative association between (familial risk for) psychotic disorder and CT was not moderated by developmental urbanicity, suggesting that reduced CT is not the outcome of familial sensitivity to the proxy environmental factor 'urban upbringing'.

Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

PubMed

Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

2015-02-01

Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sex differences and growth-related adaptations in bone microarchitecture, geometry, density and strength from childhood to early adulthood: a mixed longitudinal HR-pQCT study

PubMed Central

Gabel, Leigh; Macdonald, Heather M.; McKay, Heather A.

2016-01-01

Sex differences in bone strength and fracture risk are well-documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density and geometry that accompany gains in bone strength. Thus, our objectives are to 1) describe growth related adaptations in bone microarchitecture, geometry, density and strength at the distal tibia and radius in boys and girls; 2) compare differences in adaptations in bone microarchitecture, geometry, density and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9–20y at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity; APHV) and fit a mixed effects model to these longitudinal data. Importantly, boys demonstrated 28–63% greater estimated bone strength across 12 years of longitudinal growth. Boys demonstrated 28–80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls’ values were 2% greater than boys’. Boys demonstrated 13–48% greater cortical and total bone area across growth. Load-to-strength ratio was 26–27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to boys’ higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. PMID:27556581

[A study of complexity and power spectrum of cortical EEG and hippocampal potential in rats under different behavioral states].

PubMed

Feng, Zhou-yan; Zheng, Xiao-xiang

2002-08-01

Objective. To study the complexity and the power spectrum of cortical EEG and hippocampal potential in rats under waking and sleep states. Method. Cortical EEG and hippocampal potential were collected by implanted electrodes in freely moving rats. Algorithmic complexity (Kc), approximate entropy (ApEn), power spectral density (PSD) and gravity frequency of PSD of the potential waves were calculated. Result. The complexity of hippocampal potential was higher than that of cortical EEG under every state. The complexity of cortical EEG was lowest under the state of non rapid eye movement (NREM) sleep. The complexity of hippocampal potential was highest under waking state. The total power of both potentials in 0.5- 30 Hz frequency band showed their highest values under NREM state. Conclusion. The values of Kc and ApEn are closely related to the distributions of PSD. When there are evident peaks in PSD, the complexities of signals will decrease. The complexities may be used to distinguish the difference between cortical EEG and hippocampal potential, or large differences between the same kind of potentials under different behavioral states.

Associations of components of sarcopenic obesity with bone health and balance in older adults.

PubMed

Scott, David; Shore-Lorenti, Catherine; McMillan, Lachlan; Mesinovic, Jakub; Clark, Ross A; Hayes, Alan; Sanders, Kerrie M; Duque, Gustavo; Ebeling, Peter R

To determine characteristics of sarcopenic obesity that are independently associated with bone health and balance in older adults. Cross-sectional study of 168 community-dwelling older adults (mean age 67.7 ± 8.4 years; 55% women). Appendicular lean mass (ALM), whole-body areal BMD (aBMD) and body fat percentage were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography assessed muscle density and cortical volumetric BMD (vBMD), area, thickness, and strength-strain index (SSI) at 66% tibial length. Hand grip strength (dynamometry) and balance path length (computerised posturography) were assessed. Obesity was defined as high body fat percentage. Greater lower-leg muscle density was associated with lower balance path length in men (r = -0.36; P < .01) and women (r = -0.40; P = < .01). Obese participants by body fat percentage did not differ to non-obese on bone indices, although a trend towards lower cortical vBMD was observed in obese compared with non-obese men (1041.4 ± 39.8 vs 1058.8 ± 36.1 mg/cm 3 ; P = .051). In multivariable models, ALM was positively associated with all bone parameters in obese women, and with whole-body aBMD, proximal tibial cortical area and SSI in non-obese women, and both non-obese and obese men (all P < .05). Lower-leg muscle density was also positively associated with cortical vBMD (B = 2.91; 95% CI 0.02, 5.80) and area (2.70; 0.06, 5.33) in obese women. Amongst components of sarcopenic obesity, higher ALM is a consistent independent predictor of better bone health. Low muscle density may also compromise bone health and balance. Interventions which improve muscle mass and composition may lower fracture risk in sarcopenic obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy.

PubMed

Re, Rebecca; Muthalib, Makii; Contini, Davide; Zucchelli, Lucia; Torricelli, Alessandro; Spinelli, Lorenzo; Caffini, Matteo; Ferrari, Marco; Quaresima, Valentina; Perrey, Stephane; Kerr, Graham

2013-01-01

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity.

PubMed

Leng, Tian-Dong; Lin, Jun; Sun, Hua-Wei; Zeng, Zhao; O'Bryant, Zaven; Inoue, Koichi; Xiong, Zhi-Gang

2015-01-01

Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7-mediated intracellular Zn(2+) accumulation may represent a promising strategy in the treatment of stroke. To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn(2+) imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn(2+) accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn(2+) accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn(2+) toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity. © 2014 John Wiley & Sons Ltd.

Beyond the cortical column: abundance and physiology of horizontal connections imply a strong role for inputs from the surround.

PubMed

Boucsein, Clemens; Nawrot, Martin P; Schnepel, Philipp; Aertsen, Ad

2011-01-01

Current concepts of cortical information processing and most cortical network models largely rest on the assumption that well-studied properties of local synaptic connectivity are sufficient to understand the generic properties of cortical networks. This view seems to be justified by the observation that the vertical connectivity within local volumes is strong, whereas horizontally, the connection probability between pairs of neurons drops sharply with distance. Recent neuroanatomical studies, however, have emphasized that a substantial fraction of synapses onto neocortical pyramidal neurons stems from cells outside the local volume. Here, we discuss recent findings on the signal integration from horizontal inputs, showing that they could serve as a substrate for reliable and temporally precise signal propagation. Quantification of connection probabilities and parameters of synaptic physiology as a function of lateral distance indicates that horizontal projections constitute a considerable fraction, if not the majority, of inputs from within the cortical network. Taking these non-local horizontal inputs into account may dramatically change our current view on cortical information processing.

Cortical deficits of emotional face processing in adults with ADHD: its relation to social cognition and executive function.

PubMed

Ibáñez, Agustin; Petroni, Agustin; Urquina, Hugo; Torrente, Fernando; Torralva, Teresa; Hurtado, Esteban; Guex, Raphael; Blenkmann, Alejandro; Beltrachini, Leandro; Muravchik, Carlos; Baez, Sandra; Cetkovich, Marcelo; Sigman, Mariano; Lischinsky, Alicia; Manes, Facundo

2011-01-01

Although it has been shown that adults with attention-deficit hyperactivity disorder (ADHD) have impaired social cognition, no previous study has reported the brain correlates of face valence processing. This study looked for behavioral, neuropsychological, and electrophysiological markers of emotion processing for faces (N170) in adult ADHD compared to controls matched by age, gender, educational level, and handedness. We designed an event-related potential (ERP) study based on a dual valence task (DVT), in which faces and words were presented to test the effects of stimulus type (faces, words, or face-word stimuli) and valence (positive versus negative). Individual signatures of cognitive functioning in participants with ADHD and controls were assessed with a comprehensive neuropsychological evaluation, including executive functioning (EF) and theory of mind (ToM). Compared to controls, the adult ADHD group showed deficits in N170 emotion modulation for facial stimuli. These N170 impairments were observed in the absence of any deficit in facial structural processing, suggesting a specific ADHD impairment in early facial emotion modulation. The cortical current density mapping of N170 yielded a main neural source of N170 at posterior section of fusiform gyrus (maximum at left hemisphere for words and right hemisphere for faces and simultaneous stimuli). Neural generators of N170 (fusiform gyrus) were reduced in ADHD. In those patients, N170 emotion processing was associated with performance on an emotional inference ToM task, and N170 from simultaneous stimuli was associated with EF, especially working memory. This is the first report to reveal an adult ADHD-specific impairment in the cortical modulation of emotion for faces and an association between N170 cortical measures and ToM and EF.

Oscillatory Hierarchy Controlling Cortical Excitability and Stimulus Integration

NASA Technical Reports Server (NTRS)

Shah, A. S.; Lakatos, P.; McGinnis, T.; O'Connell, N.; Mills, A.; Knuth, K. H.; Chen, C.; Karmos, G.; Schroeder, C. E.

2004-01-01

Cortical gamma band oscillations have been recorded in sensory cortices of cats and monkeys, and are thought to aid in perceptual binding. Gamma activity has also been recorded in the rat hippocampus and entorhinal cortex, where it has been shown, that field gamma power is modulated at theta frequency. Since the power of gamma activity in the sensory cortices is not constant (gamma-bursts). we decided to examine the relationship between gamma power and the phase of low frequency oscillation in the auditory cortex of the awake macaque. Macaque monkeys were surgically prepared for chronic awake electrophysiological recording. During the time of the experiments. linear array multielectrodes were inserted in area AI to obtain laminar current source density (CSD) and multiunit activity profiles. Instantaneous theta and gamma power and phase was extracted by applying the Morlet wavelet transformation to the CSD. Gamma power was averaged for every 1 degree of low frequency oscillations to calculate power-phase relation. Both gamma and theta-delta power are largest in the supragranular layers. Power modulation of gamma activity is phase locked to spontaneous, as well as stimulus-related local theta and delta field oscillations. Our analysis also revealed that the power of theta oscillations is always largest at a certain phase of delta oscillation. Auditory stimuli produce evoked responses in the theta band (Le., there is pre- to post-stimulus addition of theta power), but there is also indication that stimuli may cause partial phase re-setting of spontaneous delta (and thus also theta and gamma) oscillations. We also show that spontaneous oscillations might play a role in the processing of incoming sensory signals by 'preparing' the cortex.

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography.

PubMed

Cheung, T F; Cheuk, K Y; Yu, F W P; Hung, V W Y; Ho, C S; Zhu, T Y; Ng, B K W; Lee, K M; Qin, L; Ho, S S Y; Wong, G W K; Cheng, J C Y; Lam, T P

2016-08-01

Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels. Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

Mapping Human Cortical Areas in vivo Based on Myelin Content as Revealed by T1- and T2-weighted MRI

PubMed Central

Glasser, Matthew F.; Van Essen, David C.

2011-01-01

Non-invasively mapping the layout of cortical areas in humans is a continuing challenge for neuroscience. We present a new method of mapping cortical areas based on myelin content as revealed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The method is generalizable across different 3T scanners and pulse sequences. We use the ratio of T1w/T2w image intensities to eliminate the MR-related image intensity bias and enhance the contrast to noise ratio for myelin. Data from each subject was mapped to the cortical surface and aligned across individuals using surface-based registration. The spatial gradient of the group average myelin map provides an observer-independent measure of sharp transitions in myelin content across the surface—i.e. putative cortical areal borders. We found excellent agreement between the gradients of the myelin maps and the gradients of published probabilistic cytoarchitectonically defined cortical areas that were registered to the same surface-based atlas. For other cortical regions, we used published anatomical and functional information to make putative identifications of dozens of cortical areas or candidate areas. In general, primary and early unimodal association cortices are heavily myelinated and higher, multi-modal, association cortices are more lightly myelinated, but there are notable exceptions in the literature that are confirmed by our results. The overall pattern in the myelin maps also has important correlations with the developmental onset of subcortical white matter myelination, evolutionary cortical areal expansion in humans compared to macaques, postnatal cortical expansion in humans, and maps of neuronal density in non-human primates. PMID:21832190

Generator localization by current source density (CSD): Implications of volume conduction and field closure at intracranial and scalp resolutions

PubMed Central

Tenke, Craig E.; Kayser, Jürgen

2012-01-01

The topographic ambiguity and reference-dependency that has plagued EEG/ERP research throughout its history are largely attributable to volume conduction, which may be concisely described by a vector form of Ohm’s Law. This biophysical relationship is common to popular algorithms that infer neuronal generators via inverse solutions. It may be further simplified as Poisson’s source equation, which identifies underlying current generators from estimates of the second spatial derivative of the field potential (Laplacian transformation). Intracranial current source density (CSD) studies have dissected the “cortical dipole” into intracortical sources and sinks, corresponding to physiologically-meaningful patterns of neuronal activity at a sublaminar resolution, much of which is locally cancelled (i.e., closed field). By virtue of the macroscopic scale of the scalp-recorded EEG, a surface Laplacian reflects the radial projections of these underlying currents, representing a unique, unambiguous measure of neuronal activity at scalp. Although the surface Laplacian requires minimal assumptions compared to complex, model-sensitive inverses, the resulting waveform topographies faithfully summarize and simplify essential constraints that must be placed on putative generators of a scalp potential topography, even if they arise from deep or partially-closed fields. CSD methods thereby provide a global empirical and biophysical context for generator localization, spanning scales from intracortical to scalp recordings. PMID:22796039

Post-traumatic transient cortical blindness in a child with occipital bone fracture.

PubMed

Ng, Rachel H C

2016-12-01

Cortical blindness as sequelae of trauma has been reported in literature but mostly in the setting of occipital cortex or visual tract damages. We present a case of transient cortical blindness in a child following a closed head injury with a non-displaced occipital bone fracture and underlying occipital lobe contusion. We discuss the pathophysiology behind Post-traumatic transient cortical blindness, relevant investigations, and current management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cortical network architecture for context processing in primate brain

PubMed Central

Chao, Zenas C; Nagasaka, Yasuo; Fujii, Naotaka

2015-01-01

Context is information linked to a situation that can guide behavior. In the brain, context is encoded by sensory processing and can later be retrieved from memory. How context is communicated within the cortical network in sensory and mnemonic forms is unknown due to the lack of methods for high-resolution, brain-wide neuronal recording and analysis. Here, we report the comprehensive architecture of a cortical network for context processing. Using hemisphere-wide, high-density electrocorticography, we measured large-scale neuronal activity from monkeys observing videos of agents interacting in situations with different contexts. We extracted five context-related network structures including a bottom-up network during encoding and, seconds later, cue-dependent retrieval of the same network with the opposite top-down connectivity. These findings show that context is represented in the cortical network as distributed communication structures with dynamic information flows. This study provides a general methodology for recording and analyzing cortical network neuronal communication during cognition. DOI: http://dx.doi.org/10.7554/eLife.06121.001 PMID:26416139

Cortical thickness correlates of psychotic experiences: examining the effect of season of birth using a genetically informative design.

PubMed

Córdova-Palomera, A; Alemany, S; Falcón, C; Bargalló, N; Goldberg, X; Crespo-Facorro, B; Nenadic, I; Fañanás, L

2014-09-01

Season of birth has been shown to influence risk for several neuropsychiatric diseases. Furthermore, it has been suggested that season of birth modifies a number of brain morphological traits. Since cortical thickness alterations have been reported across some levels of the psychosis-spectrum, this study was aimed at i) assessing the scarcely explored relationship between cortical thickness and severity of subclinical psychotic experiences (PEs) in healthy subjects, and ii) evaluating the potential impact of season of birth in the preceding thickness-PEs relationship. As both PEs and brain cortical features are heritable, the current work used monozygotic twins to separately evaluate familial and unique environmental factors. High-resolution structural MRI scans of 48 twins (24 monozygotic pairs) were analyzed to estimate cortical thickness using FreeSurfer. They were then examined in relation to PEs, accounting for the effects of birth season; putative differential relationships between PEs and cortical thickness depending on season of birth were also tested. Current results support previous findings indicative of cortical thickening in healthy individuals with high psychometrically assessed psychosis scores, probably in line with theories of compensatory aspects of brain features in non-clinical populations. Additionally, they suggest distinct patterns of cortical thickness-PEs relationships depending on birth seasonality. Familial factors underlying the presence of PEs may drive these effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. I. Quantitative analysis of cytoarchitecture.

PubMed

Sherwood, Chet C; Holloway, Ralph L; Erwin, Joseph M; Schleicher, Axel; Zilles, Karl; Hof, Patrick R

2004-01-01

Social life in anthropoid primates is mediated by interindividual communication, involving movements of the orofacial muscles for the production of vocalization and gestural expression. Although phylogenetic diversity has been reported in the auditory and visual communication systems of primates, little is known about the comparative neuroanatomy that subserves orofacial movement. The current study reports results from quantitative image analysis of the region corresponding to orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens) using the Grey Level Index method. This cortical region has been implicated in the execution of skilled motor activities such as voluntary facial expression and human speech. Density profiles of the laminar distribution of Nissl-stained neuronal somata were acquired from high-resolution images to quantify cytoarchitectural patterns. Despite general similarity in these profiles across catarrhines, multivariate analysis showed that cytoarchitectural patterns of individuals were more similar within-species versus between-species. Compared to Old World monkeys, the orofacial representation of area 4 in great apes and humans was characterized by an increased relative thickness of layer III and overall lower cell volume densities, providing more neuropil space for interconnections. These phylogenetic differences in microstructure might provide an anatomical substrate for the evolution of greater volitional fine motor control of facial expressions in great apes and humans. Copyright 2004 S. Karger AG, Basel

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia.

PubMed

Walther, Sebastian; Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-09-01

Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

PubMed

Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

2016-02-01

We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures.

PubMed

Maffezzoni, Filippo; Maddalo, Michele; Frara, Stefano; Mezzone, Monica; Zorza, Ivan; Baruffaldi, Fabio; Doglietto, Francesco; Mazziotti, Gherardo; Maroldi, Roberto; Giustina, Andrea

2016-11-01

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25-72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25-68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p < 0.05) lower bone volume/trabecular volume ratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volume ratio (p = 0.003) and mean trabecular thickness (p < 0.001) and greater mean trabecular separation (p = 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstructure.

Graph theory analysis of cortical thickness networks in adolescents with d-transposition of the great arteries.

PubMed

Watson, Christopher G; Stopp, Christian; Newburger, Jane W; Rivkin, Michael J

2018-02-01

Adolescents with d-transposition of the great arteries (d-TGA) who had the arterial switch operation in infancy have been found to have structural brain differences compared to healthy controls. We used cortical thickness measurements obtained from structural brain MRI to determine group differences in global brain organization using a graph theoretical approach. Ninety-two d-TGA subjects and 49 controls were scanned using one of two identical 1.5-Tesla MRI systems. Mean cortical thickness was obtained from 34 regions per hemisphere using Freesurfer. A linear model was used for each brain region to adjust for subject age, sex, and scanning location. Structural connectivity for each group was inferred based on the presence of high inter-regional correlations of the linear model residuals, and binary connectivity matrices were created by thresholding over a range of correlation values for each group. Graph theory analysis was performed using packages in R. Permutation tests were performed to determine significance of between-group differences in global network measures. Within-group connectivity patterns were qualitatively different between groups. At lower network densities, controls had significantly more long-range connections. The location and number of hub regions differed between groups: controls had a greater number of hubs at most network densities. The control network had a significant rightward asymmetry compared to the d-TGA group at all network densities. Using graph theory analysis of cortical thickness correlations, we found differences in brain structural network organization among d-TGA adolescents compared to controls. These may be related to the white matter and gray matter differences previously found in this cohort, and in turn may be related to the cognitive deficits this cohort presents.

What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.

PubMed

Hasselmo, Michael E

2005-01-01

The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm. Copyright 2005 Wiley-Liss, Inc.

Cortical bone fracture analysis using XFEM - case study.

PubMed

Idkaidek, Ashraf; Jasiuk, Iwona

2017-04-01

We aim to achieve an accurate simulation of human cortical bone fracture using the extended finite element method within a commercial finite element software abaqus. A two-dimensional unit cell model of cortical bone is built based on a microscopy image of the mid-diaphysis of tibia of a 70-year-old human male donor. Each phase of this model, an interstitial bone, a cement line, and an osteon, are considered linear elastic and isotropic with material properties obtained by nanoindentation, taken from literature. The effect of using fracture analysis methods (cohesive segment approach versus linear elastic fracture mechanics approach), finite element type, and boundary conditions (traction, displacement, and mixed) on cortical bone crack initiation and propagation are studied. In this study cohesive segment damage evolution for a traction separation law based on energy and displacement is used. In addition, effects of the increment size and mesh density on analysis results are investigated. We find that both cohesive segment and linear elastic fracture mechanics approaches within the extended finite element method can effectively simulate cortical bone fracture. Mesh density and simulation increment size can influence analysis results when employing either approach, and using finer mesh and/or smaller increment size does not always provide more accurate results. Both approaches provide close but not identical results, and crack propagation speed is found to be slower when using the cohesive segment approach. Also, using reduced integration elements along with the cohesive segment approach decreases crack propagation speed compared with using full integration elements. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarlymore » decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.« less

Tibial component coverage based on bone mineral density of the cut tibial surface during unicompartmental knee arthroplasty: clinical relevance of the prevention of tibial component subsidence.

PubMed

Lee, Yong Seuk; Yun, Ji Young; Lee, Beom Koo

2014-01-01

An optimally implanted tibial component during unicompartmental knee arthroplasty would be flush with all edges of the cut tibial surface. However, this is often not possible, partly because the tibial component may not be an ideal shape or because the ideal component size may not be available. In such situations, surgeons need to decide between component overhang and underhang and as to which sites must be covered and which sites could be undercovered. The objectives of this study were to evaluate the bone mineral density of the cut surface of the proximal tibia around the cortical rim and to compare the bone mineral density according to the inclusion of the cortex and the site-specific matched evaluation. One hundred and fifty consecutive patients (100 men and 50 women) were enrolled in this study. A quantitative computed tomography was used to determine the bone density of the cut tibial surface. Medial and lateral compartments were divided into anterior, middle, and posterior regions, and these three regions were further subdivided into two regions according to containment of cortex. The site-specific matched comparison (medial vs. lateral) of bone mineral density was performed. In medial sides, the mid-region, including the cortex, showed the highest bone mineral density in male and female patients. The posterior region showed the lowest bone mineral density in male patients, and the anterior and posterior regions showed the lowest bone mineral density in female patients. Regions including cortex showed higher bone mineral density than pure cancellous regions in medial sides. In lateral sides, posterior regions including cortex showed highest bone mineral density with statistical significance in both male and female patients. The anterior region showed the lowest bone mineral density in both male and female patients. The mid-region of the medial side and the posterior region of the lateral side are relatively safe without cortical coverage when the component is not flush with all edges of the tibia. Cortical coverage is strongly recommended for the prevention of subsidence of the tibial component in the posterior region of the medial side, and in the anterior region of the lateral side.

4D Infant Cortical Surface Atlas Construction using Spherical Patch-based Sparse Representation.

PubMed

Wu, Zhengwang; Li, Gang; Meng, Yu; Wang, Li; Lin, Weili; Shen, Dinggang

2017-09-01

The 4D infant cortical surface atlas with densely sampled time points is highly needed for neuroimaging analysis of early brain development. In this paper, we build the 4D infant cortical surface atlas firstly covering 6 postnatal years with 11 time points (i.e., 1, 3, 6, 9, 12, 18, 24, 36, 48, 60, and 72 months), based on 339 longitudinal MRI scans from 50 healthy infants. To build the 4D cortical surface atlas, first , we adopt a two-stage groupwise surface registration strategy to ensure both longitudinal consistency and unbiasedness. Second , instead of simply averaging over the co-registered surfaces, a spherical patch-based sparse representation is developed to overcome possible surface registration errors across different subjects. The central idea is that, for each local spherical patch in the atlas space, we build a dictionary, which includes the samples of current local patches and their spatially-neighboring patches of all co-registered surfaces, and then the current local patch in the atlas is sparsely represented using the built dictionary. Compared to the atlas built with the conventional methods, the 4D infant cortical surface atlas constructed by our method preserves more details of cortical folding patterns, thus leading to boosted accuracy in registration of new infant cortical surfaces.

Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats.

PubMed

Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

2010-09-01

The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

Cortical synaptic NMDA receptor deficits in α7 nicotinic acetylcholine receptor gene deletion models: Implications for neuropsychiatric diseases

PubMed Central

Lin, Hong; Hsu, Fu-Chun; Baumann, Bailey H.; Coulter, Douglas A.; Lynch, David R.

2014-01-01

Microdeletion of the human CHRNA7 gene (α7 nicotinic acetylcholine receptor, nAChR) as well as dysfunction in N-methyl-D-aspartate receptors (NMDARs) have been associated with cortical dysfunction in a broad spectrum of neurodevelopmental and neuropsychiatric disorders including schizophrenia. However, the pathophysiological roles of synaptic vs. extrasynaptic NMDARs and their interactions with α7 nAChRs in cortical dysfunction remain largely uncharacterized. Using a combination of in vivo and in vitro models, we demonstrate that α7 nAChR gene deletion leads to specific loss of synaptic NMDARs and their coagonist, D-serine, as well as glutamatergic synaptic deficits in mouse cortex. α7 nAChR null mice had decreased cortical NMDAR expression and glutamatergic synapse formation during postnatal development. Similar reductions in NMDAR expression and glutamatergic synapse formation were revealed in cortical cultures lacking α7 nAChRs. Interestingly, synaptic, but not extrasynaptic, NMDAR currents were specifically diminished in cultured cortical pyramidal neurons as well as in acute prefrontal cortical slices of α7 nAChR null mice. Moreover, D-serine responsive synaptic NMDAR-mediated currents and levels of the D-serine synthetic enzyme serine racemase were both reduced in α7 nAChR null cortical pyramidal neurons. Our findings thus identify specific loss of synaptic NMDARs and their coagonist, D-serine, as well as glutamatergic synaptic deficits in α7 nAChR gene deletion models of cortical dysfunction, thereby implicating α7 nAChR-mediated control of synaptic NMDARs and serine racemase/D-serine pathways in cortical dysfunction underlying many neuropsychiatric and neurodevelopmental disorders, particularly those associated with deletion of human CHRNA7. PMID:24326163

Amyloid-β Production Via Cleavage of Amyloid-β Protein Precursor is Modulated by Cell Density

PubMed Central

Zhang, Can; Browne, Andrew; DiVito, Jason R.; Stevenson, Jesse A.; Romano, Donna; Dong, Yuanlin; Xie, Zhongcong; Tanzi, Rudolph E.

2012-01-01

Mounting evidence suggests that Alzheimer disease (AD) is caused by the accumulation of the small peptide, Aβ, a proteolytic cleavage product of amyloid-β protein precursor (AβPP; or APP). Aβ is generated through a serial cleavage of APP by β- and γ-secretase. Aβ40 and Aβ42 are the two main components of amyloid plaques in AD brains, with Aβ42 being more prone to aggregation. APP can also be processed by α-secretase, which cleaves APP within the Aβ sequence, thereby preventing the generation of Aβ. Little is currently known regarding the effects of cell density on APP processing and Aβ generation. Here we assessed the effects of cell density on APP processing in neuronal and non-neuronal cell lines, as well as mouse primary cortical neurons. We found that decreased cell density significantly increases levels of Aβ40, Aβ42, total Aβ, and the ratio of Aβ42:Aβ40. These results also indicate that cell density is a significant modulator of APP processing. Overall, these findings carry profound implications for both previous and forthcoming studies aiming to assess the effects of various conditions and genetic/chemical factors, e.g. novel drugs on APP processing and Aβ generation in cell-based systems. Moreover, it is interesting to speculate whether cell density changes in vivo may also affect APP processing and Aβ levels in the AD brain. PMID:20847415

Preliminary Evidence That Excitatory Transcranial Direct Current Stimulation Extends Time to Task Failure of a Sustained, Submaximal Muscular Contraction in Older Adults.

PubMed

Oki, Kentaro; Mahato, Niladri K; Nakazawa, Masato; Amano, Shinichi; France, Christopher R; Russ, David W; Clark, Brian C

2016-08-01

Decreased cortical excitability has been proposed as a potential mechanism underlying task failure during sustained muscular contractions, and cortical excitability may decrease with old age. We tested the hypothesis that transcranial direct current stimulation, which has been reported to raise cortical excitability, would prolong the time to task failure during a sustained muscular contraction in older adults. Thirteen older adults (68.3±2.0 years; eight women and five men) performed isometric, elbow flexions to failure while receiving sham or anodal transcranial direct current stimulation. Order of stimulation was randomized, and the subjects and investigators were blinded to condition. Time to task failure was measured alongside selected psychological indices of perceived exertion and affect. Anodal transcranial direct current stimulation prolonged mean time to task failure by approximately 15% (16.9±2.2 vs 14.7±1.8 minutes) and slowed the rate of increase in rating of perceived exertion (0.29±0.03 vs 0.31±0.03) relative to the sham condition. These preliminary findings suggest that anodal transcranial direct current stimulation enhances time to task failure of a sustained, submaximal contraction in older adults by potentially increasing cortical excitability and/or influencing the perception of exertion. These results raise the question of whether interventions that acutely increase cortical excitability could enhance physical function and/or exercise-induced adaptations in older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study

PubMed Central

Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

2015-01-01

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions. PMID:26158464

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

PubMed

Muthalib, Makii; Re, Rebecca; Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

2015-01-01

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

PubMed

Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

2018-02-02

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Ultraviolet-C irradiation to titanium implants increases peri-implant bone formation without impeding mineralization in a rabbit femur model.

PubMed

Yamazaki, Makoto; Yamada, Masahiro; Ishizaki, Ken; Sakurai, Kaoru

2015-05-01

Volume and bone quality of peri-implant supporting bone, in particular, at implant neck region, as well as bone-implant contact ratio, is important for long-term stability of implants. Ultraviolet-C (UVC) irradiation is known to enhance the osseointegration capability of titanium implants. However, the histological determination was performed only on a rat model, but not pre-clinical animal model such as a rabbit model. The purpose of this study was to determine the effects of UVC irradiation on titanium implants on the volume and mineral density of peri-implant supporting bone formation in a rabbit femur model. Acid-etched pure titanium screw implants with or without 3 mW/cm2 UVC irradiation for 48 h were placed in rabbit femur diaphyses. Peri-implant bone tissue formation was analyzed at 3 and 8 weeks post-operatively by histology and micro-CT-based bone morphometry after calibration with hydroxyl apatite phantoms. UVC pre-irradiated implants accumulated a higher density of cells and thicker and longer bone tissue attachments that continued into the inner basic lamellae of the surface of existing cortical bone at 3 and 8 weeks than the implants without irradiation. Although the bone mineral density around both implants was equivalent to that of the existing cortical bone, bone volume was greater with UVC pre-irradiation in two-thirds or more of the apical region throughout the observation period. These results indicate that UVC treatment increased the volume of cortical-like bone tissue in the coronal region of titanium implants without deterioration of bone mineral density.

Postmortem 3-D brain hemisphere cortical tau and amyloid-β pathology mapping and quantification as a validation method of neuropathology imaging.

PubMed

Smid, Lojze M; Kepe, Vladimir; Vinters, Harry V; Bresjanac, Mara; Toyokuni, Tatsushi; Satyamurthy, Nagichettiar; Wong, Koon-Pong; Huang, Sung-Cheng; Silverman, Daniel H S; Miller, Karen; Small, Gary W; Barrio, Jorge R

2013-01-01

This work is aimed at correlating pre-mortem [18F]FDDNP positron emission tomography (PET) scan results in a patient with dementia with Lewy bodies (DLB), with cortical neuropathology distribution determined postmortem in three physical dimensions in whole brain coronal sections. Analysis of total amyloid-β (Aβ) distribution in frontal cortex and posterior cingulate gyrus confirmed its statistically significant correlation with cortical [18F]FDDNP PET binding values (distribution volume ratios, DVR) (p < 0.001, R = 0.97, R2 = 0.94). Neurofibrillary tangle (NFT) distribution correlated significantly with cortical [18F]FDDNP PET DVR in the temporal lobe (p < 0.001, R = 0.87, R2 = 0.76). Linear combination of Aβ and NFT densities was highly predictive of [18F]FDDNP PET DVR through all analyzed regions of interest (p < 0.0001, R = 0.92, R2 = 0.85), and both densities contributed significantly to the model. Lewy bodies were present at a much lower level than either Aβ or NFTs and did not significantly contribute to the in vivo signal. [18F]FDG PET scan results in this patient were consistent with the distinctive DLB pattern of hypometabolism. This work offers a mapping brain model applicable to all imaging probes for verification of imaging results with Aβ and/or tau neuropathology brain distribution using immunohistochemistry, fluorescence microscopy, and autoradiography.

Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia.

PubMed

Somerville, J M; Aspden, R M; Armour, K E; Armour, K J; Reid, D M

2004-05-01

Murine models are becoming increasingly important for studying skeletal growth and regulation because of the relative ease with which their genomes can be manipulated. This study measured the changes in cortical bone of tibiae from one of the more common models, the C57Bl/6, as a function of aging. A total of 97 mice, male and female, were studied at the ages of 1, 2, 3, 6, 9, and 12 months. The body weight of the animals, the length of the tibiae, the composition (in terms of mineral and organic mass fractions), and the density and modulus of the bone were measured. Peripheral quantitative computed tomography was also used to measure bone mineral density (BMD), total and cortical areas, and the cross-sectional moment of inertia. Most parameters measured followed a growth-like curve, which leveled off some time before 6 months of age. Bone composition and modulus were the same at maturity in both sexes, but there were sex-related differences in the modulus with aging. Dimensional measurements and the density of the bone showed significant differences between male and female animals at all ages, with the male mice having larger values. Skeletal maturity for most factors in C57Bl/6 mice has been reached before the age of 6 months.

Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

PubMed Central

Li, Dong; Zhou, Changsong

2011-01-01

Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications. PMID:22232576

Synchronization Tomography: Modeling and Exploring Complex Brain Dynamics

NASA Astrophysics Data System (ADS)

Fieseler, Thomas

2002-03-01

Phase synchronization (PS) plays an important role both under physiological and pathological conditions. With standard averaging techniques of MEG data, it is difficult to reliably detect cortico-cortical and cortico-muscular PS processes that are not time-locked to an external stimulus. For this reason, novel synchronization analysis techniques were developed and directly applied to MEG signals. Of course, due to the lack of an inverse modeling (i.e. source localization), the spatial resolution of this approach was limited. To detect and localize cerebral PS, we here present the synchronization tomography (ST): For this, we first estimate the cerebral current source density by means of the magnetic field tomography (MFT). We then apply the single-run PS analysis to the current source density in each voxel of the reconstruction space. In this way we study simulated PS, voxel by voxel in order to determine the spatio-temporal resolution of the ST. To this end different generators of ongoing rhythmic cerebral activity are simulated by current dipoles at different locations and directions, which are modeled by slightly detuned chaotic oscillators. MEG signals for these generators are simulated for a spherical head model and a whole-head MEG system. MFT current density solutions are calculated from these simulated signals within a hemispherical source space. We compare the spatial resolution of the ST with that of the MFT. Our results show that adjacent sources which are indistinguishable for the MFT, can nevertheless be separated with the ST, provided they are not strongly phase synchronized. This clearly demonstrates the potential of combining spatial information (i.e. source localization) with temporal information for the anatomical localization of phase synchronization in the human brain.

Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

NASA Astrophysics Data System (ADS)

Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

2008-06-01

We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

Due to the limitation of osteoporosis therapy, the alternative therapies from natural sources have been considered. In this study, we aimed to determine the antiosteoporotic effect of the combined extract of Morus alba and Polygonum odoratum leaves. Ovariectomized rats, weighing 200–220 g, were orally given the combined extract at doses of 5, 150, and 300 mg·kg−1 BW for 3 months. At the end of study, blood was collected to determine serum osteocalcin, calcium, and alkaline phosphatase level. In addition, tibia bone was isolated to determine bone oxidative stress markers, cortical bone thickness, and density of osteoblast. The combined extract decreased oxidative stress and osteoclast density but increased osteoblast density and cortical thickness. The elevation of serum calcium, alkaline phosphatase, and osteocalcin was also observed. These results suggested the antiosteoporotic effect of the combined extract via the increased growth formation together with the suppression of bone resorption. However, further studies concerning chronic toxicity and the underlying mechanism are required. PMID:25478061

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial.

PubMed

Chapurlat, R D; Laroche, M; Thomas, T; Rouanet, S; Delmas, P D; de Vernejoul, M-C

2013-01-01

We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.

Hip fracture prevalence in grandfathers is associated with reduced cortical cross-sectional bone area in their young adult grandsons.

PubMed

Rudäng, Robert; Ohlsson, Claes; Odén, Anders; Johansson, Helena; Mellström, Dan; Lorentzon, Mattias

2010-03-01

Parent hip fracture prevalence is a known risk factor for osteoporosis. The role of hip fracture prevalence in grandparents on areal bone mineral density (aBMD) and bone size in their grandsons remains unknown. The objective of the study was to examine whether hip fracture prevalence in grandparents was associated with lower aBMD and reduced cortical bone size in their grandsons. This was a population-based cohort study in Sweden. Subjects included 1015 grandsons (18.9 +/- 0.6) (mean +/- sd) and 3688 grandparents. aBMD, cortical bone size, volumetric bone mineral density and polar strength strain index of the cortex in the grandsons in relation to hip fracture prevalence in their grandparents were measured. Grandsons of grandparents with hip fracture (n = 269) had lower aBMD at the total body, radius, and lumbar spine, but not at the hip, as well as reduced cortical cross-sectional area at the radius (P < 0.05) than grandsons of grandparents without hip fracture. Subgroup analysis demonstrated that grandsons of grandfathers with hip fracture (n = 99) had substantially lower aBMD at the lumbar spine (4.9%, P < 0.001) and total femur (4.1%, P = 0.003) and lower cortical cross-sectional area of the radius (4.1%, P < 0.001) and tibia (3.3%, P < 0.011). Adjusting bone variables for grandson age, weight, height, smoking, calcium intake, and physical activity and taking grandparent age at register entry, years in register, and grandparent sex into account strengthened or did not affect these associations. Family history of a grandfather with hip fracture was associated with reduced aBMD and cortical bone size in 19-yr-old men, indicating that patient history of hip fracture in a grandfather could be of value when evaluating the risk of low bone mass in men.

The resistance of cortical bone tissue to failure under cyclic loading is reduced with alendronate.

PubMed

Bajaj, Devendra; Geissler, Joseph R; Allen, Matthew R; Burr, David B; Fritton, J C

2014-07-01

Bisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD.

PubMed

Okazaki, Narihiro; Burghardt, Andrew J; Chiba, Ko; Schafer, Anne L; Majumdar, Sharmila

2016-12-01

The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD). Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA). Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia ( r  = 0.36, p  = 0.001, and r  = 0.47, p  < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone. Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.

Tibia and radius bone geometry and volumetric density in obese compared to non-obese adolescents.

PubMed

Leonard, Mary B; Zemel, Babette S; Wrotniak, Brian H; Klieger, Sarah B; Shults, Justine; Stallings, Virginia A; Stettler, Nicolas

2015-04-01

Childhood obesity is associated with biologic and behavioral characteristics that may impact bone mineral density (BMD) and structure. The objective was to determine the association between obesity and bone outcomes, independent of sexual and skeletal maturity, muscle area and strength, physical activity, calcium intake, biomarkers of inflammation, and vitamin D status. Tibia and radius peripheral quantitative CT scans were obtained in 91 obese (BMI>97th percentile) and 51 non-obese adolescents (BMI>5th and <85th percentiles). Results were converted to sex- and race-specific Z-scores relative to age. Cortical structure, muscle area and muscle strength (by dynamometry) Z-scores were further adjusted for bone length. Obese participants had greater height Z-scores (p<0.001), and advanced skeletal maturity (p<0.0001), compared with non-obese participants. Tibia cortical section modulus and calf muscle area Z-scores were greater in obese participants (1.07 and 1.63, respectively, both p<0.0001). Tibia and radius trabecular and cortical volumetric BMD did not differ significantly between groups. Calf muscle area and strength Z-scores, advanced skeletal maturity, and physical activity (by accelerometry) were positively associated with tibia cortical section modulus Z-scores (all p<0.01). Adjustment for muscle area Z-score attenuated differences in tibia section modulus Z-scores between obese and non-obese participants from 1.07 to 0.28. After multivariate adjustment for greater calf muscle area and strength Z-scores, advanced maturity, and less moderate to vigorous physical activity, tibia section modulus Z-scores were 0.32 (95% CI -0.18, 0.43, p=0.06) greater in obese, vs. non-obese participants. Radius cortical section modulus Z-scores were 0.45 greater (p=0.08) in obese vs. non-obese participants; this difference was attenuated to 0.14 with adjustment for advanced maturity. These findings suggest that greater tibia cortical section modulus in obese adolescents is attributable to advanced skeletal maturation and greater muscle area and strength, while less moderate to vigorous physical activities offset the positive effects of these covariates. The impact of obesity on cortical structure was greater at weight bearing sites. Copyright © 2014 Elsevier Inc. All rights reserved.

Gray Matter Density Negatively Correlates with Duration of Heroin Use in Young Lifetime Heroin-Dependent Individuals

ERIC Educational Resources Information Center

Yuan, Yi; Zhu, Zude; Shi, Jinfu; Zou, Zhiling; Yuan, Fei; Liu, Yijun; Lee, Tatia M. C.; Weng, Xuchu

2009-01-01

Numerous studies have documented cognitive impairments and hypoactivity in the prefrontal and anterior cingulate cortices in drug users. However, the relationships between opiate dependence and brain structure changes in heroin users are largely unknown. In the present study, we measured the density of gray matter (DGM) with voxel-based…

[Numeric simulation of functional remodeling of the anterior alveolar bone].

PubMed

Wang, Wei-feng; Xin, Hai-tao; Zang, Shun-lai; Ding, Jie

2012-04-01

To study the remodeling of the anterior alveolar bone with parodontium under physiology loading using finite element method (FEM) and theory of bone remodeling. A FEM model of the maxillary central incisor with parodontium was established, and the change of bone density during the remodeling of alveolar bone was investigated under physiology loading (60 - 150 N) based on the theory of bone remodeling about strain energy density (SED). The finite element analysis software Abaqus user material subroutine (UMAT) were used. With the increase of physiology loading, the pressure stress on the buccal cervical margin increased gradually while the density was decreased gradually. The cortical bone was lower than its initial density 1.74 g/cm(3), which was 1.74 - 1.63 g/cm(3). The density of cancellous bone was 0.90 - 0.77 g/cm(3), which was lower than its intial density 0.90 g/cm(3). The lingual cervical margin was under tensile stress which also increased with loading, the density had no significant change. When the achieve to 120 N, the density of cortical bone was 1.74 - 1.73 g/cm(3). No significant change was found in the cancellous bone. The simulation of the perodontium remodeling is achieved and proved to be effective by the relevant research based on the method of the study. And the result will be helpful to form the basis of analysis bone remodeling process and predict the results in the clinical work.

Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone☆

PubMed Central

Vanleene, Maximilien; Shefelbine, Sandra J.

2013-01-01

Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45 Hz, 0.3 g, 15 minutes/days, 5 days/week) in young OI (oim) and wild type female mice from 3 to 8 weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the histological sections, it is possible that WBV reduced bone resorption, resulting in a relative increase in cortical thickness. Whole body vibration appears as a potential effective and innocuous means for increasing bone formation and strength, which is particularly attractive for treating the growing skeleton of children suffering from brittle bone disease or low bone density pathologies without the long term disadvantages of current pharmacological therapies. PMID:23352925

Real-time Neuroimaging and Cognitive Monitoring Using Wearable Dry EEG

PubMed Central

Mullen, Tim R.; Kothe, Christian A.E.; Chi, Mike; Ojeda, Alejandro; Kerth, Trevor; Makeig, Scott; Jung, Tzyy-Ping; Cauwenberghs, Gert

2015-01-01

Goal We present and evaluate a wearable high-density dry electrode EEG system and an open-source software framework for online neuroimaging and state classification. Methods The system integrates a 64-channel dry EEG form-factor with wireless data streaming for online analysis. A real-time software framework is applied, including adaptive artifact rejection, cortical source localization, multivariate effective connectivity inference, data visualization, and cognitive state classification from connectivity features using a constrained logistic regression approach (ProxConn). We evaluate the system identification methods on simulated 64-channel EEG data. Then we evaluate system performance, using ProxConn and a benchmark ERP method, in classifying response errors in 9 subjects using the dry EEG system. Results Simulations yielded high accuracy (AUC=0.97±0.021) for real-time cortical connectivity estimation. Response error classification using cortical effective connectivity (sdDTF) was significantly above chance with similar performance (AUC) for cLORETA (0.74±0.09) and LCMV (0.72±0.08) source localization. Cortical ERP-based classification was equivalent to ProxConn for cLORETA (0.74±0.16) but significantly better for LCMV (0.82±0.12). Conclusion We demonstrated the feasibility for real-time cortical connectivity analysis and cognitive state classification from high-density wearable dry EEG. Significance This paper is the first validated application of these methods to 64-channel dry EEG. The work addresses a need for robust real-time measurement and interpretation of complex brain activity in the dynamic environment of the wearable setting. Such advances can have broad impact in research, medicine, and brain-computer interfaces. The pipelines are made freely available in the open-source SIFT and BCILAB toolboxes. PMID:26415149

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

PubMed Central

Edwards, Dylan; Cortes, Mar; Datta, Abhishek; Minhas, Preet; Wassermann, Eric M.; Bikson, Marom

2015-01-01

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation. PMID:23370061

Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

PubMed Central

Kähönen, Mika; Raitakari, Olli; Laaksonen, Marika; Sievänen, Harri; Viikari, Jorma; Lyytikäinen, Leo-Pekka; Mellström, Dan; Karlsson, Magnus; Ljunggren, Östen; Grundberg, Elin; Kemp, John P.; Sayers, Adrian; Nethander, Maria; Evans, David M.; Vandenput, Liesbeth; Tobias, Jon H.; Ohlsson, Claes

2013-01-01

Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10−14; LOC285735, rs271170, p = 2.7×10−12; OPG, rs7839059, p = 1.2×10−10; and ESR1/C6orf97, rs6909279, p = 1.1×10−9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10−9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60–0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk. PMID:23437003

History of amenorrhoea compromises some of the exercise-induced benefits in cortical and trabecular bone in the peripheral and axial skeleton: a study in retired elite gymnasts.

PubMed

Ducher, G; Eser, P; Hill, B; Bass, S

2009-10-01

Female gymnasts frequently present with overt signs of hypoestrogenism, such as late menarche or menstrual dysfunction. The objective was to investigate the impact of history of amenorrhoea on the exercise-induced skeletal benefits in bone geometry and volumetric density in retired elite gymnasts. 24 retired artistic gymnasts, aged 17-36 years, who had been training for at least 15 h/week at the peak of their career and had been retired for 3-18 years were recruited. They had not been engaged in more than 2 h/week of regular physical activity since retirement. Former gymnasts who reported history of amenorrhoea ('AME', n=12: either primary or secondary amenorrhoea) were compared with former gymnasts ('NO-AME', n=12) and controls ('C', n=26) who did not report history of amenorrhoea. Bone mineral content (BMC), total bone area (ToA) and total volumetric density (ToD) were measured by pQCT at the radius and tibia (4% and 66%). Trabecular volumetric density (TrD) and bone strength index (BSI) were measured at the 4% sites. Cortical area (CoA), cortical thickness (CoTh), medullary area (MedA), cortical volumetric density (CoD), stress-strain index (SSI) and muscle and fat area were measured at the 66% sites. Spinal BMC, areal BMD and bone mineral apparent density (BMAD) were measured by DXA. Menarcheal age was delayed in AME when compared to NO-AME (16.4+/-0.5 years vs. 13.3+/-0.4 years, p<0.001). No differences were detected between AME and C for height-adjusted spinal BMC, aBMD and BMAD, TrD and BSI at the distal radius and tibia, CoA at the proximal radius, whereas these parameters were greater in NO-AME than C (p<0.05-0.005). AME had lower TrD and BSI at the distal radius, and lower spinal BMAD than NO-AME (p<0.05) but they had greater ToA at the distal radius (p<0.05). Greater spinal BMC, aBMD and BMAD as well as trabecular volumetric density and bone strength in the peripheral skeleton were found in former gymnasts without a history of menstrual dysfunction but not in those who reported either primary or secondary amenorrhoea. History of amenorrhoea may have compromised some of the skeletal benefits associated with high-impact gymnastics training.

Arousal from sleep: implications for obstructive sleep apnea pathogenesis and treatment.

PubMed

Eckert, Danny J; Younes, Magdy K

2014-02-01

Historically, brief awakenings from sleep (cortical arousals) have been assumed to be vitally important in restoring airflow and blood-gas disturbances at the end of obstructive sleep apnea (OSA) breathing events. Indeed, in patients with blunted chemical drive (e.g., obesity hypoventilation syndrome) and in instances when other defensive mechanisms fail, cortical arousal likely serves an important protective role. However, recent insight into the pathogenesis of OSA indicates that a substantial proportion of respiratory events do not terminate with a cortical arousal from sleep. In many cases, cortical arousals may actually perpetuate blood-gas disturbances, breathing instability, and subsequent upper airway closure during sleep. This brief review summarizes the current understanding of the mechanisms mediating respiratory-induced cortical arousal, the physiological factors that influence the propensity for cortical arousal, and the potential dual roles that cortical arousal may play in OSA pathogenesis. Finally, the extent to which existing sedative agents decrease the propensity for cortical arousal and their potential to be therapeutically beneficial for certain OSA patients are highlighted.

Frequency-selective augmenting responses by short-term synaptic depression in cat neocortex

PubMed Central

Houweling, Arthur R; Bazhenov, Maxim; Timofeev, Igor; Grenier, François; Steriade, Mircea; Sejnowski, Terrence J

2002-01-01

Thalamic stimulation at frequencies between 5 and 15 Hz elicits incremental or ‘augmenting’ cortical responses. Augmenting responses can also be evoked in cortical slices and isolated cortical slabs in vivo. Here we show that a realistic network model of cortical pyramidal cells and interneurones including short-term plasticity of inhibitory and excitatory synapses replicates the main features of augmenting responses as obtained in isolated slabs in vivo. Repetitive stimulation of synaptic inputs at frequencies around 10 Hz produced postsynaptic potentials that grew in size and carried an increasing number of action potentials resulting from the depression of inhibitory synaptic currents. Frequency selectivity was obtained through the relatively weak depression of inhibitory synapses at low frequencies, and strong depression of excitatory synapses together with activation of a calcium-activated potassium current at high frequencies. This network resonance is a consequence of short-term synaptic plasticity in a network of neurones without intrinsic resonances. These results suggest that short-term plasticity of cortical synapses could shape the dynamics of synchronized oscillations in the brain. PMID:12122156

Multi-level characterization of balanced inhibitory-excitatory cortical neuron network derived from human pluripotent stem cells.

PubMed

Nadadhur, Aishwarya G; Emperador Melero, Javier; Meijer, Marieke; Schut, Desiree; Jacobs, Gerbren; Li, Ka Wan; Hjorth, J J Johannes; Meredith, Rhiannon M; Toonen, Ruud F; Van Kesteren, Ronald E; Smit, August B; Verhage, Matthijs; Heine, Vivi M

2017-01-01

Generation of neuronal cultures from induced pluripotent stem cells (hiPSCs) serve the studies of human brain disorders. However we lack neuronal networks with balanced excitatory-inhibitory activities, which are suitable for single cell analysis. We generated low-density networks of hPSC-derived GABAergic and glutamatergic cortical neurons. We used two different co-culture models with astrocytes. We show that these cultures have balanced excitatory-inhibitory synaptic identities using confocal microscopy, electrophysiological recordings, calcium imaging and mRNA analysis. These simple and robust protocols offer the opportunity for single-cell to multi-level analysis of patient hiPSC-derived cortical excitatory-inhibitory networks; thereby creating advanced tools to study disease mechanisms underlying neurodevelopmental disorders.

Inhibition of Acid Sensing Ion Channel Currents by Lidocaine in Cultured Mouse Cortical Neurons

PubMed Central

Lin, Jun; Chu, Xiangping; Maysami, Samaneh; Li, Minghua; Si, Hongfang; Cottrell, James E.; Simon, Roger P.; Xiong, Zhigang

2012-01-01

BACKGROUND Lidocaine is a local anesthetic that has multiple pharmacological effects including antiarrhythmia, antinociception, and neuroprotection. Acid sensing ion channels (ASICs) are proton-gated cation channels that belong to the epithelial sodium channel/degenerin superfamily. Activation of ASICs by protons results in sodium and calcium influx. ASICs have been implicated in various physiological processes including learning/memory, nociception, and in acidosis-mediated neuron injury. In this study, we examined the effect of lidocaine on ASICs in cultured mouse cortical neurons. METHODS ASIC currents were activated and recorded using a whole-cell patch-clamp technique in cultured mouse cortical neurons. The effects of lidocaine at different concentrations were examined. To determine whether the inhibition of lidocaine on ASIC currents is subunit specific, we examined the effect of lidocaine on homomeric ASIC1a and ASIC2a currents expressed in Chinese hamster ovary cells. RESULTS Lidocaine significantly inhibits the ASIC currents in mouse cortical neurons. The inhibition was reversible and dose dependent. A detectable effect was noticed at a concentration of 0.3 mM lidocaine. At 30 mM, ASIC current was inhibited by approximately 90%. Analysis of the complete dose-response relationship yielded a half-maximal inhibitory concentration of 11.79 ± 1.74 mM and a Hill coefficient of 2.7 ± 0.5 (n = 10). The effect is rapid and does not depend on pH. In Chinese hamster ovary cells expressing different ASIC subunits, lidocaine inhibits the ASIC1a current without affecting the ASIC2a current. CONCLUSION ASIC currents are significantly inhibited by lidocaine. Our finding reveals a new pharmacological effect of lidocaine in neurons. PMID:21385979

Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

PubMed

Pelletier, Solenne; Vilayphiou, Nicolas; Boutroy, Stéphanie; Bacchetta, Justine; Sornay-Rendu, Elisabeth; Szulc, Pawel; Arkouche, Walid; Guebre-Egziabher, Fitsum; Fouque, Denis; Chapurlat, Roland

2012-09-01

We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

Multimodal analysis of cortical chemoarchitecture and macroscale fMRI resting‐state functional connectivity

PubMed Central

Scholtens, Lianne H.; Turk, Elise; Mantini, Dante; Vanduffel, Wim; Feldman Barrett, Lisa

2016-01-01

Abstract The cerebral cortex is well known to display a large variation in excitatory and inhibitory chemoarchitecture, but the effect of this variation on global scale functional neural communication and synchronization patterns remains less well understood. Here, we provide evidence of the chemoarchitecture of cortical regions to be associated with large‐scale region‐to‐region resting‐state functional connectivity. We assessed the excitatory versus inhibitory chemoarchitecture of cortical areas as an ExIn ratio between receptor density mappings of excitatory (AMPA, M1) and inhibitory (GABAA, M2) receptors, computed on the basis of data collated from pioneering studies of autoradiography mappings as present in literature of the human (2 datasets) and macaque (1 dataset) cortex. Cortical variation in ExIn ratio significantly correlated with total level of functional connectivity as derived from resting‐state functional connectivity recordings of cortical areas across all three datasets (human I: P = 0.0004; human II: P = 0.0008; macaque: P = 0.0007), suggesting cortical areas with an overall more excitatory character to show higher levels of intrinsic functional connectivity during resting‐state. Our findings are indicative of the microscale chemoarchitecture of cortical regions to be related to resting‐state fMRI connectivity patterns at the global system's level of connectome organization. Hum Brain Mapp 37:3103–3113, 2016. © 2016 Wiley Periodicals, Inc. PMID:27207489

High Resolution Peripheral Quantitative Computed Tomography for Assessment of Bone Quality

NASA Astrophysics Data System (ADS)

Kazakia, Galateia

2014-03-01

The study of bone quality is motivated by the high morbidity, mortality, and societal cost of skeletal fractures. Over 10 million people are diagnosed with osteoporosis in the US alone, suffering 1.5 million osteoporotic fractures and costing the health care system over 17 billion annually. Accurate assessment of fracture risk is necessary to ensure that pharmacological and other interventions are appropriately administered. Currently, areal bone mineral density (aBMD) based on 2D dual-energy X-ray absorptiometry (DXA) is used to determine osteoporotic status and predict fracture risk. Though aBMD is a significant predictor of fracture risk, it does not completely explain bone strength or fracture incidence. The major limitation of aBMD is the lack of 3D information, which is necessary to distinguish between cortical and trabecular bone and to quantify bone geometry and microarchitecture. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo assessment of volumetric BMD within specific bone compartments as well as quantification of geometric and microarchitectural measures of bone quality. HR-pQCT studies have documented that trabecular bone microstructure alterations are associated with fracture risk independent of aBMD.... Cortical bone microstructure - specifically porosity - is a major determinant of strength, stiffness, and fracture toughness of cortical tissue and may further explain the aBMD-independent effect of age on bone fragility and fracture risk. The application of finite element analysis (FEA) to HR-pQCT data permits estimation of patient-specific bone strength, shown to be associated with fracture incidence independent of aBMD. This talk will describe the HR-pQCT scanner, established metrics of bone quality derived from HR-pQCT data, and novel analyses of bone quality currently in development. Cross-sectional and longitudinal HR-pQCT studies investigating the impact of aging, disease, injury, gender, race, and therapeutics on bone quality will be discussed.

Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

PubMed Central

Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

2016-01-01

Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

Scalp and Source Power Topography in Sleepwalking and Sleep Terrors: A High-Density EEG Study.

PubMed

Castelnovo, Anna; Riedner, Brady A; Smith, Richard F; Tononi, Giulio; Boly, Melanie; Benca, Ruth M

2016-10-01

To examine scalp and source power topography in sleep arousals disorders (SADs) using high-density EEG (hdEEG). Fifteen adult subjects with sleep arousal disorders (SADs) and 15 age- and gender-matched good sleeping healthy controls were recorded in a sleep laboratory setting using a 256 channel EEG system. Scalp EEG analysis of all night NREM sleep revealed a localized decrease in slow wave activity (SWA) power (1-4 Hz) over centro-parietal regions relative to the rest of the brain in SADs compared to good sleeping healthy controls. Source modelling analysis of 5-minute segments taken from N3 during the first half of the night revealed that the local decrease in SWA power was prominent at the level of the cingulate, motor, and sensori-motor associative cortices. Similar patterns were also evident during REM sleep and wake. These differences in local sleep were present in the absence of any detectable clinical or electrophysiological sign of arousal. Overall, results suggest the presence of local sleep differences in the brain of SADs patients during nights without clinical episodes. The persistence of similar topographical changes in local EEG power during REM sleep and wakefulness points to trait-like functional changes that cross the boundaries of NREM sleep. The regions identified by source imaging are consistent with the current neurophysiological understanding of SADs as a disorder caused by local arousals in motor and cingulate cortices. Persistent localized changes in neuronal excitability may predispose affected subjects to clinical episodes. © 2016 Associated Professional Sleep Societies, LLC.

The cortical structure of consolidated memory: a hypothesis on the role of the cingulate-entorhinal cortical connection.

PubMed

Insel, Nathan; Takehara-Nishiuchi, Kaori

2013-11-01

Daily experiences are represented by networks of neurons distributed across the neocortex, bound together for rapid storage and later retrieval by the hippocampus. While the hippocampus is necessary for retrieving recent episode-based memory associations, over time, consolidation processes take place that enable many of these associations to be expressed independent of the hippocampus. It is generally thought that mechanisms of consolidation involve synaptic weight changes between cortical regions; or, in other words, the formation of "horizontal" cortico-cortical connections. Here, we review anatomical, behavioral, and physiological data which suggest that the connections in and between the entorhinal and cingulate cortices may be uniquely important for the long-term storage of memories that initially depend on the hippocampus. We propose that current theories of consolidation that divide memory into dual systems of hippocampus and neocortex might be improved by introducing a third, middle layer of entorhinal and cingulate allocortex, the synaptic weights within which are necessary and potentially sufficient for maintaining initially hippocampus-dependent associations over long time periods. This hypothesis makes a number of still untested predictions, and future experiments designed to address these will help to fill gaps in the current understanding of the cortical structure of consolidated memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical cone beam computed tomography compared to high-resolution peripheral computed tomography in the assessment of distal radius bone.

PubMed

de Charry, C; Boutroy, S; Ellouz, R; Duboeuf, F; Chapurlat, R; Follet, H; Pialat, J B

2016-10-01

Clinical cone beam computed tomography (CBCT) was compared to high-resolution peripheral quantitative computed tomography (HR-pQCT) for the assessment of ex vivo radii. Strong correlations were found for geometry, volumetric density, and trabecular structure. Using CBCT, bone architecture assessment was feasible but compared to HR-pQCT, trabecular parameters were overestimated whereas cortical ones were underestimated. HR-pQCT is the most widely used technique to assess bone microarchitecture in vivo. Yet, this technology has been only applicable at peripheral sites, in only few research centers. Clinical CBCT is more widely available but quantitative assessment of the bone structure is usually not performed. We aimed to compare the assessment of bone structure with CBCT (NewTom 5G, QR, Verona, Italy) and HR-pQCT (XtremeCT, Scanco Medical AG, Brüttisellen, Switzerland). Twenty-four distal radius specimens were scanned with these two devices with a reconstructed voxel size of 75 μm for Newtom 5G and 82 μm for XtremeCT, respectively. A rescaling-registration scheme was used to define the common volume of interest. Cortical and trabecular compartments were separated using a semiautomated double contouring method. Density and microstructure were assessed with the HR-pQCT software on both modality images. Strong correlations were found for geometry parameters (r = 0.98-0.99), volumetric density (r = 0.91-0.99), and trabecular structure (r = 0.94-0.99), all p < 0.001. Correlations were lower for cortical microstructure (r = 0.80-0.89), p < 0.001. However, absolute differences were observed between modalities for all parameters, with an overestimation of the trabecular structure (trabecular number, 1.62 ± 0.37 vs. 1.47 ± 0.36 mm(-1)) and an underestimation of the cortical microstructure (cortical porosity, 3.3 ± 1.3 vs. 4.4 ± 1.4 %) assessed on CBCT images compared to HR-pQCT images. Clinical CBCT devices are able to analyze large portions of distal bones with good spatial resolution and limited irradiation. However, compared to dedicated HR-pQCT, the assessment of microarchitecture by NewTom 5G dental CBCT showed some discrepancies, for density measurements mainly. Further technical developments are required to reach optimal assessment of bone characteristics.

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

PubMed

McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2009-12-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

A High-Density EEG Investigation into Steady State Binaural Beat Stimulation

PubMed Central

Goodin, Peter; Ciorciari, Joseph; Baker, Kate; Carrey, Anne-Marie; Harper, Michelle; Kaufman, Jordy

2012-01-01

Binaural beats are an auditory phenomenon that has been suggested to alter physiological and cognitive processes including vigilance and brainwave entrainment. Some personality traits measured by the NEO Five Factor Model have been found to alter entrainment using pulsing light stimuli, but as yet no studies have examined if this occurs using steady state presentation of binaural beats for a relatively short presentation of two minutes. This study aimed to examine if binaural beat stimulation altered vigilance or cortical frequencies and if personality traits were involved. Thirty-one participants were played binaural beat stimuli designed to elicit a response at either the Theta (7 Hz) or Beta (16 Hz) frequency bands while undertaking a zero-back vigilance task. EEG was recorded from a high-density electrode cap. No significant differences were found in vigilance or cortical frequency power during binaural beat stimulation compared to a white noise control period. Furthermore, no significant relationships were detected between the above and the Big Five personality traits. This suggests a short presentation of steady state binaural beats are not sufficient to alter vigilance or entrain cortical frequencies at the two bands examined and that certain personality traits were not more susceptible than others. PMID:22496862

A high-density EEG investigation into steady state binaural beat stimulation.

PubMed

Goodin, Peter; Ciorciari, Joseph; Baker, Kate; Carey, Anne-Marie; Carrey, Anne-Marie; Harper, Michelle; Kaufman, Jordy

2012-01-01

Binaural beats are an auditory phenomenon that has been suggested to alter physiological and cognitive processes including vigilance and brainwave entrainment. Some personality traits measured by the NEO Five Factor Model have been found to alter entrainment using pulsing light stimuli, but as yet no studies have examined if this occurs using steady state presentation of binaural beats for a relatively short presentation of two minutes. This study aimed to examine if binaural beat stimulation altered vigilance or cortical frequencies and if personality traits were involved. Thirty-one participants were played binaural beat stimuli designed to elicit a response at either the Theta (7 Hz) or Beta (16 Hz) frequency bands while undertaking a zero-back vigilance task. EEG was recorded from a high-density electrode cap. No significant differences were found in vigilance or cortical frequency power during binaural beat stimulation compared to a white noise control period. Furthermore, no significant relationships were detected between the above and the Big Five personality traits. This suggests a short presentation of steady state binaural beats are not sufficient to alter vigilance or entrain cortical frequencies at the two bands examined and that certain personality traits were not more susceptible than others.

Hypercholesterolemia Promotes an Osteoporotic Phenotype

PubMed Central

Pelton, Kristine; Krieder, Jaclynn; Joiner, Danese; Freeman, Michael R.; Goldstein, Steven A.; Solomon, Keith R.

2013-01-01

A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health. PMID:22770664

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation)

PubMed Central

McGee-Lawrence, Meghan E.; Wojda, Samantha J.; Barlow, Lindsay N.; Drummer, Thomas D.; Castillo, Alesha B.; Kennedy, Oran; Condon, Keith W.; Auger, Janene; Black, Hal L.; Nelson, O. Lynne; Robbins, Charles T.; Donahue, Seth W.

2009-01-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse induced bone loss in bears into novel treatments for osteoporosis. PMID:19703606

Setup of a bone aging experimental model in the rabbit comparing changes in cortical and trabecular bone: Morphological and morphometric study in the femur.

PubMed

Pazzaglia, Ugo E; Sibilia, Valeria; Congiu, Terenzio; Pagani, Francesca; Ravanelli, Marco; Zarattini, Guido

2015-07-01

Bone aging was studied in an experimental model (rabbit femur) in three populations aged 0.5, 1.5, and 7.5 years. Cortical bone histology was compared with a data set from a 1.5-month-old population of an earlier published paper. From 0.5-year-old onward, the mean femur length did not increase further. Thereafter, the mean marrow area increased and the cortical area decreased significantly with aging. This was associated with a structural pattern transformation from plexiform to laminar and then Haversian-like type. The distal meta-epiphysis bone trabecular density of the oldest populations also was significantly lower in specific regions of interest (ROI). Percentage sealed primary vascular canals in laminar bone significantly increased with aging without variation of percentage sealed secondary osteons. Remodeling rate reflected by the density of cutting cones did not significantly change among the age populations. These data suggest that laminar bone vascular pattern is more functional in the fast diaphyseal expansion but not much streamlined with the renewal of blood flow during secondary remodeling. Bone aging was characterized by: 1) secondary remodeling subendosteally; 2) increment of sealed primary vascular canals number; 3) increased calcium content of the cortex; 4) cortical and trabecular bone mass loss in specific ROIs. Taken together, the present data may give a morphological and morphometric basis to perform comparative studies on experimental models of osteoporosis in the rabbit. © 2015 Wiley Periodicals, Inc.

Predicting infant cortical surface development using a 4D varifold-based learning framework and local topography-based shape morphing.

