Interhemispheric Effective and Functional Cortical Connectivity Signatures of Spina Bifida Are Consistent with Callosal Anomaly

PubMed Central

Malekpour, Sheida; Li, Zhimin; Cheung, Bing Leung Patrick; Castillo, Eduardo M.; Papanicolaou, Andrew C.; Kramer, Larry A.; Fletcher, Jack M.

2012-01-01

Abstract The impact of the posterior callosal anomalies associated with spina bifida on interhemispheric cortical connectivity is studied using a method for estimating cortical multivariable autoregressive models from scalp magnetoencephalography data. Interhemispheric effective and functional connectivity, measured using conditional Granger causality and coherence, respectively, is determined for the anterior and posterior cortical regions in a population of five spina bifida and five control subjects during a resting eyes-closed state. The estimated connectivity is shown to be consistent over the randomly selected subsets of the data for each subject. The posterior interhemispheric effective and functional connectivity and cortical power are significantly lower in the spina bifida group, a result that is consistent with posterior callosal anomalies. The anterior interhemispheric effective and functional connectivity are elevated in the spina bifida group, a result that may reflect compensatory mechanisms. In contrast, the intrahemispheric effective connectivity is comparable in the two groups. The differences between the spina bifida and control groups are most significant in the θ and α bands. PMID:22571349

Impedance Spectrum in Cortical Tissue: Implications for Propagation of LFP Signals on the Microscopic Level

PubMed Central

Miceli, Stéphanie

2017-01-01

Brain research investigating electrical activity within neural tissue is producing an increasing amount of physiological data including local field potentials (LFPs) obtained via extracellular in vivo and in vitro recordings. In order to correctly interpret such electrophysiological data, it is vital to adequately understand the electrical properties of neural tissue itself. An ongoing controversy in the field of neuroscience is whether such frequency-dependent effects bias LFP recordings and affect the proper interpretation of the signal. On macroscopic scales and with large injected currents, previous studies have found various grades of frequency dependence of cortical tissue, ranging from negligible to strong, within the frequency band typically considered relevant for neuroscience (less than a few thousand hertz). Here, we performed a detailed investigation of the frequency dependence of the conductivity within cortical tissue at microscopic distances using small current amplitudes within the typical (neuro)physiological micrometer and sub-nanoampere range. We investigated the propagation of LFPs, induced by extracellular electrical current injections via patch-pipettes, in acute rat brain slice preparations containing the somatosensory cortex in vitro using multielectrode arrays. Based on our data, we determined the cortical tissue conductivity over a 100-fold increase in signal frequency (5–500 Hz). Our results imply at most very weak frequency-dependent effects within the frequency range of physiological LFPs. Using biophysical modeling, we estimated the impact of different putative impedance spectra. Our results indicate that frequency dependencies of the order measured here and in most other studies have negligible impact on the typical analysis and modeling of LFP signals from extracellular brain recordings. PMID:28197543

Impedance Spectrum in Cortical Tissue: Implications for Propagation of LFP Signals on the Microscopic Level.

PubMed

Miceli, Stéphanie; Ness, Torbjørn V; Einevoll, Gaute T; Schubert, Dirk

2017-01-01

Brain research investigating electrical activity within neural tissue is producing an increasing amount of physiological data including local field potentials (LFPs) obtained via extracellular in vivo and in vitro recordings. In order to correctly interpret such electrophysiological data, it is vital to adequately understand the electrical properties of neural tissue itself. An ongoing controversy in the field of neuroscience is whether such frequency-dependent effects bias LFP recordings and affect the proper interpretation of the signal. On macroscopic scales and with large injected currents, previous studies have found various grades of frequency dependence of cortical tissue, ranging from negligible to strong, within the frequency band typically considered relevant for neuroscience (less than a few thousand hertz). Here, we performed a detailed investigation of the frequency dependence of the conductivity within cortical tissue at microscopic distances using small current amplitudes within the typical (neuro)physiological micrometer and sub-nanoampere range. We investigated the propagation of LFPs, induced by extracellular electrical current injections via patch-pipettes, in acute rat brain slice preparations containing the somatosensory cortex in vitro using multielectrode arrays. Based on our data, we determined the cortical tissue conductivity over a 100-fold increase in signal frequency (5-500 Hz). Our results imply at most very weak frequency-dependent effects within the frequency range of physiological LFPs. Using biophysical modeling, we estimated the impact of different putative impedance spectra. Our results indicate that frequency dependencies of the order measured here and in most other studies have negligible impact on the typical analysis and modeling of LFP signals from extracellular brain recordings.

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

PubMed

Hicks, R R; Baldwin, S A; Scheff, S W

1997-01-01

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

Cortical thinning in former professional soccer players.

PubMed

Koerte, Inga K; Mayinger, Michael; Muehlmann, Marc; Kaufmann, David; Lin, Alexander P; Steffinger, Denise; Fisch, Barbara; Rauchmann, Boris-Stephan; Immler, Stefanie; Karch, Susanne; Heinen, Florian R; Ertl-Wagner, Birgit; Reiser, Maximilian; Stern, Robert A; Zafonte, Ross; Shenton, Martha E

2016-09-01

Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

Effect of micromorphology of cortical bone tissue on crack propagation under dynamic loading

NASA Astrophysics Data System (ADS)

Wang, Mayao; Gao, Xing; Abdel-Wahab, Adel; Li, Simin; Zimmermann, Elizabeth A.; Riedel, Christoph; Busse, Björn; Silberschmidt, Vadim V.

2015-09-01

Structural integrity of bone tissue plays an important role in daily activities of humans. However, traumatic incidents such as sports injuries, collisions and falls can cause bone fracture, servere pain and mobility loss. In addition, ageing and degenerative bone diseases such as osteoporosis can increase the risk of fracture [1]. As a composite-like material, a cortical bone tissue is capable of tolerating moderate fracture/cracks without complete failure. The key to this is its heterogeneously distributed microstructural constituents providing both intrinsic and extrinsic toughening mechanisms. At micro-scale level, cortical bone can be considered as a four-phase composite material consisting of osteons, Haversian canals, cement lines and interstitial matrix. These microstructural constituents can directly affect local distributions of stresses and strains, and, hence, crack initiation and propagation. Therefore, understanding the effect of micromorphology of cortical bone on crack initiation and propagation, especially under dynamic loading regimes is of great importance for fracture risk evaluation. In this study, random microstructures of a cortical bone tissue were modelled with finite elements for four groups: healthy (control), young age, osteoporosis and bisphosphonate-treated, based on osteonal morphometric parameters measured from microscopic images for these groups. The developed models were loaded under the same dynamic loading conditions, representing a direct impact incident, resulting in progressive crack propagation. An extended finite-element method (X-FEM) was implemented to realize solution-dependent crack propagation within the microstructured cortical bone tissues. The obtained simulation results demonstrate significant differences due to micromorphology of cortical bone, in terms of crack propagation characteristics for different groups, with the young group showing highest fracture resistance and the senior group the lowest.

Sensitivity analysis of brain morphometry based on MRI-derived surface models

NASA Astrophysics Data System (ADS)

Klein, Gregory J.; Teng, Xia; Schoenemann, P. T.; Budinger, Thomas F.

1998-07-01

Quantification of brain structure is important for evaluating changes in brain size with growth and aging and for characterizing neurodegeneration disorders. Previous quantification efforts using ex vivo techniques suffered considerable error due to shrinkage of the cerebrum after extraction from the skull, deformation of slices during sectioning, and numerous other factors. In vivo imaging studies of brain anatomy avoid these problems and allow repetitive studies following progression of brain structure changes due to disease or natural processes. We have developed a methodology for obtaining triangular mesh models of the cortical surface from MRI brain datasets. The cortex is segmented from nonbrain tissue using a 2D region-growing technique combined with occasional manual edits. Once segmented, thresholding and image morphological operations (erosions and openings) are used to expose the regions between adjacent surfaces in deep cortical folds. A 2D region- following procedure is then used to find a set of contours outlining the cortical boundary on each slice. The contours on all slices are tiled together to form a closed triangular mesh model approximating the cortical surface. This model can be used for calculation of cortical surface area and volume, as well as other parameters of interest. Except for the initial segmentation of the cortex from the skull, the technique is automatic and requires only modest computation time on modern workstations. Though the use of image data avoids many of the pitfalls of ex vivo and sectioning techniques, our MRI-based technique is still vulnerable to errors that may impact the accuracy of estimated brain structure parameters. Potential inaccuracies include segmentation errors due to incorrect thresholding, missed deep sulcal surfaces, falsely segmented holes due to image noise and surface tiling artifacts. The focus of this paper is the characterization of these errors and how they affect measurements of cortical surface area and volume.

Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson's disease.

PubMed

Fang, Fang; Yang, Wanlin; Florio, Jazmin B; Rockenstein, Edward; Spencer, Brian; Orain, Xavier M; Dong, Stephanie X; Li, Huayan; Chen, Xuqiao; Sung, Kijung; Rissman, Robert A; Masliah, Eliezer; Ding, Jianqing; Wu, Chengbiao

2017-06-20

Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage. Interestingly, we found that overexpressed ASYN interacted with dynein and induced a significant increase in the activated levels of small Rab GTPases such as Rab5 and Rab7, both key regulators of endocytic processes. Furthermore, expression of ASYN resulted in neuronal atrophy in DIV7 cortical cultures of either from E18 transgenic mouse model or from rat E18 embryos that were transiently transfected with ASYN-GFP for 72 hrs. Our studies suggest that excessive ASYN likely alters endocytic pathways leading to axonal dysfunction in embryonic cortical neurons in PD mouse models.

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

PubMed

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impaired cortical mitochondrial function following TBI precedes behavioral changes

PubMed Central

Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

2014-01-01

Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks.

PubMed

Landau, Itamar D; Egger, Robert; Dercksen, Vincent J; Oberlaender, Marcel; Sompolinsky, Haim

2016-12-07

Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition balance. We show that homeostatic plasticity in inhibitory synapses can align the functional connectivity to compensate for structural heterogeneity. Alternatively, spike-frequency adaptation can give rise to a novel state in which local firing rates adjust dynamically so that adaptation currents and synaptic inputs are balanced. This theory is supported by simulations of L4 barrel cortex during spontaneous and stimulus-evoked conditions. Our study shows how synaptic and cellular mechanisms yield fluctuation-driven dynamics despite structural heterogeneity in cortical circuits. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula

PubMed Central

Castro, Daniel C.; Berridge, Kent C.

2017-01-01

Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as “liking” for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the form of an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots. Opioid/orexin stimulations in either cortical hotspot activated Fos throughout a distributed “hedonic circuit” involving cortical and subcortical structures. Conversely, cortical coldspot stimulation activated circuitry for “hedonic suppression.” Finally, food intake was increased by stimulations at several prefrontal cortical sites, indicating that the anatomical substrates in cortex for enhancing the motivation to eat are discriminable from those for hedonic impact. PMID:29073109

Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function.

PubMed

Sarter, Martin; Albin, Roger L; Kucinski, Aaron; Lustig, Cindy

2014-07-01

Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson's disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive-behavioral mechanisms that produce falls and map these mechanisms onto a model of multi-system degeneration. Results from PET studies in PD fallers and findings from a recently developed animal model support the hypothesis that falls result from interactions between loss of basal forebrain cholinergic projections to the cortex and striatal dopamine loss. Striatal dopamine loss produces inefficient, low-vigor gait, posture control, and movement. Cortical cholinergic deafferentation impairs a wide range of attentional processes, including monitoring of gait, posture and complex movements. Cholinergic cell loss reveals the full impact of striatal dopamine loss on motor performance, reflecting loss of compensatory attentional supervision of movement. Dysregulation of dorsomedial striatal circuitry is an essential, albeit not exclusive, mediator of falls in this dual-system model. Because cholinergic neuromodulatory activity influences cortical circuitry primarily via stimulation of α4β2* nicotinic acetylcholine receptors, and because agonists at these receptors are known to benefit attentional processes in animals and humans, treating PD fallers with such agonists, as an adjunct to dopaminergic treatment, is predicted to reduce falls. Falls are an informative behavioral endpoint to study attentional-motor integration by striatal circuitry. Copyright © 2014 Elsevier Inc. All rights reserved.

Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function

PubMed Central

Sarter, Martin; Albin, Roger L.; Kucinski, Aaron; Lustig, Cindy

2015-01-01

Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson’s disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive–behavioral mechanisms that produce falls and map these mechanisms onto a model of multi-system degeneration. Results from PET studies in PD fallers and findings from a recently developed animal model support the hypothesis that falls result from interactions between loss of basal forebrain cholinergic projections to the cortex and striatal dopamine loss. Striatal dopamine loss produces inefficient, low-vigor gait, posture control, and movement. Cortical cholinergic deafferentation impairs a wide range of attentional processes, including monitoring of gait, posture and complex movements. Cholinergic cell loss reveals the full impact of striatal dopamine loss on motor performance, reflecting loss of compensatory attentional supervision of movement. Dysregulation of dorsomedial striatal circuitry is an essential, albeit not exclusive, mediator of falls in this dual-system model. Because cholinergic neuromodulatory activity influences cortical circuitry primarily via stimulation of α4β2* nicotinic acetylcholine receptors, and because agonists at these receptors are known to benefit attentional processes in animals and humans, treating PD fallers with such agonists, as an adjunct to dopaminergic treatment, is predicted to reduce falls. Falls are an informative behavioral endpoint to study attentional–motor integration by striatal circuitry. PMID:24805070

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

PubMed

Fjell, Anders M; Sneve, Markus H; Storsve, Andreas B; Grydeland, Håkon; Yendiki, Anastasia; Walhovd, Kristine B

2016-03-01

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Age Differences in Prefrontal Surface Area and Thickness in Middle Aged to Older Adults.

PubMed

Dotson, Vonetta M; Szymkowicz, Sarah M; Sozda, Christopher N; Kirton, Joshua W; Green, Mackenzie L; O'Shea, Andrew; McLaren, Molly E; Anton, Stephen D; Manini, Todd M; Woods, Adam J

2015-01-01

Age is associated with reductions in surface area and cortical thickness, particularly in prefrontal regions. There is also evidence of greater thickness in some regions at older ages. Non-linear age effects in some studies suggest that age may continue to impact brain structure in later decades of life, but relatively few studies have examined the impact of age on brain structure within middle-aged to older adults. We investigated age differences in prefrontal surface area and cortical thickness in healthy adults between the ages of 51 and 81 years. Participants received a structural 3-Tesla magnetic resonance imaging scan. Based on a priori hypotheses, primary analyses focused on surface area and cortical thickness in the dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex. We also performed exploratory vertex-wise analyses of surface area and cortical thickness across the entire cortex. We found that older age was associated with smaller surface area in the dorsolateral prefrontal and orbitofrontal cortices but greater cortical thickness in the dorsolateral prefrontal and anterior cingulate cortices. Vertex-wise analyses revealed smaller surface area in primarily frontal regions at older ages, but no age effects were found for cortical thickness. Results suggest age is associated with reduced surface area but greater cortical thickness in prefrontal regions during later decades of life, and highlight the differential effects age has on regional surface area and cortical thickness.

Layer-specific excitation/inhibition balances during neuronal synchronization in the visual cortex.

PubMed

Adesnik, Hillel

2018-05-01

Understanding the balance between synaptic excitation and inhibition in cortical circuits in the brain, and how this contributes to cortical rhythms, is fundamental to explaining information processing in the cortex. This study used cortical layer-specific optogenetic activation in mouse cortex to show that excitatory neurons in any cortical layer can drive powerful gamma rhythms, while inhibition balances excitation. The net impact of this is to keep activity within each layer in check, but simultaneously to promote the propagation of activity to downstream layers. The data show that rhythm-generating circuits exist in all principle layers of the cortex, and provide layer-specific balances of excitation and inhibition that affect the flow of information across the layers. Rhythmic activity can synchronize neural ensembles within and across cortical layers. While gamma band rhythmicity has been observed in all layers, the laminar sources and functional impacts of neuronal synchronization in the cortex remain incompletely understood. Here, layer-specific optogenetic stimulation demonstrates that populations of excitatory neurons in any cortical layer of the mouse's primary visual cortex are sufficient to powerfully entrain neuronal oscillations in the gamma band. Within each layer, inhibition balances excitation and keeps activity in check. Across layers, translaminar output overcomes inhibition and drives downstream firing. These data establish that rhythm-generating circuits exist in all principle layers of the cortex, but provide layer-specific balances of excitation and inhibition that may dynamically shape the flow of information through cortical circuits. These data might help explain how excitation/inhibition (E/I) balances across cortical layers shape information processing, and shed light on the diverse nature and functional impacts of cortical gamma rhythms. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Physical biology of human brain development.

PubMed

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2015-01-01

Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

Cortical response variability as a developmental index of selective auditory attention

PubMed Central

Strait, Dana L.; Slater, Jessica; Abecassis, Victor; Kraus, Nina

2014-01-01

Attention induces synchronicity in neuronal firing for the encoding of a given stimulus at the exclusion of others. Recently, we reported decreased variability in scalp-recorded cortical evoked potentials to attended compared with ignored speech in adults. Here we aimed to determine the developmental time course for this neural index of auditory attention. We compared cortical auditory-evoked variability with attention across three age groups: preschoolers, school-aged children and young adults. Results reveal an increased impact of selective auditory attention on cortical response variability with development. Although all three age groups have equivalent response variability to attended speech, only school-aged children and adults have a distinction between attend and ignore conditions. Preschoolers, on the other hand, demonstrate no impact of attention on cortical responses, which we argue reflects the gradual emergence of attention within this age range. Outcomes are interpreted in the context of the behavioral relevance of cortical response variability and its potential to serve as a developmental index of cognitive skill. PMID:24267508

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2014-09-01

NOTES 14. ABSTRACT Traumatic Brain Injury (TBI) is a well-established inducer of temporal lobe epilepsy (TLE), a frequently medically intractable... epilepsy syndrome. The controlled cortical impact (CCI) model of posttraumatic epilepsy in mice is a well established animal model of TBI that results...reduce development of post-traumatic epilepsy , and did not significantly improve memory function, but did enhance the motor recovery. These findings

The Effect Of Supraphysiologic Blood Pressure on Traumatic Brain Injury and Proximal Tissue Beds During Resuscitative Balloon Occlusion of the Aorta and Variable Aortic Control in a Porcine Model (Sus scrofa) of Polytrauma.

DTIC Science & Technology

2017-04-27

Control In A Porcine Model (Sus Scrofa) Of Polytrauma. PRINCIPAL INVESTIGATOR (PI) / TRAINING COORDINATOR (TC): Lt Col Timothy Williams DEPARTMENT... controlled cortical impact followed by 25% total blood volume rapid hemorrhage. After 30 minutes of hypotension, animals were randomized to 60

A Network Model of the Emotional Brain.

PubMed

Pessoa, Luiz

2017-05-01

Emotion is often understood in terms of a circumscribed set of cortical and subcortical brain regions. I propose, instead, that emotion should be understood in terms of large-scale network interactions spanning the entire neuroaxis. I describe multiple anatomical and functional principles of brain organization that lead to the concept of 'functionally integrated systems', cortical-subcortical systems that anchor the organization of emotion in the brain. The proposal is illustrated by describing the cortex-amygdala integrated system and how it intersects with systems involving the ventral striatum/accumbens, septum, hippocampus, hypothalamus, and brainstem. The important role of the thalamus is also highlighted. Overall, the model clarifies why the impact of emotion is wide-ranging, and how emotion is interlocked with perception, cognition, motivation, and action. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Correlation of mandibular impacted tooth and bone morphology determined by cone beam computed topography on a premise of third molar operation.

PubMed

Momin, M A; Matsumoto, K; Ejima, K; Asaumi, R; Kawai, T; Arai, Y; Honda, K; Yosue, T

2013-05-01

To determine the width and morphology of the mandible in the impacted third molar region, and to identify the location of the mandibular canal prior to planning impacted third molar operations. Cone beam computed tomography (CBCT) data of 87 mandibular third molars from 62 Japanese patients were analyzed in this study. The width of the lingual cortical bone and apex-canal distance were measured from cross-sectional images in which the cortical bone was thinnest at the lingual side in the third molar region. Images were used for measuring the space (distance between the inner border of the lingual cortical bone and outer surface of the third molar root), apex-canal distance (distance from the root of the third molar tooth to the superior border of the inferior alveolar canal) and the cortical bone (width between the inner and outer borders of the lingual cortical bone). The means of the space, apex-canal distance and lingual cortical width were 0.31, 1.99, and 0.68 mm, respectively. Impacted third molar teeth (types A-C) were observed at the following frequencies: type A (angular) 37 %; type B (horizontal), 42 %; type C (vertical), 21 %. The morphology of the mandible at the third molar region (types D-F) was observed as: type D (round), 49 %; type E (lingual extended), 18 %; and type F (lingual concave), 32 %. The width and morphology of the mandible with impacted teeth and the location of the mandibular canal at the third molar region could be clearly determined using cross-sectional CBCT images.

Nonlinear Transfer of Signal and Noise Correlations in Cortical Networks

PubMed Central

Lyamzin, Dmitry R.; Barnes, Samuel J.; Donato, Roberta; Garcia-Lazaro, Jose A.; Keck, Tara

2015-01-01

Signal and noise correlations, a prominent feature of cortical activity, reflect the structure and function of networks during sensory processing. However, in addition to reflecting network properties, correlations are also shaped by intrinsic neuronal mechanisms. Here we show that spike threshold transforms correlations by creating nonlinear interactions between signal and noise inputs; even when input noise correlation is constant, spiking noise correlation varies with both the strength and correlation of signal inputs. We characterize these effects systematically in vitro in mice and demonstrate their impact on sensory processing in vivo in gerbils. We also find that the effects of nonlinear correlation transfer on cortical responses are stronger in the synchronized state than in the desynchronized state, and show that they can be reproduced and understood in a model with a simple threshold nonlinearity. Since these effects arise from an intrinsic neuronal property, they are likely to be present across sensory systems and, thus, our results are a critical step toward a general understanding of how correlated spiking relates to the structure and function of cortical networks. PMID:26019325

Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

PubMed

Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

2016-01-01

The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

PubMed

Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

2015-05-01

This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

Research to Develop and Apply Biophotonics to Military Medicine Needs

DTIC Science & Technology

2012-06-14

brains were hit by a pneumatic (cortical) impact device and imaged by intravital two-photon confocal scanning microscopy via a polished and...Doppler optical frequency domain imaging . In this proposal, we will develop a windowed model of TBI. Using this model, we will characterize for the...following approach to study the microvascular kinetics following TBI. Optical Frequency Domain Imaging . We have developed an instrument in our lab

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

The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†.

PubMed

Fjell, Anders M; Amlien, Inge K; Sneve, Markus H; Grydeland, Håkon; Tamnes, Christian K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2015-09-01

Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of "hotspots" and "coldspots" of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion-AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Negative Correlations in Visual Cortical Networks

PubMed Central

Chelaru, Mircea I.; Dragoi, Valentin

2016-01-01

The amount of information encoded by cortical circuits depends critically on the capacity of nearby neurons to exhibit trial-to-trial (noise) correlations in their responses. Depending on their sign and relationship to signal correlations, noise correlations can either increase or decrease the population code accuracy relative to uncorrelated neuronal firing. Whereas positive noise correlations have been extensively studied using experimental and theoretical tools, the functional role of negative correlations in cortical circuits has remained elusive. We addressed this issue by performing multiple-electrode recording in the superficial layers of the primary visual cortex (V1) of alert monkey. Despite the fact that positive noise correlations decayed exponentially with the difference in the orientation preference between cells, negative correlations were uniformly distributed across the population. Using a statistical model for Fisher Information estimation, we found that a mild increase in negative correlations causes a sharp increase in network accuracy even when mean correlations were held constant. To examine the variables controlling the strength of negative correlations, we implemented a recurrent spiking network model of V1. We found that increasing local inhibition and reducing excitation causes a decrease in the firing rates of neurons while increasing the negative noise correlations, which in turn increase the population signal-to-noise ratio and network accuracy. Altogether, these results contribute to our understanding of the neuronal mechanism involved in the generation of negative correlations and their beneficial impact on cortical circuit function. PMID:25217468

A computational model of cerebral cortex folding.

PubMed

Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Stephen Miller, L; Liu, Tianming

2010-05-21

The geometric complexity and variability of the human cerebral cortex have long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3D geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: (1) Mechanical constraints of the skull regulate the cortical folding process. (2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. (3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. (4) The cortical folding pattern is dependent on the initial geometry of the cortex. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

Early detection of AD using cortical thickness measurements

NASA Astrophysics Data System (ADS)

Spjuth, M.; Gravesen, F.; Eskildsen, S. F.; Østergaard, L. R.