PubMed

Rekik, Islem; Li, Gang; Lin, Weili; Shen, Dinggang

2016-02-01

Longitudinal neuroimaging analysis methods have remarkably advanced our understanding of early postnatal brain development. However, learning predictive models to trace forth the evolution trajectories of both normal and abnormal cortical shapes remains broadly absent. To fill this critical gap, we pioneered the first prediction model for longitudinal developing cortical surfaces in infants using a spatiotemporal current-based learning framework solely from the baseline cortical surface. In this paper, we detail this prediction model and even further improve its performance by introducing two key variants. First, we use the varifold metric to overcome the limitations of the current metric for surface registration that was used in our preliminary study. We also extend the conventional varifold-based surface registration model for pairwise registration to a spatiotemporal surface regression model. Second, we propose a morphing process of the baseline surface using its topographic attributes such as normal direction and principal curvature sign. Specifically, our method learns from longitudinal data both the geometric (vertices positions) and dynamic (temporal evolution trajectories) features of the infant cortical surface, comprising a training stage and a prediction stage. In the training stage, we use the proposed varifold-based shape regression model to estimate geodesic cortical shape evolution trajectories for each training subject. We then build an empirical mean spatiotemporal surface atlas. In the prediction stage, given an infant, we select the best learnt features from training subjects to simultaneously predict the cortical surface shapes at all later timepoints, based on similarity metrics between this baseline surface and the learnt baseline population average surface atlas. We used a leave-one-out cross validation method to predict the inner cortical surface shape at 3, 6, 9 and 12 months of age from the baseline cortical surface shape at birth. Our method attained a higher prediction accuracy and better captured the spatiotemporal dynamic change of the highly folded cortical surface than the previous proposed prediction method. Copyright © 2015 Elsevier B.V. All rights reserved.

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. II. Stereologic analysis of chemoarchitecture.

PubMed

Sherwood, Chet C; Holloway, Ralph L; Erwin, Joseph M; Hof, Patrick R

2004-01-01

This study presents a comparative stereologic investigation of neurofilament protein- and calcium-binding protein-immunoreactive neurons within the region of orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens). Results showed that the density of interneurons involved in vertical interlaminar processing (i.e., calbindin- and calretinin-immunoreactive neurons) as well pyramidal neurons that supply heavily-myelinated projections (i.e., neurofilament protein-immunoreactive neurons) are correlated with overall neuronal density, whereas interneurons making transcolumnar connections (i.e., parvalbumin-immunoreactive neurons) do not exhibit such a relationship. These results suggest that differential scaling rules apply to different neuronal subtypes depending on their functional role in cortical circuitry. For example, cortical columns across catarrhine species appear to involve a similar conserved network of intracolumnar inhibitory interconnections, as represented by the distribution of calbindin- and calretinin-immunoreactive neurons. The subpopulation of horizontally-oriented wide-arbor interneurons, on the other hand, increases in density relative to other interneuron subpopulations in large brains. Due to these scaling trends, the region of orofacial representation of primary motor cortex in great apes and humans is characterized by a greater proportion of neurons enriched in neurofilament protein and parvalbumin compared to the Old World monkeys examined. These modifications might contribute to the voluntary dexterous control of orofacial muscles in great ape and human communication. Copyright 2004 S. Karger AG, Basel

Thalamocortical and intracortical laminar connectivity determines sleep spindle properties.

PubMed

Krishnan, Giri P; Rosen, Burke Q; Chen, Jen-Yung; Muller, Lyle; Sejnowski, Terrence J; Cash, Sydney S; Halgren, Eric; Bazhenov, Maxim

2018-06-27

Sleep spindles are brief oscillatory events during non-rapid eye movement (NREM) sleep. Spindle density and synchronization properties are different in MEG versus EEG recordings in humans and also vary with learning performance, suggesting spindle involvement in memory consolidation. Here, using computational models, we identified network mechanisms that may explain differences in spindle properties across cortical structures. First, we report that differences in spindle occurrence between MEG and EEG data may arise from the contrasting properties of the core and matrix thalamocortical systems. The matrix system, projecting superficially, has wider thalamocortical fanout compared to the core system, which projects to middle layers, and requires the recruitment of a larger population of neurons to initiate a spindle. This property was sufficient to explain lower spindle density and higher spatial synchrony of spindles in the superficial cortical layers, as observed in the EEG signal. In contrast, spindles in the core system occurred more frequently but less synchronously, as observed in the MEG recordings. Furthermore, consistent with human recordings, in the model, spindles occurred independently in the core system but the matrix system spindles commonly co-occurred with core spindles. We also found that the intracortical excitatory connections from layer III/IV to layer V promote spindle propagation from the core to the matrix system, leading to widespread spindle activity. Our study predicts that plasticity of intra- and inter-cortical connectivity can potentially be a mechanism for increased spindle density as has been observed during learning.

The maturation of cortical sleep rhythms and networks over early development.

PubMed

Chu, C J; Leahy, J; Pathmanathan, J; Kramer, M A; Cash, S S

2014-07-01

Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The maturation of cortical sleep rhythms and networks over early development

PubMed Central

Chu, CJ; Leahy, J; Pathmanathan, J; Kramer, MA; Cash, SS

2014-01-01

Objective Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. Methods We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. Results We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Conclusion Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. Significance This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. PMID:24418219

Cortical Power-Density Changes of Different Frequency Bands in Visually Guided Associative Learning: A Human EEG-Study

PubMed Central

Puszta, András; Katona, Xénia; Bodosi, Balázs; Pertich, Ákos; Nyujtó, Diána; Braunitzer, Gábor; Nagy, Attila

2018-01-01

The computer-based Rutgers Acquired Equivalence test (RAET) is a widely used paradigm to test the function of subcortical structures in visual associative learning. The test consists of an acquisition (pair learning) and a test (rule transfer) phase, associated with the function of the basal ganglia and the hippocampi, respectively. Obviously, such a complex task also requires cortical involvement. To investigate the activity of different cortical areas during this test, 64-channel EEG recordings were recorded in 24 healthy volunteers. Fast-Fourier and Morlet wavelet convolution analyses were performed on the recordings. The most robust power changes were observed in the theta (4–7 Hz) and gamma (>30 Hz) frequency bands, in which significant power elevation was observed in the vast majority of the subjects, over the parieto-occipital and temporo-parietal areas during the acquisition phase. The involvement of the frontal areas in the acquisition phase was remarkably weaker. No remarkable cortical power elevations were found in the test phase. In fact, the power of the alpha and beta bands was significantly decreased over the parietooccipital areas. We conclude that the initial acquisition of the image pairs requires strong cortical involvement, but once the pairs have been learned, neither retrieval nor generalization requires strong cortical contribution. PMID:29867412

Cortical Power-Density Changes of Different Frequency Bands in Visually Guided Associative Learning: A Human EEG-Study.

PubMed

Puszta, András; Katona, Xénia; Bodosi, Balázs; Pertich, Ákos; Nyujtó, Diána; Braunitzer, Gábor; Nagy, Attila

2018-01-01

The computer-based Rutgers Acquired Equivalence test (RAET) is a widely used paradigm to test the function of subcortical structures in visual associative learning. The test consists of an acquisition (pair learning) and a test (rule transfer) phase, associated with the function of the basal ganglia and the hippocampi, respectively. Obviously, such a complex task also requires cortical involvement. To investigate the activity of different cortical areas during this test, 64-channel EEG recordings were recorded in 24 healthy volunteers. Fast-Fourier and Morlet wavelet convolution analyses were performed on the recordings. The most robust power changes were observed in the theta (4-7 Hz) and gamma (>30 Hz) frequency bands, in which significant power elevation was observed in the vast majority of the subjects, over the parieto-occipital and temporo-parietal areas during the acquisition phase. The involvement of the frontal areas in the acquisition phase was remarkably weaker. No remarkable cortical power elevations were found in the test phase. In fact, the power of the alpha and beta bands was significantly decreased over the parietooccipital areas. We conclude that the initial acquisition of the image pairs requires strong cortical involvement, but once the pairs have been learned, neither retrieval nor generalization requires strong cortical contribution.

Adult Astrogenesis and the Etiology of Cortical Neurodegeneration

PubMed Central

Mohn, Tal C.; Koob, Andrew O.

2015-01-01

As more evidence points to a clear role for astrocytes in synaptic processing, synaptogenesis and cognition, continuing research on astrocytic function could lead to strategies for neurodegenerative disease prevention. Reactive astrogliosis results in astrocyte proliferation early in injury and disease states and is considered neuroprotective, indicating a role for astrocytes in disease etiology. This review describes the different types of human cortical astrocytes and the current evidence regarding adult cortical astrogenesis in injury and degenerative disease. A role for disrupted astrogenesis as a cause of cortical degeneration, with a focus on the tauopathies and synucleinopathies, will also be considered. PMID:26568684

Amyloid-β production via cleavage of amyloid-β protein precursor is modulated by cell density.

PubMed

Zhang, Can; Browne, Andrew; Divito, Jason R; Stevenson, Jesse A; Romano, Donna; Dong, Yuanlin; Xie, Zhongcong; Tanzi, Rudolph E

2010-01-01

Mounting evidence suggests that Alzheimer's disease (AD) is caused by the accumulation of the small peptide, amyloid-β (Aβ), a proteolytic cleavage product of amyloid-β protein precursor (AβPP). Aβ is generated through a serial cleavage of AβPP by β- and γ-secretase. Aβ40 and Aβ42 are the two main components of amyloid plaques in AD brains, with Aβ42 being more prone to aggregation. AβPP can also be processed by α-secretase, which cleaves AβPP within the Aβ sequence, thereby preventing the generation of Aβ. Little is currently known regarding the effects of cell density on AβPP processing and Aβ generation. Here we assessed the effects of cell density on AβPP processing in neuronal and non-neuronal cell lines, as well as mouse primary cortical neurons. We found that decreased cell density significantly increases levels of Aβ40, Aβ42, total Aβ, and the ratio of Aβ42: Aβ40. These results also indicate that cell density is a significant modulator of AβPP processing. Overall, these findings carry profound implications for both previous and forthcoming studies aiming to assess the effects of various conditions and genetic/chemical factors, e.g., novel drugs on AβPP processing and Aβ generation in cell-based systems. Moreover, it is interesting to speculate whether cell density changes in vivo may also affect AβPP processing and Aβ levels in the AD brain.

Kalirin, a Key Player in Synapse Formation, Is Implicated in Human Diseases

PubMed Central

Mandela, Prashant; Ma, Xin-Ming

2012-01-01

Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function. PMID:22548195

Kalirin, a key player in synapse formation, is implicated in human diseases.

PubMed

Mandela, Prashant; Ma, Xin-Ming

2012-01-01

Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

Linking contemporary high resolution magnetic resonance imaging to the von Economo legacy: A study on the comparison of MRI cortical thickness and histological measurements of cortical structure.

PubMed

Scholtens, Lianne H; de Reus, Marcel A; van den Heuvel, Martijn P

2015-08-01

The cerebral cortex is a distinctive part of the mammalian nervous system, displaying a spatial variety in cyto-, chemico-, and myelinoarchitecture. As part of a rich history of histological findings, pioneering anatomists von Economo and Koskinas provided detailed mappings on the cellular structure of the human cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas. Current day investigations into the structure of human cortex have embraced technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale thickness and organization of the cortical mantle in vivo. However, direct comparisons between current day MRI estimates and the quantitative measurements of early anatomists have been limited. Here, we report on a simple, but nevertheless important cross-analysis between the histological reports of von Economo and Koskinas on variation in thickness of the cortical mantle and MRI derived measurements of cortical thickness. We translated the von Economo cortical atlas to a subdivision of the commonly used Desikan-Killiany atlas (as part of the FreeSurfer Software package and a commonly used parcellation atlas in studies examining MRI cortical thickness). Next, values of "width of the cortical mantle" as provided by the measurements of von Economo and Koskinas were correlated to cortical thickness measurements derived from high-resolution anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP). Cross-correlation revealed a significant association between group-averaged MRI measurements of cortical thickness and histological recordings (r = 0.54, P < 0.001). Further validating such a correlation, we manually segmented the von Economo parcellation atlas on the standardized Colin27 brain dataset and applied the obtained three-dimensional von Economo segmentation atlas to the T1 data of each of the HCP subjects. Highly consistent with our findings for the mapping to the Desikan-Killiany regions, cross-correlation between in vivo MRI cortical thickness and von Economo histology-derived values of cortical mantle width revealed a strong positive association (r = 0.62, P < 0.001). Linking today's state-of-the-art T1-weighted imaging to early histological examinations our findings indicate that MRI technology is a valid method for in vivo assessment of thickness of human cortex. © 2015 Wiley Periodicals, Inc.

Cortical basis of communication: local computation, coordination, attention.

PubMed

Alexandre, Frederic

2009-03-01

Human communication emerges from cortical processing, known to be implemented on a regular repetitive neuronal substratum. The supposed genericity of cortical processing has elicited a series of modeling works in computational neuroscience that underline the information flows driven by the cortical circuitry. In the minimalist framework underlying the current theories for the embodiment of cognition, such a generic cortical processing is exploited for the coordination of poles of representation, as is reported in this paper for the case of visual attention. Interestingly, this case emphasizes how abstract internal referents are built to conform to memory requirements. This paper proposes that these referents are the basis for communication in humans, which is firstly a coordination and an attentional procedure with regard to their congeners.

Bone geometry, strength, and muscle size in runners with a history of stress fracture.

PubMed

Popp, Kristin L; Hughes, Julie M; Smock, Amanda J; Novotny, Susan A; Stovitz, Steven D; Koehler, Scott M; Petit, Moira A

2009-12-01

Our primary aim was to explore differences in estimates of tibial bone strength, in female runners with and without a history of stress fractures. Our secondary aim was to explore differences in bone geometry, volumetric density, and muscle size that may explain bone strength outcomes. A total of 39 competitive distance runners aged 18-35 yr, with (SFX, n = 19) or without (NSFX, n = 20) a history of stress fracture were recruited for this cross-sectional study. Peripheral quantitative computed tomography (XCT 3000; Orthometrix, White Plains, NY) was used to assess volumetric bone mineral density (vBMD, mg x mm(-3)), bone area (ToA, mm(2)), and estimated compressive bone strength (bone strength index (BSI) = ToA x total volumetric density (ToD(2))) at the distal tibia (4%). Total (ToA, mm(2)) and cortical (CoA, mm(2)) bone area, cortical vBMD, and estimated bending strength (strength-strain index (SSIp), mm(3)) were measured at the 15%, 25%, 33%, 45%, 50%, and 66% sites. Muscle cross-sectional area (MCSA) was measured at the 50% and 66% sites. Participants in the SFX group had significantly smaller (7%-8%) CoA at the 45%, 50%, and 66% sites (P

Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers.

PubMed

Hagler, Donald J; Ulbert, István; Wittner, Lucia; Erőss, Loránd; Madsen, Joseph R; Devinsky, Orrin; Doyle, Werner; Fabó, Dániel; Cash, Sydney S; Halgren, Eric

2018-03-21

Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10-16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels. Many spindles were observed in only upper or only middle channels, but approximately half occurred in both. In spindles involving both middle and upper channels, the spindle envelope onset in middle channels led upper by ∼25-50 ms on average. The phase relationship between spindle waves in upper and middle channels varied dynamically within spindle epochs, and across individuals. Current source density analysis demonstrated that upper and middle channel spindles were both generated by an excitatory supragranular current sink while an additional deep source was present for middle channel spindles only. Only middle channel spindles were accompanied by deep low (25-50 Hz) and high (70-170 Hz) gamma activity. These results suggest that upper channel spindles are generated by supragranular pyramids, and middle channel by infragranular. Possibly, middle channel spindles are generated by core thalamocortical afferents, and upper channel by matrix. The concurrence of these patterns could reflect engagement of cortical circuits in the integration of more focal (core) and distributed (matrix) aspects of memory. These results demonstrate that at least two distinct intracortical systems generate human sleep spindles. SIGNIFICANCE STATEMENT Bursts of ∼14 Hz oscillations, lasting ∼1 s, have been recognized for over 80 years as cardinal features of mammalian sleep. Recent findings suggest that they play a key role in organizing cortical activity during memory consolidation. We used linear microelectrode arrays to study their intracortical organization in humans. We found that spindles could be divided into two types. One mainly engages upper layers of the cortex, which are considered to be specialized for associative activity. The other engages both upper and middle layers, including those devoted to sensory input. The interaction of these two spindle types may help organize the interaction of sensory and associative aspects of memory consolidation. Copyright © 2018 the authors 0270-6474/18/383013-13$15.00/0.

Long-Lasting Enhancement of Visual Perception with Repetitive Noninvasive Transcranial Direct Current Stimulation

PubMed Central

Behrens, Janina R.; Kraft, Antje; Irlbacher, Kerstin; Gerhardt, Holger; Olma, Manuel C.; Brandt, Stephan A.

2017-01-01

Understanding processes performed by an intact visual cortex as the basis for developing methods that enhance or restore visual perception is of great interest to both researchers and medical practitioners. Here, we explore whether contrast sensitivity, a main function of the primary visual cortex (V1), can be improved in healthy subjects by repetitive, noninvasive anodal transcranial direct current stimulation (tDCS). Contrast perception was measured via threshold perimetry directly before and after intervention (tDCS or sham stimulation) on each day over 5 consecutive days (24 subjects, double-blind study). tDCS improved contrast sensitivity from the second day onwards, with significant effects lasting 24 h. After the last stimulation on day 5, the anodal group showed a significantly greater improvement in contrast perception than the sham group (23 vs. 5%). We found significant long-term effects in only the central 2–4° of the visual field 4 weeks after the last stimulation. We suspect a combination of two factors contributes to these lasting effects. First, the V1 area that represents the central retina was located closer to the polarization electrode, resulting in higher current density. Second, the central visual field is represented by a larger cortical area relative to the peripheral visual field (cortical magnification). This is the first study showing that tDCS over V1 enhances contrast perception in healthy subjects for several weeks. This study contributes to the investigation of the causal relationship between the external modulation of neuronal membrane potential and behavior (in our case, visual perception). Because the vast majority of human studies only show temporary effects after single tDCS sessions targeting the visual system, our study underpins the potential for lasting effects of repetitive tDCS-induced modulation of neuronal excitability. PMID:28860969

Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients

NASA Technical Reports Server (NTRS)

Zerwekh, J. E.; Antich, P. P.; Sakhaee, K.; Prior, J.; Gonzales, J.; Gottschalk, F.; Pak, C. Y.

1992-01-01

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

Marchiafava-Bignami Disease with Cortical Involvement.

PubMed

Zhao, Panpan; Zhang, Hongliang; Zhang, Ying; Sun, Li

2018-06-01

Marchiafava-Bignami disease (MBD) is a neurological degenerative disorder with a pathognomonic hallmark of symmetric demyelination in the corpus callosum (CC). Most reported cases were chronic alcoholics and some showed cortical lesions related to poor clinical prognosis. Herein we report a case of a chronic alcoholic who presented with confusion and generalized weakness. Nerve fiber integrity and metabolic changes were evaluated with Magnetic resonance imaging (MRI) sequences including diffusion tensor imaging (DTI) and MRS. MRI revealed the typical callosal lesions of MBD with bilateral frontoparietal cortical lesions. DTI and MRS showed both impaired myelin integrity and axonal density in the CC. The cortical lesions partly disappeared after intravenous administration of high-dose multivitamins and corticosteroids. The patient regained consciousness 3 months later while dysarthria and quadriplegia persisted. Three years later, the patient can interact occasionally with people and the functional activities of both upper and lower limbs have no improvement. To our knowledge, this is the first report of DTI together with MRS assisting in evaluating the prognosis of MBD.

Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

PubMed

Kittivanichkul, Donlaporn; Charoenphandhu, Narattaphol; Khemawoot, Phisit; Malaivijitnond, Suchinda

2016-11-01

Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry). © 2016 Society for Endocrinology.

Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength.

PubMed

Liu, Dong-Mei; Zhao, Lin; Liu, Ting-Ting; Jiao, Pei-Lin; Zhao, Dian-Dian; Shih, Mei-Shu; Tao, Bei; Sun, Li-Hao; Zhao, Hong-Yan; Liu, Jian-Min

2016-09-01

Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase conserved through evolution that coordinates extra cellular signals associated with cell growth. Main functions of mTOR present in the form of two complexes, namely mTORC1 and mTORC2, which are distinct in their unique components, raptor and rictor. In the current study, using a Cre/loxp system, we found an anabolic effect of mTORC2 signaling on skeleton. Osteoblast differentiation was reduced, with down-regulation of mTORC2 signaling activity in primary cultures of osteoblasts that did not contain rictor. Mice with a specific deletion of rictor in mature osteoblasts showed a significant reduction in lean mass and bone mineral density by dual energy x-ray absorptiometry analysis. Micro-computed tomography, histomorphometric, and molecular biological analyses revealed a marked impairment of the cortical bone mass and microarchitecture, as well as minor changes in trabecular bone, of the Rictorob(-/-) mice. Cortical bone mass and thickness of the femoral mid-shaft were dramatically reduced, with unusual increases in porosity and marrow area in Rictorob(-/-) mice. Thinner trabeculae were found in the L4 vertebrae with relatively normal structural indices of trabecular numbers and separation. A lower rate of bone turnover was observed, as the consequence of the decreased individual osteoblast activity and bone resorption. Furthermore, these changes were associated with significantly decreased bone biomechanical properties. In conclusion, expression of rictor in osteoblasts is essential for the maintenance of normal bone remodeling and microarchitecture, especially for the maintenance of the cortical bone. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered brain functional connectivity induced by physical exercise may improve neuropsychological functions in patients with benign epilepsy.

PubMed

Koirala, Gyan Raj; Lee, Dongpyo; Eom, Soyong; Kim, Nam-Young; Kim, Heung Dong

2017-11-01

The objective of this study was to elucidate alteration in functional connectivity (FC) in patients with benign epilepsy with centrotemporal spikes (BECTS) as induced by physical exercise therapy and their correlation to the neuropsychological (NP) functions. We analyzed 115 artifact- and spike-free 2-second epochs extracted from resting state EEG recordings before and after 5weeks of physical exercise in eight patients with BECTS. The exact Low Resolution Electromagnetic Tomography (eLORETA) was used for source reconstruction. We evaluated the cortical current source density (CSD) power across five different frequency bands (delta, theta, alpha, beta, and gamma). Altered FC between 34 regions of interests (ROIs) was then examined using lagged phase synchronization (LPS) method. We further investigated the correlation between the altered FC measures and the changes in NP test scores. We observed changes in CSD power following the exercise for all frequency bands and statistically significant increases in the right temporal region for the alpha band. There were a number of altered FC between the cortical ROIs in all frequency bands of interest. Furthermore, significant correlations were observed between FC measures and NP test scores at theta and alpha bands. The increased localization power at alpha band may be an indication of the positive impact of exercise in patients with BECTS. Frequency band-specific alterations in FC among cortical regions were associated with the modulation of cognitive and NP functions. The significant correlation between FC and NP tests suggests that physical exercise may mitigate the severity of BECTS, thereby enhancing NP function. Copyright © 2017 Elsevier Inc. All rights reserved.

New predictive model for monitoring bone remodeling.

PubMed

Bougherara, Habiba; Klika, Václav; Marsík, Frantisek; Marík, Ivo A; Yahia, L'hocine

2010-10-01

The aim of this article was to present a new thermodynamic-based model for bone remodeling which is able to predict the functional adaptation of bone in response to changes in both mechanical and biochemical environments. The model was based on chemical kinetics and irreversible thermodynamic principles, in which bone is considered as a self-organizing system that exchanges matter, energy and entropy with its surroundings. The governing equations of the mathematical model have been numerically solved using Matlab software and implemented in ANSYS software using the Finite Element Method. With the aid of this model, the whole inner structure of bone was elucidated. The current model suggested that bone remodeling was a dynamic process which was driven by mechanical loading, metabolic factors and other external contributions. The model clearly indicated that in the absence of mechanical stimulus, the bone was not completely resorbed and reaches a new steady state after about 50% of bone loss. This finding agreed with previous clinical studies. Furthermore, results of virtual computations of bone density in a composite femur showed the development of a dense cortical bone around the medullary canal and a dense trabeculae bone between the femoral head and the calcar region of the medial cortex due to compressive stresses. The comparison of the predicted bone density with the structure of the proximal femur obtained from X-rays and using strain energy density gave credibility to the current model. Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Brain regulation of muscle tone in healthy and functionally unstable ankles.

PubMed

Needle, Alan R; Palmer, Jacqueline A; Kesar, Trisha M; Binder-Macleod, Stuart A; Swanik, C Buz

2013-08-01

Current research into the etiology of joint instability has yielded inconsistent results, limiting our understanding of how to prevent and treat ligamentous injury effectively. Recently, cortical reorganization was demonstrated in patients with ligamentous injury; however, these neural changes have not been assessed relative to joint laxity. The purpose of the current study was to determine if changes in cortical excitability and inhibition occur in subjects with functional ankle instability, as well as to investigate the relationship between these measures and joint laxity. Posttest only with control group. University laboratory. 12 subjects with no history of ankle sprain (CON) and 12 subjects with a history of unilateral functional ankle instability (UNS). Subjects were tested for joint laxity using an instrumented ankle arthrometer. Cortical excitability and inhibition were assessed using transcranial magnetic stimulation (TMS) to obtain motor-evoked potentials and the cortical silent period from the lower leg muscles. Joint laxity was quantified as peak anterior displacement and inversion rotation. Active motor threshold, slope, and intensity at 50% of peak slope of TMS-derived recruitment curves were used to quantify cortical excitability from lower leg muscles, while the cortical silent period from the peroneus longus was used to represent intracortical inhibition. No significant differences were observed between groups for laxity or cortical measures. CON demonstrated a significant relationship between laxity and tibialis anterior excitability, as well as laxity and silent period, while UNS ankles demonstrated significant relationships between peroneal and soleus excitability and laxity measures. Our results support relationships between laxity and measures of excitability and inhibition that differ between healthy and unstable subjects. Future research should further investigate the mechanisms behind these findings and consider cortical influences when investigating altered joint laxity.

Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

PubMed Central

Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

2016-01-01

Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo—in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29–38, evident as higher rates of induced action potential firing at low current injections (100–200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26–28) and older animals (PD40–62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits. PMID:27065812

Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion.

PubMed

Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

2016-01-01

Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability.

PubMed

Inukai, Yasuto; Saito, Kei; Sasaki, Ryoki; Tsuiki, Shota; Miyaguchi, Shota; Kojima, Sho; Masaki, Mitsuhiro; Otsuru, Naofumi; Onishi, Hideaki

2016-01-01

Transcranial direct current stimulation (tDCS) is a representative non-invasive brain stimulation method (NIBS). tDCS increases cortical excitability not only in healthy individuals, but also in stroke patients where it contributes to motor function improvement. Recently, two additional types of transcranial electrical stimulation (tES) methods have been introduced that may also prove beneficial for stimulating cortical excitability; these are transcranial random noise stimulation (tRNS) and transcranial alternating current stimulation (tACS). However, comparison of tDCS with tRNS and tACS, in terms of efficacy in cortical excitability alteration, has not been reported thus far. We compared the efficacy of the three different tES methods for increasing cortical excitability using the same subject population and same current intensity. Fifteen healthy subjects participated in this study. Similar stimulation patterns (1.0 mA and 10 min) were used for the three conditions of stimulation (tDCS, tRNS, and tACS). Cortical excitability was explored via single-pulse TMS elicited motor evoked potentials (MEPs). Compared with pre-measurements, MEPs significantly increased with tDCS, tACS, and tRNS ( p < 0.05). Compared with sham measurements, significant increases in MEPs were also observed with tRNS and tACS ( p < 0.05), but not with tDCS. In addition, a significant correlation of the mean stimulation effect was observed between tRNS and tACS ( p = 0.019, r = 0.598). tRNS induced a significant increase in MEP compared with the Pre or Sham at all time points. tRNS resulted in the largest significant increase in MEPs. These findings suggest that tRNS is the most effective tES method and should be considered as part of a treatment plan for improving motor function in stroke patients.

Relationship between masticatory function and internal structure of the mandible based on computed tomography findings.

PubMed

Sato, Hidemasa; Kawamura, Akira; Yamaguchi, Masaru; Kasai, Kazutaka

2005-12-01

The purposes of this study were to investigate bone mineral density as a part of bone construction in human skulls and to examine the relationship between dentofacial morphology and masticatory function by using computed tomography (CT) findings. Changes in bone mineral density in the mandible because of loss of masticatory function were tested in rats by experimentally producing an environment that inhibited mastication by the molars. Data for the human study were obtained from 27 modern male Japanese skulls (mean age, 28 years) from the University of Tokyo. Cortical bone thickness (CBT) and CT value (CV) were measured by each CT scan of the first and molars. For the animal study, a metal cap was inserted between the maxillary and mandibular incisors to prevent the molars from biting in 6-week-old male Wistar rats. The rats were killed after 2, 4, or 6 weeks, and bone mineral density was measured in cancellous and cortical bone equivalent to the first molar region by using peripheral quantitative computed tomography. In the human skull study, significant negative correlations were observed between CV in the regions of the buccal side of the second molar and the angle between the Frankfort horizontal and mandibular planes. Significant negative correlations were also observed between the gonial angle and CV in the buccal and basal sides. In the animal study, cancellous bone mineral density began to decline 4 weeks after the start of the experiment in the masticatory hypofunction group compared with the control group. By week 6, cancellous bone density had declined by 11.6% on the buccal side, 16.7% on the lingual side, 12.3% at the bifurcation of the root, and 38.1% at the root apex. Cortical bone density declined by 8% to 12% on the lingual side. The results support our hypothesis that a functional adaptive response by the mandible to mechanical stress resulting from mastication occurs not only in the muscle insertion area, but also in mandibular alveolar bone in the molar region.

Use of cortical stimulation in neuropathic pain, tinnitus, depression, and movement disorders.

PubMed

Panov, Fedor; Kopell, Brian Harris

2014-07-01

Medical treatment must strike a balance between benefit and risk. As the field of neuromodulation develops, decreased invasiveness, in combination with maintenance of efficacy, has become a goal. We provide a review of the history of cortical stimulation from its origins to the current state. The first part discusses neuropathic pain and the nonpharmacological treatment options used. The second part covers transitions to tinnitus, believed by many to be another deafferentation disorder, its classification, and treatment. The third part focuses on major depression. The fourth section concludes with the discussion of the use of cortical stimulation in movement disorders. Each part discusses the development of the field, describes the current care protocols, and suggests future avenues for research needed to advance neuromodulation.

Cortical Porosity Identifies Women with Osteopenia at Increased Risk for Forearm Fractures

PubMed Central

Bala, Yohann; Zebaze, Roger; Ghasem-Zadeh, Ali; Atkinson, Elizabeth J.; Iuliano, Sandra; Peterson, James M.; Amin, Shreyasee; Bjørnerem, Åshild; Melton, L. Joseph; Johansson, Helena; Kanis, John A.; Khosla, Sundeep; Seeman, Ego

2014-01-01

Background Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. Methods We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high-resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10-year fracture probability using the country-specific FRAX tool in 68 postmenopausal women with forearm fractures and 70 age-matched community controls in Olmsted County, Minnesota. Results Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact-appearing cortical porosity predicted fracture independent of aBMD; odds ratio [OR] 1.92 (95%CI, 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with, from those without, fractures because high porosity was present in 92% and 86% of each group respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact-appearing cortex conferred an OR for fracture of 4.00 (95%CI, 1.15–13.90). Conclusion In women with osteoporosis, porosity is captured by aBMD and so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. PMID:24519558

Comparison of volumetric bone mineral density in the tibial region of interest for ACL reconstruction.

PubMed

Klein, Scott A; Nyland, John; Caborn, David N M; Kocabey, Yavuz; Nawab, Akbar

2005-12-01

Adequate tibial bone mineral density (BMD) is essential to soft tissue graft fixation during anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare volumetric bone plug density measurements at the tibial region of interest for ACL reconstruction using a standardized immersion technique and Archimedes' principle. Cancellous bone cores were harvested from the proximal, middle, and distal metaphyseal regions of the lateral tibia and from the standard tibial tunnel location used for ACL reconstruction of 18 cadaveric specimens. Proximal tibial cores displayed 32.6% greater BMD than middle tibial cores and 31.8% greater BMD than distal tibial cores, but did not differ from the BMD of the tibial tunnel cores. Correlational analysis confirmed that the cancellous BMD in the tibial tunnel related to the cancellous BMD of the proximal and distal lateral tibial metaphysis. In conjunction with its adjacent cortical bone, the cancellous BMD of the region used for standard tibial tunnel placement provides an effective foundation for ACL graft fixation. In tibia with poor BMD, bicortical fixation that incorporates cortical bone from the distal tibial tunnel region is recommended.

Groupwise connectivity-based parcellation of the whole human cortical surface using watershed-driven dimension reduction.

PubMed

Lefranc, Sandrine; Roca, Pauline; Perrot, Matthieu; Poupon, Cyril; Le Bihan, Denis; Mangin, Jean-François; Rivière, Denis

2016-05-01

Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Testosterone-related cortical maturation across childhood and adolescence.