2007-03-01

Alzheimer's disease (AD) is a neurodegenerative disorder that causes cortical atrophy and impaired cognitive functions. The diagnosis is difficult to make and is often made over a longer period of time using a combination of neuropsychological tests, and structural and functional imaging. Due to the impact of early intervention the challenge of distinguishing early AD from normal ageing has received increasing attention. This study uses cortical thickness measurements to characterize the atrophy in nine mild AD patients (mean MMSE-score 23.3 (std: 2.6)) compared to five healthy middle-aged subjects. A fully automated method based on deformable models is used for delineation of the inner and outer boundaries of the cerebral cortex from Magnetic Resonance Images. This allows observer independent high-resolution quantification of the cortical thickness. The cortex analysis facilitates detection of alterations throughout the entire cortical mantle. To perform inter-subject thickness comparison in which the spatial information is retained, a feature-based registration algorithm is developed which uses local cortical curvature, normal vector, and a distance measure. A comparison of the two study groups reveals that the lateral side of the hemispheres shows diffuse thinner areas in the mild AD group but especially the medial side shows a pronounced thinner area which can be explained by early limbic changes in AD. For classification principal component analysis is applied to reduce the high number of thickness measurements (>200,000) into fewer features. All mild AD and healthy middle-aged subjects are classified correctly (sensitivity and specificity 100%).

High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression.

PubMed

Takizawa, Tsubasa; Shibata, Mamoru; Kayama, Yohei; Shimizu, Toshihiko; Toriumi, Haruki; Ebine, Taeko; Unekawa, Miyuki; Koh, Anri; Yoshimura, Akihiko; Suzuki, Norihiro

2017-03-01

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Serotonin homeostasis and serotonin receptors as actors of cortical construction: special attention to the 5-HT3A and 5-HT6 receptor subtypes

PubMed Central

Vitalis, Tania; Ansorge, Mark S.; Dayer, Alexandre G.

2013-01-01

Cortical circuits control higher-order cognitive processes and their function is highly dependent on their structure that emerges during development. The construction of cortical circuits involves the coordinated interplay between different types of cellular processes such as proliferation, migration, and differentiation of neural and glial cell subtypes. Among the multiple factors that regulate the assembly of cortical circuits, 5-HT is an important developmental signal that impacts on a broad diversity of cellular processes. 5-HT is detected at the onset of embryonic telencephalic formation and a variety of serotonergic receptors are dynamically expressed in the embryonic developing cortex in a region and cell-type specific manner. Among these receptors, the ionotropic 5-HT3A receptor and the metabotropic 5-HT6 receptor have recently been identified as novel serotonergic targets regulating different aspects of cortical construction including neuronal migration and dendritic differentiation. In this review, we focus on the developmental impact of serotonergic systems on the construction of cortical circuits and discuss their potential role in programming risk for human psychiatric disorders. PMID:23801939

Age-Related Impairments in Object-Place Associations Are Not Due to Hippocampal Dysfunction

PubMed Central

Hernandez, Abigail R.; Maurer, Andrew P.; Reasor, Jordan E.; Turner, Sean M.; Barthle, Sarah E.; Johnson, Sarah A.; Burke, Sara N.

2016-01-01

Age-associated cognitive decline can reduce an individual’s quality of life. As no single neurobiological deficit can account for the wide spectrum of behavioral impairments observed in old age, it is critical to develop an understanding of how interactions between different brain regions change over the life span. The performance of young and aged animals on behaviors that require the hippocampus and cortical regions to interact, however, has not been well characterized. Specifically, the ability to link a spatial location with specific features of a stimulus, such as object identity, relies on the hippocampus, perirhinal and prefrontal cortices. Although aging is associated with dysfunction in each of these brain regions, behavioral measures of functional change within the hippocampus, perirhinal and prefrontal cortices in individual animals are often not correlated. Thus, how dysfunction of a single brain region within this circuit, such as the hippocampus, impacts behaviors that require communication with the perirhinal and prefrontal cortices remains unknown. To address this question, young and aged rats were tested on the interregion dependent object-place paired association task, as well as a hippocampal-dependent test of spatial reference memory. This particular cohort of aged rats did not show deficits on the hippocampal-dependent task, but were significantly impaired at acquiring object-place associations relative to young. These data suggest that behaviors requiring functional connectivity across different regions of the memory network may be particularly sensitive to aging, and can be used to develop models that will clarify the impact of systems-level dysfunction in the elderly. PMID:26413723

A fast, model-independent method for cerebral cortical thickness estimation using MRI.

PubMed

Scott, M L J; Bromiley, P A; Thacker, N A; Hutchinson, C E; Jackson, A

2009-04-01

Several algorithms for measuring the cortical thickness in the human brain from MR image volumes have been described in the literature, the majority of which rely on fitting deformable models to the inner and outer cortical surfaces. However, the constraints applied during the model fitting process in order to enforce spherical topology and to fit the outer cortical surface in narrow sulci, where the cerebrospinal fluid (CSF) channel may be obscured by partial voluming, may introduce bias in some circumstances, and greatly increase the processor time required. In this paper we describe an alternative, voxel based technique that measures the cortical thickness using inversion recovery anatomical MR images. Grey matter, white matter and CSF are identified through segmentation, and edge detection is used to identify the boundaries between these tissues. The cortical thickness is then measured along the local 3D surface normal at every voxel on the inner cortical surface. The method was applied to 119 normal volunteers, and validated through extensive comparisons with published measurements of both cortical thickness and rate of thickness change with age. We conclude that the proposed technique is generally faster than deformable model-based alternatives, and free from the possibility of model bias, but suffers no reduction in accuracy. In particular, it will be applicable in data sets showing severe cortical atrophy, where thinning of the gyri leads to points of high curvature, and so the fitting of deformable models is problematic.

EEG-Based Quantification of Cortical Current Density and Dynamic Causal Connectivity Generalized across Subjects Performing BCI-Monitored Cognitive Tasks

PubMed Central

Courellis, Hristos; Mullen, Tim; Poizner, Howard; Cauwenberghs, Gert; Iversen, John R.

2017-01-01

Quantification of dynamic causal interactions among brain regions constitutes an important component of conducting research and developing applications in experimental and translational neuroscience. Furthermore, cortical networks with dynamic causal connectivity in brain-computer interface (BCI) applications offer a more comprehensive view of brain states implicated in behavior than do individual brain regions. However, models of cortical network dynamics are difficult to generalize across subjects because current electroencephalography (EEG) signal analysis techniques are limited in their ability to reliably localize sources across subjects. We propose an algorithmic and computational framework for identifying cortical networks across subjects in which dynamic causal connectivity is modeled among user-selected cortical regions of interest (ROIs). We demonstrate the strength of the proposed framework using a “reach/saccade to spatial target” cognitive task performed by 10 right-handed individuals. Modeling of causal cortical interactions was accomplished through measurement of cortical activity using (EEG), application of independent component clustering to identify cortical ROIs as network nodes, estimation of cortical current density using cortically constrained low resolution electromagnetic brain tomography (cLORETA), multivariate autoregressive (MVAR) modeling of representative cortical activity signals from each ROI, and quantification of the dynamic causal interaction among the identified ROIs using the Short-time direct Directed Transfer function (SdDTF). The resulting cortical network and the computed causal dynamics among its nodes exhibited physiologically plausible behavior, consistent with past results reported in the literature. This physiological plausibility of the results strengthens the framework's applicability in reliably capturing complex brain functionality, which is required by applications, such as diagnostics and BCI. PMID:28566997

Anxious/Depressed Symptoms are Linked to Right Ventromedial Prefrontal Cortical Thickness Maturation in Healthy Children and Young Adults

PubMed Central

Ducharme, Simon; Albaugh, Matthew D.; Hudziak, James J.; Botteron, Kelly N.; Nguyen, Tuong-Vi; Truong, Catherine; Evans, Alan C.; Karama, Sherif; Ball, William S.; Byars, Anna Weber; Schapiro, Mark; Bommer, Wendy; Carr, April; German, April; Dunn, Scott; Rivkin, Michael J.; Waber, Deborah; Mulkern, Robert; Vajapeyam, Sridhar; Chiverton, Abigail; Davis, Peter; Koo, Julie; Marmor, Jacki; Mrakotsky, Christine; Robertson, Richard; McAnulty, Gloria; Brandt, Michael E.; Fletcher, Jack M.; Kramer, Larry A.; Yang, Grace; McCormack, Cara; Hebert, Kathleen M.; Volero, Hilda; Botteron, Kelly; McKinstry, Robert C.; Warren, William; Nishino, Tomoyuki; Almli, C. Robert; Todd, Richard; Constantino, John; McCracken, James T.; Levitt, Jennifer; Alger, Jeffrey; O'Neil, Joseph; Toga, Arthur; Asarnow, Robert; Fadale, David; Heinichen, Laura; Ireland, Cedric; Wang, Dah-Jyuu; Moss, Edward; Zimmerman, Robert A.; Bintliff, Brooke; Bradford, Ruth; Newman, Janice; Evans, Alan C.; Arnaoutelis, Rozalia; Pike, G. Bruce; Collins, D. Louis; Leonard, Gabriel; Paus, Tomas; Zijdenbos, Alex; Das, Samir; Fonov, Vladimir; Fu, Luke; Harlap, Jonathan; Leppert, Ilana; Milovan, Denise; Vins, Dario; Zeffiro, Thomas; Van Meter, John; Lange, Nicholas; Froimowitz, Michael P.; Botteron, Kelly; Almli, C. Robert; Rainey, Cheryl; Henderson, Stan; Nishino, Tomoyuki; Warren, William; Edwards, Jennifer L.; Dubois, Diane; Smith, Karla; Singer, Tish; Wilber, Aaron A.; Pierpaoli, Carlo; Basser, Peter J.; Chang, Lin-Ching; Koay, Chen Guan; Walker, Lindsay; Freund, Lisa; Rumsey, Judith; Baskir, Lauren; Stanford, Laurence; Sirocco, Karen; Gwinn-Hardy, Katrina; Spinella, Giovanna; McCracken, James T.; Alger, Jeffry R.; Levitt, Jennifer; O'Neill, Joseph

2014-01-01

The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant “CBCL Anxious/Depressed by Age” interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (<9 years), but positively associated with thickness at older ages (15–22 years), with the shift in polarity occurring around age 12. This was secondary to a slower rate of vmPFC cortical thinning in subjects with higher scores. In young adults (18–22 years), Anxious/Depressed scores were also positively associated with precuneus/posterior cingulate cortical thickness. Potential neurobiological mechanisms underlying this maturation pattern are proposed. These results demonstrate the dynamic impact of age on relations between vmPFC and negative affect in the developing brain. PMID:23749874

Is There a Canonical Cortical Circuit for the Cholinergic System? Anatomical Differences Across Common Model Systems

PubMed Central

Coppola, Jennifer J.; Disney, Anita A.

2018-01-01

Acetylcholine (ACh) is believed to act as a neuromodulator in cortical circuits that support cognition, specifically in processes including learning, memory consolidation, vigilance, arousal and attention. The cholinergic modulation of cortical processes is studied in many model systems including rodents, cats and primates. Further, these studies are performed in cortical areas ranging from the primary visual cortex to the prefrontal cortex and using diverse methodologies. The results of these studies have been combined into singular models of function—a practice based on an implicit assumption that the various model systems are equivalent and interchangeable. However, comparative anatomy both within and across species reveals important differences in the structure of the cholinergic system. Here, we will review anatomical data including innervation patterns, receptor expression, synthesis and release compared across species and cortical area with a focus on rodents and primates. We argue that these data suggest no canonical cortical model system exists for the cholinergic system. Further, we will argue that as a result, care must be taken both in combining data from studies across cortical areas and species, and in choosing the best model systems to improve our understanding and support of human health. PMID:29440996

Is There a Canonical Cortical Circuit for the Cholinergic System? Anatomical Differences Across Common Model Systems.

PubMed

Coppola, Jennifer J; Disney, Anita A

2018-01-01

Acetylcholine (ACh) is believed to act as a neuromodulator in cortical circuits that support cognition, specifically in processes including learning, memory consolidation, vigilance, arousal and attention. The cholinergic modulation of cortical processes is studied in many model systems including rodents, cats and primates. Further, these studies are performed in cortical areas ranging from the primary visual cortex to the prefrontal cortex and using diverse methodologies. The results of these studies have been combined into singular models of function-a practice based on an implicit assumption that the various model systems are equivalent and interchangeable. However, comparative anatomy both within and across species reveals important differences in the structure of the cholinergic system. Here, we will review anatomical data including innervation patterns, receptor expression, synthesis and release compared across species and cortical area with a focus on rodents and primates. We argue that these data suggest no canonical cortical model system exists for the cholinergic system. Further, we will argue that as a result, care must be taken both in combining data from studies across cortical areas and species, and in choosing the best model systems to improve our understanding and support of human health.

Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

PubMed Central

Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl

2014-01-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both ‘action’ and ‘resting’ motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the ‘effective’ connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670

Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

PubMed

Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

2014-04-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

Electromagnetic Controlled Cortical Impact Device for Precise, Graded Experimental Traumatic Brain Injury

PubMed Central

BRODY, DAVID L.; DONALD, CHRISTINE Mac; KESSENS, CHAD C.; YUEDE, CARLA; PARSADANIAN, MAIA; SPINNER, MIKE; KIM, EDDIE; SCHWETYE, KATHERINE E.; HOLTZMAN, DAVID M.; BAYLY, PHILIP V.

2008-01-01

Genetically modified mice represent useful tools for traumatic brain injury (TBI) research and attractive preclinical models for the development of novel therapeutics. Experimental methods that minimize the number of mice needed may increase the pace of discovery. With this in mind, we developed and characterized a prototype electromagnetic (EM) controlled cortical impact device along with refined surgical and behavioral testing techniques. By varying the depth of impact between 1.0 and 3.0 mm, we found that the EM device was capable of producing a broad range of injury severities. Histologically, 2.0-mm impact depth injuries produced by the EM device were similar to 1.0-mm impact depth injuries produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-, and 3.0-mm impacts impaired hidden platform and probe trial water maze performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of conditioned fear performance was detected. No differences were found between sexes of mice. Inter-operator reliability was very good. Behaviorally, we found that we could statistically distinguish between injury depths differing by 0.5 mm using 12 mice per group and between injury depths differing by 1.0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice. PMID:17439349

Modeling vocalization with ECoG cortical activity recorded during vocal production in the macaque monkey.

PubMed

Fukushima, Makoto; Saunders, Richard C; Fujii, Naotaka; Averbeck, Bruno B; Mishkin, Mortimer

2014-01-01

Vocal production is an example of controlled motor behavior with high temporal precision. Previous studies have decoded auditory evoked cortical activity while monkeys listened to vocalization sounds. On the other hand, there have been few attempts at decoding motor cortical activity during vocal production. Here we recorded cortical activity during vocal production in the macaque with a chronically implanted electrocorticographic (ECoG) electrode array. The array detected robust activity in motor cortex during vocal production. We used a nonlinear dynamical model of the vocal organ to reduce the dimensionality of `Coo' calls produced by the monkey. We then used linear regression to evaluate the information in motor cortical activity for this reduced representation of calls. This simple linear model accounted for circa 65% of the variance in the reduced sound representations, supporting the feasibility of using the dynamical model of the vocal organ for decoding motor cortical activity during vocal production.

Assessment of Cortical and Trabecular Bone Changes in Two Models of Post-Traumatic Osteoarthritis

PubMed Central

Pauly, Hannah M; Larson, Blair E; Coatney, Garrett A; Button, Keith D.; DeCamp, Charlie E; Fajardo, Ryan S; Haut, Roger C; Donahue, Tammy L Haut

2015-01-01

Subchondral bone is thought to play a significant role in the initiation and progression of the post-traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed-joint traumatic compressive impact model. Twelve weeks post-injury bones were scanned via micro-computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint-wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans. PMID:26147652

Localized cortical chronic traumatic encephalopathy pathology after single, severe axonal injury in human brain.

PubMed

Shively, Sharon B; Edgerton, Sarah L; Iacono, Diego; Purohit, Dushyant P; Qu, Bao-Xi; Haroutunian, Vahram; Davis, Kenneth L; Diaz-Arrastia, Ramon; Perl, Daniel P

2017-03-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined cortical tissues at the leucotomy site and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy site. For comparison, we analyzed brain tissues at equivalent neuroanatomical sites from non-leucotomized patients with schizophrenia, matched in age and gender. All five leucotomy cases revealed severe white matter damage with dense astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau immunoreactivity in neurons, astrocytes and cell processes encompassing blood vessels at cortical sulcal depths in irregular patterns, similar to CTE. The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype. Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients, showed minimal p-tau and β-amyloid pathology. These findings suggest that chronic axonal damage contributes to the unique pathology of CTE over time.

An integrate-and-fire model for synchronized bursting in a network of cultured cortical neurons.

PubMed

French, D A; Gruenstein, E I

2006-12-01

It has been suggested that spontaneous synchronous neuronal activity is an essential step in the formation of functional networks in the central nervous system. The key features of this type of activity consist of bursts of action potentials with associated spikes of elevated cytoplasmic calcium. These features are also observed in networks of rat cortical neurons that have been formed in culture. Experimental studies of these cultured networks have led to several hypotheses for the mechanisms underlying the observed synchronized oscillations. In this paper, bursting integrate-and-fire type mathematical models for regular spiking (RS) and intrinsic bursting (IB) neurons are introduced and incorporated through a small-world connection scheme into a two-dimensional excitatory network similar to those in the cultured network. This computer model exhibits spontaneous synchronous activity through mechanisms similar to those hypothesized for the cultured experimental networks. Traces of the membrane potential and cytoplasmic calcium from the model closely match those obtained from experiments. We also consider the impact on network behavior of the IB neurons, the geometry and the small world connection scheme.

Structural brain changes and all-cause mortality in the elderly population-the mediating role of inflammation.

PubMed

Hanning, Uta; Roesler, Andreas; Peters, Annette; Berger, Klaus; Baune, Bernhard T

2016-12-01

While MRI brain changes have been related to mortality during ageing, the role of inflammation in this relationship remains poorly understood. Hence, this study aimed to investigate the impact of MRI changes on all-cause mortality and the mediating role of cytokines. All-cause mortality was evaluated in 268 community dwelling elderly (age 65-83 years) in the MEMO study (Memory and Morbidity in Augsburg elderly). MRI markers of brain atrophy and cerebral small vessel disease (SVD), C-reactive protein (CRP) and a panel of cytokines in serum were assessed. Cox proportional hazard models were used to estimate the association of MRI changes with survival over 9 years. Regression models were used to assess the hypothesis that inflammation is mediating the relationship between MRI-brain changes and mortality. In total, 77 (29 %) deaths occurred during a mean follow up of 9 years. After adjusting for confounders, the degree of global cortical atrophy and the level of the cytokines CRP, TNF-α and IL-8 were of higher significance in study participants who had died at follow-up in comparison to survivors. In Cox proportional hazard models, higher degrees of global cortical atrophy (HR 1.56, p = 0.003) and regional atrophy of the temporal lobe (HR 1.38, p = 0.011) were associated with a significantly increased risk of mortality. Mediation analyses revealed a partial mediation by IL-6 and IL-8 of the effects of global cortical atrophy on mortality. Global cortical brain atrophy is a significant indicator of survival in the elderly. Our study supports a possible role for inflammation in the atrophy pathogenesis. If replicated in other samples, IL-6 and IL-8 level assessment may improve risk prognosis for mortality.

The Role of Neuromodulators in Cortical Plasticity. A Computational Perspective

PubMed Central

Pedrosa, Victor; Clopath, Claudia

2017-01-01

Neuromodulators play a ubiquitous role across the brain in regulating plasticity. With recent advances in experimental techniques, it is possible to study the effects of diverse neuromodulatory states in specific brain regions. Neuromodulators are thought to impact plasticity predominantly through two mechanisms: the gating of plasticity and the upregulation of neuronal activity. However, the consequences of these mechanisms are poorly understood and there is a need for both experimental and theoretical exploration. Here we illustrate how neuromodulatory state affects cortical plasticity through these two mechanisms. First, we explore the ability of neuromodulators to gate plasticity by reshaping the learning window for spike-timing-dependent plasticity. Using a simple computational model, we implement four different learning rules and demonstrate their effects on receptive field plasticity. We then compare the neuromodulatory effects of upregulating learning rate versus the effects of upregulating neuronal activity. We find that these seemingly similar mechanisms do not yield the same outcome: upregulating neuronal activity can lead to either a broadening or a sharpening of receptive field tuning, whereas upregulating learning rate only intensifies the sharpening of receptive field tuning. This simple model demonstrates the need for further exploration of the rich landscape of neuromodulator-mediated plasticity. Future experiments, coupled with biologically detailed computational models, will elucidate the diversity of mechanisms by which neuromodulatory state regulates cortical plasticity. PMID:28119596

Large-scale modeling of the primary visual cortex: influence of cortical architecture upon neuronal response.

PubMed

McLaughlin, David; Shapley, Robert; Shelley, Michael

2003-01-01

A large-scale computational model of a local patch of input layer 4 [Formula: see text] of the primary visual cortex (V1) of the macaque monkey, together with a coarse-grained reduction of the model, are used to understand potential effects of cortical architecture upon neuronal performance. Both the large-scale point neuron model and its asymptotic reduction are described. The work focuses upon orientation preference and selectivity, and upon the spatial distribution of neuronal responses across the cortical layer. Emphasis is given to the role of cortical architecture (the geometry of synaptic connectivity, of the ordered and disordered structure of input feature maps, and of their interplay) as mechanisms underlying cortical responses within the model. Specifically: (i) Distinct characteristics of model neuronal responses (firing rates and orientation selectivity) as they depend upon the neuron's location within the cortical layer relative to the pinwheel centers of the map of orientation preference; (ii) A time independent (DC) elevation in cortico-cortical conductances within the model, in contrast to a "push-pull" antagonism between excitation and inhibition; (iii) The use of asymptotic analysis to unveil mechanisms which underly these performances of the model; (iv) A discussion of emerging experimental data. The work illustrates that large-scale scientific computation--coupled together with analytical reduction, mathematical analysis, and experimental data, can provide significant understanding and intuition about the possible mechanisms of cortical response. It also illustrates that the idealization which is a necessary part of theoretical modeling can outline in sharp relief the consequences of differing alternative interpretations and mechanisms--with final arbiter being a body of experimental evidence whose measurements address the consequences of these analyses.

Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

NASA Technical Reports Server (NTRS)

Werner, Christopher R.; Mulugeta, Lealem; Myers, J. G.; Pennline, J. A.

2015-01-01

NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

Cortical Feedback Control of Olfactory Bulb Circuits

PubMed Central

Boyd, Alison M.; Sturgill, James F.; Poo, Cindy; Isaacson, Jeffry S.

2013-01-01

SUMMARY Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. PMID:23259951

Cortical feedback control of olfactory bulb circuits.

PubMed

Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

2012-12-20

Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

Investigation of the effects of graded models on the biomechanical behavior of a bone-dental implant system under osteoporotic conditions

PubMed Central

Li, Ying; Shuang Liu, Zhong; Ming Bai, Xiao; Zhang, Bin

2013-01-01

Objective: To investigate the effects of graded models on the biomechanical behavior of a bone-implant system under osteoporotic conditions. Methodology : A finite element model (FEM) of the jawbone segments with a titanium implant is used. Two types of models (a graded model and a non-graded model) are established. The graded model is established based on the graded variation of the elastic modulus of the cortical bone and the non-graded model is defined by homogeneous cortical bone. The vertical and oblique loads are adopted. The max von Mises stresses and the max displacements of the cortical bone are evaluated. Results: Comparing the two types of models, the difference in the maximum von Mises stresses of the cortical bone is more than 20%. The values of the maximum displacements in the graded models are considerably less than in the non-graded models. Conclusions: These results indicate the significance of taking into account the actual graded properties of the cortical bone so that the biomechanical behavior of the bone-implant system can be analyzed accurately. PMID:24353590

Investigation of the effects of graded models on the biomechanical behavior of a bone-dental implant system under osteoporotic conditions.

PubMed

Li, Ying; Shuang Liu, Zhong; Ming Bai, Xiao; Zhang, Bin

2013-04-01

To investigate the effects of graded models on the biomechanical behavior of a bone-implant system under osteoporotic conditions. Methodology : A finite element model (FEM) of the jawbone segments with a titanium implant is used. Two types of models (a graded model and a non-graded model) are established. The graded model is established based on the graded variation of the elastic modulus of the cortical bone and the non-graded model is defined by homogeneous cortical bone. The vertical and oblique loads are adopted. The max von Mises stresses and the max displacements of the cortical bone are evaluated. Comparing the two types of models, the difference in the maximum von Mises stresses of the cortical bone is more than 20%. The values of the maximum displacements in the graded models are considerably less than in the non-graded models. These results indicate the significance of taking into account the actual graded properties of the cortical bone so that the biomechanical behavior of the bone-implant system can be analyzed accurately.

Functional connectivity and dynamics of cortical-thalamic networks co-cultured in a dual compartment device

NASA Astrophysics Data System (ADS)

Kanagasabapathi, Thirukumaran T.; Massobrio, Paolo; Barone, Rocco Andrea; Tedesco, Mariateresa; Martinoia, Sergio; Wadman, Wytse J.; Decré, Michel M. J.

2012-06-01

Co-cultures containing dissociated cortical and thalamic cells may provide a unique model for understanding the pathophysiology in the respective neuronal sub-circuitry. In addition, developing an in vitro dissociated co-culture model offers the possibility of studying the system without influence from other neuronal sub-populations. Here we demonstrate a dual compartment system coupled to microelectrode arrays (MEAs) for co-culturing and recording spontaneous activities from neuronal sub-populations. Propagation of electrical activities between cortical and thalamic regions and their interdependence in connectivity is verified by means of a cross-correlation algorithm. We found that burst events originate in the cortical region and drive the entire cortical-thalamic network bursting behavior while mutually weak thalamic connections play a relevant role in sustaining longer burst events in cortical cells. To support these experimental findings, a neuronal network model was developed and used to investigate the interplay between network dynamics and connectivity in the cortical-thalamic system.

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.

Network analysis of corticocortical connections reveals ventral and dorsal processing streams in mouse visual cortex

PubMed Central

Wang, Quanxin; Sporns, Olaf; Burkhalter, Andreas

2012-01-01

Much of the information used for visual perception and visually guided actions is processed in complex networks of connections within the cortex. To understand how this works in the normal brain and to determine the impact of disease, mice are promising models. In primate visual cortex, information is processed in a dorsal stream specialized for visuospatial processing and guided action and a ventral stream for object recognition. Here, we traced the outputs of 10 visual areas and used quantitative graph analytic tools of modern network science to determine, from the projection strengths in 39 cortical targets, the community structure of the network. We found a high density of the cortical graph that exceeded that previously shown in monkey. Each source area showed a unique distribution of projection weights across its targets (i.e. connectivity profile) that was well-fit by a lognormal function. Importantly, the community structure was strongly dependent on the location of the source area: outputs from medial/anterior extrastriate areas were more strongly linked to parietal, motor and limbic cortex, whereas lateral extrastriate areas were preferentially connected to temporal and parahippocampal cortex. These two subnetworks resemble dorsal and ventral cortical streams in primates, demonstrating that the basic layout of cortical networks is conserved across species. PMID:22457489

Coherent ongoing subthreshold state of a cortical neural network regulated by slow- and fast-spiking interneurons.

PubMed

Hoshino, Osamu

2006-12-01

Although details of cortical interneurons in anatomy and physiology have been well understood, little is known about how they contribute to ongoing spontaneous neuronal activity that could have a great impact on subsequent neuronal information processing. Simulating a cortical neural network model of an early sensory area, we investigated whether and how two distinct types of inhibitory interneurons, or fast-spiking interneurons with narrow axonal arbors and slow-spiking interneurons with wide axonal arbors, have a spatiotemporal influence on the ongoing activity of principal cells and subsequent cognitive information processing. In the model, dynamic cell assemblies, or population activation of principal cells, expressed information about specific sensory features. Within cell assemblies, fast-spiking interneurons give a feedback inhibitory effect on principal cells. Between cell assemblies, slow-spiking interneurons give a lateral inhibitory effect on principal cells. Here, we show that these interneurons keep the network at a subthreshold level for action potential generation under the ongoing state, by which the reaction time of principal cells to sensory stimulation could be accelerated. We suggest that the best timing of inhibition mediated by fast-spiking interneurons and slow-spiking interneurons allows the network to remain near threshold for rapid responses to input.

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

PubMed Central

Jones, Theresa A.; Liput, Daniel J.; Maresh, Erin L.; Donlan, Nicole; Parikh, Toral J.; Marlowe, Dana

2012-01-01

Abstract Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3–28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI. PMID:22352953

The neuroprotective effect of rat adipose tissue-derived mesenchymal stem cell-conditioned medium on cortical neurons using an in vitro model of SCI inflammation.

PubMed

Szekiova, Eva; Slovinska, Lucia; Blasko, Juraj; Plsikova, Jana; Cizkova, Dasa

2018-04-01

Objectives In this study, a new approach was used with an in vitro model in which neural cells were exposed to conditioned media from the injured spinal cord (SCI-CM) mimicking a local inflammatory microenvironment . Subsequently, the neuroprotective effect of rat adipose tissue-derived msesenchymal stem cell-conditioned media (ATMSC-CM) was investigated through a cell-free based therapy, which was used to treat cortical neurons and astrocytes under inflammation. Methods Primary cell cultures isolated from postnatal day (P6) Wistar rat brain cortex were exposed to SCI-CM derived from the central lesion, rostral and caudal segments of injured spinal cord. After 48 h incubation, the SCI-CM was replaced and primary cultures were cultivated either in DMEM media alone or in ATMSC-CM for 72 h. The impact of ATMSC-CM on the viability of neurons and astrocytes was assessed using a CyQUANT® Direct Cell Proliferation Assay Kit as well as immunocytochemistry analysis. Results Immunocytochemical analysis revealed significant decrease in the number of MAP2 positive neurons exposed to SCI-CM compared to Control. Protection by ATMSC-CM was associated with increased survival of neurons compared to primary culture cultivated in DMEM media alone. The ATMSC-CM effect on astrocytes was more variable and without any significant impact. Conclusion The results demonstrate that SCI-CM mimicking inflammation can reduce cortical neuron survival, and subsequent exposure to ATMSC-CM can stabilize the neuronal population most likely via released neuroprotective and trophic factors. In addition, astrogliosis was not affected by ATMSC-CM.

Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

PubMed Central

Novotny, Susan A.; Mader, Tara L.; Greising, Angela G.; Lin, Angela S.; Guldberg, Robert E.; Warren, Gordon L.; Lowe, Dawn A.

2014-01-01

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice. PMID:25121503

Use-dependent dendritic regrowth is limited after unilateral controlled cortical impact to the forelimb sensorimotor cortex.

PubMed

Jones, Theresa A; Liput, Daniel J; Maresh, Erin L; Donlan, Nicole; Parikh, Toral J; Marlowe, Dana; Kozlowski, Dorothy A

2012-05-01

Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.

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.

Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice.

PubMed

Miller, Darren M; Singh, Indrapal N; Wang, Juan A; Hall, Edward D

2015-02-01

The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. Previous research has shown that neuronal mitochondria are susceptible to oxidative damage post-TBI, and thus the current study investigates whether Nrf2-ARE activation protects mitochondrial function when activated post-TBI. It was hypothesized that administration of carnosic acid (CA) would reduce oxidative damage biomarkers in the brain tissue and also preserve cortical mitochondrial respiratory function post-TBI. A mouse controlled cortical impact (CCI) model was employed with a 1.0mm cortical deformation injury. Administration of CA at 15 min post-TBI reduced cortical lipid peroxidation, protein nitration, and cytoskeletal breakdown markers in a dose-dependent manner at 48 h post-injury. Moreover, CA preserved mitochondrial respiratory function compared to vehicle animals. This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8h post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI. Copyright © 2014 Elsevier Inc. 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.

Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy.

PubMed

Jellett, Adam P; Jenks, Kyle; Lucas, Marcella; Scott, Rod C

2015-02-01

Children with epilepsy face significant cognitive and behavioral impairments. These impairments are due to a poorly characterized interaction between the underlying etiology, the effect of seizures and the effect of medication. The large variation in these factors make understanding the main drivers of cognitive impairment in humans extremely difficult. Therefore, we investigated the cognitive effect of seizures and the antiepileptic drug valproic acid in a rodent model of cortical dysplasia. Rats were divided into seizure-receiving and non-receiving groups. Rats experienced frequent early life seizures using the flurothyl inhalation method: 50 seizures between postnatal day 5 and 15 and then one seizure a day following that. Rats were further divided into drug-treated and vehicle treated groups. Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration. We show here that the main driver of cognitive impairments are the brain malformations, and that persistent seizures in animals with brain malformations and valproic acid caused no additional impact. These findings suggest that neither an appropriate dose of a standard antiepileptic drug or intractable seizures worsen cognition associated with a malformation of cortical development and that alternative treatment strategies to improve cognition are required. Copyright © 2014 Elsevier B.V. All rights reserved.

Risk Factors and Cognitive Relevance of Cortical Cerebral Microinfarcts in Patients With Ischemic Stroke or Transient Ischemic Attack.

PubMed

Wang, Zhaolu; van Veluw, Susanne J; Wong, Adrian; Liu, Wenyan; Shi, Lin; Yang, Jie; Xiong, Yunyun; Lau, Alexander; Biessels, Geert Jan; Mok, Vincent C T

2016-10-01

It was recently demonstrated that cerebral microinfarcts (CMIs) can be detected in vivo using 3.0 tesla (T) magnetic resonance imaging. We investigated the prevalence, risk factors, and the longitudinal cognitive consequence of cortical CMIs on 3.0T magnetic resonance imaging, in patients with ischemic stroke or transient ischemic attack. A total of 231 patients undergoing 3.0T magnetic resonance imaging were included. Montreal Cognitive Assessment was used to evaluate global cognitive functions and cognitive domains (memory, language, and attention visuospatial and executive functions). Cognitive changes were represented by the difference in Montreal Cognitive Assessment score between baseline and 28-month after stroke/transient ischemic attack. The cross-sectional and longitudinal associations between cortical CMIs and cognitive functions were explored using ANCOVA and regression models. Cortical CMIs were observed in 34 patients (14.7%), including 13 patients with acute (hyperintense on diffusion-weighted imaging) and 21 with chronic CMIs (isointense on diffusion-weighted imaging). Atrial fibrillation was a risk factor for all cortical CMIs (odds ratio, 4.8; 95% confidence interval, 1.5-14.9; P=0.007). Confluent white matter hyperintensities was associated with chronic CMIs (odds ratio, 2.8; 95% confidence interval, 1.0-7.8; P=0.047). The presence of cortical CMIs at baseline was associated with worse visuospatial functions at baseline and decline over 28-month follow-up (β=0.5; 95% confidence interval, 0.1-1.0; P=0.008, adjusting for brain atrophy, white matter hyperintensities, lacunes, and microbleeds). Cortical CMIs are a common finding in patients with stroke/transient ischemic attack. Associations between CMI with atrial fibrillation and white matter hyperintensities suggest that these lesions have a heterogeneous cause, involving microembolism and cerebral small vessel disease. CMI seemed to preferentially impact visuospatial functions as assessed by a cognitive screening test. © 2016 American Heart Association, Inc.

Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

PubMed

Qin, Xinghu; You, Hong; Cao, Fang; Wu, Yue; Peng, Jianhua; Pang, Jinwei; Xu, Hong; Chen, Yue; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Sun, Xiaochuan; Jiang, Yong

2017-02-15

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

A protocol for characterizing the impact of collateral flow after distal middle cerebral artery occlusion

PubMed Central

DeFazio, R. Anthony; Levy, Sean; Morales, Carmen L.; Levy, Rebecca V.; Dave, Kunjan R.; Lin, Hung W.; Abaffy, Tatjana; Watson, Brant D.; Perez-Pinzon, Miguel A.; Ohanna, Victoria

2010-01-01

I. SUMMARY In humans and in animal models of stroke, collateral blood flow between territories of the major pial arteries has a profound impact on cortical infarct size. However, there is a gap in our understanding of the genetic determinants of collateral formation and flow, as well as the signaling pathways and neurovascular interactions regulating this flow. Previous studies have demonstrated that collateral flow between branches of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) can protect mouse cortex from infarction after middle cerebral artery occlusion. Because the number and diameter of collaterals varies among mouse strains and after transgenic manipulations, a combination of methods is required to control for these variations. Here, we report an inexpensive approach to characterizing the cerebrovascular anatomy, and in vivo monitoring of cerebral blood flow as well. Further, we introduce a new, minimally invasive method for the occlusion of distal MCA branches. These methods will permit a new generation of studies on the mechanisms regulating collateral remodeling and cortical blood flow after stroke. PMID:21593993

Effects of gemfibrozil on outcome after permanent middle cerebral artery occlusion in mice

PubMed Central

Guo, Qingmin; Wang, Guangming; Liu, Xiaowei; Namura, Shobu

2009-01-01

Fibrates are lipid lowering drugs and found as ligands for peroxisome proliferator-activated receptors (PPARs). A clinical study has shown that one type of fibrate gemfibrozil reduces stroke incidence in men. However, it remains unknown whether gemfibrozil improves outcome after stroke. We hypothesized that prophylactic administration of gemfibrozil improves outcome after ischemic stroke. In this study, we measured the impact of gemfibrozil in two permanent middle cerebral artery occlusion (MCAO) models in young adult male mice on normal diet. First, we tested gemfibrozil in a filamentous MCAO model. Pretreatment with gemfibrozil (30 mg/kg) for 7 days moderately but significantly reduced infarct size at 24 h after MCAO. A higher dose (120 mg/kg) did not attenuate infarct size. Rather, it tended to increase brain swelling. Second, we tested in a distal MCAO model. Gemfibrozil (30 mg/kg) for 7 days before and after stroke significantly attenuated cortical lesion size at 7 days after MCAO. Cortical blood flow measured by laser speckle imaging was improved by gemfibrozil in the ischemic hemisphere. In non-stroke animals gemfibrozil also altered gene expression levels of PPARs in both the aorta and brain in organ specific manners; however, endothelial nitric oxide synthase (eNOS) was not significantly affected. These findings suggested the possibility that the observed infarct reductions and cortical blood flow improvements in ischemic brains were not through eNOS-mediated mechanisms. Further investigations may be meritorious to examine whether prophylactic usage of gemfibrozil against stroke is beneficial. PMID:19427843

Effects of gemfibrozil on outcome after permanent middle cerebral artery occlusion in mice.

PubMed

Guo, Qingmin; Wang, Guangming; Liu, Xiaowei; Namura, Shobu

2009-07-07

Fibrates are lipid lowering drugs and found as ligands for peroxisome proliferator-activated receptors (PPARs). A clinical study has shown that one type of fibrate gemfibrozil reduces stroke incidence in men. However, it remains unknown whether gemfibrozil improves outcome after stroke. We hypothesized that prophylactic administration of gemfibrozil improves outcome after ischemic stroke. In this study, we measured the impact of gemfibrozil in two permanent middle cerebral artery occlusion (MCAO) models in young adult male mice on normal diet. First, we tested gemfibrozil in a filamentous MCAO model. Pretreatment with gemfibrozil (30 mg/kg) for 7 days moderately but significantly reduced infarct size at 24 h after MCAO. A higher dose (120 mg/kg) did not attenuate infarct size. Rather, it tended to increase brain swelling. Second, we tested in a distal MCAO model. Gemfibrozil (30 mg/kg) for 7 days before and after stroke significantly attenuated cortical lesion size at 7 days after MCAO. Cortical blood flow measured by laser speckle imaging was improved by gemfibrozil in the ischemic hemisphere. In non-stroke animals gemfibrozil also altered gene expression levels of PPARs in both the aorta and brain in organ specific manners; however, endothelial nitric oxide synthase (eNOS) was not significantly affected. These findings suggested the possibility that the observed infarct reductions and cortical blood flow improvements in ischemic brains were not through eNOS-mediated mechanisms. Further investigations may be meritorious to examine whether prophylactic usage of gemfibrozil against stroke is beneficial.

Laminar development of receptive fields, maps and columns in visual cortex: the coordinating role of the subplate.

PubMed

Grossberg, Stephen; Seitz, Aaron

2003-08-01

How is development of cortical maps in V1 coordinated across cortical layers to form cortical columns? Previous neural models propose how maps of orientation (OR), ocular dominance (OD), and related properties develop in V1. These models show how spontaneous activity, before eye opening, combined with correlation learning and competition, can generate maps similar to those found in vivo. These models have not discussed laminar architecture or how cells develop and coordinate their connections across cortical layers. This is an important problem since anatomical evidence shows that clusters of horizontal connections form, between iso-oriented regions, in layer 2/3 before being innervated by layer 4 afferents. How are orientations in different layers aligned before these connections form? Anatomical evidence demonstrates that thalamic afferents wait in the subplate for weeks before innervating layer 4. Other evidence shows that ablation of the cortical subplate interferes with the development of OR and OD columns. The model proposes how the subplate develops OR and OD maps, which then entrain and coordinate the development of maps in other lamina. The model demonstrates how these maps may develop in layer 4 by using a known transient subplate-to-layer 4 circuit as a teacher. The model subplate also guides the early clustering of horizontal connections in layer 2/3, and the formation of the interlaminar circuitry that forms cortical columns. It is shown how layer 6 develops and helps to stabilize the network when the subplate atrophies. Finally the model clarifies how brain-derived neurotrophic factor (BDNF) manipulations may influence cortical development.

Synthetic event-related potentials: a computational bridge between neurolinguistic models and experiments.

PubMed

Barrès, Victor; Simons, Arthur; Arbib, Michael

2013-01-01

Our previous work developed Synthetic Brain Imaging to link neural and schema network models of cognition and behavior to PET and fMRI studies of brain function. We here extend this approach to Synthetic Event-Related Potentials (Synthetic ERP). Although the method is of general applicability, we focus on ERP correlates of language processing in the human brain. The method has two components: Phase 1: To generate cortical electro-magnetic source activity from neural or schema network models; and Phase 2: To generate known neurolinguistic ERP data (ERP scalp voltage topographies and waveforms) from putative cortical source distributions and activities within a realistic anatomical model of the human brain and head. To illustrate the challenges of Phase 2 of the methodology, spatiotemporal information from Friederici's 2002 model of auditory language comprehension was used to define cortical regions and time courses of activation for implementation within a forward model of ERP data. The cortical regions from the 2002 model were modeled using atlas-based masks overlaid on the MNI high definition single subject cortical mesh. The electromagnetic contribution of each region was modeled using current dipoles whose position and orientation were constrained by the cortical geometry. In linking neural network computation via EEG forward modeling to empirical results in neurolinguistics, we emphasize the need for neural network models to link their architecture to geometrically sound models of the cortical surface, and the need for conceptual models to refine and adopt brain-atlas based approaches to allow precise brain anchoring of their modules. The detailed analysis of Phase 2 sets the stage for a brief introduction to Phase 1 of the program, including the case for a schema-theoretic approach to language production and perception presented in detail elsewhere. Unlike Dynamic Causal Modeling (DCM) and Bojak's mean field model, Synthetic ERP builds on models of networks that mediate the relation between the brain's inputs, outputs, and internal states in executing a specific task. The neural networks used for Synthetic ERP must include neuroanatomically realistic placement and orientation of the cortical pyramidal neurons. These constraints pose exciting challenges for future work in neural network modeling that is applicable to systems and cognitive neuroscience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cortical Brain Malformation and Learning Impairments Induced by Developmental Thyroid Hormone Insufficiency: A Cross-Fostering Study

EPA Science Inventory

Although it is clear that severe reductions in thyroid hormones (TH) during development alter brain structure and function, the impact of low level, timing, and duration of TH insufficiency is less well understood. We have previously reported the presence of a cortical heterotopi...

Changes in Cortical Plasticity in Relation to a History of Concussion during Adolescence

PubMed Central

Meehan, Sean K.; Mirdamadi, Jasmine L.; Martini, Douglas N.; Broglio, Steven P.

2017-01-01

Adolescence and early adulthood is a critical period for neurophysiological development potentially characterized by an increased susceptibility to the long-term effects of traumatic brain injury. The current study investigated differences in motor cortical physiology and neuroplastic potential across a cohort of young adults with adolescent concussion history and those without. Transcranial magnetic stimulation (TMS) was used to assess motor evoked potential (MEP) amplitude, short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) before and after intermittent theta burst stimulation (iTBS). Pre-iTBS, MEP amplitude, but not SICI or ICF, was greater in the concussion history group. Post-iTBS, the expected increase in MEP amplitude and ICF was tempered in the concussion history group. Change in SICI was variable within the concussion history group. Post hoc assessment revealed that SICI was significantly lower in individuals whose concussion was not diagnosed at the time of injury compared to both those without a concussion history or whose concussion was medically diagnosed. Concussive impacts during adolescence appear to result in a persistent reduction of the ability to modulate facilitatory motor networks. Failure to report/identify concussive impacts close to injury during adolescence also appears to produce persistent change in inhibitory networks. These findings highlight the potential long-term impact of adolescent concussion upon motor cortical physiology. PMID:28144218

Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

PubMed

Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

2018-05-01

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

The Impact of Cortical Deafferentation on the Neocortical Slow Oscillation

PubMed Central

Lemieux, Maxime; Chen, Jen-Yung; Lonjers, Peter; Bazhenov, Maxim

2014-01-01

Slow oscillation is the main brain rhythm observed during deep sleep in mammals. Although several studies have demonstrated its neocortical origin, the extent of the thalamic contribution is still a matter of discussion. Using electrophysiological recordings in vivo on cats and computational modeling, we found that the local thalamic inactivation or the complete isolation of the neocortical slabs maintained within the brain dramatically reduced the expression of slow and fast oscillations in affected cortical areas. The slow oscillation began to recover 12 h after thalamic inactivation. The slow oscillation, but not faster activities, nearly recovered after 30 h and persisted for weeks in the isolated slabs. We also observed an increase of the membrane potential fluctuations recorded in vivo several hours after thalamic inactivation. Mimicking this enhancement in a network computational model with an increased postsynaptic activity of long-range intracortical afferents or scaling K+ leak current, but not several other Na+ and K+ intrinsic currents was sufficient for recovering the slow oscillation. We conclude that, in the intact brain, the thalamus contributes to the generation of cortical active states of the slow oscillation and mediates its large-scale synchronization. Our study also suggests that the deafferentation-induced alterations of the sleep slow oscillation can be counteracted by compensatory intracortical mechanisms and that the sleep slow oscillation is a fundamental and intrinsic state of the neocortex. PMID:24741059

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

Multiple sparse volumetric priors for distributed EEG source reconstruction.

PubMed

Strobbe, Gregor; van Mierlo, Pieter; De Vos, Maarten; Mijović, Bogdan; Hallez, Hans; Van Huffel, Sabine; López, José David; Vandenberghe, Stefaan

2014-10-15

We revisit the multiple sparse priors (MSP) algorithm implemented in the statistical parametric mapping software (SPM) for distributed EEG source reconstruction (Friston et al., 2008). In the present implementation, multiple cortical patches are introduced as source priors based on a dipole source space restricted to a cortical surface mesh. In this note, we present a technique to construct volumetric cortical regions to introduce as source priors by restricting the dipole source space to a segmented gray matter layer and using a region growing approach. This extension allows to reconstruct brain structures besides the cortical surface and facilitates the use of more realistic volumetric head models including more layers, such as cerebrospinal fluid (CSF), compared to the standard 3-layered scalp-skull-brain head models. We illustrated the technique with ERP data and anatomical MR images in 12 subjects. Based on the segmented gray matter for each of the subjects, cortical regions were created and introduced as source priors for MSP-inversion assuming two types of head models. The standard 3-layered scalp-skull-brain head models and extended 4-layered head models including CSF. We compared these models with the current implementation by assessing the free energy corresponding with each of the reconstructions using Bayesian model selection for group studies. Strong evidence was found in favor of the volumetric MSP approach compared to the MSP approach based on cortical patches for both types of head models. Overall, the strongest evidence was found in favor of the volumetric MSP reconstructions based on the extended head models including CSF. These results were verified by comparing the reconstructed activity. The use of volumetric cortical regions as source priors is a useful complement to the present implementation as it allows to introduce more complex head models and volumetric source priors in future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Abnormal cell-intrinsic and network excitability in the neocortex of serotonin-deficient Pet-1 knockout mice.

PubMed

Puzerey, Pavel A; Kodama, Nathan X; Galán, Roberto F

2016-02-01

Neurons originating from the raphe nuclei of the brain stem are the exclusive source of serotonin (5-HT) to the cortex. Their serotonergic phenotype is specified by the transcriptional regulator Pet-1, which is also necessary for maintaining their neurotransmitter identity across development. Transgenic mice in which Pet-1 is genetically ablated (Pet-1(-/-)) show a dramatic reduction (∼80%) in forebrain 5-HT levels, yet no investigations have been carried out to assess the impact of such severe 5-HT depletion on the function of target cortical neurons. Using whole cell patch-clamp methods, two-dimensional (2D) multielectrode arrays (MEAs), 3D morphological neuronal reconstructions, and animal behavior, we investigated the impact of 5-HT depletion on cortical cell-intrinsic and network excitability. We found significant changes in several parameters of cell-intrinsic excitability in cortical pyramidal cells (PCs) as well as an increase in spontaneous synaptic excitation through 5-HT3 receptors. These changes are associated with increased local network excitability and oscillatory activity in a 5-HT2 receptor-dependent manner, consistent with previously reported hypersensitivity of cortical 5-HT2 receptors. PC morphology was also altered, with a significant reduction in dendritic complexity that may possibly act as a compensatory mechanism for increased excitability. Consistent with this interpretation, when we carried out experiments with convulsant-induced seizures to asses cortical excitability in vivo, we observed no significant differences in seizure parameters between wild-type and Pet-1(-/-) mice. Moreover, MEA recordings of propagating field potentials showed diminished propagation of activity across the cortical sheath. Together these findings reveal novel functional changes in neuronal and cortical excitability in mice lacking Pet-1. Copyright © 2016 the American Physiological Society.