PubMed

Nguyen, Tuong-Vi; McCracken, James; Ducharme, Simon; Botteron, Kelly N; Mahabir, Megan; Johnson, Wendy; Israel, Mimi; Evans, Alan C; Karama, Sherif

2013-06-01

Neuroendocrine theories of brain development hold testosterone as the predominant factor mediating sex-specific cortical growth and the ensuing lateralization of hemispheric function. However, studies to date have focussed on prenatal testosterone rather than pubertal changes in testosterone. Yet, animal studies have shown a high density of androgen-sensitive receptors in multiple key cortical areas, and puberty is known to coincide with both a significant rise in testosterone and the emergence of behavioral sex differences, suggesting peripubertal influences of testosterone on brain development. Here, we used linear mixed models to examine sex-specific cortical maturation associated with changes in testosterone levels in a longitudinal sample of developmentally healthy children and adolescents. A significant "sex by age by testosterone" interaction on cortical thickness (CTh) involving widespread areas of the developing brain was found. Testosterone levels were associated with CTh changes in regions of the left hemisphere in males and of the right hemisphere in females. In both sexes, the relationship between testosterone and CTh varied across the age span. These findings show the association between testosterone and CTh to be complex, highly dynamic, and to vary, depending on sex and age; they also suggest sex-related hemispheric lateralization effects of testosterone in humans.

Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy

PubMed Central

Reinsberger, Claus; Tanaka, Naoaki; Cole, Andrew J.; Woo Lee, Jong; Dworetzky, Barbara A.; Bromfield, Edward B.; Hamiwka, Lorie; Bourgeois, Blaise F.; Golby, Alexandra J.; Madsen, Joseph R.; Stufflebeam, Steven M.

2011-01-01

To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) had vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) had ECDs that were diversely oriented and widely distributed. Group analysis of MRI data showed widespread cortical thinning in Group B compared with Group A, in the left hemisphere involving the cingulate, supramarginal, occipito-temporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery. PMID:20472073

When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger–aggression relationship

PubMed Central

Hortensius, Ruud; Schutter, Dennis J. L. G.

2012-01-01

The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression. PMID:21421731

Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy

PubMed Central

Kaski, Diego; Yong, Keir X. X.; Paterson, Ross W.; Slattery, Catherine F.; Ryan, Natalie S.; Schott, Jonathan M.; Crutch, Sebastian J.

2015-01-01

The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal ‘visual dementia’ and most common atypical Alzheimer’s disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients’ (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer’s disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer’s disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer’s disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with ‘sticky fixation’. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer’s disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer’s disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer’s disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. PMID:25895507

Evaluation of cortical bone mass, thickness and density by z-scores in osteopenic conditions and in relation to menopause and estrogen treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meema, S.; Meema, H.E.

1982-08-01

Z-scores express, differences from normals in standard deviation units, and are particularly useful for comparison of changes where normal values are age- and sex-dependent. We determined z-scores for bone mineral mass, cortical thickness, and bone mineral density in the radius in various conditions and diseases in both sexes. In the males, z-scores were calculated for age, but in the females z-scores for menopausal status (years postmenopausal exclusive of years on estrogen treatment) were found to be more appropriate. With few exceptions, changes in a disease were of a similar order in both sexes. For bone minerals mass few mean z-scoresmore » were significantly increased, but diseases with significantly decreased mean z-scores were numerous. The usefulness of z-scores in diagnosis and study of metabolic bone disease is discussed.« less

Stochastic Accumulation by Cortical Columns May Explain the Scalar Property of Multistable Perception

NASA Astrophysics Data System (ADS)

Cao, Robin; Braun, Jochen; Mattia, Maurizio

2014-08-01

The timing of certain mental events is thought to reflect random walks performed by underlying neural dynamics. One class of such events—stochastic reversals of multistable perceptions—exhibits a unique scalar property: even though timing densities vary widely, higher moments stay in particular proportions to the mean. We show that stochastic accumulation of activity in a finite number of idealized cortical columns—realizing a generalized Ehrenfest urn model—may explain these observations. Modeling stochastic reversals as the first-passage time of a threshold number of active columns, we obtain higher moments of the first-passage time density. We derive analytical expressions for noninteracting columns and generalize the results to interacting columns in simulations. The scalar property of multistable perception is reproduced by a dynamic regime with a fixed, low threshold, in which the activation of a few additional columns suffices for a reversal.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

PubMed

Hung, V W Y; Zhu, T Y; Cheung, W-H; Fong, T-N; Yu, F W P; Hung, L-K; Leung, K-S; Cheng, J C Y; Lam, T-P; Qin, L

2015-06-01

In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Curcumin reduces trabecular and cortical bone in naive and lewis lung carcinoma-bearing mice.

PubMed

Yan, Lin; Yee, John A; Cao, Jay

2013-08-01

The present study investigated the effects of curcumin on bone microstructure in non-tumor-bearing and Lewis lung carcinoma-(LLC)-bearing female C57BL/6 mice. Morphometric analysis showed that dietary supplementation with curcumin (2% or 4%) significantly reduced the bone volume to total volume ratio, connectivity density and trabecular number, and significantly increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation in vertebral bodies compared to controls in both non-tumor-bearing and LLC-bearing mice. Similar changes in trabecular bone were observed in the femoral bone in curcumin-fed mice. Curcumin significantly reduced the cortical bone area to total area ratio and cortical thickness in femoral mid-shaft, but not in vertebral bodies, in both non-tumor-bearing and LLC-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of LLC, indicating that curcumin disrupts the balance of bone remodeling. Our results demonstrated that curcumin reduced the trabecular bone volume and cortical bone density. The skeleton is a favored site of metastasis for many types of cancers, and curcumin has been investigated in clinical trials in patients with cancer for its chemopreventive effects. Our results suggest the possibility of a combined effect of cancer-induced osteolysis and curcumin-stimulated bone loss in patients using curcumin. The assessment of bone structural changes should be considered for those who participate in curcumin clinical trials to determine its effects on skeleton health, particularly for those with advanced malignancies.

Site-specific adaptive remodeling of Greyhound metacarpal cortical bone subjected to asymmetrical cyclic loading.

PubMed

Johnson, K A; Skinner, G A; Muir, P

2001-05-01

To quantify geometric, inertial, and histomorphometric properties at the mid-diaphyseal level of left and right metacarpal bones (MCB) of racing Greyhounds. MCB from 7 racing Greyhounds euthanatized for reasons unrelated to MCB abnormalities. Mid-diaphyseal transverse sections of left and right MCB were stained with H&E or microradiographed. Images of stained sections were digitized, and cross-sectional area, cortical area, and maximum and minimum area moments of inertia of each bone were determined. Histomorphometric data (osteonal density, osteonal birefringence, and endosteal new lamellar bone thickness) were collected in 4 quadrants (dorsal, palmar, lateral, medial). Values were compared between limbs and among bones and quadrants. Cross-sectional area, cortical area, and maximum and minimum moments of inertia of left MCB-IV and -V were significantly greater, compared with contralateral bones. Overall osteonal densities in the dorsal quadrants of left MCB were greater, compared with lateral and medial quadrants. Also, percentage of birefringent osteons was significantly greater in the dorsal quadrant of left MCB-III, -IV, and -V, compared with the palmar quadrant. Thickness of new endosteal lamellar bone was not significantly influenced by limb, bone, or quadrant. Increased cortical thickness and geometric properties of left MCB-IV and -V of Greyhounds, together with altered turnover and orientation of osteons in the dorsal quadrants of left MCB, are site-specific adaptive responses associated with asymmetric cyclic loading as a result of racing on circular tracks. Site-specific adaptive remodeling may be important in the etiopathogenesis of fatigue fractures in racing Greyhounds.

The Effect of Naturally Occurring Chronic Kidney Disease on the Micro-Structural and Mechanical Properties of Bone

PubMed Central

Meltzer, Hagar; Milrad, Moran; Brenner, Ori; Atkins, Ayelet; Shahar, Ron

2014-01-01

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD. PMID:25333360

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging.

PubMed

Declèves, Anne-Emilie; Rychak, Joshua J; Smith, Dan J; Sharma, Kumar

2013-11-01

Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic effects. Changes in microvascular perfusion may play a major role in kidney disease; however, these changes are difficult to assess in vivo. Here, we used perfusion ultrasound imaging to evaluate cortical blood flow in a mouse model of high-fat diet-induced kidney disease. C57BL/6J mice were randomized to a standard diet (STD) or a high-fat diet (HFD) for 30 wk and then treated either with losartan or a placebo for an additional 6 wk. Noninvasive ultrasound perfusion imaging of the kidney was performed during infusion of a microbubble contrast agent. Blood flow within the microvasculature of the renal cortex and medulla was derived from imaging data. An increase in the time required to achieve full cortical perfusion was observed for HFD mice relative to STD. This was reversed following treatment with losartan. These data were concurrent with an increased glomerular filtration rate in HFD mice compared with STD- or HFD-losartan-treated mice. Losartan treatment also abrogated fibro-inflammatory disease, assessed by markers at the protein and messenger level. Finally, a reduction in capillary density was found in HFD mice, and this was reversed upon losartan treatment. This suggests that alterations in vascular density may be responsible for the elevated perfusion time observed by imaging. These data demonstrate that ultrasound contrast imaging is a robust and sensitive method for evaluating changes in renal microvascular perfusion and that cortical perfusion time may be a useful parameter for evaluating obesity-related renal disease.

Automated cortical bone segmentation for multirow-detector CT imaging with validation and application to human studies

PubMed Central

Li, Cheng; Jin, Dakai; Chen, Cheng; Letuchy, Elena M.; Janz, Kathleen F.; Burns, Trudy L.; Torner, James C; Levy, Steven M.; Saha, Punam K

2015-01-01

Purpose: Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined. Methods: The algorithm is completed in two major steps—(1) bone filling, alignment, and region-of-interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation—(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation. Results: An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD-CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro-CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19–20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height and weight differences, males have thicker cortex (mean difference 0.33 mm and effect size 0.92 at the anterior region) with lower bone mineral density (mean difference −28.73 mg/cm3 and effect size 1.35 at the posterior region) as compared to females. Conclusions: The algorithm presented is suitable for fully automated segmentation of cortical bone in MD-CT imaging of the distal tibia with high accuracy and reproducibility. Analysis of data from a pilot study demonstrated that the cortical bone indices allow quantification of gender differences in cortical bone from MD-CT imaging. Application to larger population groups, including those with compromised bone, is needed. PMID:26233184

Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex

NASA Technical Reports Server (NTRS)

DeFelipe, J.; Arellano, J. I.; Merchan-Perez, A.; Gonzalez-Albo, M. C.; Walton, K.; Llinas, R.

2002-01-01

The establishment of the adult pattern of neocortical circuitry depends on various intrinsic and extrinsic factors, whose modification during development can lead to alterations in cortical organization and function. We report the effect of 16 days of spaceflight [Neurolab mission; from postnatal day 14 (P14) to P30] on the neocortical representation of the hindlimb synaptic circuitry in rats. As a result, we show, for the first time, that development in microgravity leads to changes in the number and morphology of cortical synapses in a laminar-specific manner. In the layers II/III and Va, the synaptic cross-sectional lengths were significantly larger in flight animals than in ground control animals. Flight animals also showed significantly lower synaptic densities in layers II/III, IV and Va. The greatest difference was found in layer II/III, where there was a difference of 344 million synapses per mm(3) (15.6% decrease). Furthermore, after a 4 month period of re-adaptation to terrestrial gravity, some changes disappeared (i.e. the alterations were transient), while conversely, some new differences also appeared. For example, significant differences in synaptic density in layers II/III and Va after re-adaptation were no longer observed, whereas in layer IV the density of synapses increased notably in flight animals (a difference of 185 million synapses per mm(3) or 13.4%). In addition, all the changes observed only affected asymmetrical synapses, which are known to be excitatory. These results indicates that terrestrial gravity is a necessary environmental parameter for normal cortical synaptogenesis. These findings are fundamental in planning future long-term spaceflights.

Propofol Anesthesia and Sleep: A High-Density EEG Study

PubMed Central

Murphy, Michael; Bruno, Marie-Aurelie; Riedner, Brady A.; Boveroux, Pierre; Noirhomme, Quentin; Landsness, Eric C.; Brichant, Jean-Francois; Phillips, Christophe; Massimini, Marcello; Laureys, Steven; Tononi, Giulio; Boly, Melanie

2011-01-01

Study Objectives: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep. Design: 256-channel EEG recordings in humans during propofol anesthesia. Setting: Hospital operating room. Patients or Participants: 8 healthy subjects (4 males) Interventions: N/A Measurements and Results: Initially, propofol induced increases in EEG power from 12–25 Hz. Loss of consciousness (LOC) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep. We compared slow waves in propofol to slow waves recorded during natural sleep and found that both populations of waves share similar cortical origins and preferentially propagate along the mesial components of the default network. However, propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity. Propofol also caused an increase in gamma (25–40 Hz) power that persisted throughout LOC. Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices. During LOC, we found increased gamma functional connectivity between these regions compared to the wakefulness. Conclusions: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity. Citation: Murphy M; Bruno MA; Riedner BA; Boveroux P; Noirhomme Q; Landsness EC; Brichant JF; Phillips C; Massimini M; Laureys S; Tononi G; Boly M. Propofol anesthesia and sleep: a high-density EEG study. SLEEP 2011;34(3):283-291. PMID:21358845

A low-cost, scalable, current-sensing digital headstage for high channel count μECoG.

PubMed

Trumpis, Michael; Insanally, Michele; Zou, Jialin; Elsharif, Ashraf; Ghomashchi, Ali; Sertac Artan, N; Froemke, Robert C; Viventi, Jonathan

2017-04-01

High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (μECoG) array. We recorded both acute and chronic μECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 d. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of μECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels.

A low-cost, scalable, current-sensing digital headstage for high channel count μECoG

NASA Astrophysics Data System (ADS)

Trumpis, Michael; Insanally, Michele; Zou, Jialin; Elsharif, Ashraf; Ghomashchi, Ali; Sertac Artan, N.; Froemke, Robert C.; Viventi, Jonathan

2017-04-01

Objective. High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (μECoG) array. Approach. We recorded both acute and chronic μECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. Main results. The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 d. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. Significance. We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of μECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels.

A low-cost, scalable, current-sensing digital headstage for high channel count μECoG

PubMed Central

Trumpis, Michael; Insanally, Michele; Zou, Jialin; Elsharif, Ashraf; Ghomashchi, Ali; Artan, N. Sertac; Froemke, Robert C.; Viventi, Jonathan

2017-01-01

Objective High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (μECoG) array. Approach We recorded both acute and chronic μECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. Main results The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 days. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. Significance We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of μECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels. PMID:28102827

Wavefront aberrations and retinal image quality in different lenticular opacity types and densities.

PubMed

Wu, Cheng-Zhe; Jin, Hua; Shen, Zhen-Nv; Li, Ying-Jun; Cui, Xun

2017-11-10

To investigate wavefront aberrations in the entire eye and in the internal optics (lens) and retinal image qualities according to different lenticular opacity types and densities. Forty-one eyes with nuclear cataract, 33 eyes with cortical cataract, and 29 eyes with posterior subcapsular cataract were examined. In each group, wavefront aberrations in the entire eye and in the internal optics and retinal image quality were measured using a raytracing aberrometer. Eyes with cortical cataracts showed significantly higher coma-like aberrations compared to the other two groups in both entire eye and internal optic aberrations (P = 0.012 and P = 0.007, respectively). Eyes with nuclear cataract had lower spherical-like aberrations than the other two groups in both entire eye and internal optics aberrations (P < 0.001 and P < 0.001, respectively). In the nuclear cataract group, nuclear lens density was negatively correlated with internal spherical aberrations (r = -0.527, P = 0.005). Wavefront technology is useful for objective and quantitative analysis of retinal image quality deterioration in eyes with different early lenticular opacity types and densities. Understanding the wavefront optical properties of different crystalline lens opacities may help ophthalmic surgeons determine the optimal time to perform cataract surgery.

Postnatal Development of Intrinsic Horizontal Axons in Macaque Inferior Temporal and Primary Visual Cortices.

PubMed

Wang, Quanxin; Tanigawa, Hisashi; Fujita, Ichiro

2017-04-01

Two distinct areas along the ventral visual stream of monkeys, the primary visual (V1) and inferior temporal (TE) cortices, exhibit different projection patterns of intrinsic horizontal axons with patchy terminal fields in adult animals. The differences between the patches in these 2 areas may reflect differences in cortical representation and processing of visual information. We studied the postnatal development of patches by injecting an anterograde tracer into TE and V1 in monkeys of various ages. At 1 week of age, labeled patches with distribution patterns reminiscent of those in adults were already present in both areas. The labeling intensity of patches decayed exponentially with projection distance in monkeys of all ages in both areas, but this trend was far less evident in TE. The number and extent of patches gradually decreased with age in V1, but not in TE. In V1, axonal and bouton densities increased postnatally only in patches with short projection distances, whereas in TE this density change occurred in patches with various projection distances. Thus, patches with area-specific distribution patterns are formed early in life, and area-specific postnatal developmental processes shape the connectivity of patches into adulthood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

PubMed

Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo-Fang

2017-07-01

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. © 2016 International Society of Neuropathology.

Selective Deletion of Astroglial FMRP Dysregulates Glutamate Transporter GLT1 and Contributes to Fragile X Syndrome Phenotypes In Vivo.

PubMed

Higashimori, Haruki; Schin, Christina S; Chiang, Ming Sum R; Morel, Lydie; Shoneye, Temitope A; Nelson, David L; Yang, Yongjie

2016-07-06

How the loss of fragile X mental retardation protein (FMRP) in different brain cell types, especially in non-neuron glial cells, induces fragile X syndrome (FXS) phenotypes has just begun to be understood. In the current study, we generated inducible astrocyte-specific Fmr1 conditional knock-out mice (i-astro-Fmr1-cKO) and restoration mice (i-astro-Fmr1-cON) to study the in vivo modulation of FXS synaptic phenotypes by astroglial FMRP. We found that functional expression of glutamate transporter GLT1 is 40% decreased in i-astro-Fmr1-cKO somatosensory cortical astrocytes in vivo, which can be fully rescued by the selective re-expression of FMRP in astrocytes in i-astro-Fmr1-cON mice. Although the selective loss of astroglial FMRP only modestly increases spine density and length in cortical pyramidal neurons, selective re-expression of FMRP in astrocytes significantly attenuates abnormal spine morphology in these neurons of i-astro-Fmr1-cON mice. Moreover, we found that basal protein synthesis levels and immunoreactivity of phosphorylated S6 ribosomal protein (p-s6P) is significantly increased in i-astro-Fmr1-cKO mice, while the enhanced cortical protein synthesis observed in Fmr1 KO mice is mitigated in i-astro-Fmr1-cON mice. Furthermore, ceftriaxone-mediated upregulation of surface GLT1 expression restores functional glutamate uptake and attenuates enhanced neuronal excitability in Fmr1 KO mice. In particular, ceftriaxone significantly decreases the growth rate of abnormally accelerated body weight and completely corrects spine abnormality in Fmr1 KO mice. Together, these results show that the selective loss of astroglial FMRP contributes to cortical synaptic deficits in FXS, presumably through dysregulated astroglial glutamate transporter GLT1 and impaired glutamate uptake. These results suggest the involvement of astrocyte-mediated mechanisms in the pathogenesis of FXS. Previous studies to understand how the loss of function of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS) have largely focused on neurons; whether the selective loss of astroglial FMRP in vivo alters astrocyte functions and contributes to the pathogenesis of FXS remain essentially unknown. This has become a long-standing unanswered question in the fragile X field, which is also relevant to autism pathogenesis. Our current study generated astrocyte-specific Fmr1 conditional knock-out and restoration mice, and provided compelling evidence that the selective loss of astroglial FMRP contributes to cortical synaptic deficits in FXS, likely through the dysregulated astroglial glutamate transporter GLT1 expression and impaired glutamate uptake. These results demonstrate previously undescribed astrocyte-mediated mechanisms in the pathogenesis of FXS. Copyright © 2016 the authors 0270-6474/16/367080-16$15.00/0.

Cell-Autonomous Regulation of Dendritic Spine Density by PirB.

PubMed

Vidal, George S; Djurisic, Maja; Brown, Kiana; Sapp, Richard W; Shatz, Carla J

2016-01-01

Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine whether PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirB fl/fl ), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature EPSCs, suggesting that they receive a greater number of synaptic inputs relative to Cre - neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to corepress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life.

Premenopausal women with early breast cancer treated with estradiol suppression have severely deteriorated bone microstructure.

PubMed

Ramchand, Sabashini K; Seeman, Ego; Wang, Xiao-Fang; Ghasem-Zadeh, Ali; Francis, Prudence A; Ponnusamy, Evangeline J; Bardin, Michele S; Bui, Minh; Zebaze, Roger; Zajac, Jeffrey D; Grossmann, Mathis

2017-10-01

In premenopausal women with early estrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition reduce estradiol production precipitously. The resulting unbalanced and rapid bone remodelling replaces older bone with less bone that is less fully mineralized. We hypothesized that these changes result in severe microstructural deterioration and reduced matrix mineralization density. Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 27 premenopausal women, mean age 43.3years (range 30.4 to 53.7) with early breast cancer made estradiol deficient for 17months (range 6-120) using ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal and 35 postmenopausal controls, mean age 62.6years (range 60.2 to 65.5). Cortical and trabecular microstructure were quantified using Strax software. Compared with premenopausal controls, the women with breast cancer had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher but cortical thickness was not reduced. Compared with postmenopausal controls 20years older, cases had comparable or lower trabecular bone volume and comparable cortical porosity and thickness. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar. The severe cortical porosity and trabecular deterioration associated with estradiol depletion and the longevity of premenopausal women with early breast cancer treated with endocrine therapy provide a compelling rationale to investigate the efficacy of antiresorptive therapy initiated at the time of breast cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Yellow-bellied Marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation

PubMed Central

Wojda, Samantha J.; McGee-Lawrence, Meghan E.; Gridley, Richard A.; Auger, Janene; Black, Hal L.; Donahue, Seth W.

2012-01-01

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. PMID:22037004

Yellow-bellied marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation.

PubMed

Wojda, Samantha J; McGee-Lawrence, Meghan E; Gridley, Richard A; Auger, Janene; Black, Hal L; Donahue, Seth W

2012-01-01

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. Copyright © 2011 Elsevier Inc. All rights reserved.

Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation: A functional MRI study.

PubMed

Kwon, Yong Hyun; Jang, Sung Ho

2012-08-25

We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.

Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

PubMed Central

Kwon, Yong Hyun; Jang, Sung Ho

2012-01-01

We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation. PMID:25624815

An evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats.

PubMed

Goto, Takakuni; Hatanaka, Rieko; Ogawa, Takeshi; Sumiyoshi, Akira; Riera, Jorge; Kawashima, Ryuta

2010-12-01

Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

Anti-correlated cortical networks arise from spontaneous neuronal dynamics at slow timescales.

PubMed

Kodama, Nathan X; Feng, Tianyi; Ullett, James J; Chiel, Hillel J; Sivakumar, Siddharth S; Galán, Roberto F

2018-01-12

In the highly interconnected architectures of the cerebral cortex, recurrent intracortical loops disproportionately outnumber thalamo-cortical inputs. These networks are also capable of generating neuronal activity without feedforward sensory drive. It is unknown, however, what spatiotemporal patterns may be solely attributed to intrinsic connections of the local cortical network. Using high-density microelectrode arrays, here we show that in the isolated, primary somatosensory cortex of mice, neuronal firing fluctuates on timescales from milliseconds to tens of seconds. Slower firing fluctuations reveal two spatially distinct neuronal ensembles, which correspond to superficial and deeper layers. These ensembles are anti-correlated: when one fires more, the other fires less and vice versa. This interplay is clearest at timescales of several seconds and is therefore consistent with shifts between active sensing and anticipatory behavioral states in mice.

Are milk and alternatives and fruit and vegetable intakes during adolescence associated with cortical and trabecular bone structure, density, and strength in adulthood?

PubMed

Z Movassagh, E; Kontulainen, S; Baxter-Jones, A D G; Whiting, S; Szafron, M; Papadimitropoulos, M; Vatanparast, H

2017-02-01

We investigated the impact of food group intake during adolescence on bone structure and strength during adulthood. In females, we found a beneficial effect of adolescent milk and alternatives and fruit and vegetable intake on adult radius shaft and distal tibia bone structure, respectively. No association was observed in males. The purpose of this study was to investigate whether adolescents with high intake of milk and alternatives (M&A) or fruit and vegetables (F&V) had better adult bone structure and strength compared to those with low intake levels. We analyzed data from 47 males and 69 females enrolled in the Pediatric Bone Mineral Accrual Study (PBMAS 1991-2011), who had one peripheral quantitative computed tomography scan at age 29 ± 2 years. We measured radius and tibia shaft total area (ToA), cortical area (CoA), cortical content (CoC), cortical density, bone strength (SSI p ), and muscle area, as well as distal radius and tibia ToA, total density, trabecular area, trabecular content, trabecular density, and bone strength (BSI c ). Sequential 24-h recalls were used to assess M&A and F&V intake; participants were grouped for their mean intake during adolescence (low = bottom quartile, moderate = middle quartiles, high = top quartile) and were compared using multivariate analysis of covariance while adjusting for adult height, muscle area, physical activity, energy and calcium intake and adolescent energy intake, and physical activity. Females with high M&A intake compared to low M&A intake group (mean 3.8 vs. 1.3 servings/day, respectively) had greater adult ToA (14 %, p < 0.05), CoA (15 %, p < 0.01), and CoC (16 %, p < 0.01) at radius shaft. Females with moderate F&V intake compared to low F&V intake group (mean 3.7 vs. 2.1 servings/day, respectively) had greater adult ToA (8.5 %, p < 0.05) at distal tibia. Higher intake of M&A or F&V during adolescence had a long-term beneficial effect on bone structure in females, an association not observed in males.

Opportunities for exercise during pullet rearing, Part II: Long-term effects on bone characteristics of adult laying hens at the end-of-lay.

PubMed

Casey-Trott, T M; Korver, D R; Guerin, M T; Sandilands, V; Torrey, S; Widowski, T M

2017-08-01

Osteoporosis in laying hens has been a production and welfare concern for several decades. The objective of this study was to determine whether differing opportunities for exercise during pullet rearing influences long-term bone quality characteristics in end-of-lay hens. A secondary objective was to assess whether differing opportunities for exercise in adult housing systems alters bone quality characteristics in end-of-lay hens. Four flock replicates of 588 Lohmann Selected Leghorn-Lite pullets were reared in either conventional cages (Conv) or an aviary rearing system (Avi) and placed into conventional cages (CC), 30-bird furnished cages (FC-S), or 60-bird furnished cages (FC-L) for adult housing. Wing and leg bones were collected at the end-of-lay to quantify bone composition and strength using quantitative computed tomography and bone breaking strength (BBS). At the end-of-lay, Avi hens had greater total and cortical cross-sectional area (P < 0.05) for the radius and tibia, greater total bone mineral content of the radius (P < 0.001), and greater tibial cortical bone mineral content (P = 0.029) than the Conv hens; however, total bone mineral density of the radius (P < 0.001) and cortical bone mineral density of the radius and tibia (P < 0.001) were greater in the Conv hens. Hens in the FC-L had greater total bone mineral density for the radius and tibia (P < 0.05) and greater trabecular bone mineral density for the radius (P = 0.027), compared to hens in the FC-S and CC. Total bone mineral content of the tibia (P = 0.030) and cortical bone mineral content of the radius (P = 0.030) and tibia (P = 0.013) were greater in the FC-L compared to the CC. The humerus of Conv hens had greater BBS than the Avi hens (P < 0.001), and the tibiae of FC-L and FC-S hens had greater BBS than CC hens (P = 0.006). Increased opportunities for exercise offered by the aviary rearing system provided improved bone quality characteristics lasting through to the end-of-lay. © The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal.

PubMed

Chaplais, Elodie; Greene, David; Hood, Anita; Telfer, Scott; du Toit, Verona; Singh-Grewal, Davinder; Burns, Joshua; Rome, Keith; Schiferl, Daniel J; Hendry, Gordon J

2014-07-19

Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec(-1). The reference line was positioned at the most distal portion of the 2(nd) metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI - mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI - mid shaft (ICC 0.99; CV% 3.2). The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2(nd) metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures.

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal

PubMed Central

2014-01-01

Background Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Methods Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Results Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI – mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI – mid shaft (ICC 0.99; CV% 3.2). Conclusions The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures. PMID:25037451

A systems approach for data compression and latency reduction in cortically controlled brain machine interfaces.

PubMed

Oweiss, Karim G

2006-07-01

This paper suggests a new approach for data compression during extracutaneous transmission of neural signals recorded by high-density microelectrode array in the cortex. The approach is based on exploiting the temporal and spatial characteristics of the neural recordings in order to strip the redundancy and infer the useful information early in the data stream. The proposed signal processing algorithms augment current filtering and amplification capability and may be a viable replacement to on chip spike detection and sorting currently employed to remedy the bandwidth limitations. Temporal processing is devised by exploiting the sparseness capabilities of the discrete wavelet transform, while spatial processing exploits the reduction in the number of physical channels through quasi-periodic eigendecomposition of the data covariance matrix. Our results demonstrate that substantial improvements are obtained in terms of lower transmission bandwidth, reduced latency and optimized processor utilization. We also demonstrate the improvements qualitatively in terms of superior denoising capabilities and higher fidelity of the obtained signals.

Imaging fast electrical activity in the brain with electrical impedance tomography

PubMed Central

Aristovich, Kirill Y.; Packham, Brett C.; Koo, Hwan; Santos, Gustavo Sato dos; McEvoy, Andy; Holder, David S.

2016-01-01

Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2 ms and < 200 μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7 × 5 × 2 mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures. PMID:26348559

Cortical gyrification is abnormal in children with prenatal alcohol exposure.

PubMed

Hendrickson, Timothy J; Mueller, Bryon A; Sowell, Elizabeth R; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Wozniak, Jeffrey R

2017-01-01

Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined. Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure. Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ). Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.

Rapid extraction of auditory feature contingencies.

PubMed

Bendixen, Alexandra; Prinz, Wolfgang; Horváth, János; Trujillo-Barreto, Nelson J; Schröger, Erich

2008-07-01

Contingent relations between sensory events render the environment predictable and thus facilitate adaptive behavior. The human capacity to detect such relations has been comprehensively demonstrated in paradigms in which contingency rules were task-relevant or in which they applied to motor behavior. The extent to which contingencies can also be extracted from events that are unrelated to the current goals of the organism has remained largely unclear. The present study addressed the emergence of contingency-related effects for behaviorally irrelevant auditory stimuli and the cortical areas involved in the processing of such contingency rules. Contingent relations between different features of temporally separate events were embedded in a new dynamic protocol. Participants were presented with the auditory stimulus sequences while their attention was captured by a video. The mismatch negativity (MMN) component of the event-related brain potential (ERP) was employed as an electrophysiological correlate of contingency detection. MMN generators were localized by means of scalp current density (SCD) and primary current density (PCD) analyses with variable resolution electromagnetic tomography (VARETA). Results show that task-irrelevant contingencies can be extracted from about fifteen to twenty successive events conforming to the contingent relation. Topographic and tomographic analyses reveal the involvement of the auditory cortex in the processing of contingency violations. The present data provide evidence for the rapid encoding of complex extrapolative relations in sensory areas. This capacity is of fundamental importance for the organism in its attempt to model the sensory environment outside the focus of attention.

Classification of micro-CT images using 3D characterization of bone canal patterns in human osteogenesis imperfecta

NASA Astrophysics Data System (ADS)

Abidin, Anas Z.; Jameson, John; Molthen, Robert; Wismüller, Axel

2017-03-01

Few studies have analyzed the microstructural properties of bone in cases of Osteogenenis Imperfecta (OI), or `brittle bone disease'. Current approaches mainly focus on bone mineral density measurements as an indirect indicator of bone strength and quality. It has been shown that bone strength would depend not only on composition but also structural organization. This study aims to characterize 3D structure of the cortical bone in high-resolution micro CT images. A total of 40 bone fragments from 28 subjects (13 with OI and 15 healthy controls) were imaged using micro tomography using a synchrotron light source (SRµCT). Minkowski functionals - volume, surface, curvature, and Euler characteristics - describing the topological organization of the bone were computed from the images. The features were used in a machine learning task to classify between healthy and OI bone. The best classification performance (mean AUC - 0.96) was achieved with a combined 4-dimensional feature of all Minkowski functionals. Individually, the best feature performance was seen using curvature (mean AUC - 0.85), which characterizes the edges within a binary object. These results show that quantitative analysis of cortical bone microstructure, in a computer-aided diagnostics framework, can be used to distinguish between healthy and OI bone with high accuracy.

Compensating Level-Dependent Frequency Representation in Auditory Cortex by Synaptic Integration of Corticocortical Input

PubMed Central

Happel, Max F. K.; Ohl, Frank W.

2017-01-01

Robust perception of auditory objects over a large range of sound intensities is a fundamental feature of the auditory system. However, firing characteristics of single neurons across the entire auditory system, like the frequency tuning, can change significantly with stimulus intensity. Physiological correlates of level-constancy of auditory representations hence should be manifested on the level of larger neuronal assemblies or population patterns. In this study we have investigated how information of frequency and sound level is integrated on the circuit-level in the primary auditory cortex (AI) of the Mongolian gerbil. We used a combination of pharmacological silencing of corticocortically relayed activity and laminar current source density (CSD) analysis. Our data demonstrate that with increasing stimulus intensities progressively lower frequencies lead to the maximal impulse response within cortical input layers at a given cortical site inherited from thalamocortical synaptic inputs. We further identified a temporally precise intercolumnar synaptic convergence of early thalamocortical and horizontal corticocortical inputs. Later tone-evoked activity in upper layers showed a preservation of broad tonotopic tuning across sound levels without shifts towards lower frequencies. Synaptic integration within corticocortical circuits may hence contribute to a level-robust representation of auditory information on a neuronal population level in the auditory cortex. PMID:28046062

Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis.