Abnormal cell-intrinsic and network excitability in the neocortex of serotonin-deficient Pet-1 knockout mice

PubMed Central

Puzerey, Pavel A.; Kodama, Nathan X.

2015-01-01

Neurons originating from the raphe nuclei of the brain stem are the exclusive source of serotonin (5-HT) to the cortex. Their serotonergic phenotype is specified by the transcriptional regulator Pet-1, which is also necessary for maintaining their neurotransmitter identity across development. Transgenic mice in which Pet-1 is genetically ablated (Pet-1−/−) show a dramatic reduction (∼80%) in forebrain 5-HT levels, yet no investigations have been carried out to assess the impact of such severe 5-HT depletion on the function of target cortical neurons. Using whole cell patch-clamp methods, two-dimensional (2D) multielectrode arrays (MEAs), 3D morphological neuronal reconstructions, and animal behavior, we investigated the impact of 5-HT depletion on cortical cell-intrinsic and network excitability. We found significant changes in several parameters of cell-intrinsic excitability in cortical pyramidal cells (PCs) as well as an increase in spontaneous synaptic excitation through 5-HT3 receptors. These changes are associated with increased local network excitability and oscillatory activity in a 5-HT2 receptor-dependent manner, consistent with previously reported hypersensitivity of cortical 5-HT2 receptors. PC morphology was also altered, with a significant reduction in dendritic complexity that may possibly act as a compensatory mechanism for increased excitability. Consistent with this interpretation, when we carried out experiments with convulsant-induced seizures to asses cortical excitability in vivo, we observed no significant differences in seizure parameters between wild-type and Pet-1−/− mice. Moreover, MEA recordings of propagating field potentials showed diminished propagation of activity across the cortical sheath. Together these findings reveal novel functional changes in neuronal and cortical excitability in mice lacking Pet-1. PMID:26609119

Cortical Thickness Changes Correlate with Cognition Changes after Cognitive Training: Evidence from a Chinese Community Study

PubMed Central

Jiang, Lijuan; Cao, Xinyi; Li, Ting; Tang, Yingying; Li, Wei; Wang, Jijun; Chan, Raymond C.; Li, Chunbo

2016-01-01

The aim of this study was to investigate whether changes in cortical thickness correlated with cognitive function changes in healthy older adults after receiving cognitive training interventions. Moreover, it also aimed to examine the differential impacts of a multi-domain and a single-domain cognitive training interventions. Longitudinal magnetic resonance imaging (MRI) scanning was performed on participants 65–75 years of age using the Siemens 3.0 T Trio Tim with the Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence. The cortical thickness was determined using FreeSurfer Software. Cognitive functioning was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant group × time interaction effects on the left supramarginal, the left frontal pole cortical regions; and a marginal significant group × time interaction effects on visuospatial/constructional and delayed memory scores. In a multi-domain cognitive training group, a number of cortical region changes were significantly positively correlated with changes in attention, delayed memory, and the total score, but significantly negatively correlated with changes in immediate memory and language scores. In the single-domain cognitive training group, some cortical region changes were significantly positively associated with changes in immediate memory, delayed memory, and the total score, while they were significantly negatively associated with changes in visuospatial/constructional, language, and attention scores. Overall, multi-domain cognitive training offered more advantages in visuospatial/constructional, attention, and delayed memory abilities, while single-domain cognitive training benefited immediate memory ability more effectively. These findings suggest that healthy older adults benefit more from the multi-domain cognitive training than single-domain cognitive training. Cognitive training has impacted on cortical thickness changes in healthy elderly. PMID:27252649

Craniotomy: true sham for traumatic brain injury, or a sham of a sham?

PubMed

Cole, Jeffrey T; Yarnell, Angela; Kean, William S; Gold, Eric; Lewis, Bobbi; Ren, Ming; McMullen, David C; Jacobowitz, David M; Pollard, Harvey B; O'Neill, J Timothy; Grunberg, Neil E; Dalgard, Clifton L; Frank, Joseph A; Watson, William D

2011-03-01

Abstract Neurological dysfunction after traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use "sham" (craniotomy alone) animals as controls. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. To test this hypothesis, 38 adult female rats were assigned to one of three groups: control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. The rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses compared to trephine or naïve rats. Finally, of the seven tested cytokines, KC-GRO and IFN-γ showed significant increases in both craniotomy models compared to naïve rats. We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating "sham" procedures should distinguish among sham, experimentally injured, and healthy/naïve animals, to help reduce confounding factors.

Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures.

PubMed

Schwerin, Susan C; Hutchinson, Elizabeth B; Radomski, Kryslaine L; Ngalula, Kapinga P; Pierpaoli, Carlo M; Juliano, Sharon L

2017-06-15

Although rodent TBI studies provide valuable information regarding the effects of injury and recovery, an animal model with neuroanatomical characteristics closer to humans may provide a more meaningful basis for clinical translation. The ferret has a high white/gray matter ratio, gyrencephalic neocortex, and ventral hippocampal location. Furthermore, ferrets are amenable to behavioral training, have a body size compatible with pre-clinical MRI, and are cost-effective. We optimized the surgical procedure for controlled cortical impact (CCI) using 9 adult male ferrets. We used subject-specific brain/skull morphometric data from anatomical MRIs to overcome across-subject variability for lesion placement. We also reflected the temporalis muscle, closed the craniotomy, and used antibiotics. We then gathered MRI, behavioral, and immunohistochemical data from 6 additional animals using the optimized surgical protocol: 1 control, 3 mild, and 1 severely injured animals (surviving one week) and 1 moderately injured animal surviving sixteen weeks. The optimized surgical protocol resulted in consistent injury placement. Astrocytic reactivity increased with injury severity showing progressively greater numbers of astrocytes within the white matter. The density and morphological changes of microglia amplified with injury severity or time after injury. Motor and cognitive impairments scaled with injury severity. The optimized surgical methods differ from those used in the rodent, and are integral to success using a ferret model. We optimized ferret CCI surgery for consistent injury placement. The ferret is an excellent animal model to investigate pathophysiological and behavioral changes associated with TBI. Published by Elsevier B.V.

PET staging of amyloidosis using striatum.

PubMed

Hanseeuw, Bernard J; Betensky, Rebecca A; Mormino, Elizabeth C; Schultz, Aaron P; Sepulcre, Jorge; Becker, John A; Jacobs, Heidi I L; Buckley, Rachel F; LaPoint, Molly R; Vanini, Patrizia; Donovan, Nancy J; Chhatwal, Jasmeer P; Marshall, Gad A; Papp, Kathryn V; Amariglio, Rebecca E; Rentz, Dorene M; Sperling, Reisa A; Johnson, Keith A

2018-05-21

Amyloid PET data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid. PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research. Copyright © 2018. Published by Elsevier Inc.

Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow.

PubMed

Emans, Tonja W; Janssen, Ben J; Pinkham, Maximilian I; Ow, Connie P C; Evans, Roger G; Joles, Jaap A; Malpas, Simon C; Krediet, C T Paul; Koeners, Maarten P

2016-11-01

Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min -1 . Equi-pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin-angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PO2. This could be reversed within minutes by pharmacological angiotensin-II receptor type 1 (AT 1 R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT 1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm.

PubMed

Dura-Bernal, Salvador; Zhou, Xianlian; Neymotin, Samuel A; Przekwas, Andrzej; Francis, Joseph T; Lytton, William W

2015-01-01

Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of limb prosthetics.

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

Brain structure–function associations in multi-generational families genetically enriched for bipolar disorder

PubMed Central

Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K.; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C.; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier I.; Glahn, David C.; Thompson, Paul M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Cantor, Rita M.; Freimer, Nelson B.; Bearden, Carrie E.

2015-01-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain–behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain–behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18–87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain–behaviour associations and test whether brain–behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain–behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain–behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure–function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. PMID:25943422

Predonation Volume of Future Remnant Cortical Kidney Helps Predict Postdonation Renal Function in Live Kidney Donors.

PubMed

Fananapazir, Ghaneh; Benzl, Robert; Corwin, Michael T; Chen, Ling-Xin; Sageshima, Junichiro; Stewart, Susan L; Troppmann, Christoph

2018-07-01

Purpose To determine whether the predonation computed tomography (CT)-based volume of the future remnant kidney is predictive of postdonation renal function in living kidney donors. Materials and Methods This institutional review board-approved, retrospective, HIPAA-compliant study included 126 live kidney donors who had undergone predonation renal CT between January 2007 and December 2014 as well as 2-year postdonation measurement of estimated glomerular filtration rate (eGFR). The whole kidney volume and cortical volume of the future remnant kidney were measured and standardized for body surface area (BSA). Bivariate linear associations between the ratios of whole kidney volume to BSA and cortical volume to BSA were obtained. A linear regression model for 2-year postdonation eGFR that incorporated donor age, sex, and either whole kidney volume-to-BSA ratio or cortical volume-to-BSA ratio was created, and the coefficient of determination (R 2 ) for the model was calculated. Factors not statistically additive in assessing 2-year eGFR were removed by using backward elimination, and the coefficient of determination for this parsimonious model was calculated. Results Correlation was slightly better for cortical volume-to-BSA ratio than for whole kidney volume-to-BSA ratio (r = 0.48 vs r = 0.44, respectively). The linear regression model incorporating all donor factors had an R 2 of 0.66. The only factors that were significantly additive to the equation were cortical volume-to-BSA ratio and predonation eGFR (P = .01 and P < .01, respectively), and the final parsimonious linear regression model incorporating these two variables explained almost the same amount of variance (R 2 = 0.65) as did the full model. Conclusion The cortical volume of the future remnant kidney helped predict postdonation eGFR at 2 years. The cortical volume-to-BSA ratio should thus be considered for addition as an important variable to living kidney donor evaluation and selection guidelines. © RSNA, 2018.

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

Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact.

PubMed

Yen, Ting-Lin; Chang, Chao-Chien; Chung, Chi-Li; Ko, Wen-Chin; Yang, Chih-Hao; Hsieh, Cheng-Ying

2018-04-06

Traumatic brain injury (TBI) is one of the leading causes of mortality worldwide and leads to persistent cognitive, sensory, motor dysfunction, and emotional disorders. TBI-caused primary injury results in structural damage to brain tissues. Following the primary injury, secondary injuries which are accompanied by neuroinflammation, microglial activation, and additional cell death subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers, and some types of acute inflammation. In the present study, the neuroprotective effects of platonin against TBI were explored in a controlled cortical impact (CCI) injury model in mice. Treatment with platonin (200 µg/kg) significantly reduced the neurological severity score, general locomotor activity, and anxiety-related behavior, and improved the rotarod performance of CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin also suppressed messenger (m)RNA levels of caspase-3, caspase-1, cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. On the other hand, free radical production after TBI was obviously attenuated in platonin-treated mice. Treatment with platonin exhibited prominent neuroprotective properties against TBI in a CCI mouse model through its anti-inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence collectively indicates that platonin may be a potential therapeutic medicine for use with TBIs.

Kollidon VA64, a membrane-resealing agent, reduces histopathology and improves functional outcome after controlled cortical impact in mice.

PubMed

Mbye, Lamin H; Keles, Eyup; Tao, Luyang; Zhang, Jimmy; Chung, Joonyong; Larvie, Mykol; Koppula, Rajani; Lo, Eng H; Whalen, Michael J

2012-03-01

Loss of plasma membrane integrity is a feature of acute cellular injury/death in vitro and in vivo. Plasmalemma-resealing agents are protective in acute central nervous system injury models, but their ability to reseal cell membranes in vivo has not been reported. Using a mouse controlled cortical impact (CCI) model, we found that propidium iodide-positive (PI+) cells pulse labeled at 6, 24, or 48 hours maintained a degenerative phenotype and disappeared from the injured brain by 7 days, suggesting that plasmalemma permeability is a biomarker of fatal cellular injury after CCI. Intravenous or intracerebroventricular administration of Kollidon VA64, poloxamer P188, or polyethylene glycol 8000 resealed injured cell membranes in vivo (P<0.05 versus vehicle or poloxamer P407). Kollidon VA64 (1 mmol/L, 500 μL) administered intravenously to mice 1  hour after CCI significantly reduced acute cellular degeneration, chronic brain tissue damage, brain edema, blood-brain barrier damage, and postinjury motor deficits (all P<0.05 versus vehicle). However, VA64 did not rescue pulse-labeled PI+ cells from eventual demise. We conclude that PI permeability within 48 hours of CCI is a biomarker of eventual cell death/loss. Kollidon VA64 reduces secondary damage after CCI by mechanisms other than or in addition to resealing permeable cells.

Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation.

PubMed

Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

2012-08-15

The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms.

Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation

PubMed Central

Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

2012-01-01

The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms. PMID:22641778

Traumatic brain injury decreases serotonin transporter expression in the rat cerebrum.

PubMed

Abe, Keiichi; Shimada, Ryo; Okada, Yoshikazu; Kibayashi, Kazuhiko

2016-04-01

An association has been postulated between traumatic brain injury (TBI) and depression. The serotonin transporter (SERT) regulates the concentration of serotonin in the synaptic cleft and represents a molecular target for antidepressants. We hypothesized that SERT expression in the brain changes following TBI. We performed immunohistochemistry, real-time polymerase chain reaction analysis for mRNA and western blot analysis for protein to examine the time-dependent changes in SERT expression in the cerebrum during the first 14 days after TBI, using a controlled cortical impact model in rats. SERT immunoreactivity in neuronal fibres within the area adjacent to the cortical contusion decreased 1 to 14 days after injury. Significantly decreased SERT mRNA and protein expression were noted in the area adjacent to the cortical contusion 7 days after injury. There were no significant changes in SERT expression in the cingulum of the injured brain. The findings of this study indicate that TBI decreases SERT expression in the cerebral cortex. The decreased levels of SERT expression after TBI may result in decreased serotonin neurotransmission in the brain and indicate a possible relationship with depression following TBI.

Apathy is related to cortex morphology in CADASIL. A sulcal-based morphometry study.

PubMed

Jouvent, E; Reyes, S; Mangin, J-F; Roca, P; Perrot, M; Thyreau, B; Hervé, D; Dichgans, M; Chabriat, H

2011-04-26

Apathy is a debilitating symptom in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the pathophysiology of which remains poorly understood. The aim of this study was to evaluate the neuroanatomic correlates of apathy, using new MRI postprocessing methods based on the identification of cortical sulci, in a large cohort of patients with CADASIL. A total of 132 patients with genetically confirmed diagnosis were included in this prospective cohort study. Global cognitive performances were assessed by the Mattis Dementia Rating Scale (MDRS) and disability by the modified Rankin score (mRS). Apathy was defined according to standard criteria. Depth, width, and cortical thickness of 10 large sulci of the frontal lobe in each hemisphere were measured. Logistic regression modeling was used to evaluate the links between apathy and cortical thickness, depth, or width of the different sulci. All models were adjusted for age, gender, level of education, MDRS, mRS, depression, and global brain volume. Complete MRI datasets of high quality were available in 119 patients. Depth of the posterior cingulate sulcus exhibited the strongest association with apathy in fully adjusted models (right: p value = 0.0006; left: p value = 0.004). Depth and width of cortical sulci in mediofrontal and orbitofrontal areas were independently associated with apathy. By contrast, cortical thickness was not. Cortical morphology in mediofrontal and orbitofrontal areas, by contrast to cortical thickness, is strongly and independently associated with apathy. These results suggest that apathy is related to a reduction of cortical surface rather than of cortical thickness secondary to lesion accumulation in CADASIL.

Development and Validation of an Older Occupant Finite Element Model of a Mid-Sized Male for Investigation of Age-related Injury Risk.

PubMed

Schoell, Samantha L; Weaver, Ashley A; Urban, Jillian E; Jones, Derek A; Stitzel, Joel D; Hwang, Eunjoo; Reed, Matthew P; Rupp, Jonathan D; Hu, Jingwen

2015-11-01

The aging population is a growing concern as the increased fragility and frailty of the elderly results in an elevated incidence of injury as well as an increased risk of mortality and morbidity. To assess elderly injury risk, age-specific computational models can be developed to directly calculate biomechanical metrics for injury. The first objective was to develop an older occupant Global Human Body Models Consortium (GHBMC) average male model (M50) representative of a 65 year old (YO) and to perform regional validation tests to investigate predicted fractures and injury severity with age. Development of the GHBMC M50 65 YO model involved implementing geometric, cortical thickness, and material property changes with age. Regional validation tests included a chest impact, a lateral impact, a shoulder impact, a thoracoabdominal impact, an abdominal bar impact, a pelvic impact, and a lateral sled test. The second objective was to investigate age-related injury risks by performing a frontal US NCAP simulation test with the GHBMC M50 65 YO and the GHBMC M50 v4.2 models. Simulation results were compared to the GHBMC M50 v4.2 to evaluate the effect of age on occupant response and risk for head injury, neck injury, thoracic injury, and lower extremity injury. Overall, the GHBMC M50 65 YO model predicted higher probabilities of AIS 3+ injury for the head and thorax.

Adaptations of young adult rat cortical bone to 14 days of spaceflight

NASA Technical Reports Server (NTRS)

Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

1992-01-01

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Evidence Accumulator or Decision Threshold – Which Cortical Mechanism are We Observing?

PubMed Central

Simen, Patrick

2012-01-01

Most psychological models of perceptual decision making are of the accumulation-to-threshold variety. The neural basis of accumulation in parietal and prefrontal cortex is therefore a topic of great interest in neuroscience. In contrast, threshold mechanisms have received less attention, and their neural basis has usually been sought in subcortical structures. Here I analyze a model of a decision threshold that can be implemented in the same cortical areas as evidence accumulators, and whose behavior bears on two open questions in decision neuroscience: (1) When ramping activity is observed in a brain region during decision making, does it reflect evidence accumulation? (2) Are changes in speed-accuracy tradeoffs and response biases more likely to be achieved by changes in thresholds, or in accumulation rates and starting points? The analysis suggests that task-modulated ramping activity, by itself, is weak evidence that a brain area mediates evidence accumulation as opposed to threshold readout; and that signs of modulated accumulation are as likely to indicate threshold adaptation as adaptation of starting points and accumulation rates. These conclusions imply that how thresholds are modeled can dramatically impact accumulator-based interpretations of this data. PMID:22737136

Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring

PubMed Central

Miner, Daniel; Triesch, Jochen

2016-01-01

Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non-random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring. PMID:26866369

Cortical Measures of Phoneme-Level Speech Encoding Correlate with the Perceived Clarity of Natural Speech

PubMed Central

2018-01-01

Abstract In real-world environments, humans comprehend speech by actively integrating prior knowledge (P) and expectations with sensory input. Recent studies have revealed effects of prior information in temporal and frontal cortical areas and have suggested that these effects are underpinned by enhanced encoding of speech-specific features, rather than a broad enhancement or suppression of cortical activity. However, in terms of the specific hierarchical stages of processing involved in speech comprehension, the effects of integrating bottom-up sensory responses and top-down predictions are still unclear. In addition, it is unclear whether the predictability that comes with prior information may differentially affect speech encoding relative to the perceptual enhancement that comes with that prediction. One way to investigate these issues is through examining the impact of P on indices of cortical tracking of continuous speech features. Here, we did this by presenting participants with degraded speech sentences that either were or were not preceded by a clear recording of the same sentences while recording non-invasive electroencephalography (EEG). We assessed the impact of prior information on an isolated index of cortical tracking that reflected phoneme-level processing. Our findings suggest the possibility that prior information affects the early encoding of natural speech in a dual manner. Firstly, the availability of prior information, as hypothesized, enhanced the perceived clarity of degraded speech, which was positively correlated with changes in phoneme-level encoding across subjects. In addition, P induced an overall reduction of this cortical measure, which we interpret as resulting from the increase in predictability. PMID:29662947

A cortical integrate-and-fire neural network model for blind decoding of visual prosthetic stimulation.

PubMed

Eiber, Calvin D; Morley, John W; Lovell, Nigel H; Suaning, Gregg J

2014-01-01

We present a computational model of the optic pathway which has been adapted to simulate cortical responses to visual-prosthetic stimulation. This model reproduces the statistically observed distributions of spikes for cortical recordings of sham and maximum-intensity stimuli, while simultaneously generating cellular receptive fields consistent with those observed using traditional visual neuroscience methods. By inverting this model to generate candidate phosphenes which could generate the responses observed to novel stimulation strategies, we hope to aid the development of said strategies in-vivo before being deployed in clinical settings.

Corticostriatal circuit mechanisms of value-based action selection: Implementation of reinforcement learning algorithms and beyond.

PubMed

Morita, Kenji; Jitsev, Jenia; Morrison, Abigail

2016-09-15

Value-based action selection has been suggested to be realized in the corticostriatal local circuits through competition among neural populations. In this article, we review theoretical and experimental studies that have constructed and verified this notion, and provide new perspectives on how the local-circuit selection mechanisms implement reinforcement learning (RL) algorithms and computations beyond them. The striatal neurons are mostly inhibitory, and lateral inhibition among them has been classically proposed to realize "Winner-Take-All (WTA)" selection of the maximum-valued action (i.e., 'max' operation). Although this view has been challenged by the revealed weakness, sparseness, and asymmetry of lateral inhibition, which suggest more complex dynamics, WTA-like competition could still occur on short time scales. Unlike the striatal circuit, the cortical circuit contains recurrent excitation, which may enable retention or temporal integration of information and probabilistic "soft-max" selection. The striatal "max" circuit and the cortical "soft-max" circuit might co-implement an RL algorithm called Q-learning; the cortical circuit might also similarly serve for other algorithms such as SARSA. In these implementations, the cortical circuit presumably sustains activity representing the executed action, which negatively impacts dopamine neurons so that they can calculate reward-prediction-error. Regarding the suggested more complex dynamics of striatal, as well as cortical, circuits on long time scales, which could be viewed as a sequence of short WTA fragments, computational roles remain open: such a sequence might represent (1) sequential state-action-state transitions, constituting replay or simulation of the internal model, (2) a single state/action by the whole trajectory, or (3) probabilistic sampling of state/action. Copyright © 2016. Published by Elsevier B.V.

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.

Multispectral brain morphometry in Tourette syndrome persisting into adulthood

PubMed Central

Martino, Davide; Cavanna, Andrea E.; Hutton, Chloe; Orth, Michael; Robertson, Mary M.; Critchley, Hugo D.; Frackowiak, Richard S.

2010-01-01

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change. PMID:21071387

Micromechanical modeling of elastic properties of cortical bone accounting for anisotropy of dense tissue.

PubMed

Salguero, Laura; Saadat, Fatemeh; Sevostianov, Igor

2014-10-17

The paper analyzes the connection between microstructure of the osteonal cortical bone and its overall elastic properties. The existing models either neglect anisotropy of the dense tissue or simplify cortical bone microstructure (accounting for Haversian canals only). These simplifications (related mostly to insufficient mathematical apparatus) complicate quantitative analysis of the effect of microstructural changes - produced by age, microgravity, or some diseases - on the overall mechanical performance of cortical bone. The present analysis fills this gap; it accounts for anisotropy of the dense tissue and uses realistic model of the porous microstructure. The approach is based on recent results of Sevostianov et al. (2005) and Saadat et al. (2012) on inhomogeneities in a transversely-isotropic material. Bone's microstructure is modeled according to books of Martin and Burr (1989), Currey (2002), and Fung (1993) and includes four main families of pores. The calculated elastic constants for porous cortical bone are in agreement with available experimental data. The influence of each of the pore types on the overall moduli is examined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Model-driven harmonic parameterization of the cortical surface: HIP-HOP.

PubMed

Auzias, G; Lefèvre, J; Le Troter, A; Fischer, C; Perrot, M; Régis, J; Coulon, O

2013-05-01

In the context of inter subject brain surface matching, we present a parameterization of the cortical surface constrained by a model of cortical organization. The parameterization is defined via an harmonic mapping of each hemisphere surface to a rectangular planar domain that integrates a representation of the model. As opposed to previous landmark-based registration methods we do not match folds between individuals but instead optimize the fit between cortical sulci and specific iso-coordinate axis in the model. This strategy overcomes some limitation to sulcus-based registration techniques such as topological variability in sulcal landmarks across subjects. Experiments on 62 subjects with manually traced sulci are presented and compared with the result of the Freesurfer software. The evaluation involves a measure of dispersion of sulci with both angular and area distortions. We show that the model-based strategy can lead to a natural, efficient and very fast (less than 5 min per hemisphere) method for defining inter subjects correspondences. We discuss how this approach also reduces the problems inherent to anatomically defined landmarks and open the way to the investigation of cortical organization through the notion of orientation and alignment of structures across the cortex.

Biomechanical investigation of thoracolumbar spine in different postures during ejection using a combined finite element and multi-body approach.

PubMed

Du, Chengfei; Mo, Zhongjun; Tian, Shan; Wang, Lizhen; Fan, Jie; Liu, Songyang; Fan, Yubo

2014-11-01

The aim of this study is to investigate the dynamic response of a multi-segment model of the thoracolumbar spine and determine how the sitting posture affects the response under the impact of ejection. A nonlinear finite element model of the thoracolumbar-pelvis complex (T9-S1) was developed and validated. A multi-body dynamic model of a pilot was also constructed so an ejection seat restraint system could be incorporated into the finite element model. The distribution of trunk mass on each vertebra was also considered in the model. Dynamics analysis showed that ejection impact induced obvious axial compression and anterior flexion of the spine, which may contribute to spinal injuries. Compared with a normal posture, the relaxed posture led to an increase in stress on the cortical wall, endplate, and intradiscal pressure of 43%, 10%, 13%, respectively, and accordingly increased the risk of inducing spinal injuries. Copyright © 2014 John Wiley & Sons, Ltd.

A feedback model of visual attention.

PubMed

Spratling, M W; Johnson, M H

2004-03-01

Feedback connections are a prominent feature of cortical anatomy and are likely to have a significant functional role in neural information processing. We present a neural network model of cortical feedback that successfully simulates neurophysiological data associated with attention. In this domain, our model can be considered a more detailed, and biologically plausible, implementation of the biased competition model of attention. However, our model is more general as it can also explain a variety of other top-down processes in vision, such as figure/ground segmentation and contextual cueing. This model thus suggests that a common mechanism, involving cortical feedback pathways, is responsible for a range of phenomena and provides a unified account of currently disparate areas of research.

Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.

PubMed

Frieler, Ryan A; Nadimpalli, Sameera; Boland, Lauren K; Xie, Angela; Kooistra, Laura J; Song, Jianrui; Chung, Yutein; Cho, Kae W; Lumeng, Carey N; Wang, Michael M; Mortensen, Richard M

2015-10-22

Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models. Copyright © 2015 Elsevier B.V. All rights reserved.

Regional growth and atlasing of the developing human brain

PubMed Central

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V.; Edwards, A. David; Counsell, Serena J.; Rueckert, Daniel

2016-01-01

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45 weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. PMID:26499811

Regional growth and atlasing of the developing human brain.

PubMed

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

2016-01-15

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Reconstructing cortical current density by exploring sparseness in the transform domain

NASA Astrophysics Data System (ADS)

Ding, Lei

2009-05-01

In the present study, we have developed a novel electromagnetic source imaging approach to reconstruct extended cortical sources by means of cortical current density (CCD) modeling and a novel EEG imaging algorithm which explores sparseness in cortical source representations through the use of L1-norm in objective functions. The new sparse cortical current density (SCCD) imaging algorithm is unique since it reconstructs cortical sources by attaining sparseness in a transform domain (the variation map of cortical source distributions). While large variations are expected to occur along boundaries (sparseness) between active and inactive cortical regions, cortical sources can be reconstructed and their spatial extents can be estimated by locating these boundaries. We studied the SCCD algorithm using numerous simulations to investigate its capability in reconstructing cortical sources with different extents and in reconstructing multiple cortical sources with different extent contrasts. The SCCD algorithm was compared with two L2-norm solutions, i.e. weighted minimum norm estimate (wMNE) and cortical LORETA. Our simulation data from the comparison study show that the proposed sparse source imaging algorithm is able to accurately and efficiently recover extended cortical sources and is promising to provide high-accuracy estimation of cortical source extents.

Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex.

PubMed

Ruiz-Mejias, Marcel; Martinez de Lagran, Maria; Mattia, Maurizio; Castano-Prat, Patricia; Perez-Mendez, Lorena; Ciria-Suarez, Laura; Gener, Thomas; Sancristobal, Belen; García-Ojalvo, Jordi; Gruart, Agnès; Delgado-García, José M; Sanchez-Vives, Maria V; Dierssen, Mara

2016-03-30

The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinase involved in neuronal differentiation and synaptic plasticity and a major candidate of Down syndrome brain alterations and cognitive deficits. DYRK1A is strongly expressed in the cerebral cortex, and its overexpression leads to defective cortical pyramidal cell morphology, synaptic plasticity deficits, and altered excitation/inhibition balance. These previous observations, however, do not allow predicting how the behavior of the prefrontal cortex (PFC) network and the resulting properties of its emergent activity are affected. Here, we integrate functional, anatomical, and computational data describing the prefrontal network alterations in transgenic mice overexpressingDyrk1A(TgDyrk1A). Usingin vivoextracellular recordings, we show decreased firing rate and gamma frequency power in the prefrontal network of anesthetized and awakeTgDyrk1Amice. Immunohistochemical analysis identified a selective reduction of vesicular GABA transporter punctae on parvalbumin positive neurons, without changes in the number of cortical GABAergic neurons in the PFC ofTgDyrk1Amice, which suggests that selective disinhibition of parvalbumin interneurons would result in an overinhibited functional network. Using a conductance-based computational model, we quantitatively demonstrate that this alteration could explain the observed functional deficits including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. DYRK1Ais a major candidate gene in Down syndrome. Its overexpression results into altered cognitive abilities, explained by defective cortical microarchitecture and excitation/inhibition imbalance. An open question is how these deficits impact the functionality of the prefrontal cortex network. Combining functional, anatomical, and computational approaches, we identified decreased neuronal firing rate and deficits in gamma frequency in the prefrontal cortices of transgenic mice overexpressingDyrk1A We also identified a reduction of vesicular GABA transporter punctae specifically on parvalbumin positive interneurons. Using a conductance-based computational model, we demonstrate that this decreased inhibition on interneurons recapitulates the observed functional deficits, including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. Copyright © 2016 the authors 0270-6474/16/363649-12$15.00/0.

Rib fractures under anterior-posterior dynamic loads: experimental and finite-element study.

PubMed

Li, Zuoping; Kindig, Matthew W; Kerrigan, Jason R; Untaroiu, Costin D; Subit, Damien; Crandall, Jeff R; Kent, Richard W

2010-01-19

The purpose of this study was to investigate whether using a finite-element (FE) mesh composed entirely of hexahedral elements to model cortical and trabecular bone (all-hex model) would provide more accurate simulations than those with variable thickness shell elements for cortical bone and hexahedral elements for trabecular bone (hex-shell model) in the modeling human ribs. First, quasi-static non-injurious and dynamic injurious experiments were performed using the second, fourth, and tenth human thoracic ribs to record the structural behavior and fracture tolerance of individual ribs under anterior-posterior bending loads. Then, all-hex and hex-shell FE models for the three ribs were developed using an octree-based and multi-block hex meshing approach, respectively. Material properties of cortical bone were optimized using dynamic experimental data and the hex-shell model of the fourth rib and trabecular bone properties were taken from the literature. Overall, the reaction force-displacement relationship predicted by both all-hex and hex-shell models with nodes in the offset middle-cortical surfaces compared well with those measured experimentally for all the three ribs. With the exception of fracture locations, the predictions from all-hex and offset hex-shell models of the second and fourth ribs agreed better with experimental data than those from the tenth rib models in terms of reaction force at fracture (difference <15.4%), ultimate failure displacement and time (difference <7.3%), and cortical bone strains. The hex-shell models with shell nodes in outer cortical surfaces increased static reaction forces up to 16.6%, compared to offset hex-shell models. These results indicated that both all-hex and hex-shell modeling strategies were applicable for simulating rib responses and bone fractures for the loading conditions considered, but coarse hex-shell models with constant or variable shell thickness were more computationally efficient and therefore preferred. Copyright 2009 Elsevier Ltd. All rights reserved.

Longitudinal trajectory of clinical insight and covariation with cortical thickness in first-episode psychosis.

PubMed

Buchy, Lisa; Makowski, Carolina; Malla, Ashok; Joober, Ridha; Lepage, Martin

2017-03-01

Among people with a first-episode of psychosis, those with poorer clinical insight show neuroanatomical abnormalities in frontal, temporal and parietal cortices compared to those with better clinical insight. Whether changes in clinical insight are associated with progressive structural brain changes is unknown. We aimed to evaluate 1) associations between clinical insight and cortical thickness at a baseline assessment, 2) covariation between clinical insight and cortical thickness across baseline, one-year and two-year follow-up assessments, and 3) the predictive value of clinical insight for cortical thickness at one-year and two-year follow-ups. Scale for the assessment of Unawareness of Mental Disorder ratings and magnetic resonance imaging scans were acquired at baseline, one-year, and two-year follow-ups in 128, 74, and 44 individuals with a first-episode psychosis, respectively. Cortical thickness metrics were then computed at baseline, one-year and two-year follow-ups and analyzed with linear mixed models. At baseline, clinical insight was not significantly associated with cortical thickness in any region. Longitudinal mixed effects models showed that a worsening in clinical insight between the one-year and two-year assessments was significantly associated with cortical thinning in dorsal pre-central and post-central gyri. Cortical thinning in left fusiform gyrus at two-years was predicted by poorer clinical insight at baseline. Results suggest that poor clinical insight soon after the onset of a first-episode psychosis may lead to progressive cortical changes in temporal lobe, while changes in clinical insight during the second year covary with cortical thinning in circumscribed dorsal frontal and parietal cortices. Copyright © 2016 Elsevier Ltd. All rights reserved.

An image-based skeletal dosimetry model for the ICRP reference adult female—internal electron sources

NASA Astrophysics Data System (ADS)

O'Reilly, Shannon E.; DeWeese, Lindsay S.; Maynard, Matthew R.; Rajon, Didier A.; Wayson, Michael B.; Marshall, Emily L.; Bolch, Wesley E.

2016-12-01

An image-based skeletal dosimetry model for internal electron sources was created for the ICRP-defined reference adult female. Many previous skeletal dosimetry models, which are still employed in commonly used internal dosimetry software, do not properly account for electron escape from trabecular spongiosa, electron cross-fire from cortical bone, and the impact of marrow cellularity on active marrow self-irradiation. Furthermore, these existing models do not employ the current ICRP definition of a 50 µm bone endosteum (or shallow marrow). Each of these limitations was addressed in the present study. Electron transport was completed to determine specific absorbed fractions to both active and shallow marrow of the skeletal regions of the University of Florida reference adult female. The skeletal macrostructure and microstructure were modeled separately. The bone macrostructure was based on the whole-body hybrid computational phantom of the UF series of reference models, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 years-old female cadaver. The active and shallow marrow are typically adopted as surrogate tissue regions for the hematopoietic stem cells and osteoprogenitor cells, respectively. Source tissues included active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume, and cortical bone surfaces. Marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. All other sources were run at the defined ICRP Publication 70 cellularity for each bone site. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or analytically modeled. The method of combining skeletal macrostructure and microstructure absorbed fractions assessed using MCNPX electron transport was found to yield results similar to those determined with the PIRT model applied to the UF adult male skeletal dosimetry model. Calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) but did not follow results from skeletal models based upon assumptions of an infinite expanse of trabecular spongiosa.

Theory of mind, empathy and emotion perception in cortical and subcortical neurodegenerative diseases.

PubMed

Fortier, J; Besnard, J; Allain, P

2018-04-01

Although the impact of neurodegenerative diseases on everyday interactions is well known in the literature, their impact on social cognitive processes remains unclear. The concept of social cognition refers to a set of skills, all of which are essential for living in a community. It involves social knowledge, perception and processing of social cues, and representation of mental states. This report is a review of recent findings on the impact of cortical and subcortical neurodegenerative diseases on three social cognitive processes, namely, the theory of mind, empathy and processing emotions. The focus here is on a conceptual approach to each of these skills and their cerebral underpinnings. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Dissociable meta-analytic brain networks contribute to coordinated emotional processing.

PubMed

Riedel, Michael C; Yanes, Julio A; Ray, Kimberly L; Eickhoff, Simon B; Fox, Peter T; Sutherland, Matthew T; Laird, Angela R

2018-06-01

Meta-analytic techniques for mining the neuroimaging literature continue to exert an impact on our conceptualization of functional brain networks contributing to human emotion and cognition. Traditional theories regarding the neurobiological substrates contributing to affective processing are shifting from regional- towards more network-based heuristic frameworks. To elucidate differential brain network involvement linked to distinct aspects of emotion processing, we applied an emergent meta-analytic clustering approach to the extensive body of affective neuroimaging results archived in the BrainMap database. Specifically, we performed hierarchical clustering on the modeled activation maps from 1,747 experiments in the affective processing domain, resulting in five meta-analytic groupings of experiments demonstrating whole-brain recruitment. Behavioral inference analyses conducted for each of these groupings suggested dissociable networks supporting: (1) visual perception within primary and associative visual cortices, (2) auditory perception within primary auditory cortices, (3) attention to emotionally salient information within insular, anterior cingulate, and subcortical regions, (4) appraisal and prediction of emotional events within medial prefrontal and posterior cingulate cortices, and (5) induction of emotional responses within amygdala and fusiform gyri. These meta-analytic outcomes are consistent with a contemporary psychological model of affective processing in which emotionally salient information from perceived stimuli are integrated with previous experiences to engender a subjective affective response. This study highlights the utility of using emergent meta-analytic methods to inform and extend psychological theories and suggests that emotions are manifest as the eventual consequence of interactions between large-scale brain networks. © 2018 Wiley Periodicals, Inc.

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction.

PubMed

Makropoulos, Antonios; Robinson, Emma C; Schuh, Andreas; Wright, Robert; Fitzgibbon, Sean; Bozek, Jelena; Counsell, Serena J; Steinweg, Johannes; Vecchiato, Katy; Passerat-Palmbach, Jonathan; Lenz, Gregor; Mortari, Filippo; Tenev, Tencho; Duff, Eugene P; Bastiani, Matteo; Cordero-Grande, Lucilio; Hughes, Emer; Tusor, Nora; Tournier, Jacques-Donald; Hutter, Jana; Price, Anthony N; Teixeira, Rui Pedro A G; Murgasova, Maria; Victor, Suresh; Kelly, Christopher; Rutherford, Mary A; Smith, Stephen M; Edwards, A David; Hajnal, Joseph V; Jenkinson, Mark; Rueckert, Daniel

2018-06-01

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Deep Residual Network Predicts Cortical Representation and Organization of Visual Features for Rapid Categorization.

PubMed

Wen, Haiguang; Shi, Junxing; Chen, Wei; Liu, Zhongming

2018-02-28

The brain represents visual objects with topographic cortical patterns. To address how distributed visual representations enable object categorization, we established predictive encoding models based on a deep residual network, and trained them to predict cortical responses to natural movies. Using this predictive model, we mapped human cortical representations to 64,000 visual objects from 80 categories with high throughput and accuracy. Such representations covered both the ventral and dorsal pathways, reflected multiple levels of object features, and preserved semantic relationships between categories. In the entire visual cortex, object representations were organized into three clusters of categories: biological objects, non-biological objects, and background scenes. In a finer scale specific to each cluster, object representations revealed sub-clusters for further categorization. Such hierarchical clustering of category representations was mostly contributed by cortical representations of object features from middle to high levels. In summary, this study demonstrates a useful computational strategy to characterize the cortical organization and representations of visual features for rapid categorization.

Assessment of compressive failure process of cortical bone materials using damage-based model.

PubMed

Ng, Theng Pin; R Koloor, S S; Djuansjah, J R P; Abdul Kadir, M R

2017-02-01

The main failure factors of cortical bone are aging or osteoporosis, accident and high energy trauma or physiological activities. However, the mechanism of damage evolution coupled with yield criterion is considered as one of the unclear subjects in failure analysis of cortical bone materials. Therefore, this study attempts to assess the structural response and progressive failure process of cortical bone using a brittle damaged plasticity model. For this reason, several compressive tests are performed on cortical bone specimens made of bovine femur, in order to obtain the structural response and mechanical properties of the material. Complementary finite element (FE) model of the sample and test is prepared to simulate the elastic-to-damage behavior of the cortical bone using the brittle damaged plasticity model. The FE model is validated in a comparative method using the predicted and measured structural response as load-compressive displacement through simulation and experiment. FE results indicated that the compressive damage initiated and propagated at central region where maximum equivalent plastic strain is computed, which coincided with the degradation of structural compressive stiffness followed by a vast amount of strain energy dissipation. The parameter of compressive damage rate, which is a function dependent on damage parameter and the plastic strain is examined for different rates. Results show that considering a similar rate to the initial slope of the damage parameter in the experiment would give a better sense for prediction of compressive failure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Examining the volume efficiency of the cortical architecture in a multi-processor network model.

PubMed

Ruppin, E; Schwartz, E L; Yeshurun, Y

1993-01-01

The convoluted form of the sheet-like mammalian cortex naturally raises the question whether there is a simple geometrical reason for the prevalence of cortical architecture in the brains of higher vertebrates. Addressing this question, we present a formal analysis of the volume occupied by a massively connected network or processors (neurons) and then consider the pertaining cortical data. Three gross macroscopic features of cortical organization are examined: the segregation of white and gray matter, the circumferential organization of the gray matter around the white matter, and the folded cortical structure. Our results testify to the efficiency of cortical architecture.

Proximal femoral anatomy and collared stems in hip arthroplasty: is a single collar size sufficient?

PubMed

Bonin, Nicolas; Gedouin, Jean-Emmanuel; Pibarot, Vincent; Bejui-Hughues, Jacques; Bothorel, Hugo; Saffarini, Mo; Batailler, Cécile

2017-10-03

Even if the benefits of collars are unclear, they remain widely used, in several femoral stem designs. This study aimed to determine whether collar size should be proportional to hip dimensions and morphology. The hypothesis was that the collar should be larger for greater stem sizes and for varus femoral necks. Computed Tomography scans of 204 healthy hips were digitally analysed and manually templated to determine principle dimensions, appropriate stem size and model, as well as cortical distance at the femoral calcar (ideal collar size). Univariable analysis revealed that cortical distance was moderately correlated with mediolateral offset (r = 0.572; p < 0.0001) and stem model (r = 0.520; p < 0.0001). Cortical distance was weakly correlated with head diameter (r = 0.399; p < 0.0001), stem size (r = 0.200; p = 0.017), and patient gender (r = 0.361; p < 0.0001). Multivariable analysis confirmed that stem model (p < 0.0001) and head diameter (p = 0.0162) are directly correlated to cortical distance. We found that cortical distance along the femoral calcar is directly correlated with the model of the stem implanted ('standard' or 'varus') and with the head diameter. This cortical distance indicates optimal collar size, which would grant maximum calcar coverage without prosthetic overhang. Collar size should be proportional to the size of the operated hip, and should be larger for 'varus' stem models than for 'standard' stem models.

Network Receptive Field Modeling Reveals Extensive Integration and Multi-feature Selectivity in Auditory Cortical Neurons.

PubMed

Harper, Nicol S; Schoppe, Oliver; Willmore, Ben D B; Cui, Zhanfeng; Schnupp, Jan W H; King, Andrew J

2016-11-01

Cortical sensory neurons are commonly characterized using the receptive field, the linear dependence of their response on the stimulus. In primary auditory cortex neurons can be characterized by their spectrotemporal receptive fields, the spectral and temporal features of a sound that linearly drive a neuron. However, receptive fields do not capture the fact that the response of a cortical neuron results from the complex nonlinear network in which it is embedded. By fitting a nonlinear feedforward network model (a network receptive field) to cortical responses to natural sounds, we reveal that primary auditory cortical neurons are sensitive over a substantially larger spectrotemporal domain than is seen in their standard spectrotemporal receptive fields. Furthermore, the network receptive field, a parsimonious network consisting of 1-7 sub-receptive fields that interact nonlinearly, consistently better predicts neural responses to auditory stimuli than the standard receptive fields. The network receptive field reveals separate excitatory and inhibitory sub-fields with different nonlinear properties, and interaction of the sub-fields gives rise to important operations such as gain control and conjunctive feature detection. The conjunctive effects, where neurons respond only if several specific features are present together, enable increased selectivity for particular complex spectrotemporal structures, and may constitute an important stage in sound recognition. In conclusion, we demonstrate that fitting auditory cortical neural responses with feedforward network models expands on simple linear receptive field models in a manner that yields substantially improved predictive power and reveals key nonlinear aspects of cortical processing, while remaining easy to interpret in a physiological context.

Network Receptive Field Modeling Reveals Extensive Integration and Multi-feature Selectivity in Auditory Cortical Neurons

PubMed Central

Willmore, Ben D. B.; Cui, Zhanfeng; Schnupp, Jan W. H.; King, Andrew J.

2016-01-01

Cortical sensory neurons are commonly characterized using the receptive field, the linear dependence of their response on the stimulus. In primary auditory cortex neurons can be characterized by their spectrotemporal receptive fields, the spectral and temporal features of a sound that linearly drive a neuron. However, receptive fields do not capture the fact that the response of a cortical neuron results from the complex nonlinear network in which it is embedded. By fitting a nonlinear feedforward network model (a network receptive field) to cortical responses to natural sounds, we reveal that primary auditory cortical neurons are sensitive over a substantially larger spectrotemporal domain than is seen in their standard spectrotemporal receptive fields. Furthermore, the network receptive field, a parsimonious network consisting of 1–7 sub-receptive fields that interact nonlinearly, consistently better predicts neural responses to auditory stimuli than the standard receptive fields. The network receptive field reveals separate excitatory and inhibitory sub-fields with different nonlinear properties, and interaction of the sub-fields gives rise to important operations such as gain control and conjunctive feature detection. The conjunctive effects, where neurons respond only if several specific features are present together, enable increased selectivity for particular complex spectrotemporal structures, and may constitute an important stage in sound recognition. In conclusion, we demonstrate that fitting auditory cortical neural responses with feedforward network models expands on simple linear receptive field models in a manner that yields substantially improved predictive power and reveals key nonlinear aspects of cortical processing, while remaining easy to interpret in a physiological context. PMID:27835647

Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm

PubMed Central

Dura-Bernal, Salvador; Zhou, Xianlian; Neymotin, Samuel A.; Przekwas, Andrzej; Francis, Joseph T.; Lytton, William W.

2015-01-01

Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of limb prosthetics. PMID:26635598

Model-Based Segmentation of Cortical Regions of Interest for Multi-subject Analysis of fMRI Data

NASA Astrophysics Data System (ADS)

Engel, Karin; Brechmann, Andr'e.; Toennies, Klaus

The high inter-subject variability of human neuroanatomy complicates the analysis of functional imaging data across subjects. We propose a method for the correct segmentation of cortical regions of interest based on the cortical surface. First results on the segmentation of Heschl's gyrus indicate the capability of our approach for correct comparison of functional activations in relation to individual cortical patterns.

Estimates of projection overlap and zones of convergence within frontal-striatal circuits.

PubMed

Averbeck, Bruno B; Lehman, Julia; Jacobson, Moriah; Haber, Suzanne N

2014-07-16

Frontal-striatal circuits underlie important decision processes, and pathology in these circuits is implicated in many psychiatric disorders. Studies have shown a topographic organization of cortical projections into the striatum. However, work has also shown that there is considerable overlap in the striatal projection zones of nearby cortical regions. To characterize this in detail, we quantified the complete striatal projection zones from 34 cortical injection locations in rhesus monkeys. We first fit a statistical model that showed that the projection zone of a cortical injection site could be predicted with considerable accuracy using a cross-validated model estimated on only the other injection sites. We then examined the fraction of overlap in striatal projection zones as a function of distance between cortical injection sites, and found that there was a highly regular relationship. Specifically, nearby cortical locations had as much as 80% overlap, and the amount of overlap decayed exponentially as a function of distance between the cortical injection sites. Finally, we found that some portions of the striatum received inputs from all the prefrontal regions, making these striatal zones candidates as information-processing hubs. Thus, the striatum is a site of convergence that allows integration of information spread across diverse prefrontal cortical areas. Copyright © 2014 the authors 0270-6474/14/339497-09$15.00/0.