PubMed

Kim, Minah; Cho, Kang Ik Kevin; Yoon, Youngwoo Bryan; Lee, Tae Young; Kwon, Jun Soo

2017-02-01

Although disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis. MMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups. Schizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups. Impairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis. These findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Spontaneous, synchronous electrical activity in neonatal mouse cortical neurones

PubMed Central

Corlew, Rebekah; Bosma, Martha M; Moody, William J

2004-01-01

Spontaneous [Ca2+]i transients were measured in the mouse neocortex from embryonic day 16 (E16) to postnatal day 6 (P6). On the day of birth (P0), cortical neurones generated widespread, highly synchronous [Ca2+]i transients over large areas. On average, 52% of neurones participated in these transients, and in 20% of slices, an average of 80% participated. These transients were blocked by TTX and nifedipine, indicating that they resulted from Ca2+ influx during electrical activity, and occurred at a mean frequency of 0.91 min−1. The occurrence of this activity was highly centred at P0: at E16 and P2 an average of only 15% and 24% of neurones, respectively, participated in synchronous transients, and they occurred at much lower frequencies at both E16 and P2 than at P0. The overall frequency of [Ca2+]i transients in individual cells did not change between E16 and P2, just the degree of their synchronicity. The onset of this spontaneous, synchronous activity correlated with a large increase in Na+ current density that occurred just before P0, and its cessation with a large decrease in resting resistance that occurred just after P2. This widespread, synchronous activity may serve a variety of functions in the neonatal nervous system. PMID:15297578

Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

PubMed Central

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M.; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction. PMID:23326379

Cortical thickness abnormalities in late adolescence with online gaming addiction.

PubMed

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

Do Studies on Cortical Plasticity Provide a Rationale for Using Non-Invasive Brain Stimulation as a Treatment for Parkinson’s Disease Patients?

PubMed Central

Koch, Giacomo

2013-01-01

Animal models of Parkinson’s disease (PD) have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of l-DOPA. However, it is still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms by applying repetitive sessions of repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS). The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field. PMID:24223573

Imaging laminar structures in the gray matter with diffusion MRI.

PubMed

Assaf, Yaniv

2018-01-05

The cortical layers define the architecture of the gray matter and its neuroanatomical regions and are essential for brain function. Abnormalities in cortical layer development, growth patterns, organization, or size can affect brain physiology and cognition. Unfortunately, while large population studies are underway that will greatly increase our knowledge about these processes, current non-invasive techniques for characterizing the cortical layers remain inadequate. For decades, high-resolution T1 and T2 Weighted Magnetic Resonance Imaging (MRI) have been the method-of-choice for gray matter and layer characterization. In the past few years, however, diffusion MRI has shown increasing promise for its unique insights into the fine structure of the cortex. Several different methods, including surface analysis, connectivity exploration, and sub-voxel component modeling, are now capable of exploring the diffusion characteristics of the cortex. In this review, we will discuss current advances in the application of diffusion imaging for cortical characterization and its unique features, with a particular emphasis on its spatial resolution, arguably its greatest limitation. In addition, we will explore the relationship between the diffusion MRI signal and the cellular components of the cortex, as visualized by histology. While the obstacles facing the widespread application of cortical diffusion imaging remain daunting, the information it can reveal may prove invaluable. Within the next few years, we predict a surge in the application of this technique and a concomitant expansion of our knowledge of cortical layers. Copyright © 2018 Elsevier Inc. All rights reserved.

Spatiotemporal characteristics of sleep spindles depend on cortical location.

PubMed

Piantoni, Giovanni; Halgren, Eric; Cash, Sydney S

2017-02-01

Since their discovery almost one century ago, sleep spindles, 0.5-2s long bursts of oscillatory activity at 9-16Hz during NREM sleep, have been thought to be global and relatively uniform throughout the cortex. Recent work, however, has brought this concept into question but it remains unclear to what degree spindles are global or local and if their properties are uniform or location-dependent. We addressed this question by recording sleep in eight patients undergoing evaluation for epilepsy with intracranial electrocorticography, which combines high spatial resolution with extensive cortical coverage. We find that spindle characteristics are not uniform but are strongly influenced by the underlying cortical regions, particularly for spindle density and fundamental frequency. We observe both highly isolated and spatially distributed spindles, but in highly skewed proportions: while most spindles are restricted to one or very few recording channels at any given time, there are spindles that occur over widespread areas, often involving lateral prefrontal cortices and superior temporal gyri. Their co-occurrence is affected by a subtle but significant propagation of spindles from the superior prefrontal regions and the temporal cortices towards the orbitofrontal cortex. This work provides a brain-wide characterization of sleep spindles as mostly local graphoelements with heterogeneous characteristics that depend on the underlying cortical area. We propose that the combination of local characteristics and global organization reflects the dual properties of the thalamo-cortical generators and provides a flexible framework to support the many functions ascribed to sleep in general and spindles specifically. Copyright © 2016 Elsevier Inc. All rights reserved.

Evolution of cytoarchitectural landscapes in the mammalian isocortex: Sirenians (Trichechus manatus) in comparison with other mammals.

PubMed

Charvet, Christine J; Reep, Roger L; Finlay, Barbara L

2016-03-01

The isocortex of several primates and rodents shows a systematic increase in the number of neurons per unit of cortical surface area from its rostrolateral to caudomedial border. The steepness of the gradient in neuronal number and density is positively correlated with cortical volume. The relative duration of neurogenesis along the same rostrocaudal gradient predicts a substantial fraction of this variation in neuron number and laminar position, which is produced principally from layers II-IV neurons. However, virtually all of our quantitative knowledge about total and laminar variation in cortical neuron numbers and neurogenesis comes from rodents and primates, leaving whole taxonomic groups and many intermediate-sized brains unexplored. Thus, the ubiquity in mammals of the covariation of longer cortical neurogenesis and increased cortical neuron number deriving from cortical layers II-IV is undetermined. To begin to address this gap, we examined the isocortex of the manatee using the optical disector method in sectioned tissue, and also assembled partial data from published reports of the domestic cat brain. The manatee isocortex has relatively fewer neurons per total volume, and fewer II-IV neurons than primates with equivalently sized brains. The gradient in number of neurons from the rostral to the caudal pole is intermediate between primates and rodents, and, like those species, is observed only in the upper cortical layers. The cat isocortex (Felis domesticus) shows a similar structure. Key species for further tests of the origin, ubiquity, and significance of this organizational feature are discussed. © 2015 Wiley Periodicals, Inc.

State of the mineral component of rat bone tissue during hypokinesia and the recovery period

NASA Technical Reports Server (NTRS)

Volozhin, A. I.; Stupakov, G. P.; Pavlova, M. N.; Muradov, I. S.

1980-01-01

Experiments were conducted on young growing rats. Hypokinesia lasting from 20 to 200 days caused retarded gain in weight and volume of the femur and delayed development of the cortical layer of the diaphysis. In contrast, the density of the cortical layer of the femoral diaphysis increased due to elevation of the mineral saturation of the bone tissue microstructures. Incorporation of Ca into the bone tissue in hypokinesia had a tendency to reduce. Partial normalization of the bone tissue mineral component occurred during a 20 day recovery period following hypokinesia.

Cortical reorganization in postlingually deaf cochlear implant users: Intra-modal and cross-modal considerations.

PubMed

Stropahl, Maren; Chen, Ling-Chia; Debener, Stefan

2017-01-01

With the advances of cochlear implant (CI) technology, many deaf individuals can partially regain their hearing ability. However, there is a large variation in the level of recovery. Cortical changes induced by hearing deprivation and restoration with CIs have been thought to contribute to this variation. The current review aims to identify these cortical changes in postlingually deaf CI users and discusses their maladaptive or adaptive relationship to the CI outcome. Overall, intra-modal and cross-modal reorganization patterns have been identified in postlingually deaf CI users in visual and in auditory cortex. Even though cross-modal activation in auditory cortex is considered as maladaptive for speech recovery in CI users, a similar activation relates positively to lip reading skills. Furthermore, cross-modal activation of the visual cortex seems to be adaptive for speech recognition. Currently available evidence points to an involvement of further brain areas and suggests that a focus on the reversal of visual take-over of the auditory cortex may be too limited. Future investigations should consider expanded cortical as well as multi-sensory processing and capture different hierarchical processing steps. Furthermore, prospective longitudinal designs are needed to track the dynamics of cortical plasticity that takes place before and after implantation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Communication and wiring in the cortical connectome

PubMed Central

Budd, Julian M. L.; Kisvárday, Zoltán F.

2012-01-01

In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimize communication there is a trade-off between spatial (construction) and temporal (routing) costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fiber tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for cortical wiring patterns. PMID:23087619

Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

2015-07-01

The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer's disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer's disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Relationships between cortical myeloarchitecture and electrophysiological networks

PubMed Central

Hunt, Benjamin A. E.; Tewarie, Prejaas K.; Mougin, Olivier E.; Geades, Nicolas; Singh, Krish D.; Morris, Peter G.; Gowland, Penny A.; Brookes, Matthew J.

2016-01-01

The human brain relies upon the dynamic formation and dissolution of a hierarchy of functional networks to support ongoing cognition. However, how functional connectivities underlying such networks are supported by cortical microstructure remains poorly understood. Recent animal work has demonstrated that electrical activity promotes myelination. Inspired by this, we test a hypothesis that gray-matter myelin is related to electrophysiological connectivity. Using ultra-high field MRI and the principle of structural covariance, we derive a structural network showing how myelin density differs across cortical regions and how separate regions can exhibit similar myeloarchitecture. Building upon recent evidence that neural oscillations mediate connectivity, we use magnetoencephalography to elucidate networks that represent the major electrophysiological pathways of communication in the brain. Finally, we show that a significant relationship exists between our functional and structural networks; this relationship differs as a function of neural oscillatory frequency and becomes stronger when integrating oscillations over frequency bands. Our study sheds light on the way in which cortical microstructure supports functional networks. Further, it paves the way for future investigations of the gray-matter structure/function relationship and its breakdown in pathology. PMID:27830650

Bone Mineral 31P and Matrix-Bound Water Densities Measured by Solid-State 1H and 31P MRI

PubMed Central

Seifert, Alan C.; Li, Cheng; Rajapakse, Chamith S.; Bashoor- Zadeh, Mahdieh; Bhagat, Yusuf A.; Wright, Alexander C.; Zemel, Babette S.; Zavaliangos, Antonios; Wehrli, Felix W.

2014-01-01

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging due to extremely short transverse relaxation times, but solid-state imaging sequences exist that can acquire the short-lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI-based measurement on clinical scanners of bone mineral and collagen-bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors’ age. Mineral and matrix-bound water images of reference phantoms and cortical bone from 16 human donors, ages 27-97 years, were acquired by zero-echo-time 31P and 1H MRI on whole body 7T and 3T scanners, respectively. Images were corrected for relaxation and RF inhomogeneity to obtain density maps. Cortical porosity was measured by micro-CT, and apparent mineral density by pQCT. MRI-derived densities were compared to x-ray-based measurements by least-squares regression. Mean bone mineral 31P density was 6.74±1.22 mol/L (corresponding to 1129±204 mg/cc mineral), and mean bound water 1H density was 31.3±4.2 mol/L (corresponding to 28.3±3.7 %v/v). Both 31P and bound water (BW) densities were correlated negatively with porosity (31P: R2 = 0.32, p < 0.005; BW: R2 = 0.63, p < 0.0005) and age (31P: R2 = 0.39, p < 0.05; BW: R2 = 0.70, p < 0.0001), and positively with pQCT density (31P: R2 = 0.46, p < 0.05; BW: R2 = 0.50, p < 0.005). In contrast, the bone mineralization ratio (expressed here as the ratio of 31P density to bound water density), which is proportional to true bone mineralization, was found to be uncorrelated with porosity, age, or pQCT density. This work establishes the feasibility of image-based quantification of bone mineral and bound water densities using clinical hardware. PMID:24846186

Determinants of prevalent vertebral fractures and progressive bone loss in long-term hemodialysis patients.

PubMed

Mares, Jan; Ohlidalova, Kristina; Opatrna, Sylvie; Ferda, Jiri

2009-01-01

Skeletal fractures are common in hemodialysis (HD) patients. However, consensus regarding technique and site of bone examination has not been reached in HD patients. Seventy-two patients (44% females) aged 65 (1.4) years, treated with HD for 43 (4.6) months were examined with quantitative computed tomography and 53 of them re-examined after 1 year. Bone mineral density (BMD) of lumbar spine was established separately for cortical and trabecular bone, prevalent vertebral fractures were determined. Data are given as mean (standard error). At least one vertebral fracture was discovered in 15 (21%) patients. In a logistic regression model, fractures were best predicted by cortical BMD: OR 0.96 (CI 0.94, 0.99), p < 0.005. With a multiple regression analysis, time on dialysis was found to be independently correlated to cortical BMD (R = 0.35, p < 0.005). On follow-up, a decrease of BMD was detected, which occurred only in the cortical region and was significantly greater in females than in males: -7% (1.7) versus 1.2% (1.9), p < 0.005. A time-dependent loss of vertebral cortical bone occurs in HD patients, especially in females. This decrement may impose an increased risk of fractures on long-term dialysis patients.

Sex differences in parameters of bone strength in new recruits: beyond bone density.

PubMed

Evans, Rachel K; Negus, Charles; Antczak, Amanda J; Yanovich, Ran; Israeli, Eran; Moran, Daniel S

2008-11-01

Stress fracture (SF) injuries in new recruits have long been attributed to low bone mineral density (BMD). Low areal BMD assessed using two-dimensional dual-energy x-ray absorptiometry imaging, however, reflects structural density and is affected by smaller measures of bone geometry. Recent studies support a relationship between bone size and SF and indicate that slender bones are more susceptible to damage under identical loading conditions. Peripheral quantitative computed tomography (pQCT) is a three-dimensional imaging tool that provides measures of tissue density and geometry parameters of the tibia, a common site of SF. To evaluate sex differences in parameters of volumetric BMD (vBMD), geometry, and strength of the tibia in new recruits using a novel pQCT image analysis procedure. pQCT images were obtained from 128 healthy men and women (20 male, 108 female, aged 18-21 yr) entering a 4-month gender-integrated combat training program in the Israeli Defense Forces. Tibial scans taken at sites 4% (trabecular bone), 38%, and 66% (cortical bone) from the distal end plate were analyzed using MATLAB to assess whole-bone and regional parameters. Measures included vBMD, geometry (diameter, area, cortical thickness, and canal radius), and strength (moments of inertia and bone strength and slenderness indices). With the exception of normalized canal radius, which did not differ between sexes, all measures of bone geometry (P < 0.0001) and strength (P < 0.0001 to P = 0.07) were greater in men. Women exhibited 2.7% to 3.0% greater cortical vBMD than men, whereas trabecular vBMD was 8.4% lower in women (P < 0.001). These differences remained significant after adjusting for body size. Sex differences in bone geometry and mineralization of the tibia may contribute to a decreased ability to withstand the demands imposed by novel, repetitive exercise in untrained individuals entering recruit training.

Three-dimensional visualization and characterization of bone structure using reconstructed in-vitro μCT images: A pilot study for bone microarchitecture analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latief, Fourier Dzar Eljabbar, E-mail: fourier@fi.itb.ac.id; Dewi, Dyah Ekashanti Octorina; Shari, Mohd Aliff Bin Mohd

Micro Computed Tomography (μCT) has been largely used to perform micrometer scale imaging of specimens, bone biopsies and small animals for the study of porous or cavity-containing objects. One of its favored applications is for assessing structural properties of bone. In this research, we perform a pilot study to visualize and characterize bone structure of a chicken bone thigh, as well as to delineate its cortical and trabecular bone regions. We utilize an In-Vitro μCT scanner Skyscan 1173 to acquire a three dimensional image data of a chicken bone thigh. The thigh was scanned using X-ray voltage of 45 kVmore » and current of 150 μA. The reconstructed images have spatial resolution of 142.50 μm/pixel. Using image processing and analysis e.i segmentation by thresholding the gray values (which represent the pseudo density) and binarizing the images, we were able to visualize each part of the bone, i.e., the cortical and trabecular regions. Total volume of the bone is 4663.63 mm{sup 3}, and the surface area of the bone is 7913.42 mm{sup 2}. The volume of the cortical is approximately 1988.62 mm{sup 3} which is nearly 42.64% of the total bone volume. This pilot study has confirmed that the μCT is capable of quantifying 3D bone structural properties and defining its regions separately. For further development, these results can be improved for understanding the pathophysiology of bone abnormality, testing the efficacy of pharmaceutical intervention, or estimating bone biomechanical properties.« less

Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations.

PubMed

Kometer, Michael; Pokorny, Thomas; Seifritz, Erich; Volleinweider, Franz X

2015-10-01

During the last years, considerable progress has been made toward understanding the neuronal basis of consciousness by using sophisticated behavioral tasks, brain-imaging techniques, and various psychoactive drugs. Nevertheless, the neuronal mechanisms underlying some of the most intriguing states of consciousness, including spiritual experiences, remain unknown. To elucidate state of consciousness-related neuronal mechanisms, human subjects were given psilocybin, a naturally occurring serotonergic agonist and hallucinogen that has been used for centuries to induce spiritual experiences in religious and medical rituals. In this double-blind, placebo-controlled study, 50 healthy human volunteers received a moderate dose of psilocybin, while high-density electroencephalogram (EEG) recordings were taken during eyes-open and eyes-closed resting states. The current source density and the lagged phase synchronization of neuronal oscillations across distributed brain regions were computed and correlated with psilocybin-induced altered states of consciousness. Psilocybin decreased the current source density of neuronal oscillations at 1.5-20 Hz within a neural network comprising the anterior and posterior cingulate cortices and the parahippocampal regions. Most intriguingly, the intensity levels of psilocybin-induced spiritual experience and insightfulness correlated with the lagged phase synchronization of delta oscillations (1.5-4 Hz) between the retrosplenial cortex, the parahippocampus, and the lateral orbitofrontal area. These results provide systematic evidence for the direct association of a specific spatiotemporal neuronal mechanism with spiritual experiences and enhanced insight into life and existence. The identified mechanism may constitute a pathway for modulating mental health, as spiritual experiences can promote sustained well-being and psychological resilience.

Osteoporosis Imaging: State of the Art and Advanced Imaging

PubMed Central

2012-01-01

Osteoporosis is becoming an increasingly important public health issue, and effective treatments to prevent fragility fractures are available. Osteoporosis imaging is of critical importance in identifying individuals at risk for fractures who would require pharmacotherapy to reduce fracture risk and also in monitoring response to treatment. Dual x-ray absorptiometry is currently the state-of-the-art technique to measure bone mineral density and to diagnose osteoporosis according to the World Health Organization guidelines. Motivated by a 2000 National Institutes of Health consensus conference, substantial research efforts have focused on assessing bone quality by using advanced imaging techniques. Among these techniques aimed at better characterizing fracture risk and treatment effects, high-resolution peripheral quantitative computed tomography (CT) currently plays a central role, and a large number of recent studies have used this technique to study trabecular and cortical bone architecture. Other techniques to analyze bone quality include multidetector CT, magnetic resonance imaging, and quantitative ultrasonography. In addition to quantitative imaging techniques measuring bone density and quality, imaging needs to be used to diagnose prevalent osteoporotic fractures, such as spine fractures on chest radiographs and sagittal multidetector CT reconstructions. Radiologists need to be sensitized to the fact that the presence of fragility fractures will alter patient care, and these fractures need to be described in the report. This review article covers state-of-the-art imaging techniques to measure bone mineral density, describes novel techniques to study bone quality, and focuses on how standard imaging techniques should be used to diagnose prevalent osteoporotic fractures. © RSNA, 2012 PMID:22438439

Neuron density is decreased in the prefrontal cortex in Williams syndrome.

PubMed

Lew, Caroline Horton; Brown, Chelsea; Bellugi, Ursula; Semendeferi, Katerina

2017-01-01

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res 2017, 10: 99-112. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

PubMed Central

Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

2012-01-01

We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

PubMed

Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

2016-01-19

The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

Characterising the grey matter correlates of leukoaraiosis in cerebral small vessel disease.

PubMed

Lambert, Christian; Sam Narean, Janakan; Benjamin, Philip; Zeestraten, Eva; Barrick, Thomas R; Markus, Hugh S

2015-01-01

Cerebral small vessel disease (SVD) is a heterogeneous group of pathological disorders that affect the small vessels of the brain and are an important cause of cognitive impairment. The ischaemic consequences of this disease can be detected using MRI, and include white matter hyperintensities (WMH), lacunar infarcts and microhaemorrhages. The relationship between SVD disease severity, as defined by WMH volume, in sporadic age-related SVD and cortical thickness has not been well defined. However, regional cortical thickness change would be expected due to associated phenomena such as underlying ischaemic white matter damage, and the observation that widespread cortical thinning is observed in the related genetic condition CADASIL (Righart et al., 2013). Using MRI data, we have developed a semi-automated processing pipeline for the anatomical analysis of individuals with cerebral small vessel disease and applied it cross-sectionally to 121 subjects diagnosed with this condition. Using a novel combined automated white matter lesion segmentation algorithm and lesion repair step, highly accurate warping to a group average template was achieved. The volume of white matter affected by WMH was calculated, and used as a covariate of interest in a voxel-based morphometry and voxel-based cortical thickness analysis. Additionally, Gaussian Process Regression (GPR) was used to assess if the severity of SVD, measured by WMH volume, could be predicted from the morphometry and cortical thickness measures. We found significant (Family Wise Error corrected p < 0.05) volumetric decline with increasing lesion load predominately in the parietal lobes, anterior insula and caudate nuclei bilaterally. Widespread significant cortical thinning was found bilaterally in the dorsolateral prefrontal, parietal and posterio-superior temporal cortices. These represent distinctive patterns of cortical thinning and volumetric reduction compared to ageing effects in the same cohort, which exhibited greater changes in the occipital and sensorimotor cortices. Using GPR, the absolute WMH volume could be significantly estimated from the grey matter density and cortical thickness maps (Pearson's coefficients 0.80 and 0.75 respectively). We demonstrate that SVD severity is associated with regional cortical thinning. Furthermore a quantitative measure of SVD severity (WMH volume) can be predicted from grey matter measures, supporting an association between white and grey matter damage. The pattern of cortical thinning and volumetric decline is distinctive for SVD severity compared to ageing. These results, taken together, suggest that there is a phenotypic pattern of atrophy associated with SVD severity.

Role of endocortical contouring methods on precision of HR-pQCT-derived cortical micro-architecture in postmenopausal women and young adults.

PubMed

Kawalilak, C E; Johnston, J D; Cooper, D M L; Olszynski, W P; Kontulainen, S A

2016-02-01

Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P < 0.05. CV%RMS ranged from 0.9 to 16.3 %. Within-group precision did not differ between evaluation methods. Compared to young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to generally higher cortical bone properties when compared to the automated method, while no between-method differences were observed in young adults.

Throwing enhances humeral shaft cortical bone properties in pre-pubertal baseball players: a 12-month longitudinal pilot study.

PubMed

Weatherholt, Alyssa M; Warden, Stuart J

2018-06-01

To explore throwing athletes as a prospective, within-subject controlled model for studying the response of the skeleton to exercise. Male pre-pubertal throwing athletes (n=12; age=10.3±0.6 yrs) had distal humerus cortical volumetric bone mineral density (Ct.vBMD), cortical bone mineral content (Ct.BMC), total area (Tt.Ar), cortical area (Ct.Ar), medullary area (Me.Ar), cortical thickness (Ct.Th) and polar moment of inertia (IP) assessed within their throwing (exercised) and nonthrowing (control) arms by peripheral quantitative computed tomography at baseline and 12 months. Throwing-to-nonthrowing arm percent differences (i.e. bilateral asymmetry) were compared over time. Over 12 months, the throwing arm gained 4.3% (95% Cl=1.1% to 7.5%), 2.9% (95% Cl=0.3% to 5.4%), 3.9% (95% Cl=0.7% to 7.0%), and 8.2% (95% Cl=2.0% to 6.8%) more Ct.BMC, Ct.Ar, Tt.Ar, and I P than the nonthrowing arm, respectively (all p<0.05). There was no significant effect of throwing on Ct.vBMD, Ct.Th and Me.Ar (all p=0.18-0.82). Throwing induced surface-specific cortical bone adaptation at the distal humeral diaphysis that contributed to a gain in estimated strength. These longitudinal pilot data support the utility of throwing athletes as a within-subject controlled model to explore factors influencing exercise-induced bone adaptation during the critical growing years.

Spatial resolution dependence on spectral frequency in human speech cortex electrocorticography.

PubMed

Muller, Leah; Hamilton, Liberty S; Edwards, Erik; Bouchard, Kristofer E; Chang, Edward F

2016-10-01

Electrocorticography (ECoG) has become an important tool in human neuroscience and has tremendous potential for emerging applications in neural interface technology. Electrode array design parameters are outstanding issues for both research and clinical applications, and these parameters depend critically on the nature of the neural signals to be recorded. Here, we investigate the functional spatial resolution of neural signals recorded at the human cortical surface. We empirically derive spatial spread functions to quantify the shared neural activity for each frequency band of the electrocorticogram. Five subjects with high-density (4 mm center-to-center spacing) ECoG grid implants participated in speech perception and production tasks while neural activity was recorded from the speech cortex, including superior temporal gyrus, precentral gyrus, and postcentral gyrus. The cortical surface field potential was decomposed into traditional EEG frequency bands. Signal similarity between electrode pairs for each frequency band was quantified using a Pearson correlation coefficient. The correlation of neural activity between electrode pairs was inversely related to the distance between the electrodes; this relationship was used to quantify spatial falloff functions for cortical subdomains. As expected, lower frequencies remained correlated over larger distances than higher frequencies. However, both the envelope and phase of gamma and high gamma frequencies (30-150 Hz) are largely uncorrelated (<90%) at 4 mm, the smallest spacing of the high-density arrays. Thus, ECoG arrays smaller than 4 mm have significant promise for increasing signal resolution at high frequencies, whereas less additional gain is achieved for lower frequencies. Our findings quantitatively demonstrate the dependence of ECoG spatial resolution on the neural frequency of interest. We demonstrate that this relationship is consistent across patients and across cortical areas during activity.

In vivo tibial stiffness is maintained by whole bone morphology and cross-sectional geometry in growing female mice

PubMed Central

Main, Russell P.; Lynch, Maureen E.; van der Meulen, Marjolein C.H.

2010-01-01

Whole bone morphology, cortical geometry, and tissue material properties modulate skeletal stresses and strains that in turn influence skeletal physiology and remodeling. Understanding how bone stiffness, the relationship between applied load and tissue strain, is regulated by developmental changes in bone structure and tissue material properties is important in implementing biophysical strategies for promoting healthy bone growth and preventing bone loss. The goal of this study was to relate developmental patterns of in vivo whole bone stiffness to whole bone morphology, cross-sectional geometry, and tissue properties using a mouse axial loading model. We measured in vivo tibial stiffness in three age groups (6wks, 10wks, 16wks old) of female C57Bl/6 mice during cyclic tibial compression. Tibial stiffness was then related to cortical geometry, longitudinal bone curvature, and tissue mineral density using microcomputed tomography (microCT). Tibial stiffness and the stresses induced by axial compression were generally maintained from 6 to 16wks of age. Growth-related increases in cortical cross-sectional geometry and longitudinal bone curvature had counteracting effects on induced bone stresses and, therefore, maintained tibial stiffness similarly with growth. Tissue mineral density increased slightly from 6 to 16wks of age, and although the effects of this increase on tibial stiffness were not directly measured, its role in the modulation of whole bone stiffness was likely minor over the age range examined. Thus, whole bone morphology, as characterized by longitudinal curvature, along with cortical geometry, plays an important role in modulating bone stiffness during development and should be considered when evaluating and designing in vivo loading studies and biophysical skeletal therapies. PMID:20673665

Spatial resolution dependence on spectral frequency in human speech cortex electrocorticography

NASA Astrophysics Data System (ADS)

Muller, Leah; Hamilton, Liberty S.; Edwards, Erik; Bouchard, Kristofer E.; Chang, Edward F.

2016-10-01

Objective. Electrocorticography (ECoG) has become an important tool in human neuroscience and has tremendous potential for emerging applications in neural interface technology. Electrode array design parameters are outstanding issues for both research and clinical applications, and these parameters depend critically on the nature of the neural signals to be recorded. Here, we investigate the functional spatial resolution of neural signals recorded at the human cortical surface. We empirically derive spatial spread functions to quantify the shared neural activity for each frequency band of the electrocorticogram. Approach. Five subjects with high-density (4 mm center-to-center spacing) ECoG grid implants participated in speech perception and production tasks while neural activity was recorded from the speech cortex, including superior temporal gyrus, precentral gyrus, and postcentral gyrus. The cortical surface field potential was decomposed into traditional EEG frequency bands. Signal similarity between electrode pairs for each frequency band was quantified using a Pearson correlation coefficient. Main results. The correlation of neural activity between electrode pairs was inversely related to the distance between the electrodes; this relationship was used to quantify spatial falloff functions for cortical subdomains. As expected, lower frequencies remained correlated over larger distances than higher frequencies. However, both the envelope and phase of gamma and high gamma frequencies (30-150 Hz) are largely uncorrelated (<90%) at 4 mm, the smallest spacing of the high-density arrays. Thus, ECoG arrays smaller than 4 mm have significant promise for increasing signal resolution at high frequencies, whereas less additional gain is achieved for lower frequencies. Significance. Our findings quantitatively demonstrate the dependence of ECoG spatial resolution on the neural frequency of interest. We demonstrate that this relationship is consistent across patients and across cortical areas during activity.

Validation of DTI Tractography-Based Measures of Primary Motor Area Connectivity in the Squirrel Monkey Brain

PubMed Central

Gao, Yurui; Choe, Ann S.; Stepniewska, Iwona; Li, Xia; Avison, Malcolm J.; Anderson, Adam W.

2013-01-01

Diffusion tensor imaging (DTI) tractography provides noninvasive measures of structural cortico-cortical connectivity of the brain. However, the agreement between DTI-tractography-based measures and histological ‘ground truth’ has not been quantified. In this study, we reconstructed the 3D density distribution maps (DDM) of fibers labeled with an anatomical tracer, biotinylated dextran amine (BDA), as well as DTI tractography-derived streamlines connecting the primary motor (M1) cortex to other cortical regions in the squirrel monkey brain. We evaluated the agreement in M1-cortical connectivity between the fibers labeled in the brain tissue and DTI streamlines on a regional and voxel-by-voxel basis. We found that DTI tractography is capable of providing inter-regional connectivity comparable to the neuroanatomical connectivity, but is less reliable measuring voxel-to-voxel variations within regions. PMID:24098365

Hippocampal coupling with cortical and subcortical structures in the context of memory consolidation.

PubMed

Skelin, Ivan; Kilianski, Scott; McNaughton, Bruce L

2018-04-13

Memory consolidation is a gradual process through which episodic memories become incorporated into long-term 'semantic' representations. It likely involves reactivation of neural activity encoding the recent experience during non-REM sleep. A critical prerequisite for memory consolidation is precise coordination of reactivation events between the hippocampus and cortical/subcortical structures, facilitated by the coupling of local field potential (LFP) oscillations (slow oscillations, sleep spindles and sharp wave/ripples) between these structures. We review the rapidly expanding literature on the qualitative and quantitative aspects of hippocampal oscillatory and neuronal coupling with cortical/subcortical structures in the context of memory reactivation. Reactivation in the hippocampus and cortical/subcortical structures is tightly coupled with sharp wave/ripples. Hippocampal-cortical/subcortical coupling is rich in dimensionality and this dimensionality is likely underestimated due to the limitations of the current methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI.

PubMed

Gulban, Omer F; De Martino, Federico; Vu, An T; Yacoub, Essa; Uğurbil, Kamil; Lenglet, Christophe

2018-05-10

Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which provide complementary (e.g. to anatomical and functional MRI) microstructural information about the cortex architectonic. Several ex-vivo and in-vivo MRI studies have recently addressed this question, however predominantly with an emphasis on specific cortical areas. There is currently no whole brain in-vivo data leveraging multi-shell diffusion MRI acquisition at high spatial resolution, and depth dependent analysis, to characterize the complex organization of cortical fibers. Here, we present unique in-vivo human 7T diffusion MRI data, and a dedicated cortical depth dependent analysis pipeline. We leverage the high spatial (1.05 mm isotropic) and angular (198 diffusion gradient directions) resolution of this whole brain dataset to improve cortical fiber orientations mapping, and study neurites (axons and/or dendrites) trajectories across cortical depths. Tangential fibers in superficial cortical depths and crossing fiber configurations in deep cortical depths are identified. Fibers gradually inserting into the gyral walls are visualized, which contributes to mitigating the gyral bias effect. Quantitative radiality maps and histograms in individual subjects and cortex-based aligned datasets further support our results. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics

PubMed Central

Handel, Adam E.; Chintawar, Satyan; Lalic, Tatjana; Whiteley, Emma; Vowles, Jane; Giustacchini, Alice; Argoud, Karene; Sopp, Paul; Nakanishi, Mahito; Bowden, Rory; Cowley, Sally; Newey, Sarah; Akerman, Colin; Ponting, Chris P.; Cader, M. Zameel

2016-01-01

Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single-cell multiplex reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Totally, 93.6% of single cells derived from iPSCs expressed genes indicative of neuronal identity. High proportions of single neurons derived from iPSCs expressed glutamatergic receptors and synaptic genes. And, 68.4% of iPSC-derived neurons expressing at least one layer marker could be assigned to a laminar identity using canonical cortical layer marker genes. We compared single-cell RNA-seq of our iPSC-derived neurons to available single-cell RNA-seq data from human fetal and adult brain and found that iPSC-derived cortical neurons closely resembled primary fetal brain cells. Unexpectedly, a subpopulation of iPSC-derived neurons co-expressed canonical fetal deep and upper cortical layer markers. However, this appeared to be concordant with data from primary cells. Our results therefore provide reassurance that iPSC-derived cortical neurons are highly similar to primary cortical neurons at the level of single cells but suggest that current layer markers, although effective, may not be able to disambiguate cortical layer identity in all cells. PMID:26740550

Fructose Consumption Does Not Worsen Bone Deficits Resulting From High-Fat Feeding in Young Male Rats

PubMed Central

Yarrow, Joshua F.; Toklu, Hale Z.; Balaez, Alex; Phillips, Ean G.; Otzel, Dana M.; Chen, Cong; Wronski, Thomas J.; Aguirre, J. Ignacio; Sakarya, Yasemin; Tümer, Nihal; Scarpace, Philip J.