Visual attention and flexible normalization pools

PubMed Central

Schwartz, Odelia; Coen-Cagli, Ruben

2013-01-01

Attention to a spatial location or feature in a visual scene can modulate the responses of cortical neurons and affect perceptual biases in illusions. We add attention to a cortical model of spatial context based on a well-founded account of natural scene statistics. The cortical model amounts to a generalized form of divisive normalization, in which the surround is in the normalization pool of the center target only if they are considered statistically dependent. Here we propose that attention influences this computation by accentuating the neural unit activations at the attended location, and that the amount of attentional influence of the surround on the center thus depends on whether center and surround are deemed in the same normalization pool. The resulting form of model extends a recent divisive normalization model of attention (Reynolds & Heeger, 2009). We simulate cortical surround orientation experiments with attention and show that the flexible model is suitable for capturing additional data and makes nontrivial testable predictions. PMID:23345413

Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

PubMed Central

Kerkhofs, Amber; Xavier, Ana C.; da Silva, Beatriz S.; Canas, Paula M.; Idema, Sander; Baayen, Johannes C.; Ferreira, Samira G.; Cunha, Rodrigo A.; Mansvelder, Huibert D.

2018-01-01

Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R), neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM) on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans. PMID:29354052

Brain structure mediates the association between height and cognitive ability.

PubMed

Vuoksimaa, Eero; Panizzon, Matthew S; Franz, Carol E; Fennema-Notestine, Christine; Hagler, Donald J; Lyons, Michael J; Dale, Anders M; Kremen, William S

2018-05-11

Height and general cognitive ability are positively associated, but the underlying mechanisms of this relationship are not well understood. Both height and general cognitive ability are positively associated with brain size. Still, the neural substrate of the height-cognitive ability association is unclear. We used a sample of 515 middle-aged male twins with structural magnetic resonance imaging data to investigate whether the association between height and cognitive ability is mediated by cortical size. In addition to cortical volume, we used genetically, ontogenetically and phylogenetically distinct cortical metrics of total cortical surface area and mean cortical thickness. Height was positively associated with general cognitive ability and total cortical volume and cortical surface area, but not with mean cortical thickness. Mediation models indicated that the well-replicated height-general cognitive ability association is accounted for by individual differences in total cortical volume and cortical surface area (highly heritable metrics related to global brain size), and that the genetic association between cortical surface area and general cognitive ability underlies the phenotypic height-general cognitive ability relationship.

Cortical parvalbumin GABAergic deficits with α7 nicotinic acetylcholine receptor deletion: Implications for schizophrenia

PubMed Central

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

2014-01-01

Dysfunction of cortical parvalbumin (PV)-containing GABAergic interneurons has been implicated in cognitive deficits of schizophrenia. In humans microdeletion of the CHRNA7 (α7 nicotinic acetylcholine receptor, nAChR) gene is associated with cortical dysfunction in a broad spectrum of neurodevelopmental and neuropsychiatric disorders including schizophrenia while in mice similar deletion causes analogous abnormalities including impaired attention, working-memory and learning. However, the pathophysiological roles of α7 nAChRs in cortical PV GABAergic development remain largely uncharacterized. In both in vivo and in vitro models, we identify here that deletion of the α7 nAChR gene in mice impairs cortical PV GABAergic development and recapitulates many of the characteristic neurochemical deficits in PV-positive GABAergic interneurons found in schizophrenia. α7 nAChR null mice had decreased cortical levels of GABAergic markers including PV, Glutamic Acid Decarboxylase 65/67 (GAD65/67) and the α1 subunit of GABAA receptors, particularly reductions of PV and GAD67 levels in cortical PV-positive interneurons during late postnatal life and adulthood. Cortical GABAergic synaptic deficits were identified in the prefrontal cortex of α7 nAChR null mice and α7 nAChR null cortical cultures. Similar disruptions in development of PV-positive GABAergic interneurons and perisomatic synapses were found in cortical cultures lacking α7 nAChRs. Moreover, NMDA receptor expression was reduced in GABAergic interneurons, implicating NMDA receptor hypofunction in GABAergic deficits in α7 nAChR null mice. Our findings thus demonstrate impaired cortical PV GABAergic development and multiple characteristic neurochemical deficits reminiscent of schizophrenia in cortical PV-positive interneurons in α7 nAChR gene deletion models. This implicates crucial roles of α7 nAChRs in cortical PV GABAergic development and dysfunction in schizophrenia and other neuropsychiatric disorders. PMID:24983521

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

PubMed Central

Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory intracortical interneuron-networks, cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and validation need to be dedicated to this question to confirm this relationship. PMID:25612896

Modeling and Theories of Pathophysiology and Physiology of the Basal Ganglia–Thalamic–Cortical System: Critical Analysis

PubMed Central

Montgomery Jr., Erwin B.

2016-01-01

Theories impact the movement disorders clinic, not only affecting the development of new therapies but determining how current therapies are used. Models are theories that are procedural rather than declarative. Theories and models are important because, as argued by Kant, one cannot know the thing-in-itself (das Ding an sich) and only a model is knowable. Further, biological variability forces higher level abstraction relevant for all variants. It is that abstraction that is raison d’être of theories and models. Theories “connect the dots” to move from correlation to causation. The necessity of theory makes theories helpful or counterproductive. Theories and models of the pathophysiology and physiology of the basal ganglia–thalamic–cortical system do not spontaneously arise but have a history and consequently are legacies. Over the last 40 years, numerous theories and models of the basal ganglia have been proposed only to be forgotten or dismissed, rarely critiqued. It is not harsh to say that current popular theories positing increased neuronal activities in the Globus Pallidus Interna (GPi), excessive beta oscillations and increased synchronization not only fail to provide an adequate explication but are inconsistent with many observations. It is likely that their shared intellectual and epistemic inheritance plays a factor in their shared failures. These issues are critically examined. How one is to derive theories and models and have hope these will be better is explored as well. PMID:27708569

A BEHAVIORAL AND HISTOLOGICAL COMPARISON OF FLUID PERCUSSION INJURY AND CONTROLLED CORTICAL IMPACT INJURY TO THE RAT SENSORIMOTOR CORTEX

PubMed Central

Peterson, Todd C.; Maass, William R.; Anderson, Jordan R.; Anderson, Gail D.; Hoane, Michael R.

2015-01-01

Our primary goal was to evaluate the behavioral and histological outcome of fluid percussion injury (FPI) and cortical contusion injury (CCI) to the sensorimotor cortex (SMC). The SMC has been used to evaluate neuroplasticity following CCI, but has not been extensively examined with FPI. In both the CCI and FPI models, a mechanical force of 4 mm in diameter was applied over the SMC, allowing for a direct comparison to measure the relative rates of histology and recovery of function in these models. Gross behavioral deficits were found on the sensory task (tactile adhesive removal task) and multiple motor assessments (forelimb asymmetry task, forelimb placing task, and rotorod). These sensorimotor deficits occurred in the absence of cognitive deficits in the water maze. The CCI model creates focal damage with a localized injury wheras the FPI model creates a more diffuse injury causing widespread damage. Both behavioral and histological deficits ensued following both models of injury to the SMC. The neuroplastic changes and ease at which damage to this area can be measured behaviorally make this an excellent location to assess traumatic brain injury (TBI) treatments. No injury model can completely mimic the full spectrum of human TBI and any potential treatments should be validated across both focal and diffuse injury models. Both of these injury models to the SMC produce severe and enduring behavioral deficits, which are ideal for evaluating treatment options. PMID:26275924

A Nuclear Attack on Traumatic Brain Injury: Sequestration of Cell Death in the Nucleus.

PubMed

Tajiri, Naoki; De La Peña, Ike; Acosta, Sandra A; Kaneko, Yuji; Tamir, Sharon; Landesman, Yosef; Carlson, Robert; Shacham, Sharon; Borlongan, Cesar V

2016-04-01

Exportin 1 (XPO1/CRM1) plays prominent roles in the regulation of nuclear protein export. Selective inhibitors of nuclear export (SINE) are small orally bioavailable molecules that serve as drug-like inhibitors of XPO1, with potent anti-cancer properties. Traumatic brain injury (TBI) presents with a secondary cell death characterized by neuroinflammation that is putatively regulated by nuclear receptors. Here, we report that the SINE compounds (KPT-350 or KPT-335) sequestered TBI-induced neuroinflammation-related proteins (NF-(k)B, AKT, FOXP1) within the nucleus of cultured primary rat cortical neurons, which coincided with protection against TNF-α (20 ng/mL)-induced neurotoxicity as shown by at least 50% and 100% increments in preservation of cell viability and cellular enzymatic activity, respectively, compared to non-treated neuronal cells (P's < 0.05). In parallel, using an in vivo controlled cortical impact (CCI) model of TBI, we demonstrate that adult Sprague-Dawley rats treated post-injury with SINE compounds exhibited significant reductions in TBI-induced behavioral and histological deficits. Animals that received KPT-350 orally starting at 2 h post-TBI and once a day thereafter over the next 4 days exhibited significantly better motor coordination, and balance in the rotorod test and motor asymmetry test by 100-200% improvements, as early as 4 h after initial SINE compound injection that was sustained during subsequent KPT-350 dosing, and throughout the 18-day post-TBI study period compared to vehicle treatment (P's < 0.05). Moreover, KPT-350 reduced cortical core impact area and peri-impact cell death compared to vehicle treatment (P's < 0.05). Both in vitro and in vivo experiments revealed that KPT-350 increased XPO1, AKT, and FOXP1 nuclear expression and relegated NF-(k)B expression within the neuronal nuclei. Altogether, these findings advance the utility of SINE compounds to stop trafficking of cell death proteins within the nucleus as an efficacious treatment for TBI. © 2016 John Wiley & Sons Ltd.

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

PubMed

Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

2011-01-07

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

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.

Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

NASA Astrophysics Data System (ADS)

Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

2016-06-01

Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

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

Karunamuni, Roshan; Bartsch, Hauke; White, Nathan S.

Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thicknessmore » between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.« less

Branching angles of pyramidal cell dendrites follow common geometrical design principles in different cortical areas.

PubMed

Bielza, Concha; Benavides-Piccione, Ruth; López-Cruz, Pedro; Larrañaga, Pedro; DeFelipe, Javier

2014-08-01

Unraveling pyramidal cell structure is crucial to understanding cortical circuit computations. Although it is well known that pyramidal cell branching structure differs in the various cortical areas, the principles that determine the geometric shapes of these cells are not fully understood. Here we analyzed and modeled with a von Mises distribution the branching angles in 3D reconstructed basal dendritic arbors of hundreds of intracellularly injected cortical pyramidal cells in seven different cortical regions of the frontal, parietal, and occipital cortex of the mouse. We found that, despite the differences in the structure of the pyramidal cells in these distinct functional and cytoarchitectonic cortical areas, there are common design principles that govern the geometry of dendritic branching angles of pyramidal cells in all cortical areas.

Branching angles of pyramidal cell dendrites follow common geometrical design principles in different cortical areas

PubMed Central

Bielza, Concha; Benavides-Piccione, Ruth; López-Cruz, Pedro; Larrañaga, Pedro; DeFelipe, Javier

2014-01-01

Unraveling pyramidal cell structure is crucial to understanding cortical circuit computations. Although it is well known that pyramidal cell branching structure differs in the various cortical areas, the principles that determine the geometric shapes of these cells are not fully understood. Here we analyzed and modeled with a von Mises distribution the branching angles in 3D reconstructed basal dendritic arbors of hundreds of intracellularly injected cortical pyramidal cells in seven different cortical regions of the frontal, parietal, and occipital cortex of the mouse. We found that, despite the differences in the structure of the pyramidal cells in these distinct functional and cytoarchitectonic cortical areas, there are common design principles that govern the geometry of dendritic branching angles of pyramidal cells in all cortical areas. PMID:25081193

Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation

PubMed Central

Markus, Steven M.; Lee, Wei-Lih

2011-01-01

During animal development, microtubules (MTs) play a major role in directing cellular and subcellular patterning, impacting cell polarization and subcellular organization, thereby affecting cell fate determination and tissue architecture. In particular, when progenitor cells divide asymmetrically along an anterior-posterior or apical-basal axis, MTs must coordinate the position of the mitotic spindle with the site of cell division to ensure normal distribution of cell fate determinants and equal sequestration of genetic material into the two daughter cells. Emerging data from diverse model systems have led to the prevailing view that, during mitotic spindle positioning, polarity cues at the cell cortex signal for the recruitment of NuMA and the minus-end directed MT motor cytoplasmic dynein.1 The NuMA/dynein complex is believed to connect, in turn, to the mitotic spindle via astral MTs, thus aligning and tethering the spindle, but how this connection is achieved faithfully is unclear. Do astral MTs need to search for and then capture cortical NuMA/dynein? How does dynein capture the astral MTs emanating from the correct spindle pole? Recently, using the classical model of asymmetric cell division—budding yeast S. cerevisiae—we successfully demonstrated that astral MTs assume an active role in cortical dynein targeting, in that astral MTs utilize their distal plus ends to deliver dynein to the daughter cell cortex, the site where dynein activity is needed to perform its spindle alignment function. This observation introduced the novel idea that, during mitotic spindle orientation processes, polarity cues at the cell cortex may actually signal to prime the cortical receptors for MT-dependent dynein delivery. This model is consistent with the observation that dynein/dynactin accumulate prominently at the astral MT plus ends during metaphase in a wide range of cultured mammalian cells. PMID:22754610

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

High-expanding cortical regions in human development and evolution are related to higher intellectual abilities.

PubMed

Fjell, Anders M; Westlye, Lars T; Amlien, Inge; Tamnes, Christian K; Grydeland, Håkon; Engvig, Andreas; Espeseth, Thomas; Reinvang, Ivar; Lundervold, Astri J; Lundervold, Arvid; Walhovd, Kristine B

2015-01-01

Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Regional microstructural organization of the cerebral cortex is affected by preterm birth.

PubMed

Bouyssi-Kobar, Marine; Brossard-Racine, Marie; Jacobs, Marni; Murnick, Jonathan; Chang, Taeun; Limperopoulos, Catherine

2018-01-01

To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort. We prospectively enrolled very preterm infants (gestational age (GA) at birth<32 weeks; birthweight<1500 g) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI. We studied 91 preterm infants at TEA and 69 full-term controls. Preterm infants demonstrated significantly higher diffusivity in the prefrontal, parietal, motor, somatosensory, and visual cortices suggesting delayed maturation of these cortical areas. Additionally, postnatal hydrocortisone treatment was related to accelerated microstructural organization in the prefrontal and somatosensory cortices. Preterm birth alters regional microstructural organization of the cerebral cortex in both neurocognitive brain regions and areas with primary sensory/motor functions. We also report for the first time a potential protective effect of postnatal hydrocortisone administration on cerebral cortical development in preterm infants.

Broach Handle Design Changes Force Distribution in the Femur During Total Hip Arthroplasty.

PubMed

Greenhill, Dustin A; Abbasi, Pooyan; Darvish, Kurosh; Star, Andrew M

2017-06-01

Curved broach handles were developed to overcome limited surgical exposures during total hip arthroplasty. Some authors report increased intraoperative fracture rates during limited exposures. This study evaluates mechanical force ratios transmitted to the bone while broaching with curved vs straight handles. An experimental model utilized a 6-axis load cell to measure force distributions produced by 4 different broach handles, each with increasing offset and curvature. Handles were separately impacted and dynamic variables assessed. Handles were then digitized using a high-resolution optical system and a finite element analysis (FEA) was performed to account for trabecular bone and vary the location of mallet impact. Off-axis forces, broaching construct moments, and stress within surrounding bone were computed. Using the experimental model, high-offset handles lost on average 4% more hammering force to the horizontal axis. When the FEA utilized moduli of elasticity to estimate broaching through osteoporotic trabecular bone, horizontally displaced forces (toward cortical bone) were magnified from 4% to a maximum value of 52%. Both the experimental construct and FEA confirmed that larger offset handles increase moment-to-force ratios up to 163%-235%, thus rotating the proximal and distal ends of the broach toward cortical bone. Broach handle design is an important determinant of resultant forces transmitted to the broach (and ultimately the bone) during total hip arthroplasty. Unwanted off-axis forces and enhanced rotational dynamics may play a role in intraoperative fractures during femoral canal preparation. Copyright © 2016 Elsevier Inc. All rights reserved.

Body Topography Parcellates Human Sensory and Motor Cortex.

PubMed

Kuehn, Esther; Dinse, Juliane; Jakobsen, Estrid; Long, Xiangyu; Schäfer, Andreas; Bazin, Pierre-Louis; Villringer, Arno; Sereno, Martin I; Margulies, Daniel S

2017-07-01

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing. © The Author 2017. Published by Oxford University Press.

Effect of blood vessels on light distribution in optogenetic stimulation of cortex.

PubMed

Azimipour, Mehdi; Atry, Farid; Pashaie, Ramin

2015-05-15

In this Letter, the impact of blood vessels on light distribution during photostimulation of cortical tissue in small rodents is investigated. Brain optical properties were extracted using a double-integrating sphere setup, and optical coherence tomography was used to image cortical vessels and capillaries to generate a three-dimensional angiogram of the cortex. By combining these two datasets, a complete volumetric structure of the cortical tissue was developed and linked to a Monte Carlo code which simulates light propagation in this inhomogeneous structure and illustrates the effect of blood vessels on the penetration depth and pattern preservation in optogenetic stimulation.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

PubMed

Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

2015-07-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thalamic Mechanisms in Language: A Reconsideration Based on Recent Findings and Concepts

PubMed Central

Crosson, Bruce

2012-01-01

Recent literature on thalamic aphasia and thalamic activity during neuroimaging is selectively reviewed followed by a consideration of recent anatomic and physiological findings regarding thalamic structure and functions. It is concluded that four related corticothalamic and/or thalamocortical mechanisms impact language processing: (1) selective engagement of task-relevant cortical areas in a heightened state of responsiveness in part through the nucleus reticularis (NR), (2) passing information from one cortical area to another through corticothalamo-cortical mechanisms, (3) sharpening the focus on task-relevant information through corticothalamo-cortical feedback mechanisms, and (4) selection of one language unit over another in the expression of a concept, accomplished in concert with basal ganglia loops. The relationship and interaction of these mechanisms is discussed and integrated with thalamic aphasia and neuroimaging data into a theory of thalamic functions in language. PMID:22831779

Push-Pull Receptive Field Organization and Synaptic Depression: Mechanisms for Reliably Encoding Naturalistic Stimuli in V1

PubMed Central

Kremkow, Jens; Perrinet, Laurent U.; Monier, Cyril; Alonso, Jose-Manuel; Aertsen, Ad; Frégnac, Yves; Masson, Guillaume S.

2016-01-01

Neurons in the primary visual cortex are known for responding vigorously but with high variability to classical stimuli such as drifting bars or gratings. By contrast, natural scenes are encoded more efficiently by sparse and temporal precise spiking responses. We used a conductance-based model of the visual system in higher mammals to investigate how two specific features of the thalamo-cortical pathway, namely push-pull receptive field organization and fast synaptic depression, can contribute to this contextual reshaping of V1 responses. By comparing cortical dynamics evoked respectively by natural vs. artificial stimuli in a comprehensive parametric space analysis, we demonstrate that the reliability and sparseness of the spiking responses during natural vision is not a mere consequence of the increased bandwidth in the sensory input spectrum. Rather, it results from the combined impacts of fast synaptic depression and push-pull inhibition, the later acting for natural scenes as a form of “effective” feed-forward inhibition as demonstrated in other sensory systems. Thus, the combination of feedforward-like inhibition with fast thalamo-cortical synaptic depression by simple cells receiving a direct structured input from thalamus composes a generic computational mechanism for generating a sparse and reliable encoding of natural sensory events. PMID:27242445

Cortical Dynamics of Figure-Ground Separation in Response to 2D Pictures and 3D Scenes: How V2 Combines Border Ownership, Stereoscopic Cues, and Gestalt Grouping Rules

PubMed Central

Grossberg, Stephen

2016-01-01

The FACADE model, and its laminar cortical realization and extension in the 3D LAMINART model, have explained, simulated, and predicted many perceptual and neurobiological data about how the visual cortex carries out 3D vision and figure-ground perception, and how these cortical mechanisms enable 2D pictures to generate 3D percepts of occluding and occluded objects. In particular, these models have proposed how border ownership occurs, but have not yet explicitly explained the correlation between multiple properties of border ownership neurons in cortical area V2 that were reported in a remarkable series of neurophysiological experiments by von der Heydt and his colleagues; namely, border ownership, contrast preference, binocular stereoscopic information, selectivity for side-of-figure, Gestalt rules, and strength of attentional modulation, as well as the time course during which such properties arise. This article shows how, by combining 3D LAMINART properties that were discovered in two parallel streams of research, a unified explanation of these properties emerges. This explanation proposes, moreover, how these properties contribute to the generation of consciously seen 3D surfaces. The first research stream models how processes like 3D boundary grouping and surface filling-in interact in multiple stages within and between the V1 interblob—V2 interstripe—V4 cortical stream and the V1 blob—V2 thin stripe—V4 cortical stream, respectively. Of particular importance for understanding figure-ground separation is how these cortical interactions convert computationally complementary boundary and surface mechanisms into a consistent conscious percept, including the critical use of surface contour feedback signals from surface representations in V2 thin stripes to boundary representations in V2 interstripes. Remarkably, key figure-ground properties emerge from these feedback interactions. The second research stream shows how cells that compute absolute disparity in cortical area V1 are transformed into cells that compute relative disparity in cortical area V2. Relative disparity is a more invariant measure of an object's depth and 3D shape, and is sensitive to figure-ground properties. PMID:26858665

Cortical Dynamics of Figure-Ground Separation in Response to 2D Pictures and 3D Scenes: How V2 Combines Border Ownership, Stereoscopic Cues, and Gestalt Grouping Rules.

PubMed

Grossberg, Stephen

2015-01-01

The FACADE model, and its laminar cortical realization and extension in the 3D LAMINART model, have explained, simulated, and predicted many perceptual and neurobiological data about how the visual cortex carries out 3D vision and figure-ground perception, and how these cortical mechanisms enable 2D pictures to generate 3D percepts of occluding and occluded objects. In particular, these models have proposed how border ownership occurs, but have not yet explicitly explained the correlation between multiple properties of border ownership neurons in cortical area V2 that were reported in a remarkable series of neurophysiological experiments by von der Heydt and his colleagues; namely, border ownership, contrast preference, binocular stereoscopic information, selectivity for side-of-figure, Gestalt rules, and strength of attentional modulation, as well as the time course during which such properties arise. This article shows how, by combining 3D LAMINART properties that were discovered in two parallel streams of research, a unified explanation of these properties emerges. This explanation proposes, moreover, how these properties contribute to the generation of consciously seen 3D surfaces. The first research stream models how processes like 3D boundary grouping and surface filling-in interact in multiple stages within and between the V1 interblob-V2 interstripe-V4 cortical stream and the V1 blob-V2 thin stripe-V4 cortical stream, respectively. Of particular importance for understanding figure-ground separation is how these cortical interactions convert computationally complementary boundary and surface mechanisms into a consistent conscious percept, including the critical use of surface contour feedback signals from surface representations in V2 thin stripes to boundary representations in V2 interstripes. Remarkably, key figure-ground properties emerge from these feedback interactions. The second research stream shows how cells that compute absolute disparity in cortical area V1 are transformed into cells that compute relative disparity in cortical area V2. Relative disparity is a more invariant measure of an object's depth and 3D shape, and is sensitive to figure-ground properties.

A GPU-accelerated cortical neural network model for visually guided robot navigation.

PubMed

Beyeler, Michael; Oros, Nicolas; Dutt, Nikil; Krichmar, Jeffrey L

2015-12-01

Humans and other terrestrial animals use vision to traverse novel cluttered environments with apparent ease. On one hand, although much is known about the behavioral dynamics of steering in humans, it remains unclear how relevant perceptual variables might be represented in the brain. On the other hand, although a wealth of data exists about the neural circuitry that is concerned with the perception of self-motion variables such as the current direction of travel, little research has been devoted to investigating how this neural circuitry may relate to active steering control. Here we present a cortical neural network model for visually guided navigation that has been embodied on a physical robot exploring a real-world environment. The model includes a rate based motion energy model for area V1, and a spiking neural network model for cortical area MT. The model generates a cortical representation of optic flow, determines the position of objects based on motion discontinuities, and combines these signals with the representation of a goal location to produce motor commands that successfully steer the robot around obstacles toward the goal. The model produces robot trajectories that closely match human behavioral data. This study demonstrates how neural signals in a model of cortical area MT might provide sufficient motion information to steer a physical robot on human-like paths around obstacles in a real-world environment, and exemplifies the importance of embodiment, as behavior is deeply coupled not only with the underlying model of brain function, but also with the anatomical constraints of the physical body it controls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward a theory of the general-anesthetic-induced phase transition of the cerebral cortex. I. A thermodynamics analogy

NASA Astrophysics Data System (ADS)

Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Sleigh, J. W.; Wilcocks, Lara C.