2016-01-01

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12 weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8 weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23–34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that “westernized” HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development. PMID:26855373

Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats.

PubMed

Yarrow, Joshua F; Toklu, Hale Z; Balaez, Alex; Phillips, Ean G; Otzel, Dana M; Chen, Cong; Wronski, Thomas J; Aguirre, J Ignacio; Sakarya, Yasemin; Tümer, Nihal; Scarpace, Philip J

2016-04-01

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23-34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that "westernized" HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development. Published by Elsevier Inc.

Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo μCT.

PubMed

Bock, Oliver; Börst, Hendrikje; Beller, Gisela; Armbrecht, Gabriele; Degner, Corina; Martus, Peter; Roth, Heinz-Jürgen; Felsenberg, Dieter

2012-01-01

The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. μCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue-volume and trabecular separation at the distal tibia (p≥0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p=0.045). Analysis of secondary end-points showed greater increases in distal tibia cortical thickness, cortical density and total density (p≤0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA-BMD (p≤0.017). Ibandronate use resulted in a marked reduction in bone turnover (p<0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation. Copyright © 2011 Elsevier Inc. All rights reserved.

Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players.

PubMed

Warden, S J; Weatherholt, A M; Gudeman, A S; Mitchell, D C; Thompson, W R; Fuchs, R K

2017-07-01

Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. Throwing athletes (n = 90) and controls (n = 51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (<-2, -2 to 2, 2 to 4, 4 to 10, and >10 years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSI P ) were assessed. Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSI P resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p < 0.05) and (2) throwing-to-nonthrowing arm differences in throwers being progressively greater across maturity groups (all p < 0.05). Regional analyses revealed greatest adaptation in medial and lateral sectors, particularly in the three post-maturity groups. Years throwing predicted 59% of the variance of the variance in throwing-to-nonthrowing arm difference in SSI P (p < 0.001). These data suggest that physical activity has skeletal benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits.

Functional changes in glutamate transporters and astrocyte biophysical properties in a rodent model of focal cortical dysplasia

PubMed Central

Campbell, Susan L.; Hablitz, John J.; Olsen, Michelle L.

2014-01-01

Cortical dysplasia is associated with intractable epilepsy and developmental delay in young children. Recent work with the rat freeze-induced focal cortical dysplasia (FCD) model has demonstrated that hyperexcitability in the dysplastic cortex is due in part to higher levels of extracellular glutamate. Astrocyte glutamate transporters play a pivotal role in cortical maintaining extracellular glutamate concentrations. Here we examined the function of astrocytic glutamate transporters in a FCD model in rats. Neocortical freeze lesions were made in postnatal day (PN) 1 rat pups and whole cell electrophysiological recordings and biochemical studies were performed at PN 21–28. Synaptically evoked glutamate transporter currents in astrocytes showed a near 10-fold reduction in amplitude compared to sham operated controls. Astrocyte glutamate transporter currents from lesioned animals were also significantly reduced when challenged exogenously applied glutamate. Reduced astrocytic glutamate transport clearance contributed to increased NMDA receptor-mediated current decay kinetics in lesioned animals. The electrophysiological profile of astrocytes in the lesion group was also markedly changed compared to sham operated animals. Control astrocytes demonstrate large-amplitude linear leak currents in response to voltage-steps whereas astrocytes in lesioned animals demonstrated significantly smaller voltage-activated inward and outward currents. Significant decreases in astrocyte resting membrane potential and increases in input resistance were observed in lesioned animals. However, Western blotting, immunohistochemistry and quantitative PCR demonstrated no differences in the expression of the astrocytic glutamate transporter GLT-1 in lesioned animals relative to controls. These data suggest that, in the absence of changes in protein or mRNA expression levels, functional changes in astrocytic glutamate transporters contribute to neuronal hyperexcitability in the FCD model. PMID:25565960

[Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

PubMed

Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

2014-05-20

Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Genetic and Dynamic Analyses of Murine Peak Bone Density

DTIC Science & Technology

1999-10-01

DAMD17-96-1-6309 differences, the location of bone regulatory genes with strong and modifier effects , the mode of inheritance for each gene, the...estimate the cortical cross-sectional area, most likely due to partial volume effects . Thus, the high density bone area was consistently estimated to be...significant or highly significant linkage with BMD; b) 9 Beamer, WG DAMD17-96-1-6309 none of the loci exhibited significant interaction effects by ANOVA

The relationship between dental implant stability and trabecular bone structure using cone-beam computed tomography

PubMed Central

2016-01-01

Purpose The objective of this study was to investigate the relationships between primary implant stability as measured by impact response frequency and the structural parameters of trabecular bone using cone-beam computed tomography(CBCT), excluding the effect of cortical bone thickness. Methods We measured the impact response of a dental implant placed into swine bone specimens composed of only trabecular bone without the cortical bone layer using an inductive sensor. The peak frequency of the impact response spectrum was determined as an implant stability criterion (SPF). The 3D microstructural parameters were calculated from CT images of the bone specimens obtained using both micro-CT and CBCT. Results SPF had significant positive correlations with trabecular bone structural parameters (BV/TV, BV, BS, BSD, Tb.Th, Tb.N, FD, and BS/BV) (P<0.01) while SPF demonstrated significant negative correlations with other microstructural parameters (Tb.Sp, Tb.Pf, and SMI) using micro-CT and CBCT (P<0.01). Conclusions There was an increase in implant stability prediction by combining BV/TV and SMI in the stepwise forward regression analysis. Bone with high volume density and low surface density shows high implant stability. Well-connected thick bone with small marrow spaces also shows high implant stability. The combination of bone density and architectural parameters measured using CBCT can predict the implant stability more accurately than the density alone in clinical diagnoses. PMID:27127692

Localized tissue mineralization regulated by bone remodelling: A computational approach

PubMed Central

Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

2017-01-01

Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments

PubMed Central

Zhang, Yanshuai; McNerny, Erin Gatenby; Terajima, Masahiko; Raghavan, Mekhala; Romanowicz, Genevieve; Zhang, Zhanpeng; Zhang, Honghao; Kamiya, Nobuhiro; Tantillo, Margaret; Zhu, Peizhi; Scott, Gregory J.; Ray, Manas K.; Lynch, Michelle; Ma, Peter X.; Morris, Michael D.; Yamauchi, Mitsuo; Kohn, David H.; Mishina, Yuji

2016-01-01

Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment. These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments. PMID:27113526

Investigating the effects of a sensorimotor rhythm-based BCI training on the cortical activity elicited by mental imagery

NASA Astrophysics Data System (ADS)

Toppi, J.; Risetti, M.; Quitadamo, L. R.; Petti, M.; Bianchi, L.; Salinari, S.; Babiloni, F.; Cincotti, F.; Mattia, D.; Astolfi, L.

2014-06-01

Objective. It is well known that to acquire sensorimotor (SMR)-based brain-computer interface (BCI) control requires a training period before users can achieve their best possible performances. Nevertheless, the effect of this training procedure on the cortical activity related to the mental imagery ability still requires investigation to be fully elucidated. The aim of this study was to gain insights into the effects of SMR-based BCI training on the cortical spectral activity associated with the performance of different mental imagery tasks. Approach. Linear cortical estimation and statistical brain mapping techniques were applied on high-density EEG data acquired from 18 healthy participants performing three different mental imagery tasks. Subjects were divided in two groups, one of BCI trained subjects, according to their previous exposure (at least six months before this study) to motor imagery-based BCI training, and one of subjects who were naive to any BCI paradigms. Main results. Cortical activation maps obtained for trained and naive subjects indicated different spectral and spatial activity patterns in response to the mental imagery tasks. Long-term effects of the previous SMR-based BCI training were observed on the motor cortical spectral activity specific to the BCI trained motor imagery task (simple hand movements) and partially generalized to more complex motor imagery task (playing tennis). Differently, mental imagery with spatial attention and memory content could elicit recognizable cortical spectral activity even in subjects completely naive to (BCI) training. Significance. The present findings contribute to our understanding of BCI technology usage and might be of relevance in those clinical conditions when training to master a BCI application is challenging or even not possible.

Complement is activated in progressive multiple sclerosis cortical grey matter lesions.

PubMed

Watkins, Lewis M; Neal, James W; Loveless, Sam; Michailidou, Iliana; Ramaglia, Valeria; Rees, Mark I; Reynolds, Richard; Robertson, Neil P; Morgan, B Paul; Howell, Owain W

2016-06-22

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the irreversible progression of MS.

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

PubMed Central

de Bakker, Chantal M. J.; Altman-Singles, Allison R.; Li, Yihan; Tseng, Wei-Ju; Li, Connie; Liu, X. Sherry

2017-01-01

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. PMID:28109138

Investigating the effects of a sensorimotor rhythm-based BCI training on the cortical activity elicited by mental imagery.

PubMed

Toppi, J; Risetti, M; Quitadamo, L R; Petti, M; Bianchi, L; Salinari, S; Babiloni, F; Cincotti, F; Mattia, D; Astolfi, L

2014-06-01

It is well known that to acquire sensorimotor (SMR)-based brain-computer interface (BCI) control requires a training period before users can achieve their best possible performances. Nevertheless, the effect of this training procedure on the cortical activity related to the mental imagery ability still requires investigation to be fully elucidated. The aim of this study was to gain insights into the effects of SMR-based BCI training on the cortical spectral activity associated with the performance of different mental imagery tasks. Linear cortical estimation and statistical brain mapping techniques were applied on high-density EEG data acquired from 18 healthy participants performing three different mental imagery tasks. Subjects were divided in two groups, one of BCI trained subjects, according to their previous exposure (at least six months before this study) to motor imagery-based BCI training, and one of subjects who were naive to any BCI paradigms. Cortical activation maps obtained for trained and naive subjects indicated different spectral and spatial activity patterns in response to the mental imagery tasks. Long-term effects of the previous SMR-based BCI training were observed on the motor cortical spectral activity specific to the BCI trained motor imagery task (simple hand movements) and partially generalized to more complex motor imagery task (playing tennis). Differently, mental imagery with spatial attention and memory content could elicit recognizable cortical spectral activity even in subjects completely naive to (BCI) training. The present findings contribute to our understanding of BCI technology usage and might be of relevance in those clinical conditions when training to master a BCI application is challenging or even not possible.

Sleep affects cortical source modularity in temporal lobe epilepsy: A high-density EEG study.

PubMed

Del Felice, Alessandra; Storti, Silvia Francesca; Manganotti, Paolo

2015-09-01

Interictal epileptiform discharges (IEDs) constitute a perturbation of ongoing cerebral rhythms, usually more frequent during sleep. The aim of the study was to determine whether sleep influences the spread of IEDs over the scalp and whether their distribution depends on vigilance-related modifications in cortical interactions. Wake and sleep 256-channel electroencephalography (EEG) data were recorded in 12 subjects with right temporal lobe epilepsy (TLE) differentiated by whether they had mesial or neocortical TLE. Spikes were selected during wake and sleep. The averaged waking signal was subtracted from the sleep signal and projected on a bidimensional scalp map; sleep and wake spike distributions were compared by using a t-test. The superimposed signal of sleep and wake traces was obtained; the rising phase of the spike, the peak, and the deflections following the spike were identified, and their cortical generator was calculated using low-resolution brain electromagnetic tomography (LORETA) for each group. A mean of 21 IEDs in wake and 39 in sleep per subject were selected. As compared to wake, a larger IED scalp projection was detected during sleep in both mesial and neocortical TLE (p<0.05). A series of EEG deflections followed the spike, the cortical sources of which displayed alternating activations of different cortical areas in wake, substituted by isolated, stationary activations in sleep in mesial TLE and a silencing in neocortical TLE. During sleep, the IED scalp region increases, while cortical interaction decreases. The interaction of cortical modules in sleep and wake in TLE may influence the appearance of IEDs on scalp EEG; in addition, IEDs could be proxies for cerebral oscillation perturbation. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Racial differences in cortical bone and their relationship to biochemical variables in black and white children in the early stages of puberty

PubMed Central

Warden, Stuart J.; Hill, Kathleen M.; Ferira, Ashley J.; Laing, Emma M.; Martin, Berdine R.; Hausman, Dorothy B.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

2014-01-01

Introduction Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of black and white children in the early stages of puberty, and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties. Methods A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n=155 males; n=164 blacks) in the early stages of puberty. Results Blacks had greater cortical volumetric bone mineral density, mass and size compared to whites (all p<0.01), contributing to blacks having 17.0% greater tibial strength (polar strength-strain index [SSIP]) (p<0.001). Turnover markers indicated blacks had higher bone formation (osteocalcin [OC] and bone specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than whites (all p<0.01). Blacks also had lower 25-hydroxyvitamin D [25(OH)D], and higher 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) (all p<0.05). There were no correlations between tibial bone properties, and 25(OH)D and PTH in whites (all p≥0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in blacks, respectively (all p≤0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH and OC. Conclusions Divergence in tibial cortical bone properties between blacks and whites is established by the early stages of puberty with the enhanced cortical bone properties in black children possibly being explained by higher PTH and OC. PMID:23093348

The relation between schizotypy and early attention to rejecting interactions: The influence of neuroticism

PubMed Central

Premkumar, Preethi; Onwumere, Juliana; Albert, Jacobo; Kessel, Dominique; Kumari, Veena; Kuipers, Elizabeth; Carretié, Luis

2015-01-01

Abstract Objectives: Schizotypy relates to rejection sensitivity (anxiety reflecting an expectancy of social exclusion) and neuroticism (excessive evaluation of negative emotions). Positive schizotypy (e.g., perceptual aberrations and odd beliefs) and negative schizotypy (e.g., social and physical anhedonia) could relate to altered attention to rejection because of neuroticism. Methods: Forty-one healthy individuals were assessed on positive and negative schizotypy and neuroticism, and event-related potentials during rejecting, accepting and neutral scenes. Participants were categorised into high, moderate and low neuroticism groups. Using temporo-spatial principal components analyses, P200 (peak latency =290 ms) and P300 amplitudes (peak latency = 390 ms) were measured, reflecting mobilisation of attention and early attention, respectively. Results: Scalp-level and cortical source analysis revealed elevated fronto-parietal N300/P300 amplitude and P200-related dorsal anterior cingulate current density during rejection than acceptance/neutral scenes. Positive schizotypy related inversely to parietal P200 amplitude during rejection. Negative schizotypy related positively to P200 middle occipital current density. Negative schizotypy related positively to parietal P300, where the association was stronger in high and moderate, than low, neuroticism groups. Conclusions: Positive and negative schizotypy relate divergently to attention to rejection. Positive schizotypy attenuates, but negative schizotypy increases rejection-related mobilisation of attention. Negative schizotypy increases early attention to rejection partly due to elevated neuroticism. PMID:26452584

Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging.

PubMed

Duan, Yunbo; Beck, Thomas J; Wang, Xiao-Fang; Seeman, Ego

2003-10-01

The structural basis for sex differences in femoral neck (FN) fragility was studied in 1196 subjects and 307 patients with hip fracture. The absolute and relative patterns of modeling and remodeling on the periosteal and endocortical envelopes during growth and aging produce changes in FN geometry and structure that results in FN fragility in both sexes and sexual dimorphism in hip fracture risk in old age. Femoral neck (FN) fragility in old age is usually attributed to age-related bone loss, while the sex differences in hip fracture rate are attributed to less bone loss in men than in women. The purpose of this study was to define the structural and biomechanical basis underlying the increase in FN fragility in elderly men and women and the structural basis of sex differences in hip fracture incidence in old age. We measured FN dimensions and areal bone mineral density in 1196 healthy subjects (801 females) 18-92 years of age and 307 patients (180 females) with hip fracture using DXA. We then used the DXA-derived FN areal bone mineral density (BMD) and measured periosteal diameter to estimate endocortical diameter, cortical thickness, section modulus (a measure of bending strength), and buckling ratio (indices for structural stability). Neither FN cortical thickness nor volumetric density differed in young adult women and men after height and weight adjustment. The sex differences in geometry were confined to the further displacement of the cortex from the FN neutral axis in young men, which produced 13.4% greater bending strength than in young women. Aging amplified this geometric difference; widening of the periosteal and endocortical diameters continued in both sexes but was greater in men, shifting the cortex even further from the neutral axis maintaining bending strength in men, not in women. In both sexes, less age-related periosteal than endocortical widening produced cortical thinning increasing the risk for structural failure by local buckling of the enlarged thin walled FN. Relative to age-matched controls, women and men with hip fractures had reduced cortical thickness, but FN periosteal diameter was increased in women and reduced in men, differences are likely to be originated in growth. The absolute and relative patterns of modeling and remodeling on the periosteal and endocortical envelopes during growth and aging produce changes in FN diameters, cortical thickness, and geometry that results in FN fragility in both sexes and sexual dimorphism in hip fracture risk in old age.

Adrenarche and bone modeling and remodeling at the proximal radius: weak androgens make stronger cortical bone in healthy children.

PubMed

Remer, Thomas; Boye, Kai R; Hartmann, Michaela; Neu, Christina M; Schoenau, Eckhard; Manz, Friedrich; Wudy, Stefan A

2003-08-01

Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children. Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth. Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6-18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry. We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001)--reflecting, at least in part, reduction in intracortical remodeling-were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables (except PC) when, instead of C19 and C21, specific dehydroepiandrosterone metabolites were included as independent variables in the multiple regression model. During development of pubic hair (pubarche), muscularity and pubertal stage rather than adrenarchal hormones seemed to influence bone variables. Our study shows that especially the prepubarchal increase in adrenal androgen secretion plays an independent role in the accretion of proximal radial diaphyseal bone strength in healthy children.

Olig1 function is required to repress Dlx1/2 and interneuron production in mammalian brain

PubMed Central

Silbereis, John C.; Nobuta, Hiroko; Tsai, Hui-Hsin; Heine, Vivi M.; McKinsey, Gabriel L.; Meijer, Dimphna H.; Howard, MacKenzie A.; Petryniak, Magda A.; Potter, Gregory B.; Alberta, John A.; Baraban, Scott C.; Stiles, Charles D.; Rubenstein, John L.R.; Rowitch, David H.

2014-01-01

Summary Abnormal GABAergic interneuron density, and imbalance of excitatory versus inhibitory tone, is thought to result in epilepsy, neurodevelopmental disorders and psychiatric disease. Recent studies indicate that interneuron cortical density is determined primarily by the size of the precursor pool in the embryonic telencephalon. However, factors essential to regulate interneuron allocation from telencephalic multipotent precursors are poorly understood. Here we report that Olig1 represses production of GABAergic interneurons throughout the mouse brain. Olig1 deletion in mutant mice results in ectopic expression and upregulation of Dlx1/2 genes in the ventral medial ganglionic eminences and adjacent regions of the septum resulting in a ~30% increase in adult cortical interneuron numbers. We show that Olig1 directly represses the Dlx1/2 I12b intergenic enhancer and that Dlx1/2 functions genetically downstream of Olig1. These findings establish Olig1 as an essential repressor of Dlx1/2 and interneuron production in developing mammalian brain. PMID:24507192

Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain.

PubMed

Trovero, F; Gobbi, M; Weil-Fuggaza, J; Besson, M J; Brochet, D; Pirot, S

2000-09-29

Chronic treatment of rats by sulbutiamine induced no change in density of N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the cingular cortex, but a significant decrease of the kainate binding sites, as measured by quantitative autoradiography. In the same treated animals, an increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex, while no modification of the D2 binding sites was detected. Furthermore, an acute sulbutiamine administration induced a decrease of kainate binding sites but no change of the density of D1 and D2 DA receptors. Acute sulbutiamine injection led to a decrease of the DA levels in the prefrontal cortex and 3,4-dihydroxyphenylacetic acid levels in both the cingular and the prefrontal cortex. These observations are discussed in terms of a modulatory effect of sulbutiamine on both dopaminergic and glutamatergic cortical transmissions.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

PubMed

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-11-15

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans

PubMed Central

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-01-01

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications. PMID:12949224

Effects of Hypocretin/Orexin and Major Transmitters of Arousal on Fast Spiking Neurons in Mouse Cortical Layer 6B

PubMed Central

Wenger Combremont, Anne-Laure; Bayer, Laurence; Dupré, Anouk; Mühlethaler, Michel; Serafin, Mauro

2016-01-01

Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells. PMID:27235100

The effect of the anodal transcranial direct current stimulation over the cerebellum on the motor cortex excitability.

PubMed

Ates, Mehlika Panpalli; Alaydin, Halil Can; Cengiz, Bulent

2018-04-25

This study was designed to investigate whether the cerebellum has an inhibitory effect on motor cortical excitability. Sixteen healthy adults (age range, 25-50 years, five female) participated in the study. Anodal cerebellar transcranial direct current stimulation (a-cTDCS) was used to modulate cerebellar excitability. A-cTDCS was given for 20 min at 1 mA intensity. The automatic threshold tracking method was used to investigate cortical excitability. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), intracortical facilitation (ICF), and the input output curve (I-O curve) were motor cortical excitability parameters. a-cTDCS caused a reduction in overall SICI and the reduced SICF for interstimulus intervals (ISIs) to 2.4-4.4 ms. a-cTDCS has no effect on ICF, RMT, and the I-O curve. There were no significant changes in any of these cortical excitability parameters after sham cTDCS. Results of the study indicate that a-cTDCS has a dual (both inhibitory and excitatory) effect on motor cortical excitability, rather than a simple inhibitory effect. The cerebellum modulates both the inhibitory and facilitatory activities of motor cortex (M1) and suggest that cerebello-cerebral motor connectivity is more complex than solely inhibitory or facilitatory connections. Copyright © 2018 Elsevier Inc. All rights reserved.

Cortical functional connectivity decodes subconscious, task-irrelevant threat-related emotion processing

PubMed Central

Pantazatos, Spiro P.; Talati, Ardesheer; Pavlidis, Paul; Hirsch, Joy

2012-01-01

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the ‘low-road’ vs. ‘many-roads’ hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. ‘subcortical alarm’ and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing. PMID:22484206

Cortical functional connectivity decodes subconscious, task-irrelevant threat-related emotion processing.

PubMed

Pantazatos, Spiro P; Talati, Ardesheer; Pavlidis, Paul; Hirsch, Joy

2012-07-16

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the 'low-road' vs. 'many-roads' hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. 'subcortical alarm' and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing. Published by Elsevier Inc.

Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

PubMed

Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

2015-07-01

Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness-which increased trabecular network heterogeneity-and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet. Copyright © 2015 Elsevier Inc. All rights reserved.

Aphasia: Current Concepts in Theory and Practice

PubMed Central

Tippett, Donna C.; Niparko, John K.; Hillis, Argye E.

2014-01-01

Recent advances in neuroimaging contribute to a new insights regarding brain-behavior relationships and expand understanding of the functional neuroanatomy of language. Modern concepts of the functional neuroanatomy of language invoke rich and complex models of language comprehension and expression, such as dual stream networks. Increasingly, aphasia is seen as a disruption of cognitive processes underlying language. Rehabilitation of aphasia incorporates evidence based and person-centered approaches. Novel techniques, such as methods of delivering cortical brain stimulation to modulate cortical excitability, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, are just beginning to be explored. In this review, we discuss the historical context of the foundations of neuroscientific approaches to language. We sample the emergent theoretical models of the neural substrates of language and cognitive processes underlying aphasia that contribute to more refined and nuanced concepts of language. Current concepts of aphasia rehabilitation are reviewed, including the promising role of cortical stimulation as an adjunct to behavioral therapy and changes in therapeutic approaches based on principles of neuroplasticity and evidence-based/person-centered practice to optimize functional outcomes. PMID:24904925

Cortical pyramidal cells as non-linear oscillators: experiment and spike-generation theory.

PubMed

Brumberg, Joshua C; Gutkin, Boris S

2007-09-26

Cortical neurons are capable of generating trains of action potentials in response to current injections. These discharges can take different forms, e.g., repetitive firing that adapts during the period of current injection or bursting behaviors. We have used a combined experimental and computational approach to characterize the dynamics leading to action potential responses in single neurons. Specifically we investigated the origin of complex firing patterns in response to sinusoidal current injections. Using a reduced model, the theta-neuron, alongside recordings from cortical pyramidal cells we show that both real and simulated neurons show phase-locking to sine wave stimuli up to a critical frequency, above which period skipping and 1-to-x phase-locking occurs. The locking behavior follows a complex "devil's staircase" phenomena, where locked modes are interleaved with irregular firing. We further show that the critical frequency depends on the time scale of spike generation and on the level of spike frequency adaptation. These results suggest that phase-locking of neuronal responses to complex input patterns can be explained by basic properties of the spike-generating machinery.

Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation.

PubMed

Geula, C

1998-07-01

Severe pathology in Alzheimer's disease (AD) results in marked disruption of cortical circuitry. Formation of neurofibrillary tangles, neuronal loss, decrease in dendritic extent, and synaptic depletion combine to halt communication among various cortical areas, resulting in anatomic isolation and fragmentation of many cortical zones. The clinical manifestation of this disruption is severe and debilitating cognitive dysfunction, often accompanied by psychiatric and behavioral disturbances and a diminished ability to perform activities of daily living. However, different cortical circuits are not equally vulnerable to AD pathology. In particular, two cortical systems that appear to be involved in the neural processing of memory are selectively vulnerable to degeneration in AD. One consists of connections between the hippocampus and its neighboring cortical structures within the temporal lobe. The second is the cortical cholinergic system that originates in neurons within the basal forebrain and innervates the entire cortical mantle. The circuitry in these systems shows early and severe degenerative changes in the course of AD. The selective vulnerability of these circuits is the probable reason for the early and marked loss of memory observed in these patients. This review presents current knowledge of the general pattern of cortical circuitry, followed by a summary of abnormalities of this circuitry in AD. The cortical circuits that exhibit selective pathology in AD are described in greater detail. Therapeutic implications of the abnormal circuitry in AD are also discussed. For therapies to be effective, early diagnosis of AD is necessary. Future efforts at AD therapy must be combined with an equally intense effort to develop tools capable of early diagnosis of AD, preferably at a preclinical stage before the onset of cognitive symptoms.

Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms.

PubMed

Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

2016-01-01

Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. © 2016 Associated Professional Sleep Societies, LLC.

N400-like responses to three-chord harmonic sequences with unexpected out of key endings: scalp topography, cortical sources, and perspectives for a clinical use.

PubMed

Bonfiglio, Luca; Virgillito, Alessandra; Magrini, Massimo; Piarulli, Andrea; Bergamasco, Massimo; Barcaro, Umberto; Rossi, Bruno; Salvetti, Ovidio; Carboncini, Maria Chiara

2015-03-01

A series of ERP components, each provided with both a precise timing with respect to stimulation and a specific cortical localization, reflects the temporal succession of processing stages of music information. This makes the musical stimulus potentially usable to probe residual brain functions in non-communicating patients with disorders of consciousness. In an attempt to find a simple stimulation protocol that was suitable for use in a clinical setting, the purpose of this study was to verify whether a minimum-length musical stimulus, provided with a definite music-syntactic connotation, was still able to elicit musical ERPs in a group of eight healthy subjects. The stimulus was composed of the minimum number of chords necessary and sufficient to enable the subject to predict a plausible closure of the sequence (priming) and, at the same time, to provide him/her with the closing chord of the sequence (target), either congruous (probable closing) or not (improbable closing) to the tonal context. The subject's task was to discriminate and recognize the irregular targets. The components that were expected to be elicited, in this experimental situation, were ERAN, N5, P600/LPC. Conversely, in addition to these former components, we unexpectedly observed a N400-like component. To determine whether this component was a real N400, we submitted our data to a sLORETA analysis in order to identify its cortical generators. Irregular chords showed higher current densities with respect to regular ones on the right-sided medial and superior temporal gyri, superior and inferior parietal lobules, fusiform and parahippocampal gyri, and on the bilateral posterior cingulate cortex. In particular, the N400-like wave seems to share with the word-primed music-elicited N400 certain generators that are located in cortical areas BA 21/37 and BA 22. This suggests that even chord-primed chord targets can convey extra-musical meanings and that, consequently, they might be useful in assessing residual higher-order information-processing capabilities in non-communicating patients with disorders of consciousness.

Vestibulo-cortical Hemispheric Dominance: the link between Anxiety and the Vestibular System?

PubMed

Bednarczuk, Nadja F; Casanovas Ortega, Marta; Fluri, Anne-Sophie; Arshad, Qadeer

2018-05-16

Vestibular processing and anxiety networks are functionally intertwined, as demonstrated by reports of reciprocal influences upon each other. Yet whether there is an underlying link between these two systems remains unknown Previous findings have highlighted the involvement of hemispheric lateralisation in processing of both anxiety and vestibular signals. Accordingly, we explored the interaction between vestibular cortical processing and anxiety by assessing the relationship between anxiety levels and the degree of hemispheric lateralisation of vestibulo-cortical processing in 64 right-handed, healthy individuals. Vestibulo-cortical hemispheric lateralisation was determined by gaging the degree of caloric-induced nystagmus suppression following modulation of cortical excitability using trans-cranial direct current stimulation targeted over the posterior parietal cortex, an area implicated in the processing of vestibular signals. The degree of nystagmus suppression yields an objective biomarker, allowing the quantification of the degree of right vestibulo-cortical hemisphere dominance. Anxiety levels were quantified using the Trait component of the Spielberger State-Trait Anxiety Questionnaire. Our findings demonstrate that the degree of an individual's vestibulo-cortical hemispheric dominance correlates with their anxiety levels. That is, those individuals with greater right hemispheric vestibulo-cortical dominance exhibited lower levels of anxiety. By extension, our results support the notion that hemispheric lateralisation determines an individual's emotional processing, thereby linking cortical circuits involved in processing anxiety and vestibular signals respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Linking sleep and general anesthesia mechanisms: this is no walkover.

PubMed

Bonhomme, V; Boveroux, P; Vanhaudenhuyse, A; Hans, P; Brichant, J F; Jaquet, O; Boly, M; Laureys, S

2011-01-01

This review aims at defining the link between physiological sleep and general anesthesia. Despite common behavioral and electrophysiological characteristics between both states, current literature suggests that the transition process between waking and sleep or anesthesia-induced alteration of consciousness is not driven by the same sequence of events. On the one hand, sleep originates in sub-cortical structures with subsequent repercussions on thalamo-cortical interactions and cortical activity. On the other hand, anesthesia seems to primarily affect the cortex with subsequent repercussions on the activity of sub-cortical networks. This discrepancy has yet to be confirmed by further functional brain imaging and electrophysiological experiments. The relationship between the observed functional modifications of brain activity during anesthesia and the known biochemical targets of hypnotic anesthetic agents also remains to be determined.

Useful signals from motor cortex

PubMed Central

Schwartz, Andrew B

2007-01-01

Historically, the motor cortical function has been explained as a funnel to muscle activation. This invokes the idea that motor cortical neurons, or ‘upper motoneurons’, directly cause muscle contraction just like spinal motoneurons. Thus, the motor cortex and muscle activity are inextricably entwined like a puppet master and his marionette. Recently, this concept has been challenged by current experimentation showing that many behavioural aspects of action are represented in motor cortical activity. Although this activity may still be related to muscle activation, the relation between the two is likely to be indirect and complex, whereas the relation between cortical activity and kinematic parameters is simple and robust. These findings show how to extract useful signals that help explain the underlying process that generates behaviour and to harness these signals for potentially therapeutic applications. PMID:17255162

Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation.

PubMed

Chen, Albert; Yao, Jun; Kuiken, Todd; Dewald, Julius P A

2013-01-01

Previous studies have postulated that the amount of brain reorganization following peripheral injuries may be correlated with negative symptoms or consequences. However, it is unknown whether restoring effective limb function may then be associated with further changes in the expression of this reorganization. Recently, targeted reinnervation (TR), a surgical technique that restores a direct neural connection from amputated sensorimotor nerves to new peripheral targets such as muscle, has been successfully applied to upper-limb amputees. It has been shown to be effective in restoring both peripheral motor and sensory functions via the reinnervated nerves as soon as a few months after the surgery. However, it was unclear whether TR could also restore normal cortical motor representations for control of the missing limb. To answer this question, we used high-density electroencephalography (EEG) to localize cortical activity related to cued motor tasks generated by the intact and missing limb. Using a case study of 3 upper-limb amputees, 2 of whom went through pre and post-TR experiments, we present unique quantitative evidence for the re-mapping of motor representations for the missing limb closer to their original locations following TR. This provides evidence that an effective restoration of peripheral function from TR can be linked to the return of more normal cortical expression for the missing limb. Therefore, cortical mapping may be used as a potential guide for monitoring rehabilitation following peripheral injuries.

Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice.

PubMed

Fonseca, Raquel; Carvalho, Rui A; Lemos, Cristina; Sequeira, Ana C; Pita, Inês R; Carvalho, Fábio; Silva, Carlos D; Prediger, Rui D S; Jarak, Ivana; Cunha, Rodrigo A; Fontes Ribeiro, Carlos A; Köfalvi, Attila; Pereira, Frederico C

2017-02-01

We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown. Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i.p.), and their frontal cortical metabolic status was characterized after probing their mood and anxiety-related phenotypes 3 days postinjection. Methamphetamine induced depressive-like behavior, as indicated by the decreased grooming time in the splash test and by a transient decrease in sucrose preference. At this time, METH did not alter anxiety-like behavior or motor functions. Depolarization-induced glucose uptake was reduced in frontocortical slices from METH-treated mice compared to controls. Consistently, astrocytic glucose transporter (GluT1) density was lower in the METH group. A proton high rotation magic angle spinning (HRMAS) spectroscopic approach revealed that METH induced a significant decrease in N-acetyl aspartate (NAA) and glutamate levels, suggesting that METH decreased neuronal glutamatergic function in frontal cortex. We report, for the first time, that a single METH injection triggers early self-care and hedonic deficits and impairs frontal cortical energetics in mice. © 2016 John Wiley & Sons Ltd.

Measures of Cortical Grey Matter Structure and Development in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Mak-Fan, Kathleen M.; Taylor, Margot J.; Roberts, Wendy; Lerch, Jason P.

2012-01-01

The current study examined group differences in cortical volume, surface area, and thickness with age, in a group of typically developing children and a group of children with ASD aged 6-15 years. Results showed evidence of age by group interactions, suggesting atypicalities in the relation between these measures and age in the ASD group.…

Differential neuroendocrine responses to chronic variable stress in adult Long Evans rats exposed to handling-maternal separation as neonates.

PubMed

Ladd, Charlotte O; Thrivikraman, K V; Huot, Rebecca L; Plotsky, Paul M

2005-07-01

Burgeoning evidence supports a preeminent role for early- and late-life stressors in the development of physio- and psychopathology. Handling-maternal separation (HMS) in neonatal Long Evans hooded rats leads to stable phenotypes ranging from resilient to vulnerable to later stressor exposure. Handling with 180 min of maternal separation yields a phenotype of stress hyper-responsiveness associated with facilitation of regional CRF neurocircuits and glucocorticoid resistance. This study assessed whether or not prolonged HMS (180 min/day, HMS180) on post-natal days 2-14 sensitizes the adult limbic hypothalamo-pituitary-adrenal (LHPA) axis to chronic variable stress (CS) compared to brief HMS (15 min/day, HMS15). We examined regional mRNA densities of corticotropin-releasing factor (CRF), its receptor CRF1, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR); regional CRF1 and CRF2alpha binding, and pituitary-adrenal responses to an acute air-puff startle (APS) stressor in four groups: HMS15, nonstressed; HMS15, stressed; HMS180, nonstressed; HMS180, stressed. As expected we observed exaggerated pituitary-adrenal responses to APS, increased regional CRF mRNA density, decreased regional CRF1 binding, and decreased cortical GR mRNA density in nonstressed HMS180 vs. HMS15 animals. However, in contrast to our hypothesis, CS decreased pituitary-adrenal reactivity and central amygdala CRF mRNA density in HMS180 rats, while increasing cortical GR mRNA density and CRF1 binding. CS had no effect on the pituitary-adrenal response to APS in HMS15 rats, despite tripling hypothalamic paraventricular CRF mRNA density. The data suggest that many effects of prolonged HMS are reversible in adulthood by CS, while the neuroendocrine adaptations imbued by brief HMS are sufficiently stable to restrain pituitary-adrenal stress responses even following CS.

Hyperlipidemia affects multiscale structure and strength of murine femur.

PubMed

Ascenzi, Maria-Grazia; Lutz, Andre; Du, Xia; Klimecky, Laureen; Kawas, Neal; Hourany, Talia; Jahng, Joelle; Chin, Jesse; Tintut, Yin; Nackenhors, Udo; Keyak, Joyce

2014-07-18

To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because (i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone׳s micro-structural strength; and, (ii) hyperlipidemia affects collagen orientation and μCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr(-/-), a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups and that microindentation results strongly correlate with elastic modulus of collagen-density models (r(2)=0.85, p=10(-5)). Collagen-density models yielded (1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and (2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta.

PubMed

Albert, Carolyne; Jameson, John; Tarima, Sergey; Smith, Peter; Harris, Gerald

2017-11-07

Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32-65% lower in the OI group (p<0.001). Yield strain did not differ between groups (p≥0.197). In both groups, modulus and strength were lower in the transverse direction (p≤0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p<0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p=0.086). Volumetric bone mineral density was lower in the OI group (p<0.001), but volumetric tissue mineral density was not (p=0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p≤0.024) but not volumetric tissue mineral density (p≥0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

PubMed

Canali, Paola; Sferrazza Papa, Giovanna; Casali, Adenauer G; Schiena, Giandomenico; Fecchio, Matteo; Pigorini, Andrea; Smeraldi, Enrico; Colombo, Cristina; Benedetti, Francesco

2014-12-01

It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Histological Evaluation of a Chronically-implanted Electrocorticographic Electrode Grid in a Non-human Primate

PubMed Central

Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

2016-01-01

Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically-implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. We implanted a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 days. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically-viable brain-machine interface systems. PMID:27351722

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate

NASA Astrophysics Data System (ADS)

Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

2016-08-01

Objective. Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. Approach. We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. Main results. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. Significance. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

Neuroelectrical Correlates of Trustworthiness and Dominance Judgments Related to the Observation of Political Candidates

PubMed Central

Vecchiato, Giovanni; Toppi, Jlenia; Maglione, Anton Giulio; Olejarczyk, Elzbieta; Astolfi, Laura; Mattia, Donatella; Colosimo, Alfredo; Babiloni, Fabio

2014-01-01

The present research investigates the neurophysiological activity elicited by fast observations of faces of real candidates during simulated political elections. We used simultaneous recording of electroencephalographic (EEG) signals as well as galvanic skin response (GSR) and heart rate (HR) as measurements of central and autonomic nervous systems. Twenty healthy subjects were asked to give judgments on dominance, trustworthiness, and a preference of vote related to the politicians' faces. We used high-resolution EEG techniques to map statistical differences of power spectral density (PSD) cortical activity onto a realistic head model as well as partial directed coherence (PDC) and graph theory metrics to estimate the functional connectivity networks and investigate the role of cortical regions of interest (ROIs). Behavioral results revealed that judgment of dominance trait is the most predictive of the outcome of the simulated elections. Statistical comparisons related to PSD and PDC values highlighted an asymmetry in the activation of frontal cortical areas associated with the valence of the judged trait as well as to the probability to cast the vote. Overall, our results highlight the existence of cortical EEG features which are correlated with the prediction of vote and with the judgment of trustworthy and dominant faces. PMID:25214884

Elastic properties of external cortical bone in the craniofacial skeleton of the rhesus monkey.

PubMed

Wang, Qian; Dechow, Paul C

2006-11-01

Knowledge of elastic properties and of their variation in the cortical bone of the craniofacial skeleton is indispensable for creating accurate finite-element models to explore the biomechanics and adaptation of the skull in primates. In this study, we measured elastic properties of the external cortex of the rhesus monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight cylindrical cortical specimens were removed from each of six craniofacial skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal and transverse ultrasonic velocities were measured on each specimen to allow calculation of the elastic properties in three dimensions, according to equations derived from Newton's second law and Hooke's law. The axes of maximum stiffness were determined by fitting longitudinal velocities measured along the perimeter of each cortical specimen to a sinusoidal function. Results showed significant differences in elastic properties between different functional areas of the rhesus cranium, and that many sites have a consistent orientation of maximum stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull can be modeled as orthotropic in many regions, and as transversely isotropic in some regions, e.g., the supraorbital region. There are differences from human crania, suggesting that structural differences in skeletal form relate to differences in cortical material properties across species. These differences also suggest that we require more comparative data on elastic properties in primate craniofacial skeletons to explore effectively the functional significance of these differences, especially when these differences are elucidated through modeling approaches, such as finite-element modeling. (c) 2006 Wiley-Liss, Inc.

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chalmers, D.T.; Dewar, D.; Graham, D.I.

1990-02-01

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-(3H)aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. (3H)Kainate receptor binding was significantly increased bymore » approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-(3H)methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive (3H)glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. (3H)Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others.« less

Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa.

PubMed

DiVasta, A D; Feldman, H A; O'Donnell, J M; Long, J; Leonard, M B; Gordon, C M

2016-12-01

We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA. Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN. Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures. Trabecular vBMD Z-scores were lower in AN compared to controls (AN -0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs -0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57-0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all). This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study.

Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa

PubMed Central

DiVasta, A. D.; Feldman, H. A.; O’Donnell, J. M.; Long, J.; Leonard, M. B.; Gordon, C. M.

2018-01-01

Summary We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA. Introduction Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN. Methods Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures. Results Trabecular vBMD Z-scores were lower in AN compared to controls (AN −0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs −0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57–0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all). Conclusions This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study. PMID:27392467

Sost deficiency does not alter bone's lacunar or vascular porosity in mice

NASA Astrophysics Data System (ADS)

Mosey, Henry; Núñez, Juan A.; Goring, Alice; Clarkin, Claire E.; Staines, Katherine A.; Lee, Peter D.; Pitsillides, Andrew A.; Javaheri, Behzad

2017-09-01

SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation and activity. Recent in vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the mechanisms responsible for SCLEROSTIN action, no previous studies have examined whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT) counterparts with high resolution CT to examine whether lack of SCLEROSTIN influences the morphometric properties of lacunae and vascular canal porosity relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice (n = 6 /group) were sacrificed at 12 weeks of age. Fixed tibiae were analysed using microCT to examine cortical bone mass and architecture. Then, samples were imaged by using benchtop and synchrotron nanoCT at the tibiofibular junction. Our data, consistent with previous studies show that, Sost deficiency leads to significant enhancement of bone mass by cortical thickening and bigger cross-sectional area and we find that this occurs without modifications of tibial ellipticity, a measure of bone shape. In addition, our data show that there are no significant differences in any lacunar or vascular morphometric or geometric parameters between Sost KO mouse tibia and WT counterparts. We therefore conclude that the significant increases in bone mass induced by Sost deficiency are not accompanied by any significant modification in the density, organisation or shape of osteocyte lacunae or vascular content within the cortical bone. These data may imply that SCLEROSTIN does not modify the frequency of osteocytogenic recruitment of osteoblasts to initiate terminal osteocytic differentiation in mice.

Saturation in Phosphene Size with Increasing Current Levels Delivered to Human Visual Cortex.

PubMed

Bosking, William H; Sun, Ping; Ozker, Muge; Pei, Xiaomei; Foster, Brett L; Beauchamp, Michael S; Yoshor, Daniel

2017-07-26

Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. SIGNIFICANCE STATEMENT Understanding the neural basis for phosphenes, the visual percepts created by electrical stimulation of visual cortex, is fundamental to the development of a visual cortical prosthetic. Our experiments in human subjects implanted with electrodes over visual cortex show that it is the activity of a large population of cells spread out across several millimeters of tissue that supports the perception of a phosphene. In addition, we describe an important feature of the production of phosphenes by electrical stimulation: phosphene size saturates at a relatively low current level. This finding implies that, with current methods, visual prosthetics will have a limited dynamic range available to control the production of spatial forms and that more advanced stimulation methods may be required. Copyright © 2017 the authors 0270-6474/17/377188-10$15.00/0.

Cortical Thickness Changes and Their Relationship to Dual-Task Performance following Mild Traumatic Brain Injury in Youth.

PubMed

Urban, Karolina J; Riggs, Lily; Wells, Greg D; Keightley, Michelle; Chen, Jen-Kai; Ptito, Alain; Fait, Philippe; Taha, Tim; Sinopoli, Katia J

2017-02-15

Mild traumatic brain injury (mTBI) is common in youth, especially in those who participate in sport. Recent investigations from our group have shown that asymptomatic children and adolescents with mTBI continue to exhibit alterations in neural activity and cognitive performance compared with those without a history of mTBI. This is an intriguing finding, given that current return-to-learn and return-to-play protocols rely predominately on subjective symptom reports, which may not be sensitive enough to detect subtle injury-related changes. As a result, youth may be at greater risk for re-injury and long-term consequences if they are cleared for activity while their brains continue to be compromised. It is currently unknown whether mTBI also affects brain microstructure in the developing brain, particularly cortical thickness, and whether such changes are also related to cognitive performance. The present study examined cortical thickness in 13 asymptomatic youth (10-14 years old) who had sustained an mTBI 3-8 months prior to testing compared with 14 age-matched typically developing controls. Cortical thickness was also examined in relation to working memory performance during single and dual task paradigms. The results show that youth who had sustained an mTBI had thinner cortices in the left dorsolateral prefrontal region and right anterior and posterior inferior parietal lobes. Additionally, cortical thinning was associated with slower reaction time during the dual-task condition in the injured youth only. The results also point to a possible relationship between functional and structural alterations as a result of mTBI in youth, and lend evidence for neural changes beyond symptom resolution.

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity.

PubMed

Osima, Marit; Kral, Rita; Borgen, Tove T; Høgestøl, Ingvild K; Joakimsen, Ragnar M; Eriksen, Erik F; Bjørnerem, Åshild

2017-04-01

Increased cortical porosity has been suggested as a possible factor increasing fracture propensity in patients with type 2 diabetes mellitus (T2DM). This is a paradox because cortical porosity is generally associated with high bone turnover, while bone turnover is reduced in patients with T2DM. We therefore wanted to test the hypothesis that women with T2DM have lower bone turnover markers (BTM) and lower cortical porosity than those without diabetes, and that higher serum glucose and body mass index (BMI) are associated with lower BTM, and with lower cortical porosity. This cross-sectional study is based on a prior nested case-control study including 443 postmenopausal women aged 54-94years from the Tromsø Study, 211 with non-vertebral fracture and 232 fracture-free controls. Of those 443 participants, 22 women exhibited T2DM and 421 women did not have diabetes. All had fasting blood samples assayed for procollagen type I N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX) and glucose, and femoral subtrochanteric architecture was quantified using low-resolution clinical CT and StrAx1.0 software. Women with T2DM had higher serum glucose (7.2 vs. 5.3mmol/L), BMI (29.0 vs. 26.4kg/m 2 ), and higher femoral subtrochanteric total volumetric bone mineral density (vBMD) (783 vs. 715mgHA/cm 3 ), but lower cortical porosity (40.9 vs. 42.8%) than nondiabetic women (all p<0.05). Each standard deviation (SD) increment in glucose was associated with 0.10-0.12 SD lower PINP and CTX, and 0.13 SD lower cortical porosity (all p<0.05). Each SD increment in BMI was associated with 0.10-0.18 SD lower serum PINP and CTX, and 0.19 SD thicker cortices (all p<0.05). Increasing glucose and BMI were associated with lower bone turnover suggesting that reduced intracortical and endocortical remodeling leads to reduced porosity and thicker cortices. Using low-resolution clinical CT, cortical porosity was lower in women with T2DM compared to women without diabetes. This indicates that other changes in bone qualities, not increased cortical porosity, are likely to explain the increased fracture propensity in patients with T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

Intra- and interregional cortical interactions related to sharp-wave ripples and dentate spikes.

PubMed

Headley, Drew B; Kanta, Vasiliki; Paré, Denis

2017-02-01

The hippocampus generates population events termed sharp-wave ripples (SWRs) and dentate spikes (DSs). While little is known about DSs, SWR-related hippocampal discharges during sleep are thought to replay prior waking activity, reactivating the cortical networks that encoded the initial experience. During slow-wave sleep, such reactivations likely occur during up-states, when most cortical neurons are depolarized. However, most studies have examined the relationship between SWRs and up-states measured in single neocortical regions. As a result, it is currently unclear whether SWRs are associated with particular patterns of widely distributed cortical activity. Additionally, no such investigation has been carried out for DSs. The present study addressed these questions by recording SWRs and DSs from the dorsal hippocampus simultaneously with prefrontal, sensory (visual and auditory), perirhinal, and entorhinal cortices in naturally sleeping rats. We found that SWRs and DSs were associated with up-states in all cortical regions. Up-states coinciding with DSs and SWRs exhibited increased unit activity, power in the gamma band, and intraregional gamma coherence. Unexpectedly, interregional gamma coherence rose much more strongly in relation to DSs than to SWRs. Whereas the increase in gamma coherence was time locked to DSs, that seen in relation to SWRs was not. These observations suggest that SWRs are related to the strength of up-state activation within individual regions throughout the neocortex but not so much to gamma coherence between different regions. Perhaps more importantly, DSs coincided with stronger periods of interregional gamma coherence, suggesting that they play a more important role than previously assumed. Off-line cortico-hippocampal interactions are thought to support memory consolidation. We surveyed the relationship between hippocampal sharp-wave ripples (SWRs) and dentate spikes (DSs) with up-states across multiple cortical regions. SWRs and DSs were associated with increased cortical gamma oscillations. Interregional gamma coherence rose much more strongly in relation to DSs than to SWRs. Moreover, it was time locked to DSs but not SWRs. These results have important implications for current theories of systems memory consolidation during sleep. Copyright © 2017 the American Physiological Society.

A fuzzy system for helping medical diagnosis of malformations of cortical development.

PubMed

Alayón, Silvia; Robertson, Richard; Warfield, Simon K; Ruiz-Alzola, Juan

2007-06-01

Malformations of the cerebral cortex are recognized as a common cause of developmental delay, neurological deficits, mental retardation and epilepsy. Currently, the diagnosis of cerebral cortical malformations is based on a subjective interpretation of neuroimaging characteristics of the cerebral gray matter and underlying white matter. There is no automated system for aiding the observer in making the diagnosis of a cortical malformation. In this paper a fuzzy rule-based system is proposed as a solution for this problem. The system collects the available expert knowledge about cortical malformations and assists the medical observer in arriving at a correct diagnosis. Moreover, the system allows the study of the influence of the various factors that take part in the decision. The evaluation of the system has been carried out by comparing the automated diagnostic algorithm with known case examples of various malformations due to abnormal cortical organization. An exhaustive evaluation of the system by comparison with published cases and a ROC analysis is presented in the paper.

A Fuzzy System for Helping Medical Diagnosis of Malformations of Cortical Development

PubMed Central

Alayón, Silvia; Robertson, Richard; Warfield, Simon K.; Ruiz-Alzola, Juan

2007-01-01

Malformations of the cerebral cortex are recognized as a common cause of developmental delay, neurological deficits, mental retardation and epilepsy. Currently, the diagnosis of cerebral cortical malformations is based on a subjective interpretation of neuroimaging characteristics of the cerebral gray matter and underlying white matter. There is no automated system for aiding the observer in making the diagnosis of a cortical malformation. In this paper a fuzzy rule-based system is proposed as a solution for this problem. The system collects the available expert knowledge about cortical malformations and assists the medical observer in arriving at a correct diagnosis. Moreover, the system allows the study of the influence of the various factors that take part in the decision. The evaluation of the system has been carried out by comparing the automated diagnostic algorithm with known case examples of various malformations due to abnormal cortical organization. An exhaustive evaluation of the system by comparison with published cases and a ROC analysis is presented in the paper. PMID:17197247

Neurogliaform cortical interneurons derive from cells in the preoptic area

PubMed Central

Cadilhac, Christelle; Prados, Julien; Holtmaat, Anthony

2018-01-01

Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3AR-expressing Hmx3+ cells located in the preoptic area (POA). Hmx3-derived 5-HT3AR+ cortical interneurons (INs) expressed the transcription factors PROX1, NR2F2, the marker reelin but not VIP and exhibited the molecular, morphological and electrophysiological profile of NGCs. Overall, these results indicate that NGCs are a distinct class of INs with a unique developmental trajectory and open the possibility to study their specific functional contribution to cortical inhibitory microcircuit motifs. PMID:29557780

Lipids and collagen matrix restrict the hydraulic permeability within the porous compartment of adult cortical bone

PubMed Central

Wen, Demin; Androjna, Caroline; Vasanji, Amit; Belovich, Joanne; Midura, Ronald J.

2010-01-01

In vivo the hydraulic permeability of cortical bone influences the transport of nutrients, waste products and signaling molecules, thus influencing the metabolic functions of osteocytes and osteoblasts. In the current study two hypotheses were tested: the presence of (1) lipids and (2) collagen matrix in the porous compartment of cortical bone restricts its permeability. Our approach was to measure the radial permeability of adult canine cortical bone before and after extracting lipids with acetone-methanol, and before and after digesting collagen with bacterial collagenase. Our results showed that the permeability of adult canine cortical bone was below 4.0 × 10−17 m2, a value consistent with prior knowledge. After extracting lipids, permeability increased to a median value of 8.6 × 10−16 m2. After further digesting with collagenase, permeability increased to a median value of 1.4 × 10−14 m2. We conclude that the presence of both lipids and collagen matrix within the porous compartment of cortical bone restricts its radial permeability. These novel findings suggest that the chemical composition of the tissue matrix within the porous compartment of cortical bone influences the transport and exchange of nutrients and waste products, and possibly influences the metabolic functions of osteocytes and osteoblasts. PMID:19967451

Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

PubMed

Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

2015-01-22

Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms

PubMed Central

Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

2016-01-01

Study Objectives: Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). Methods: The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Results: Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Conclusion: Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. Citation: Suh S, Kim H, Dang-Vu TT, Joo E, Shin C. Cortical thinning and altered cortico-cortical structural covariance of the default mode network in patients with persistent insomnia symptoms. SLEEP 2016;39(1):161–171. PMID:26414892

Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine.

PubMed

Barker, Anthony T; Shields, Kevin

2017-03-01

Transcranial magnetic stimulation (TMS) is a neurophysiological technique with a long established pedigree of safety, tolerability, and efficacy. Initially TMS was used to study the function of the cerebral cortex, but it has now become a treatment for migraine, one of the most common and debilitating neurological conditions. In this review we discuss the scientific background and development of the technique. We explore its application for the treatment of migraine and ponder the possible mechanisms of action in this most common neurological condition. The generation of brief magnetic pulses by a suitable coil can induce electrical fields in the body. When applied to the cerebral cortex, currents are painlessly induced in cortical neurons. These currents can lead to neuronal depolarization and may influence cortical excitability by means that are as yet not fully understood. This ability to modulate cortical excitability has been exploited as a treatment for migraine with aura. Aura is implicated in the pathophysiology of migraine. Experimental studies have shown that transcranial magnetic pulses can block waves of cortical spreading depression - the experimental equivalent of migrainous aura. Migraine is a debilitating condition characterized by headache, nausea, and sensory hypersensitivity. It may affect up to 15% of the population, yet current drug treatments are often poorly tolerated. Clinical studies have shown that TMS is an effective treatment for migraine. In addition, it has the added advantages of being safe and well tolerated by patients. © 2016 American Headache Society.

sec-Butylpropylacetamide (SPD) has antimigraine properties

PubMed Central

Kaufmann, Dan; Bates, Emily A; Yagen, Boris; Bialer, Meir; Saunders, Gerald H; Wilcox, Karen; White, H Steve; Brennan, KC

2016-01-01

Background Though migraine is disabling and affects 12%–15% of the population, there are few drugs that have been developed specifically for migraine prevention. Valproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that is also used for migraine prophylaxis, but its clinical use is limited by its side effect profile. sec-Butylpropylacetamide (SPD) is a novel VPA derivative, designed to be more potent and tolerable than VPA, that has shown efficacy in animal seizure and pain models. Methods We evaluated SPD’s antimigraine potential in the cortical spreading depression (CSD) and nitroglycerin (NTG) models of migraine. To evaluate SPD’s mechanism of action, we performed whole-cell recordings on cultured cortical neurons and neuroblastoma cells. Results In the CSD model, the SPD-treated group showed a significantly lower median number of CSDs compared to controls. In the NTG-induced mechanical allodynia model, SPD dose-dependently reduced mechanical sensitivity compared to controls. SPD showed both a significant potentiation of GABA-mediated currents and a smaller but significant decrease in NMDA currents in cultured cortical neurons. Kainic acid-evoked currents and voltage-dependent sodium channel currents were not changed by SPD. Conclusions These results demonstrate SPD’s potential as a promising novel antimigraine compound, and suggest a GABAergic mechanism of action. PMID:26568161

PET-Based Confirmation of Orientation Sensitivity of TMS-Induced Cortical Activation in Humans

PubMed Central

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2017-01-01

Background Currently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks. Objective/hypothesis To more thoroughly investigate this inconsistency, we sought to determine whether neocortical surface orientation was a critical determinant of regional activation. Methods MR images were used to construct cortical and scalp surfaces for 18 subjects. The angle (θ) between the cortical surface normal and its nearest scalp normal for ~50,000 cortical points per subject was used to quantify cortical location (i.e., gyral vs. sulcal). TMS-induced activations of primary motor cortex (M1) were compared to brain activations recorded during a finger-tapping task using concurrent positron emission tomographic (PET) imaging. Results Brain activations were primarily sulcal for both the TMS and task activations (P < 0.001 for both) compared to the overall cortical surface orientation. Also, the location of maximal blood flow in response to either TMS or finger-tapping correlated well using the cortical surface orientation angle or distance to scalp (P < 0.001 for both) as criteria for comparison between different neocortical activation modalities. Conclusion This study provides further evidence that a major factor in cortical activation using TMS is the orientation of the cortical surface with respect to the induced electric field. The results show that, despite the gyral crown of the cortex being subjected to a larger magnetic field magnitude, the sulcal bank of M1 had larger cerebral blood flow (CBF) responses during TMS. PMID:23827648

[Origin of cortical interneurons: basic concepts and clinical implications].

PubMed

Marín, O

Introduction and development. GABAergic interneurons play a prominent role in the function of the cerebral cortex, since they allow the synchronization of pyramidal neurons and greatly influence their differentiation and maturation during development. Until recently it has been thought that cortical interneurons and pyramidal neurons originate from progenitor cells located in the dorsal region of the telencephalon, the pallium. Recent studies, however, have demonstrated that a large number of cortical GABAergic neurons arise from progenitors located in the subpallium the region of the telencephalon that gives rise to the basal ganglia, and that they arise in the cerebral cortex after a long tangential migration. Aims. In this review I have summarized our current knowledge of the factors that control the specification of cortical interneurons, as well as the mechanisms that direct their migration to the cortex.

Cortical Thickness Reduction in Combat Exposed U.S. Veterans with and without PTSD

PubMed Central

Wrocklage, Kristen M.; Averill, Lynnette A.; Scott, J. Cobb; Averill, Christopher L.; Schweinsburg, Brian; Trejo, Marcia; Roy, Alicia; Weisser, Valerie; Kelly, Christopher; Martini, Brenda; Harpaz-Rotem, Ilan; Southwick, Steven M.; Krystal, John H.; Abdallah, Chadi G.

2017-01-01

We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Veterans completed high-resolution magnetic resonance imaging (MRI) scans to estimate cortical thickness. The Clinician Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES) assessments were completed to measure current PTSD and historical combat severity, respectively. PTSD symptom dimensions (numbing, avoidance, reexperiencing, anxious arousal, and dysphoric arousal) were studied. Vertex-wise whole cerebrum analyses were conducted. We found widespread negative correlations between CAPS severity and cortical thickness, particularly within the prefrontal cortex. This prefrontal correlation remained significant after controlling for depression severity, medication status, and other potential confounds. PTSD dimensions, except anxious arousal, negatively correlated with cortical thickness in various unique brain regions. CES negatively correlated with cortical thickness in the left lateral prefrontal, regardless of PTSD diagnosis. A significant interaction between CES and PTSD diagnosis was found, such that CES negatively correlated with cortical thickness in the non-PTSD, but not in the PTSD, participants. The results underscore the severity of cortical thinning in U.S. Veterans suffering from high level of PTSD symptoms, as well as in Veterans with no PTSD diagnosis but severe combat exposure. The latter finding raises considerable concerns about a concealed injury potentially related to combat exposure in the post-9/11 era. PMID:28279623

Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD.

PubMed

Wrocklage, Kristen M; Averill, Lynnette A; Cobb Scott, J; Averill, Christopher L; Schweinsburg, Brian; Trejo, Marcia; Roy, Alicia; Weisser, Valerie; Kelly, Christopher; Martini, Brenda; Harpaz-Rotem, Ilan; Southwick, Steven M; Krystal, John H; Abdallah, Chadi G

2017-05-01

We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Veterans completed high-resolution magnetic resonance imaging (MRI) scans to estimate cortical thickness. The Clinician Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES) assessments were completed to measure current PTSD and historical combat severity, respectively. PTSD symptom dimensions (numbing, avoidance, reexperiencing, anxious arousal, and dysphoric arousal) were studied. Vertex-wise whole cerebrum analyses were conducted. We found widespread negative correlations between CAPS severity and cortical thickness, particularly within the prefrontal cortex. This prefrontal correlation remained significant after controlling for depression severity, medication status, and other potential confounds. PTSD dimensions, except anxious arousal, negatively correlated with cortical thickness in various unique brain regions. CES negatively correlated with cortical thickness in the left lateral prefrontal, regardless of PTSD diagnosis. A significant interaction between CES and PTSD diagnosis was found, such that CES negatively correlated with cortical thickness in the non-PTSD, but not in the PTSD, participants. The results underscore the severity of cortical thinning in U.S. Veterans suffering from high level of PTSD symptoms, as well as in Veterans with no PTSD diagnosis but severe combat exposure. The latter finding raises considerable concerns about a concealed injury potentially related to combat exposure in the post-9/11 era. Published by Elsevier B.V.

Cortical and subcortical abnormalities in youths with conduct disorder and elevated callous-unemotional traits.

PubMed

Wallace, Gregory L; White, Stuart F; Robustelli, Briana; Sinclair, Stephen; Hwang, Soonjo; Martin, Alex; Blair, R James R

2014-04-01

Although there is growing evidence of brain abnormalities among individuals with conduct disorder (CD), the structural neuroimaging literature is mixed and frequently aggregates cortical volume rather than differentiating cortical thickness from surface area. The current study assesses CD-related differences in cortical thickness, surface area, and gyrification as well as volume differences in subcortical structures critical to neurodevelopmental models of CD (amygdala; striatum) in a carefully characterized sample. We also examined whether group structural differences were related to severity of callous-unemotional (CU) traits in the CD sample. Participants were 49 community adolescents aged 10 to 18 years, 22 with CD and 27 healthy comparison youth. Structural MRI was collected and the FreeSurfer image analysis suite was used to provide measures of cortical thickness, surface area, and local gyrification as well as subcortical (amygdala and striatum) volumes. Youths with CD showed reduced cortical thickness in the superior temporal cortex. There were also indications of reduced gyrification in the ventromedial frontal cortex, particularly for youths with CD without comorbid attention-deficit/hyperactivity disorder. There were no group differences in cortical surface area. However, youths with CD also showed reduced amygdala and striatum (putamen and pallidum) volumes. Right temporal cortical thickness was significantly inversely related to severity of CU traits. Youths with CD show reduced cortical thickness within superior temporal regions, some indication of reduced gyrification within ventromedial frontal cortex and reduced amygdala and striatum (putamen and pallidum) volumes. These results are discussed with reference to neurobiological models of CD. Published by Elsevier Inc.

Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction.

PubMed

Jiang, T; Xu, R X; Zhang, A W; Di, W; Xiao, Z J; Miao, J Y; Luo, N; Fang, Y N

2012-12-13

The aim of this study was to investigate the effects of transcranial direct current stimulation (TDCS) on hemichannel pannexin-1 (PX1) in cortical neurons and neural plasticity, and explore the optimal time window of TDCS therapy after stroke. Adult male Sprague-Dawley rats (n=90) were randomly assigned to sham operation, middle cerebral artery occlusion (MCAO), and TDCS groups, and underwent sham operation, unilateral middle cerebral artery (MCA) electrocoagulation, and unilateral MCA electrocoagulation plus TDCS (daily anodal and cathodal 10 Hz, 0.1 mA TDCS for 30 min beginning day 1 after stroke), respectively. Motor function was assessed using the beam walking test (BWT), and density of dendritic spines (DS) and PX1 mRNA expression were compared among groups on days 3, 7, and 14 after stroke. Effects of PX1 blockage on DS in hippocampal neurons after hypoxia-ischemia were observed. TDCS significantly improved motor function on days 7 and 14 after stroke as indicated by reduced BWT scores compared with the MCAO group. The density of DS was decreased after stroke; the TDCS group had increased DS density compared with the MCAO group on days 3, 7, and 14 (all P<0.0001). Cerebral infarction induced increased PX1 mRNA expression on days 3, 7, and 14 (P<0.0001), and the peak PX1 mRNA expression was observed on day 7. TDCS did not decrease the up-regulated PX1 mRNA expression after stroke on day 3, but did reduce the increased post-stroke PX1 mRNA expression on days 7 and 14 (P<0.0001). TDCS increased the DS density after stroke, indicating that it may promote neural plasticity after stroke. TDCS intervention from day 7 to day 14 after stroke demonstrated motor function improvement and can down-regulate the elevated PX1 mRNA expression after stroke. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex.

PubMed

Berns, Gregory S; Moore, Sara; Capra, C Monica

2009-08-26

Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60). The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness

PubMed Central

Russell, Theron A.; Blizinsky, Katherine D.; Cobia, Derin J.; Cahill, Michael; Xie, Zhong; Sweet, Robert A.; Duan, Jubao; Gejman, Pablo V.; Wang, Lei; Csernansky, John G.; Penzes, Peter

2014-01-01

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability catalyze the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homolog of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex. PMID:25224588

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness.

PubMed

Russell, Theron A; Blizinsky, Katherine D; Cobia, Derin J; Cahill, Michael E; Xie, Zhong; Sweet, Robert A; Duan, Jubao; Gejman, Pablo V; Wang, Lei; Csernansky, John G; Penzes, Peter

2014-09-16

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability to catalyse the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homologue of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex.

Common molecular basis of the sentence comprehension network revealed by neurotransmitter receptor fingerprints.

PubMed

Zilles, Karl; Bacha-Trams, Maraike; Palomero-Gallagher, Nicola; Amunts, Katrin; Friederici, Angela D

2015-02-01

The language network is a well-defined large-scale neural network of anatomically and functionally interacting cortical areas. The successful language process requires the transmission of information between these areas. Since neurotransmitter receptors are key molecules of information processing, we hypothesized that cortical areas which are part of the same functional language network may show highly similar multireceptor expression pattern ("receptor fingerprint"), whereas those that are not part of this network should have different fingerprints. Here we demonstrate that the relation between the densities of 15 different excitatory, inhibitory and modulatory receptors in eight language-related areas are highly similar and differ considerably from those of 18 other brain regions not directly involved in language processing. Thus, the fingerprints of all cortical areas underlying a large-scale cognitive domain such as language is a characteristic, functionally relevant feature of this network and an important prerequisite for the underlying neuronal processes of language functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Common molecular basis of the sentence comprehension network revealed by neurotransmitter receptor fingerprints

PubMed Central

Zilles, Karl; Bacha-Trams, Maraike; Palomero-Gallagher, Nicola; Amunts, Katrin; Friederici, Angela D.

2015-01-01

The language network is a well-defined large-scale neural network of anatomically and functionally interacting cortical areas. The successful language process requires the transmission of information between these areas. Since neurotransmitter receptors are key molecules of information processing, we hypothesized that cortical areas which are part of the same functional language network may show highly similar multireceptor expression pattern (“receptor fingerprint”), whereas those that are not part of this network should have different fingerprints. Here we demonstrate that the relation between the densities of 15 different excitatory, inhibitory and modulatory receptors in eight language-related areas are highly similar and differ considerably from those of 18 other brain regions not directly involved in language processing. Thus, the fingerprints of all cortical areas underlying a large-scale cognitive domain such as language is a characteristic, functionally relevant feature of this network and an important prerequisite for the underlying neuronal processes of language functions. PMID:25243991

In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.

PubMed

Buijs, Mathijs; Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; van Lew, Baldur; Milles, Julien; van der Grond, Jeroen; van Buchem, Mark A

2017-05-01

Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation.

PubMed

Ferreira-Marques, Marisa; Aveleira, Célia A; Carmo-Silva, Sara; Botelho, Mariana; Pereira de Almeida, Luís; Cavadas, Cláudia

2016-07-01

Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process.

Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation

PubMed Central

Carmo-Silva, Sara; Botelho, Mariana; de Almeida, Luís Pereira; Cavadas, Cláudia

2016-01-01

Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process. PMID:27441412

Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain

PubMed Central

You, Jiang; Volkow, Nora D.; Park, Kicheon; Zhang, Qiujia; Clare, Kevin; Du, Congwu

2017-01-01

Occurrence of transient ischemic attacks (TIA) and cerebral strokes is a recognized risk associated with cocaine abuse. Here, we use a rodent model along with optical imaging to study cocaine-induced TIA and the associated dynamic changes in cerebral blood flow velocity (CBFv) and cerebrovasculature. We show that chronic cocaine exposure in mice resulted in marked cortical hypoperfusion, in significant arterial and venous vasoconstriction, and in a sensitized vascular response to an acute cocaine injection. Starting after 10 days of exposure, an acute cocaine challenge to these mice resulted in a TIA, which presented as hemiparalysis and was associated with an abrupt exacerbation of CBFv. The severity of the TIA correlated with the decreases in cortical CBFv such that the greater the decreases in flow, the longer the TIA duration. The severity of TIA peaked around 17–22 days of cocaine exposure and decreased thereafter in parallel to a reorganization of CBFv from superficial to deep cortical layers, along with an increase in vessel density into these layers. Here, we document for the first time to our knowledge evidence of a TIA in an animal model of chronic cocaine exposure that was associated with profound decreases in CBFv, and we revealed that while the severity of the TIA initially increased with repeated exposures, it subsequently improved in parallel to an increase in the vessel density. This suggests that strategies to accelerate cerebrovascular recovery might be therapeutically beneficial in cocaine abusers. PMID:28289715

Regulation of microglial development: a novel role for thyroid hormone.

PubMed

Lima, F R; Gervais, A; Colin, C; Izembart, M; Neto, V M; Mallat, M

2001-03-15

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

Recovery of directed intracortical connectivity from fMRI data

NASA Astrophysics Data System (ADS)

Gilson, Matthieu; Ritter, Petra; Deco, Gustavo

2016-06-01

The brain exhibits complex spatio-temporal patterns of activity. In particular, its baseline activity at rest has a specific structure: imaging techniques (e.g., fMRI, EEG and MEG) show that cortical areas experience correlated fluctuations, which is referred to as functional connectivity (FC). The present study relies on our recently developed model in which intracortical white-matter connections shape noise-driven fluctuations to reproduce FC observed in experimental data (here fMRI BOLD signal). Here noise has a functional role and represents the variability of neural activity. The model also incorporates anatomical information obtained using diffusion tensor imaging (DTI), which estimates the density of white-matter fibers (structural connectivity, SC). After optimization to match empirical FC, the model provides an estimation of the efficacies of these fibers, which we call effective connectivity (EC). EC differs from SC, as EC not only accounts for the density of neural fibers, but also the concentration of synapses formed at their end, the type of neurotransmitters associated and the excitability of target neural populations. In summary, the model combines anatomical SC and activity FC to evaluate what drives the neural dynamics, embodied in EC. EC can then be analyzed using graph theory to understand how it generates FC and to seek for functional communities among cortical areas (parcellation of 68 areas). We find that intracortical connections are not symmetric, which affects the dynamic range of cortical activity (i.e., variety of states it can exhibit).

Effect of Denosumab on Peripheral Compartmental Bone Density, Microarchitecture and Estimated Bone Strength in De Novo Kidney Transplant Recipients.

PubMed

Bonani, Marco; Meyer, Ursina; Frey, Diana; Graf, Nicole; Bischoff-Ferrari, Heike A; Wüthrich, Rudolf P

2016-01-01

In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14). Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336). These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis. © 2016 The Author(s) Published by S. Karger AG, Basel.

Characterizing the Spatial Density Functions of Neural Arbors

NASA Astrophysics Data System (ADS)

Teeter, Corinne Michelle

Recently, it has been proposed that a universal function describes the way in which all arbors (axons and dendrites) spread their branches over space. Data from fish retinal ganglion cells as well as cortical and hippocampal arbors from mouse, rat, cat, monkey and human provide evidence that all arbor density functions (adf) can be described by a Gaussian function truncated at approximately two standard deviations. A Gaussian density function implies that there is a minimal set of parameters needed to describe an adf: two or three standard deviations (depending on the dimensionality of the arbor) and an amplitude. However, the parameters needed to completely describe an adf could be further constrained by a scaling law found between the product of the standard deviations and the amplitude of the function. In the following document, I examine the scaling law relationship in order to determine the minimal set of parameters needed to describe an adf. First, I find that the at, two-dimensional arbors of fish retinal ganglion cells require only two out of the three fundamental parameters to completely describe their density functions. Second, the three-dimensional, volume filling, cortical arbors require four fundamental parameters: three standard deviations and the total length of an arbor (which corresponds to the amplitude of the function). Next, I characterize the shape of arbors in the context of the fundamental parameters. I show that the parameter distributions of the fish retinal ganglion cells are largely homogenous. In general, axons are bigger and less dense than dendrites; however, they are similarly shaped. The parameter distributions of these two arbor types overlap and, therefore, can only be differentiated from one another probabilistically based on their adfs. Despite artifacts in the cortical arbor data, different types of arbors (apical dendrites, non-apical dendrites, and axons) can generally be differentiated based on their adfs. In addition, within arbor type, there is evidence of different neuron classes (such as interneurons and pyramidal cells). How well different types and classes of arbors can be differentiated is quantified using the Random ForestTM supervised learning algorithm.

Changes in cortical N-methyl-D-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide.

PubMed

Dean, Brian; Gibbons, Andrew S; Boer, Simone; Uezato, Akihito; Meador-Woodruff, James; Scarr, Elizabeth; McCullumsmith, Robert E

2016-03-01

In humans, depending on dose, blocking the N-methyl-D-aspartate receptor (NMDAR) with ketamine can cause psychomimetic or antidepressant effects. The overall outcome for drugs such as ketamine depends on dose and the number of its available binding sites in the central nervous system, and to understand something of the latter variable we measure NMDAR in the frontal pole, dorsolateral prefrontal, anterior cingulate and parietal cortices from people with schizophrenia, bipolar disorder, major depressive disorders and age/sex matched controls. We measured levels of NMDARs (using [(3)H]MK-801 binding) and NMDAR sub-unit mRNAs (GRINs: using in situ hybridisation) as well as post-synaptic density protein 95 (anterior cingulate cortex only; not major depressive disorders: an NMDAR post-synaptic associated protein) in bipolar disorder, schizophrenia and controls. Compared to controls, levels of NMDAR were lower in the outer laminae of the dorsolateral prefrontal cortex (-17%, p = 0.01) in people with schizophrenia. In bipolar disorder, levels of NMDAR binding (laminae IV-VI; -19%, p < 0.01) and GRIN2C mRNA (laminae I-VI; -27%, p < 0.05) were lower in the anterior cingulate cortex and NMDAR binding was lower in the outer lamina IV of the dorsolateral prefrontal cortex (-19%, p < 0.01). In major depressive disorders, levels of GRIN2D mRNA were higher in frontal pole (+22%, p < 0.05). In suicide completers, levels of GRIN2B mRNA were higher in parietal cortex (+20%, p < 0.01) but lower (-35%, p = 0.02) in dorsolateral prefrontal cortex while post-synaptic density protein 95 was higher (+26%, p < 0.05) in anterior cingulate cortex. These data suggest that differences in cortical NMDAR expression and post-synaptic density protein 95 are present in psychiatric disorders and suicide completion and may contribute to different responses to ketamine. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood.

PubMed

Gennatas, Efstathios D; Avants, Brian B; Wolf, Daniel H; Satterthwaite, Theodore D; Ruparel, Kosha; Ciric, Rastko; Hakonarson, Hakon; Gur, Raquel E; Gur, Ruben C

2017-05-17

Developmental structural neuroimaging studies in humans have long described decreases in gray matter volume (GMV) and cortical thickness (CT) during adolescence. Gray matter density (GMD), a measure often assumed to be highly related to volume, has not been systematically investigated in development. We used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to study age-related effects and sex differences in four regional gray matter measures in 1189 youths ranging in age from 8 to 23 years. Custom T1 segmentation and a novel high-resolution gray matter parcellation were used to extract GMD, GMV, gray matter mass (GMM; defined as GMD × GMV), and CT from 1625 brain regions. Nonlinear models revealed that each modality exhibits unique age-related effects and sex differences. While GMV and CT generally decrease with age, GMD increases and shows the strongest age-related effects, while GMM shows a slight decline overall. Females have lower GMV but higher GMD than males throughout the brain. Our findings suggest that GMD is a prime phenotype for the assessment of brain development and likely cognition and that periadolescent gray matter loss may be less pronounced than previously thought. This work highlights the need for combined quantitative histological MRI studies. SIGNIFICANCE STATEMENT This study demonstrates that different MRI-derived gray matter measures show distinct age and sex effects and should not be considered equivalent but complementary. It is shown for the first time that gray matter density increases from childhood to young adulthood, in contrast with gray matter volume and cortical thickness, and that females, who are known to have lower gray matter volume than males, have higher density throughout the brain. A custom preprocessing pipeline and a novel high-resolution parcellation were created to analyze brain scans of 1189 youths collected as part of the Philadelphia Neurodevelopmental Cohort. A clear understanding of normal structural brain development is essential for the examination of brain-behavior relationships, the study of brain disease, and, ultimately, clinical applications of neuroimaging. Copyright © 2017 the authors 0270-6474/17/375065-09$15.00/0.

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

PubMed

Van Caenegem, E; Wierckx, K; Taes, Y; Schreiner, T; Vandewalle, S; Toye, K; Kaufman, J-M; T'Sjoen, G

2015-01-01

Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Reduced Current Spread by Concentric Electrodes in Transcranial Electrical Stimulation (tES).

PubMed

Bortoletto, M; Rodella, C; Salvador, R; Miranda, P C; Miniussi, C

2016-01-01

We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

Semi-automated Anatomical Labeling and Inter-subject Warping of High-Density Intracranial Recording Electrodes in Electrocorticography.

PubMed

Hamilton, Liberty S; Chang, David L; Lee, Morgan B; Chang, Edward F

2017-01-01

In this article, we introduce img_pipe, our open source python package for preprocessing of imaging data for use in intracranial electrocorticography (ECoG) and intracranial stereo-EEG analyses. The process of electrode localization, labeling, and warping for use in ECoG currently varies widely across laboratories, and it is usually performed with custom, lab-specific code. This python package aims to provide a standardized interface for these procedures, as well as code to plot and display results on 3D cortical surface meshes. It gives the user an easy interface to create anatomically labeled electrodes that can also be warped to an atlas brain, starting with only a preoperative T1 MRI scan and a postoperative CT scan. We describe the full capabilities of our imaging pipeline and present a step-by-step protocol for users.

Semi-automated Anatomical Labeling and Inter-subject Warping of High-Density Intracranial Recording Electrodes in Electrocorticography

PubMed Central

Hamilton, Liberty S.; Chang, David L.; Lee, Morgan B.; Chang, Edward F.

2017-01-01

In this article, we introduce img_pipe, our open source python package for preprocessing of imaging data for use in intracranial electrocorticography (ECoG) and intracranial stereo-EEG analyses. The process of electrode localization, labeling, and warping for use in ECoG currently varies widely across laboratories, and it is usually performed with custom, lab-specific code. This python package aims to provide a standardized interface for these procedures, as well as code to plot and display results on 3D cortical surface meshes. It gives the user an easy interface to create anatomically labeled electrodes that can also be warped to an atlas brain, starting with only a preoperative T1 MRI scan and a postoperative CT scan. We describe the full capabilities of our imaging pipeline and present a step-by-step protocol for users. PMID:29163118

Creating virtual electrodes with 2D current steering

NASA Astrophysics Data System (ADS)

Spencer, Thomas C.; Fallon, James B.; Shivdasani, Mohit N.

2018-06-01

Objective. Current steering techniques have shown promise in retinal prostheses as a way to increase the number of distinct percepts elicitable without increasing the number of implanted electrodes. Previously, it has been shown that ‘virtual’ electrodes can be created between simultaneously stimulated electrode pairs, producing unique cortical response patterns. This study investigated whether virtual electrodes could be created using 2D current steering, and whether these virtual electrodes can produce cortical responses with predictable spatial characteristics. Approach. Normally-sighted eyes of seven adult anaesthetised cats were implanted with a 42-channel electrode array in the suprachoroidal space and multi-unit neural activity was recorded from the visual cortex. Stimuli were delivered to individual physical electrodes, or electrodes grouped into triangular, rectangular, and hexagonal arrangements. Varying proportions of charge were applied to each electrode in a group to ‘steer’ current and create virtual electrodes. The centroids of cortical responses to stimulation of virtual electrodes were compared to those evoked by stimulation of single physical electrodes. Main results. Responses to stimulation of groups of up to six electrodes with equal ratios of charge on each electrode resulted in cortical activation patterns that were similar to those elicited by the central physical electrode (centroids: RM ANOVA on ranks, p  >  0.05 neural spread: one-way ANOVA on Ranks, p  >  0.05). We were also able to steer the centroid of activation towards the direction of any of the electrodes of the group by applying a greater charge to that electrode, but the movement in the centroid was not found to be significant. Significance. The results suggest that current steering is possible in two dimensions between up to at least six electrodes, indicating it may be possible to increase the number of percepts in patients without increasing the number of physical electrodes. Being able to reproduce spatial characteristics of responses to individual physical electrodes suggests that this technique could also be used to compensate for faulty electrodes.

Increased density and periosteal expansion of the tibia in young adult men following short-term arduous training.

PubMed

Izard, Rachel M; Fraser, William D; Negus, Charles; Sale, Craig; Greeves, Julie P

2016-07-01

Few human studies have reported early structural adaptations of bone to weight-bearing exercise, which provide a greater contribution to improved bone strength than increased density. This prospective study examined site- and regional-specific adaptations of the tibia during arduous training in a cohort of male military (infantry) recruits to better understand how bone responds in vivo to mechanical loading. Tibial bone density and geometry were measured in 90 British Army male recruits (ages 21±3years, height: 1.78±0.06m, body mass: 73.9±9.8kg) in weeks 1 (Baseline) and 10 of initial military training. Scans were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional sectors. T-tests determined significant differences between time points (P<0.05). Bone density of trabecular and cortical compartments increased significantly at all measured sites. Bone geometry (cortical area and thickness) and bone strength (i, MMi and BSI) at the diaphyseal sites (38 and 66%) were also significantly higher in week 10. Regional changes in density and geometry were largely observed in the anterior, medial-anterior and anterior-posterior sectors. Calf muscle density and area (66% site) increased significantly at week 10 (P<0.01). In vivo mechanical loading improves bone strength of the human tibia by increased density and periosteal expansion, which varies by site and region of the bone. These changes may occur in response to the nature and distribution of forces originating from bending, torsional and shear stresses of military training. These improvements are observed early in training when the osteogenic stimulus is sufficient, which may be close to the fracture threshold in some individuals. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.

PubMed

Di Pietro, N C; Seamans, J K

2007-12-01

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity.

PubMed

Frazer, Ashlyn; Williams, Jacqueline; Spittles, Michael; Rantalainen, Timo; Kidgell, Dawson

2016-11-01

We examined the cumulative effect of 4 consecutive bouts of noninvasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain-derived neurotrophic factor (BDNF) polymorphism. In a randomized double-blinded cross-over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N = 13). We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared with sham tDCS. The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism. Muscle Nerve 54: 903-913, 2016. © 2016 Wiley Periodicals, Inc.

Chronic lead exposure reduces doublecortin-expressing immature neurons in young adult guinea pig cerebral cortex.

PubMed

Huang, JuFang; Huang, Kai; Shang, Lei; Wang, Hui; Zhang, Mengqi; Fan, Chun-Ling; Chen, Dan; Yan, Xiaoxin; Xiong, Kun

2012-07-19

Chronic lead (Pb) poisoning remains an environmental risk especially for the pediatric population, and it may affect brain development. Immature neurons expressing doublecortin (DCX+) exist around cortical layer II in various mammals, including adult guinea pigs and humans. Using young adult guinea pigs as an experimental model, the present study explored if chronic Pb exposure affects cortical DCX + immature neurons and those around the subventricular and subgranular zones (SVZ, SGZ). Two month-old guinea pigs were treated with 0.2% lead acetate in drinking water for 2, 4 and 6 months. Blood Pb levels in these animals reached 10.27 ± 0.62, 16.25 ± 0.78 and 19.03 ± 0.86 μg/dL at the above time points, respectively, relative to ~3 μg/dL in vehicle controls. The density of DCX + neurons was significantly reduced around cortical layer II, SVZ and SGZ in Pb-treated animals surviving 4 and 6 months relative to controls. Bromodeoxyuridine (BrdU) pulse-chasing studies failed to find cellular colocalization of this DNA synthesis indicator in DCX + cells around layer II in Pb-treated and control animals. These cortical immature neurons were not found to coexist with active caspase-3 or Fluoro-Jade C labeling. Chronic Pb exposure can lead to significant reduction in the number of the immature neurons around cortical layer II and in the conventional neurogenic sites in young adult guinea pigs. No direct evidence could be identified to link the reduced cortical DCX expression with alteration in local neurogenesis or neuronal death.

Increased resistance during jump exercise does not enhance cortical bone formation.

PubMed

Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G; Wiggs, Michael P; Hogan, Harry A; Fluckey, James D; Bloomfield, Susan A

2014-01-01

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

Cannabis use and progressive cortical thickness loss in areas rich in CB1 receptors during the first five years of schizophrenia.

PubMed

Rais, Monica; van Haren, Neeltje E M; Cahn, Wiepke; Schnack, Hugo G; Lepage, Claude; Collins, Louis; Evans, Alan C; Hulshoff Pol, Hilleke E; Kahn, René S

2010-12-01

Cerebral grey matter volume reductions are progressive in schizophrenia, with larger grey matter volume decreases associated with cannabis use. It is unknown whether this grey matter loss is globally distributed over the entire brain or more pronounced in specific cortical brain regions. Fifty-one patients with recent-onset schizophrenia and 31 matched healthy subjects were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion and at 5-year follow-up. Nineteen patients (ab-)used cannabis but no other illicit drugs; 32 patients and the healthy comparison subjects did not use any drugs during the 5-year follow-up. At follow-up, clinical outcome was measured. To evaluate the local differences in cortical thickness change over five years between the two groups regression analysis was carried out over the cortical surface. At inclusion cortical thickness did not differ between patients and controls and between cannabis-using and non-using patients. Over the follow-up period we found excessive thinning of the right supplementary motor cortex, inferior frontal cortex, superior temporal gyrus, angular gyrus, occipital and parietal lobe in patients relative to controls after controlling for cannabis use. Patients who used cannabis showed additional thinning in the left dorsolateral prefrontal cortex (DLPFC), left anterior cingulate cortex (ACC) and left occipital lobe as compared to those patients that did not use cannabis during the scan interval. First-episode schizophrenia patients who use cannabis show a more pronounced cortical thinning than non-using patients in areas known for their high density of CB1 receptors, such as the ACC and the DLPFC. Copyright © 2010 Elsevier B.V. All rights reserved.

Prenatal alcohol exposure affects vasculature development in the neonatal brain.

PubMed

Jégou, Sylvie; El Ghazi, Faiza; de Lendeu, Pamela Kwetieu; Marret, Stéphane; Laudenbach, Vincent; Uguen, Arnaud; Marcorelles, Pascale; Roy, Vincent; Laquerrière, Annie; Gonzalez, Bruno José

2012-12-01

In humans, antenatal alcohol exposure elicits various developmental disorders, in particular in the brain. Numerous studies focus on the deleterious effects of alcohol on neural cells. Although recent studies suggest that alcohol can affect angiogenesis in adults, the impact of prenatal alcohol exposure on brain microvasculature remains poorly understood. We used a mouse model to investigate effects of prenatal alcohol exposure on the cortical microvascular network in vivo and ex vivo and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF) on activity, plasticity, and survival of microvessels. We used quantitative reverse transcriptase polymerase chain reaction, Western blot, immunohistochemistry, calcimetry, and videomicroscopy. We characterized the effect of prenatal alcohol exposure on the cortical microvascular network in human controls and fetal alcohol syndrome (FAS)/partial FAS (pFAS) patients at different developmental stages. In mice, prenatal alcohol exposure induced a reduction of cortical vascular density, loss of the radial orientation of microvessels, and altered expression of VEGF receptors. Time-lapse experiments performed on brain slices revealed that ethanol inhibited glutamate-induced calcium mobilization in endothelial cells, affected plasticity, and promoted death of microvessels. These effects were prevented by VEGF. In humans, we evidenced a stage-dependent alteration of the vascular network in the cortices of fetuses with pFAS/FAS. Whereas no modification was observed from gestational week 20 (WG20) to WG22, the radial organization of cortical microvessels was clearly altered in pFAS/FAS patients from WG30 to WG38. Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol-induced brain abnormalities. Copyright © 2012 American Neurological Association.

Effects of in utero pestivirus infection on bovine fetal bone geometry, biomechanical properties and composition.

PubMed

Webb, Brett T; McGilvray, Kirk C; Smirnova, Natalia P; Hansen, Thomas R; Norrdin, Robert W

2013-11-01

Transplacental viral infection of the fetus can result in abnormal trabecular and cortical bone modeling in long bones through impaired bone resorption and formation. Although such infections are frequently associated with neonatal fractures in humans and animals, their effect on the biomechanical properties of the developing skeleton remain poorly understood. The goal of this study was to determine the effects of transplacental bovine viral diarrhea virus (BVDV) infection on the biomechanical properties of fetal femora. Pregnant heifers were inoculated intranasally with non-cytopathic BVDV or media alone on day 75 of gestation to produce persistently infected (PI) and control fetuses, respectively, which were then removed on days 192 and 245 of gestation. Histomorphometry, compositional analysis and 'four-point bending until failure' were performed on fetal femora. Altered cortical geometry largely accounted for differences in calculated elastic modulus (PI vs. control, and day 192 vs. day 245) and ultimate stress (day 192 vs. day 245). Fetal infection with BVDV did not significantly impair inherent biomechanical properties of bone but rather resulted in decreased periosteal apposition rates, manifested as smaller femoral mid-diaphyseal diameters. There were no differences between PI and control fetuses in cortical thickness ratio, ash density or calcium/phosphorous content; however, cortical thickness ratio decreased with fetal age. Thus even when cortical thickness ratios are similar, differences in mid-diaphyseal diameter affect the error associated with the calculation of stress and strain by classical beam theory equations. Copyright © 2013. Published by Elsevier Ltd.

Controlled electro-implementation of fluoride in titanium implant surfaces enhances cortical bone formation and mineralization.

PubMed

Taxt-Lamolle, Sébastien F; Rubert, Marina; Haugen, Håvard J; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Monjo, Marta

2010-03-01

Previous studies have shown that bone-to-implant attachment of titanium implants to cortical bone is improved when the surface is modified with hydrofluoric acid. The aim of this study was to investigate if biological factors are involved in the improved retention of these implants. Fluoride was implemented in implant surfaces by cathodic reduction with increasing concentrations of HF in the electrolyte. The modified implants were placed in the cortical bone in the tibias of New Zealand white rabbits. After 4 weeks of healing, wound fluid collected from the implant site showed lower lactate dehydrogenase activity and less bleeding in fluoride-modified implants compared to control. A significant increase in gene expression levels of osteocalcin and tartrate-resistant acid phosphatase (TRAP) was found in the cortical bone attached to Ti implants modified with 0.001 and 0.01 vol.% HF, while Ti implants modified with 0.1% HF showed only induced TRAP mRNA levels. These results were supported by the performed micro-CT analyses. The volumetric bone mineral density of the cortical bone hosting Ti implants modified with 0.001% and 0.01% HF was higher both in the newly woven bone (<100 microm from the interface) and in the older Haversian bone (>100 microm). In conclusion, the modulation of these biological factors by surface modification of titanium implants with low concentrations of HF using cathodic reduction may explain their improved osseointegration properties. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Spreading Depolarizations Have Prolonged Direct Current Shifts and Are Associated with Poor Outcome in Brain Trauma

DTIC Science & Technology

2011-01-01

prognosis. Keywords: cortical spreading depression; electroencephalography; craniotomy ; signal processing; acute brain injury Introduction Cortical...Mannheim, Germany). Inclusion criteria were the clinical decision for craniotomy for lesion evacuation and/or decompression and age ~ 18 years...externalized through a burr hole in the skull (if the bone flap was replaced) and tu nne lied beneath the scalp to exit 2-3 em from the craniotomy

Physiological gain leads to high ISI variability in a simple model of a cortical regular spiking cell.

PubMed

Troyer, T W; Miller, K D

1997-07-01

To understand the interspike interval (ISI) variability displayed by visual cortical neurons (Softky & Koch, 1993), it is critical to examine the dynamics of their neuronal integration, as well as the variability in their synaptic input current. Most previous models have focused on the latter factor. We match a simple integrate-and-fire model to the experimentally measured integrative properties of cortical regular spiking cells (McCormick, Connors, Lighthall, & Prince, 1985). After setting RC parameters, the post-spike voltage reset is set to match experimental measurements of neuronal gain (obtained from in vitro plots of firing frequency versus injected current). Examination of the resulting model leads to an intuitive picture of neuronal integration that unifies the seemingly contradictory 1/square root of N and random walk pictures that have previously been proposed. When ISIs are dominated by postspike recovery, 1/square root of N arguments hold and spiking is regular; after the "memory" of the last spike becomes negligible, spike threshold crossing is caused by input variance around a steady state and spiking is Poisson. In integrate-and-fire neurons matched to cortical cell physiology, steady-state behavior is predominant, and ISIs are highly variable at all physiological firing rates and for a wide range of inhibitory and excitatory inputs.

Adolescence physical activity is associated with higher tibial pQCT bone values in adulthood after 28-years of follow-up--the Cardiovascular Risk in Young Finns Study.

PubMed

Tolonen, S; Sievänen, H; Mikkilä, V; Telama, R; Oikonen, M; Laaksonen, M; Viikari, J; Kähönen, M; Raitakari, O T

2015-06-01

High peak bone mass and strong bone phenotype are known to be partly explained by physical activity during growth but there are few prospective studies on this topic. In this 28-year follow-up of Cardiovascular Risk in Young Finns Study cohort, we assessed whether habitual childhood and adolescence physical activity or inactivity at the age of 3-18 years were associated with adult phenotype of weight-bearing tibia and the risk of low-energy fractures. Baseline physical activity and data on clinical, nutritional and lifestyle factors were assessed separately for females and males aged 3-6-years (N=395-421) and 9-18-years (N=923-965). At the age of 31-46-years, the prevalence of low-energy fractures was assessed with a questionnaire and several tibial traits were measured with pQCT (bone mineral content (BMC; mg), total and cortical cross-sectional areas (mm(2)), trabecular (for the distal site only) and cortical (for the shaft only) bone densities (mg/cm(3)), stress-strain index (SSI; mm(3), for the shaft only), bone strength index (BSI; mg(2)/cm(4), for the distal site only) and the cortical strength index (CSI, for the shaft only)). For the statistical analysis, each bone trait was categorized as below the cohort median or the median and above and the adjusted odds ratios (OR) were determined. In females, frequent physical activity at the age of 9-18-years was associated with higher adulthood values of BSI, total and cortical areas, BMC, CSI and SSI at the tibia independently of many health and lifestyle factors (ORs 0.33-0.53, P≤0.05; P-values for trend 0.002-0.05). Cortical density at the tibial shaft showed the opposite trend (P-value for trend 0.03). Similarly in males, frequent physical activity was associated with higher values of adult total and cortical areas and CSI at the tibia (ORs 0.48-0.53, P≤0.05; P-values for trend 0.01-0.02). However, there was no evidence that childhood or adolescence physical activity was associated with lower risk of low energy fractures during the follow-up. In conclusion, frequent habitual physical activity in adolescence seems to confer benefits on tibial bone size and geometry in adulthood. Copyright © 2015. Published by Elsevier Inc.

Neocortical Maturation during Adolescence: Change in Neuronal Soma Dimension

ERIC Educational Resources Information Center

Rabinowicz, Theodore; Petetot, Jean MacDonald-Comber; Khoury, Jane C.; de Courten-Myers, Gabrielle M.

2009-01-01

During adolescence, cognitive abilities increase robustly. To search for possible related structural alterations of the cerebral cortex, we measured neuronal soma dimension (NSD = width times height), cortical thickness and neuronal densities in different types of neocortex in post-mortem brains of five 12-16 and five 17-24 year-olds (each 2F,…

Sleep EEG Changes during Adolescence: An Index of a Fundamental Brain Reorganization

ERIC Educational Resources Information Center

Feinberg, Irwin; Campbell, Ian G.

2010-01-01

Delta (1-4 Hz) EEG power in non-rapid eye movement (NREM) sleep declines massively during adolescence. This observation stimulated the hypothesis that during adolescence the human brain undergoes an extensive reorganization driven by synaptic elimination. The parallel declines in synaptic density, delta wave amplitude and cortical metabolic rate…

Olig1 function is required to repress dlx1/2 and interneuron production in Mammalian brain.

PubMed

Silbereis, John C; Nobuta, Hiroko; Tsai, Hui-Hsin; Heine, Vivi M; McKinsey, Gabriel L; Meijer, Dimphna H; Howard, Mackenzie A; Petryniak, Magda A; Potter, Gregory B; Alberta, John A; Baraban, Scott C; Stiles, Charles D; Rubenstein, John L R; Rowitch, David H

2014-02-05

Abnormal GABAergic interneuron density, and imbalance of excitatory versus inhibitory tone, is thought to result in epilepsy, neurodevelopmental disorders, and psychiatric disease. Recent studies indicate that interneuron cortical density is determined primarily by the size of the precursor pool in the embryonic telencephalon. However, factors essential for regulating interneuron allocation from telencephalic multipotent precursors are poorly understood. Here we report that Olig1 represses production of GABAergic interneurons throughout the mouse brain. Olig1 deletion in mutant mice results in ectopic expression and upregulation of Dlx1/2 genes in the ventral medial ganglionic eminences and adjacent regions of the septum, resulting in an ∼30% increase in adult cortical interneuron numbers. We show that Olig1 directly represses the Dlx1/2 I12b intergenic enhancer and that Dlx1/2 functions genetically downstream of Olig1. These findings establish Olig1 as an essential repressor of Dlx1/2 and interneuron production in developing mammalian brain. Copyright © 2014 Elsevier Inc. All rights reserved.