2001-07-01

In a recent paper the authors developed a stochastic model for the response of the cerebral cortex to a general anesthetic agent. The model predicted that there would be an anesthetic-induced phase change at the point of transition into unconsciousness, manifested as a divergence in the electroencephalogram spectral power, and a change in spectral energy distribution from being relatively broadband in the conscious state to being strongly biased towards much lower frequencies in the unconscious state. Both predictions have been verified in recent clinical measurements. In the present paper we extend the model by calculating the equilibrium distribution function for the cortex, allowing us to establish a correspondence between the cortical phase transition and the more familiar thermodynamic phase transitions. This correspondence is achieved by first identifying a cortical free energy function, then by postulating that there exists an inverse relationship between an anesthetic effect and a quantity we define as cortical excitability, which plays a role analogous to temperature in thermodynamic phase transitions. We follow standard thermodynamic theory to compute a cortical entropy and a cortical ``heat capacity,'' and we investigate how these will vary with anesthetic concentration. The significant result is the prediction that the entropy will decrease discontinuously at the moment of induction into unconsciousness, concomitant with a release of ``latent heat'' which should manifest as a divergence in the analogous heat capacity. There is clear clinical evidence of heat capacity divergence in historical anesthetic-effect measurements performed in 1977 by Stullken et al. [Anesthesiology 46, 28 (1977)]. The discontinuous step change in cortical entropy suggests that the cortical phase transition is analogous to a first-order thermodynamic transition in which the comatose-quiescent state is strongly ordered, while the active cortical state is relatively disordered.

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

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.

A Task-Optimized Neural Network Replicates Human Auditory Behavior, Predicts Brain Responses, and Reveals a Cortical Processing Hierarchy.

PubMed

Kell, Alexander J E; Yamins, Daniel L K; Shook, Erica N; Norman-Haignere, Sam V; McDermott, Josh H

2018-05-02

A core goal of auditory neuroscience is to build quantitative models that predict cortical responses to natural sounds. Reasoning that a complete model of auditory cortex must solve ecologically relevant tasks, we optimized hierarchical neural networks for speech and music recognition. The best-performing network contained separate music and speech pathways following early shared processing, potentially replicating human cortical organization. The network performed both tasks as well as humans and exhibited human-like errors despite not being optimized to do so, suggesting common constraints on network and human performance. The network predicted fMRI voxel responses substantially better than traditional spectrotemporal filter models throughout auditory cortex. It also provided a quantitative signature of cortical representational hierarchy-primary and non-primary responses were best predicted by intermediate and late network layers, respectively. The results suggest that task optimization provides a powerful set of tools for modeling sensory systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials.

PubMed

Fisher, Jonathan A N; Huang, Stanley; Ye, Meijun; Nabili, Marjan; Wilent, W Bryan; Krauthamer, Victor; Myers, Matthew R; Welle, Cristin G

2016-09-01

Rapid detection and diagnosis of a traumatic brain injury (TBI) can significantly improve the prognosis for recovery. Helmet-mounted sensors that detect impact severity based on measurements of acceleration or pressure show promise for aiding triage and transport decisions in active, field environments such as professional sports or military combat. The detected signals, however, report on the mechanics of an impact rather than directly indicating the presence and severity of an injury. We explored the use of cortical somatosensory evoked electroencephalographic potentials (SSEPs) to detect and track, in real-time, neural electrophysiological abnormalities within the first hour following head injury in an animal model. To study the immediate electrophysiological effects of injury in vivo, we developed an experimental paradigm involving focused ultrasound that permits continuous, real-time measurements and minimizes mechanical artifact. Injury was associated with a dramatic reduction of amplitude over the damaged hemisphere directly after the injury. The amplitude systematically improved over time but remained significantly decreased at one hour, compared with baseline. In contrast, at one hour there was a concomitant enhancement of the cortical SSEP amplitude evoked from the uninjured hemisphere. Analysis of the inter-trial electroencephalogram (EEG) also revealed significant changes in low-frequency components and an increase in EEG entropy up to 30 minutes after injury, likely reflecting altered EEG reactivity to somatosensory stimuli. Injury-induced alterations in SSEPs were also observed using noninvasive epidermal electrodes, demonstrating viability of practical implementation. These results suggest cortical SSEPs recorded at just a few locations by head-mounted sensors and associated multiparametric analyses could potentially be used to rapidly detect and monitor brain injury in settings that normally present significant levels of mechanical and electrical noise.

Elastic interactions between single microcrack and single osteon microstructure of human femur cortical bone

NASA Astrophysics Data System (ADS)

Mansor, N. N.; Daud, R.; Basaruddin, K. S.; Mat, F.; Bajuri, Y.; Ariffin, A. K.

2017-09-01

Inmultiscale Haversian system of cortical bone fracture, a homogenous bone modeling consideration is limited to only one Young modulus was significant for each cortex without having any constituents in that bone. A two dimension model of human femur cortical bone is presented by considering the anatomical positions of four cortices, e.g anterior, posterior, medial and lateral. The Haversian system is modeled under tensile loading by considering the interstitial matrix, osteon and cement line mechanical properties. The interaction between single microcrack and single osteon is evaluated using linear elastic fracture mechanics theory, and was determined using of stress intensity factor, strain energy release rate, and the critical stress intensity factor and critical strain energy release rate parameter. The results indicate that the medial cortex has the highest SIFs while the lowest was posterior cortex. The Young modulus of material was greatly influence the fracture parameters. More stiff the material, the SIF was reduced.

Investigation of hyperelastic models for nonlinear elastic behavior of demineralized and deproteinized bovine cortical femur bone.

PubMed

Hosseinzadeh, M; Ghoreishi, M; Narooei, K

2016-06-01

In this study, the hyperelastic models of demineralized and deproteinized bovine cortical femur bone were investigated and appropriate models were developed. Using uniaxial compression test data, the strain energy versus stretch was calculated and the appropriate hyperelastic strain energy functions were fitted on data in order to calculate the material parameters. To obtain the mechanical behavior in other loading conditions, the hyperelastic strain energy equations were investigated for pure shear and equi-biaxial tension loadings. The results showed the Mooney-Rivlin and Ogden models cannot predict the mechanical response of demineralized and deproteinized bovine cortical femur bone accurately, while the general exponential-exponential and general exponential-power law models have a good agreement with the experimental results. To investigate the sensitivity of the hyperelastic models, a variation of 10% in material parameters was performed and the results indicated an acceptable stability for the general exponential-exponential and general exponential-power law models. Finally, the uniaxial tension and compression of cortical femur bone were studied using the finite element method in VUMAT user subroutine of ABAQUS software and the computed stress-stretch curves were shown a good agreement with the experimental data. Copyright © 2016 Elsevier Ltd. All rights reserved.

Auditory cortical activation and plasticity after cochlear implantation measured by PET using fluorodeoxyglucose.

PubMed

Łukaszewicz-Moszyńska, Zuzanna; Lachowska, Magdalena; Niemczyk, Kazimierz

2014-01-01

The purpose of this study was to evaluate possible relationships between duration of cochlear implant use and results of positron emission tomography (PET) measurements in the temporal lobes performed while subjects listened to speech stimuli. Other aspects investigated were whether implantation side impacts significantly on cortical representations of functions related to understanding speech (ipsi- or contralateral to the implanted side) and whether any correlation exists between cortical activation and speech therapy results. Objective cortical responses to acoustic stimulation were measured, using PET, in nine cochlear implant patients (age range: 15 to 50 years). All the patients suffered from bilateral deafness, were right-handed, and had no additional neurological deficits. They underwent PET imaging three times: immediately after the first fitting of the speech processor (activation of the cochlear implant), and one and two years later. A tendency towards increasing levels of activation in areas of the primary and secondary auditory cortex on the left side of the brain was observed. There was no clear effect of the side of implantation (left or right) on the degree of cortical activation in the temporal lobe. However, the PET results showed a correlation between degree of cortical activation and speech therapy results.

Auditory cortical activation and plasticity after cochlear implantation measured by PET using fluorodeoxyglucose

PubMed Central

Łukaszewicz-Moszyńska, Zuzanna; Lachowska, Magdalena; Niemczyk, Kazimierz

2014-01-01

Summary The purpose of this study was to evaluate possible relationships between duration of cochlear implant use and results of positron emission tomography (PET) measurements in the temporal lobes performed while subjects listened to speech stimuli. Other aspects investigated were whether implantation side impacts significantly on cortical representations of functions related to understanding speech (ipsi- or contralateral to the implanted side) and whether any correlation exists between cortical activation and speech therapy results. Objective cortical responses to acoustic stimulation were measured, using PET, in nine cochlear implant patients (age range: 15 to 50 years). All the patients suffered from bilateral deafness, were right-handed, and had no additional neurological deficits. They underwent PET imaging three times: immediately after the first fitting of the speech processor (activation of the cochlear implant), and one and two years later. A tendency towards increasing levels of activation in areas of the primary and secondary auditory cortex on the left side of the brain was observed. There was no clear effect of the side of implantation (left or right) on the degree of cortical activation in the temporal lobe. However, the PET results showed a correlation between degree of cortical activation and speech therapy results. PMID:25306122

Temperature Values Variability in Piezoelectric Implant Site Preparation: Differences between Cortical and Corticocancellous Bovine Bone.

PubMed

Lamazza, Luca; Garreffa, Girolamo; Laurito, Domenica; Lollobrigida, Marco; Palmieri, Luigi; De Biase, Alberto

2016-01-01

Various parameters can influence temperature rise and detection during implant site preparation. The aim of this study is to investigate local temperature values in cortical and corticocancellous bovine bone during early stages of piezoelectric implant site preparation. 20 osteotomies were performed using a diamond tip (IM1s, Mectron Medical Technology, Carasco, Italy) on two different types of bovine bone samples, cortical and corticocancellous, respectively. A standardized protocol was designed to provide constant working conditions. Temperatures were measured in real time at a fixed position by a fiber optic thermometer. Significantly higher drilling time (154.90 sec versus 99.00 sec; p < 0.0001) and temperatures (39.26°C versus 34.73°C; p = 0.043) were observed in the cortical group compared to the corticocancellous group. A remarkable variability of results characterized the corticocancellous blocks as compared to the blocks of pure cortical bone. Bone samples can influence heat generation during in vitro implant site preparation. When compared to cortical bone, corticocancellous samples present more variability in temperature values. Even controlling most experimental factors, the impact of bone samples still remains one of the main causes of temperature variability.

Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex.

PubMed

Lübke, Joachim; Feldmeyer, Dirk

2007-07-01

A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal 'microcircuits'. In the last decade the 'barrel' field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.

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.

Systematic study of the effects of stimulus parameters and stimulus location on afterdischarges elicited by electrical stimulation in the rat.

PubMed

Shigeto, Hiroshi; Boongird, Atthaporn; Baker, Kenneth; Kellinghaus, Christoph; Najm, Imad; Lüders, Hans

2013-03-01

Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs. Copyright © 2012 Elsevier B.V. All rights reserved.

Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry.

PubMed

Orr, Joseph M; Paschall, Courtnie J; Banich, Marie T

2016-01-01

A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well-controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP) consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure.

Computational Study of the Effect of Cortical Porosity on Ultrasound Wave Propagation in Healthy and Osteoporotic Long Bones

PubMed Central

T. Potsika, Vassiliki; N. Grivas, Konstantinos; Gortsas, Theodoros; Iori, Gianluca; C. Protopappas, Vasilios; Raum, Kay; Polyzos, Demosthenes; I. Fotiadis, Dimitrios

2016-01-01

Computational studies on the evaluation of bone status in cases of pathologies have gained significant interest in recent years. This work presents a parametric and systematic numerical study on ultrasound propagation in cortical bone models to investigate the effect of changes in cortical porosity and the occurrence of large basic multicellular units, simply called non-refilled resorption lacunae (RL), on the velocity of the first arriving signal (FAS). Two-dimensional geometries of cortical bone are established for various microstructural models mimicking normal and pathological tissue states. Emphasis is given on the detection of RL formation which may provoke the thinning of the cortical cortex and the increase of porosity at a later stage of the disease. The central excitation frequencies 0.5 and 1 MHz are examined. The proposed configuration consists of one point source and multiple successive receivers in order to calculate the FAS velocity in small propagation paths (local velocity) and derive a variation profile along the cortical surface. It was shown that: (a) the local FAS velocity can capture porosity changes including the occurrence of RL with different number, size and depth of formation; and (b) the excitation frequency 0.5 MHz is more sensitive for the assessment of cortical microstructure. PMID:28773331

On the Origin of Tremor in Parkinson’s Disease

PubMed Central

Dovzhenok, Andrey; Rubchinsky, Leonid L.

2012-01-01

The exact origin of tremor in Parkinson’s disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson’s disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop. PMID:22848541

The Bat as a New Model of Cortical Development.

PubMed

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Ariza, Jeanelle; Rogers, Hailee; Horton-Sparks, Kayla; Kreutz, Anna; Behringer, Richard; Rasweiler, John J; Noctor, Stephen C

2017-11-09

The organization of the mammalian cerebral cortex shares fundamental features across species. However, while the radial thickness of grey matter varies within one order of magnitude, the tangential spread of the cortical sheet varies by orders of magnitude across species. A broader sample of model species may provide additional clues for understanding mechanisms that drive cortical expansion. Here, we introduce the bat Carollia perspicillata as a new model species. The brain of C. perspicillata is similar in size to that of mouse but has a cortical neurogenic period at least 5 times longer than mouse, and nearly as long as that of the rhesus macaque, whose brain is 100 times larger. We describe the development of laminar and regional structures, neural precursor cell identity and distribution, immune cell distribution, and a novel population of Tbr2+ cells in the caudal ganglionic eminence of the developing neocortex of C. perspicillata. Our data indicate that unique mechanisms guide bat cortical development, particularly concerning cell cycle length. The bat model provides new perspective on the evolution of developmental programs that regulate neurogenesis in mammalian cerebral cortex, and offers insight into mechanisms that contribute to tangential expansion and gyri formation in the cerebral cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Biomechanics of Single Cortical Neurons

PubMed Central

Bernick, Kristin B.; Prevost, Thibault P.; Suresh, Subra; Socrate, Simona

2011-01-01

This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude – 10, 1, and 0.1 μm/s. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper-) elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. PMID:20971217

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

PubMed Central

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

PubMed

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

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.

Utilizing multiple scale models to improve predictions of extra-axial hemorrhage in the immature piglet.

PubMed

Scott, Gregory G; Margulies, Susan S; Coats, Brittany

2016-10-01

Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. To help understand and better predict TBI, researchers have developed complex finite element (FE) models of the head which incorporate many biological structures such as scalp, skull, meninges, brain (with gray/white matter differentiation), and vasculature. However, most models drastically simplify the membranes and substructures between the pia and arachnoid membranes. We hypothesize that substructures in the pia-arachnoid complex (PAC) contribute substantially to brain deformation following head rotation, and that when included in FE models accuracy of extra-axial hemorrhage prediction improves. To test these hypotheses, microscale FE models of the PAC were developed to span the variability of PAC substructure anatomy and regional density. The constitutive response of these models were then integrated into an existing macroscale FE model of the immature piglet brain to identify changes in cortical stress distribution and predictions of extra-axial hemorrhage (EAH). Incorporating regional variability of PAC substructures substantially altered the distribution of principal stress on the cortical surface of the brain compared to a uniform representation of the PAC. Simulations of 24 non-impact rapid head rotations in an immature piglet animal model resulted in improved accuracy of EAH prediction (to 94 % sensitivity, 100 % specificity), as well as a high accuracy in regional hemorrhage prediction (to 82-100 % sensitivity, 100 % specificity). We conclude that including a biofidelic PAC substructure variability in FE models of the head is essential for improved predictions of hemorrhage at the brain/skull interface.

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

PubMed Central

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita

2011-01-01

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20. We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP. PMID:21876530

Lateral fluid percussion: model of traumatic brain injury in mice.

PubMed

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

2011-08-22

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20). We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.

Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.

PubMed

King, Christopher; Robinson, Timothy; Dixon, C Edward; Rao, Gutti R; Larnard, Donald; Nemoto, C Edwin M

2010-10-01

Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. We evaluated the effects on brain temperature of a cooling device called the ChillerPad,™ which is applied to the dura in a non-human primate TBI model using controlled cortical impact (CCI). The cortical surface was rapidly cooled to approximately 15°C and maintained at that level for 24 h, followed by rewarming over about 10 h. Brain temperatures fell to 34-35°C at a depth of 15 mm at the cortical gray/white matter interface, and to 28-32°C at 10 mm deep. Intracranial pressure was mildly elevated (8-12 mm Hg) after cooling and rewarming, likely due to TBI. Other physiological variables were unchanged. Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.

Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue

PubMed Central

Chaigneau, Emmanuelle; Wright, Amanda J.; Poland, Simon P.; Girkin, John M.; Silver, R. Angus

2011-01-01

Two-photon (2P) microscopy is widely used in neuroscience, but the optical properties of brain tissue are poorly understood. We have investigated the effect of brain tissue on the 2P point spread function (PSF2P) by imaging fluorescent beads through living cortical slices. By combining this with measurements of the mean free path of the excitation light, adaptive optics and vector-based modeling that includes phase modulation and scattering, we show that tissue-induced wavefront distortions are the main determinant of enlargement and distortion of the PSF2P at intermediate imaging depths. Furthermore, they generate surrounding lobes that contain more than half of the 2P excitation. These effects reduce the resolution of fine structures and contrast and they, together with scattering, limit 2P excitation. Our results disentangle the contributions of scattering and wavefront distortion in shaping the cortical PSF2P, thereby providing a basis for improved 2P microscopy. PMID:22109156

Unique membrane properties and enhanced signal processing in human neocortical neurons.

PubMed

Eyal, Guy; Verhoog, Matthijs B; Testa-Silva, Guilherme; Deitcher, Yair; Lodder, Johannes C; Benavides-Piccione, Ruth; Morales, Juan; DeFelipe, Javier; de Kock, Christiaan Pj; Mansvelder, Huibert D; Segev, Idan

2016-10-06

The advanced cognitive capabilities of the human brain are often attributed to our recently evolved neocortex. However, it is not known whether the basic building blocks of the human neocortex, the pyramidal neurons, possess unique biophysical properties that might impact on cortical computations. Here we show that layer 2/3 pyramidal neurons from human temporal cortex (HL2/3 PCs) have a specific membrane capacitance ( C m ) of ~0.5 µF/cm 2 , half of the commonly accepted 'universal' value (~1 µF/cm 2 ) for biological membranes. This finding was predicted by fitting in vitro voltage transients to theoretical transients then validated by direct measurement of C m in nucleated patch experiments. Models of 3D reconstructed HL2/3 PCs demonstrated that such low C m value significantly enhances both synaptic charge-transfer from dendrites to soma and spike propagation along the axon. This is the first demonstration that human cortical neurons have distinctive membrane properties, suggesting important implications for signal processing in human neocortex.

An in silico agent-based model demonstrates Reelin function in directing lamination of neurons during cortical development.

PubMed

Caffrey, James R; Hughes, Barry D; Britto, Joanne M; Landman, Kerry A

2014-01-01

The characteristic six-layered appearance of the neocortex arises from the correct positioning of pyramidal neurons during development and alterations in this process can cause intellectual disabilities and developmental delay. Malformations in cortical development arise when neurons either fail to migrate properly from the germinal zones or fail to cease migration in the correct laminar position within the cortical plate. The Reelin signalling pathway is vital for correct neuronal positioning as loss of Reelin leads to a partially inverted cortex. The precise biological function of Reelin remains controversial and debate surrounds its role as a chemoattractant or stop signal for migrating neurons. To investigate this further we developed an in silico agent-based model of cortical layer formation. Using this model we tested four biologically plausible hypotheses for neuron motility and four biologically plausible hypotheses for the loss of neuron motility (conversion from migration). A matrix of 16 combinations of motility and conversion rules was applied against the known structure of mouse cortical layers in the wild-type cortex, the Reelin-null mutant, the Dab1-null mutant and a conditional Dab1 mutant. Using this approach, many combinations of motility and conversion mechanisms can be rejected. For example, the model does not support Reelin acting as a repelling or as a stopping signal. In contrast, the study lends very strong support to the notion that the glycoprotein Reelin acts as a chemoattractant for neurons. Furthermore, the most viable proposition for the conversion mechanism is one in which conversion is affected by a motile neuron sensing in the near vicinity neurons that have already converted. Therefore, this model helps elucidate the function of Reelin during neuronal migration and cortical development.

A knowledge-guided active model method of cortical structure segmentation on pediatric MR images.

PubMed

Shan, Zuyao Y; Parra, Carlos; Ji, Qing; Jain, Jinesh; Reddick, Wilburn E

2006-10-01

To develop an automated method for quantification of cortical structures on pediatric MR images. A knowledge-guided active model (KAM) approach was proposed with a novel object function similar to the Gibbs free energy function. Triangular mesh models were transformed to images of a given subject by maximizing entropy, and then actively slithered to boundaries of structures by minimizing enthalpy. Volumetric results and image similarities of 10 different cortical structures segmented by KAM were compared with those traced manually. Furthermore, the segmentation performances of KAM and SPM2, (statistical parametric mapping, a MATLAB software package) were compared. The averaged volumetric agreements between KAM- and manually-defined structures (both 0.95 for structures in healthy children and children with medulloblastoma) were higher than the volumetric agreement for SPM2 (0.90 and 0.80, respectively). The similarity measurements (kappa) between KAM- and manually-defined structures (0.95 and 0.93, respectively) were higher than those for SPM2 (both 0.86). We have developed a novel automatic algorithm, KAM, for segmentation of cortical structures on MR images of pediatric patients. Our preliminary results indicated that when segmenting cortical structures, KAM was in better agreement with manually-delineated structures than SPM2. KAM can potentially be used to segment cortical structures for conformal radiation therapy planning and for quantitative evaluation of changes in disease or abnormality. Copyright (c) 2006 Wiley-Liss, Inc.

Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema.

PubMed

Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

2016-12-13

BACKGROUND Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). MATERIAL AND METHODS TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. RESULTS We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (p<0.05 and p<0.001, respectively) and decreased the cortical lesion volume (p<0.05 and p<0.001, respectively) compared with vehicle-only treatment. PA treatment at the dose of 125 mg/kg attenuated brain edema and ameliorated BBB integrity. In addition, PA treatment significantly reduced the loss of ATP (p<0.01), reduced lactic acid levels (p<0.001), and increased the activity of Na+/K+-ATPase (p<0.01). CONCLUSIONS Our results indicate PA has neuroprotective effects on TBI through increasing ATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA.

Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.

PubMed

Arata, Yukinobu; Hiroshima, Michio; Pack, Chan-Gi; Ramanujam, Ravikrishna; Motegi, Fumio; Nakazato, Kenichi; Shindo, Yuki; Wiseman, Paul W; Sawa, Hitoshi; Kobayashi, Tetsuya J; Brandão, Hugo B; Shibata, Tatsuo; Sako, Yasushi

2016-08-23

Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

When intelligence loses its impact: neural efficiency during reasoning in a familiar area.

PubMed

Grabner, Roland H; Stern, Elsbeth; Neubauer, Aljoscha C

2003-08-01

Several studies have revealed that persons with a lower IQ show more cortical activity when solving intelligence-related tasks than more intelligent persons do. Such results are interpreted in terms of neural efficiency: the more intelligent a person is, the fewer mental resources have to be activated. In an experiment with 31 experienced taxi drivers of varying IQs (measured by Raven's advanced progressive matrices test), we investigated cortical activation by measuring the amount of event-related desynchronization in the electroencephalogram during a familiar task (thinking about routes to take in their city) and a novel task (memorizing routes of an artificial map). A comparison of participants with lower and higher IQs (median split) revealed higher cortical activation in the less intelligent group for the novel task, but not for the familiar task. These results suggest that long-term experience can compensate for lower intellectual ability, even at the level of cortical activation.

APLP2 regulates neuronal stem cell differentiation during cortical development.

PubMed

Shariati, S Ali M; Lau, Pierre; Hassan, Bassem A; Müller, Ulrike; Dotti, Carlos G; De Strooper, Bart; Gärtner, Annette

2013-03-01

Expression of amyloid precursor protein (APP) and its two paralogues, APLP1 and APLP2 during brain development coincides with key cellular events such as neuronal differentiation and migration. However, genetic knockout and shRNA studies have led to contradictory conclusions about their role during embryonic brain development. To address this issue, we analysed in depth the role of APLP2 during neurogenesis by silencing APLP2 in vivo in an APP/APLP1 double knockout mouse background. We find that under these conditions cortical progenitors remain in their undifferentiated state much longer, displaying a higher number of mitotic cells. In addition, we show that neuron-specific APLP2 downregulation does not impact the speed or position of migrating excitatory cortical neurons. In summary, our data reveal that APLP2 is specifically required for proper cell cycle exit of neuronal progenitors, and thus has a distinct role in priming cortical progenitors for neuronal differentiation.

Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention.

PubMed

Szulc-Lerch, Kamila U; Timmons, Brian W; Bouffet, Eric; Laughlin, Suzanne; de Medeiros, Cynthia B; Skocic, Jovanka; Lerch, Jason P; Mabbott, Donald J

2018-01-01

There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation. We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline. Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline. Overall, our results indicate that exercise training in pediatric brain tumor patients treated with radiation has a beneficial impact on brain structure. We argue that exercise training should be incorporated into the development of neuro-rehabilitative treatments for long-term pediatric brain tumor survivors and other populations with acquired brain injury. (ClinicalTrials.gov, NCT01944761).

Brain connections of words, perceptions and actions: A neurobiological model of spatio-temporal semantic activation in the human cortex.

PubMed

Tomasello, Rosario; Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

2017-04-01

Neuroimaging and patient studies show that different areas of cortex respectively specialize for general and selective, or category-specific, semantic processing. Why are there both semantic hubs and category-specificity, and how come that they emerge in different cortical regions? Can the activation time-course of these areas be predicted and explained by brain-like network models? In this present work, we extend a neurocomputational model of human cortical function to simulate the time-course of cortical processes of understanding meaningful concrete words. The model implements frontal and temporal cortical areas for language, perception, and action along with their connectivity. It uses Hebbian learning to semantically ground words in aspects of their referential object- and action-related meaning. Compared with earlier proposals, the present model incorporates additional neuroanatomical links supported by connectivity studies and downscaled synaptic weights in order to control for functional between-area differences purely due to the number of in- or output links of an area. We show that learning of semantic relationships between words and the objects and actions these symbols are used to speak about, leads to the formation of distributed circuits, which all include neuronal material in connector hub areas bridging between sensory and motor cortical systems. Therefore, these connector hub areas acquire a role as semantic hubs. By differentially reaching into motor or visual areas, the cortical distributions of the emergent 'semantic circuits' reflect aspects of the represented symbols' meaning, thus explaining category-specificity. The improved connectivity structure of our model entails a degree of category-specificity even in the 'semantic hubs' of the model. The relative time-course of activation of these areas is typically fast and near-simultaneous, with semantic hubs central to the network structure activating before modality-preferential areas carrying semantic information. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Simulation study of axial ultrasound transmission in heterogeneous cortical bone model

NASA Astrophysics Data System (ADS)

Takano, Koki; Nagatani, Yoshiki; Matsukawa, Mami

2017-07-01

Ultrasound propagation in a heterogeneous cortical bone was studied. Using a bovine radius, the longitudinal wave velocity distribution in the axial direction was experimentally measured in the MHz range. The bilinear interpolation and piecewise cubic Hermite interpolation methods were applied to create a three-dimensional (3D) precise velocity model of the bone using experimental data. By assuming the uniaxial anisotropy of the bone, the distributions of all elastic moduli of a 3D heterogeneous model were estimated. The elastic finite-difference time-domain method was used to simulate axial ultrasonic wave propagation. The wave propagation in the initial model was compared with that in the thinner model, where the inner part of the cortical bone model was removed. The wave front of the first arriving signal (FAS) slightly depended on the heterogeneity in each model. Owing to the decrease in bone thickness, the propagation behavior also changed and the FAS velocity clearly decreased.

Language Mapping Using fMRI and Direct Cortical Stimulation for Brain Tumor Surgery

PubMed Central

Brennan, Nicole Petrovich; Peck, Kyung K.; Holodny, Andrei

2016-01-01

Language functional magnetic resonance imaging for neurosurgical planning is a useful but nuanced technique. Consideration of primary and secondary language anatomy, task selection, and data analysis choices all impact interpretation. In the following chapter, we consider practical considerations and nuances alike for language functional magnetic resonance imaging in the support of and comparison with the neurosurgical gold standard, direct cortical stimulation. Pitfalls and limitations are discussed. PMID:26848555

Freesurfer cortical normative data for adults using Desikan-Killiany-Tourville and ex vivo protocols.

PubMed

Potvin, Olivier; Dieumegarde, Louis; Duchesne, Simon

2017-08-01

We recently built normative data for FreeSurfer morphometric estimates of cortical regions using its default atlas parcellation (Desikan-Killiany or DK) according to individual and scanner characteristics. We aimed to produced similar normative values for Desikan-Killianny-Tourville (DKT) and ex vivo-based labeling protocols, as well as examine the differences between these three atlases. Surfaces, thicknesses, and volumes of cortical regions were produced using cross-sectional magnetic resonance scans from the same 2713 healthy individuals aged 18-94 years as used in the reported DK norms. Models predicting regional cortical estimates of each hemisphere were produced using age, sex, estimated intracranial volume (eTIV), scanner manufacturer and magnetic field strength (MFS) as predictors. The DKT and DK models generally included the same predictors and produced similar R 2 . Comparison between DK, DKT, ex vivo atlases normative cortical measures showed that the three protocols generally produced similar normative values. Copyright © 2017 Elsevier Inc. All rights reserved.

Synchronous behaviour in network model based on human cortico-cortical connections.

PubMed

Protachevicz, Paulo Ricardo; Borges, Rafael Ribaski; Reis, Adriane da Silva; Borges, Fernando da Silva; Iarosz, Kelly Cristina; Caldas, Ibere Luiz; Lameu, Ewandson Luiz; Macau, Elbert Einstein Nehrer; Viana, Ricardo Luiz; Sokolov, Igor M; Ferrari, Fabiano A S; Kurths, Jürgen; Batista, Antonio Marcos

2018-06-22

We consider a network topology according to the cortico-cortical connec- tion network of the human brain, where each cortical area is composed of a random network of adaptive exponential integrate-and-fire neurons. Depending on the parameters, this neuron model can exhibit spike or burst patterns. As a diagnostic tool to identify spike and burst patterns we utilise the coefficient of variation of the neuronal inter-spike interval. In our neuronal network, we verify the existence of spike and burst synchronisation in different cortical areas. Our simulations show that the network arrangement, i.e., its rich-club organisation, plays an important role in the transition of the areas from desynchronous to synchronous behaviours. © 2018 Institute of Physics and Engineering in Medicine.

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.

Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson's disease.

PubMed

Eggers, Carsten; Fink, Gereon R; Nowak, Dennis A

2010-10-01

The purpose of this study was to investigate whether a period of continuous theta burst stimulation (cTBS) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson's disease. In eight patients with Parkinson's disease (two females; mean age: 68.5 ± 5 years; disease duration: 4 ± 3 years) electrophysiological (motor evoked potentials, contralateral and ipsilateral silent period) and behavioural (Purdue pegboard test, UPDRS motor subscore) parameters were evaluated before (baseline condition) and after a 40-s period of (1) real or (2) sham continuous theta burst stimulation over the primary motor cortex contralateral to the more affected body side off dopaminergic drugs. Compared to baseline, cTBS did change neither measures of cortical excitability nor behavioural measures. cTBS over the primary motor cortex does not impact on cortical excitability or motor function of the upper limb in Parkinson's disease. We interpret these data to reflect impaired cortical plasticity in Parkinson's disease. This study is an important contribution to the knowledge about impaired plasticity in Parkinson's disease.

Altered Markers of Brain Development in Crohn’s Disease with Extraintestinal Manifestations – A Pilot Study

PubMed Central

Thomann, Philipp A.; Wolf, Robert C.; Hirjak, Dusan; Schmahl, Christian; Ebert, Matthias P.; Szabo, Kristina; Reindl, Wolfgang; Griebe, Martin

2016-01-01

Background and Objective Alterations of brain morphology in Crohn’s disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn’s disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development. Methods In a pilot study, brains of 15 patients with Crohn’s disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling. Results The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons. Conclusions Our findings lend further support to the hypothesis that Crohn’s disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn’s disease or its predisposition during brain development. PMID:27655165

Recursive grid partitioning on a cortical surface model: an optimized technique for the localization of implanted subdural electrodes.

PubMed

Pieters, Thomas A; Conner, Christopher R; Tandon, Nitin

2013-05-01

Precise localization of subdural electrodes (SDEs) is essential for the interpretation of data from intracranial electrocorticography recordings. Blood and fluid accumulation underneath the craniotomy flap leads to a nonlinear deformation of the brain surface and of the SDE array on postoperative CT scans and adversely impacts the accurate localization of electrodes located underneath the craniotomy. Older methods that localize electrodes based on their identification on a postimplantation CT scan with coregistration to a preimplantation MR image can result in significant problems with accuracy of the electrode localization. The authors report 3 novel methods that rely on the creation of a set of 3D mesh models to depict the pial surface and a smoothed pial envelope. Two of these new methods are designed to localize electrodes, and they are compared with 6 methods currently in use to determine their relative accuracy and reliability. The first method involves manually localizing each electrode using digital photographs obtained at surgery. This is highly accurate, but requires time intensive, operator-dependent input. The second uses 4 electrodes localized manually in conjunction with an automated, recursive partitioning technique to localize the entire electrode array. The authors evaluated the accuracy of previously published methods by applying the methods to their data and comparing them against the photograph-based localization. Finally, the authors further enhanced the usability of these methods by using automatic parcellation techniques to assign anatomical labels to individual electrodes as well as by generating an inflated cortical surface model while still preserving electrode locations relative to the cortical anatomy. The recursive grid partitioning had the least error compared with older methods (672 electrodes, 6.4-mm maximum electrode error, 2.0-mm mean error, p < 10(-18)). The maximum errors derived using prior methods of localization ranged from 8.2 to 11.7 mm for an individual electrode, with mean errors ranging between 2.9 and 4.1 mm depending on the method used. The authors also noted a larger error in all methods that used CT scans alone to localize electrodes compared with those that used both postoperative CT and postoperative MRI. The large mean errors reported with these methods are liable to affect intermodal data comparisons (for example, with functional mapping techniques) and may impact surgical decision making. The authors have presented several aspects of using new techniques to visualize electrodes implanted for localizing epilepsy. The ability to use automated labeling schemas to denote which gyrus a particular electrode overlies is potentially of great utility in planning resections and in corroborating the results of extraoperative stimulation mapping. Dilation of the pial mesh model provides, for the first time, a sense of the cortical surface not sampled by the electrode, and the potential roles this "electrophysiologically hidden" cortex may play in both eloquent function and seizure onset.

Training of Working Memory Impacts Neural Processing of Vocal Pitch Regulation

PubMed Central

Li, Weifeng; Guo, Zhiqiang; Jones, Jeffery A.; Huang, Xiyan; Chen, Xi; Liu, Peng; Chen, Shaozhen; Liu, Hanjun

2015-01-01

Working memory training can improve the performance of tasks that were not trained. Whether auditory-motor integration for voice control can benefit from working memory training, however, remains unclear. The present event-related potential (ERP) study examined the impact of working memory training on the auditory-motor processing of vocal pitch. Trained participants underwent adaptive working memory training using a digit span backwards paradigm, while control participants did not receive any training. Before and after training, both trained and control participants were exposed to frequency-altered auditory feedback while producing vocalizations. After training, trained participants exhibited significantly decreased N1 amplitudes and increased P2 amplitudes in response to pitch errors in voice auditory feedback. In addition, there was a significant positive correlation between the degree of improvement in working memory capacity and the post-pre difference in P2 amplitudes. Training-related changes in the vocal compensation, however, were not observed. There was no systematic change in either vocal or cortical responses for control participants. These findings provide evidence that working memory training impacts the cortical processing of feedback errors in vocal pitch regulation. This enhanced cortical processing may be the result of increased neural efficiency in the detection of pitch errors between the intended and actual feedback. PMID:26553373

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

PubMed

Jin, Guang; DeMoya, Marc A; Duggan, Michael; Knightly, Thomas; Mejaddam, Ali Y; Hwabejire, John; Lu, Jennifer; Smith, William Michael; Kasotakis, Georgios; Velmahos, George C; Socrate, Simona; Alam, Hasan B

2012-07-01

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

Differential impact of partial cortical blindness on gaze strategies when sitting and walking - an immersive virtual reality study

PubMed Central

Iorizzo, Dana B.; Riley, Meghan E.; Hayhoe, Mary; Huxlin, Krystel R.

2011-01-01

The present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ~80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls - with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ~90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life. PMID:21414339

Differential impact of partial cortical blindness on gaze strategies when sitting and walking - an immersive virtual reality study.

PubMed

Iorizzo, Dana B; Riley, Meghan E; Hayhoe, Mary; Huxlin, Krystel R

2011-05-25

The present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ∼80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls - with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ∼90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Age-related changes in bone strength from HR-pQCT derived microarchitectural parameters with an emphasis on the role of cortical porosity.

PubMed

Vilayphiou, Nicolas; Boutroy, Stephanie; Sornay-Rendu, Elisabeth; Van Rietbergen, Bert; Chapurlat, Roland

2016-02-01

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r(2)=0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia. Copyright © 2015 Elsevier Inc. All rights reserved.

Wound ballistics of the pig mandibular angle: a preliminary finite element analysis and experimental study.

PubMed

Chen, Yubin; Miao, Yingyun; Xu, Chuan; Zhang, Gang; Lei, Tao; Tan, Yinghui

2010-04-19

To study wound ballistics of the mandibular angle, a combined hexahedral-tetrahedral finite element (FE) model of the pig mandible was developed to simulate ballistic impact. An experimental study was carried out by measuring impact load parameters from 14 fresh pig mandibles that were shot at the mandibular angle by a standard 7.62 mm M43 bullet. FE analysis was executed through the LS-DYNA code under impact loads similar to those obtained from the experimental study. The resulting residual velocity, the transferred energy from the bullet to the mandible, and the surface area of the entrance wound had no statistical differences between the FE simulation and the experimental study. However, the mean surface area of the exit wounds in the experimental study was significantly larger than that in the simulation. According to the FE analysis, the stress concentrated zones were mainly located at the region of impact, condylar neck, coronoid process and mandibular body. The simulation results also indicated that trabecular bone had less stress concentration and a lower speed of stress propagation compared with cortical bone. The FE model is appropriate and conforms to the basic principles of wound ballistics. This modeling system will be helpful for further investigations of the biomechanical mechanisms of wound ballistics. Copyright 2009 Elsevier Ltd. All rights reserved.

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.

Acute inactivation of the contralesional hemisphere for longer durations improves recovery after cortical injury.

PubMed

Mansoori, Babak K; Jean-Charles, Loyda; Touvykine, Boris; Liu, Aihua; Quessy, Stephan; Dancause, Numa

2014-04-01

A rapidly growing number of studies using inhibition of the contralesional hemisphere after stroke are reporting improvement in motor performance of the paretic hand. These studies have used different treatment onset time, duration and non-invasive methods of inhibition. Whereas these results are encouraging, several questions regarding the mechanisms of inhibition and the most effective treatment parameters are currently unanswered. In the present study, we used a rat model of cortical lesion to study the effects of GABA-mediated inactivation on motor recovery. In particular, we were interested in understanding better the effect of inactivation duration when it is initiated within hours following a cortical lesion. Cortical lesions were induced with endothelin-1 microinjections. The contralesional hemisphere was inactivated with continuous infusion of the GABA-A agonist Muscimol for 3, 7 or 14days in three different groups of animals. In a fourth group, Muscimol was infused at slower rate for 14days to provide additional insights on the relation between the effects of inactivation on the non-paretic forelimb behavior and the recovery of the paretic forelimb. In spontaneously recovered animals, the lesion caused a sustained bias to use the non-paretic forelimb and long-lasting grasping deficits with the paretic forelimb. Contralesional inactivation produced a general decrease of behavioral activity, affected the spontaneous use of the forelimbs and caused a specific reduction of the non-paretic forelimb function. The intensity and the duration of these behavioral effects varied in the different experimental groups. For the paretic forelimb, increasing inactivation duration accelerated the recovery of grasping function. Both groups with 14days of inactivation had similar recovery profiles and performed better than animals that spontaneously recovered. Whereas the plateau performance of the paretic forelimb correlated with the duration of contralesional inactivation, it was not correlated with the spontaneous use of the forelimbs or with grasping performance of the non-paretic hand. Our results support that contralesional inactivation initiated within hours after a cortical lesion can improve recovery of the paretic forelimb. In our model, increasing the duration of the inactivation improved motor outcomes but the spontaneous use and motor performance of the non-paretic forelimb had no impact on recovery of the paretic forelimb. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Columnar organization of orientation domains in V1

NASA Astrophysics Data System (ADS)

Liedtke, Joscha; Wolf, Fred

In the primary visual cortex (V1) of primates and carnivores, the functional architecture of basic stimulus selectivities appears similar across cortical layers (Hubel & Wiesel, 1962) justifying the use of two-dimensional cortical models and disregarding organization in the third dimension. Here we show theoretically that already small deviations from an exact columnar organization lead to non-trivial three-dimensional functional structures. We extend two-dimensional random field models (Schnabel et al., 2007) to a three-dimensional cortex by keeping a typical scale in each layer and introducing a correlation length in the third, columnar dimension. We examine in detail the three-dimensional functional architecture for different cortical geometries with different columnar correlation lengths. We find that (i) topological defect lines are generally curved and (ii) for large cortical curvatures closed loops and reconnecting topological defect lines appear. This theory extends the class of random field models by introducing a columnar dimension and provides a systematic statistical assessment of the three-dimensional functional architecture of V1 (see also (Tanaka et al., 2011)).

A network of networks model to study phase synchronization using structural connection matrix of human brain

NASA Astrophysics Data System (ADS)

Ferrari, F. A. S.; Viana, R. L.; Reis, A. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.

2018-04-01

The cerebral cortex plays a key role in complex cortical functions. It can be divided into areas according to their function (motor, sensory and association areas). In this paper, the cerebral cortex is described as a network of networks (cortex network), we consider that each cortical area is composed of a network with small-world property (cortical network). The neurons are assumed to have bursting properties with the dynamics described by the Rulkov model. We study the phase synchronization of the cortex network and the cortical networks. In our simulations, we verify that synchronization in cortex network is not homogeneous. Besides, we focus on the suppression of neural phase synchronization. Synchronization can be related to undesired and pathological abnormal rhythms in the brain. For this reason, we consider the delayed feedback control to suppress the synchronization. We show that delayed feedback control is efficient to suppress synchronous behavior in our network model when an appropriate signal intensity and time delay are defined.

Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

PubMed

Aldrin-Kirk, Patrick; Davidsson, Marcus; Holmqvist, Staffan; Li, Jia-Yi; Björklund, Tomas

2014-01-01

Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB) are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV) vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable to α-synuclein over-expression. This animal model provides a powerful new tool for studies of neuronal degeneration in conditions of widespread cortical α-synuclein pathology, such as DLB, as well an attractive model for the exploration of novel biomarkers.

Statistical shape analysis of clavicular cortical bone with applications to the development of mean and boundary shape models.

PubMed

Lu, Yuan-Chiao; Untaroiu, Costin D

2013-09-01

During car collisions, the shoulder belt exposes the occupant's clavicle to large loading conditions which often leads to a bone fracture. To better understand the geometric variability of clavicular cortical bone which may influence its injury tolerance, twenty human clavicles were evaluated using statistical shape analysis. The interior and exterior clavicular cortical bone surfaces were reconstructed from CT-scan images. Registration between one selected template and the remaining 19 clavicle models was conducted to remove translation and rotation differences. The correspondences of landmarks between the models were then established using coordinates and surface normals. Three registration methods were compared: the LM-ICP method; the global method; and the SHREC method. The LM-ICP registration method showed better performance than the global and SHREC registration methods, in terms of compactness, generalization, and specificity. The first four principal components obtained by using the LM-ICP registration method account for 61% and 67% of the overall anatomical variation for the exterior and interior cortical bone shapes, respectively. The length was found to be the most significant variation mode of the human clavicle. The mean and two boundary shape models were created using the four most significant principal components to investigate the size and shape variation of clavicular cortical bone. In the future, boundary shape models could be used to develop probabilistic finite element models which may help to better understand the variability in biomechanical responses and injuries to the clavicle. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

Effects of Loading Duration and Short Rest Insertion on Cancellous and Cortical Bone Adaptation in the Mouse Tibia

PubMed Central

Yang, Haisheng; Embry, Rachel E.; Main, Russell P.

2017-01-01

The skeleton’s osteogenic response to mechanical loading can be affected by loading duration and rest insertion during a series of loading events. Prior animal loading studies have shown that the cortical bone response saturates quickly and short rest insertions between load cycles can enhance cortical bone formation. However, it remains unknown how loading duration and short rest insertion affect load-induced osteogenesis in the mouse tibial compressive loading model, and particularly in cancellous bone. To address this issue, we applied cyclic loading (-9 N peak load; 4 Hz) to the tibiae of three groups of 16 week-old female C57BL/6 mice for two weeks, with a different number of continuous load cycles applied daily to each group (36, 216 and 1200). A fourth group was loaded under 216 daily load cycles with a 10 s rest insertion after every fourth cycle. We found that as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone. Furthermore, while cortical bone area and thickness continued to increase through 1200 cycles, the incremental increase in the osteogenic response decreased as load number increased, indicating a reduced benefit of the increasing number of load cycles. In the proximal metaphyseal cancellous bone, trabecular thickness increased with load up to 216 cycles. We also found that insertion of a 10 s rest between load cycles did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading in this model given the age and sex of the mice and the loading parameters used here. These results suggest that relatively few load cycles (e.g. 36) are sufficient to induce osteogenic responses in both cortical and cancellous bone in the mouse tibial loading model. Mechanistic studies using the mouse tibial loading model to examine bone formation and skeletal mechanobiology could be accomplished with relatively few load cycles. PMID:28076363

Correlation of panoramic radiography and cone beam CT findings in the assessment of the relationship between impacted mandibular third molars and the mandibular canal

PubMed Central

Neves, F S; Souza, T C; Almeida, S M; Haiter-Neto, F; Freitas, D Q; Bóscolo, F N

2012-01-01

Objectives The aim of this study was to assess the reliability of four panoramic radiographic findings, both individually and in association, in predicting the absence of corticalization between the mandibular canal and the third molar on cone beam CT (CBCT) images. Methods The sample consisted of 72 individuals (142 mandibular third molars) who underwent pre-operative radiographic evaluation before extraction of impacted mandibular third molars. On panoramic radiographs, the most common signs of corticalization (darkening of roots, diversion of mandibular canal, narrowing of mandibular canal and interruption of white line) and the presence or absence of corticalization between the mandibular third molar and the mandibular canal on CBCT images were evaluated. Results Darkening of roots and interruption of white line associated with the absence of corticalization between the mandibular third molar and the mandibular canal on CBCT images were statistically significant, both as isolated findings (p = 0.0001 and p = 0.0006, respectively) and in association (p = 0.002). No statistically significant association was observed for the other panoramic radiographic findings, either individually or in association (p > 0.05). Conclusion Darkening of roots and interruption of white line observed on panoramic radiographs, both as isolated findings and in association, were effective in determining the risk relationship between the tooth roots and the mandibular canal, requiring three-dimensional evaluation of the case. PMID:22282507

The role of cortical oscillations in a spiking neural network model of the basal ganglia.

PubMed

Fountas, Zafeirios; Shanahan, Murray

2017-01-01

Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8-12Hz) and beta (13-30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus-globus pallidus loop. In contrast, gamma (30-90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders.

Corticomuscular transmission of tremor signals by propriospinal neurons in Parkinson's disease.

PubMed

Hao, Manzhao; He, Xin; Xiao, Qin; Alstermark, Bror; Lan, Ning

2013-01-01

Cortical oscillatory signals of single and double tremor frequencies act together to cause tremor in the peripheral limbs of patients with Parkinson's disease (PD). But the corticospinal pathway that transmits the tremor signals has not been clarified, and how alternating bursts of antagonistic muscle activations are generated from the cortical oscillatory signals is not well understood. This paper investigates the plausible role of propriospinal neurons (PN) in C3-C4 in transmitting the cortical oscillatory signals to peripheral muscles. Kinematics data and surface electromyogram (EMG) of tremor in forearm were collected from PD patients. A PN network model was constructed based on known neurophysiological connections of PN. The cortical efferent signal of double tremor frequencies were integrated at the PN network, whose outputs drove the muscles of a virtual arm (VA) model to simulate tremor behaviors. The cortical efferent signal of single tremor frequency actuated muscle spindles. By comparing tremor data of PD patients and the results of model simulation, we examined two hypotheses regarding the corticospinal transmission of oscillatory signals in Parkinsonian tremor. Hypothesis I stated that the oscillatory cortical signals were transmitted via the mono-synaptic corticospinal pathways bypassing the PN network. The alternative hypothesis II stated that they were transmitted by way of PN multi-synaptic corticospinal pathway. Simulations indicated that without the PN network, the alternating burst patterns of antagonistic muscle EMGs could not be reliably generated, rejecting the first hypothesis. However, with the PN network, the alternating burst patterns of antagonist EMGs were naturally reproduced under all conditions of cortical oscillations. The results suggest that cortical commands of single and double tremor frequencies are further processed at PN to compute the alternating burst patterns in flexor and extensor muscles, and the neuromuscular dynamics demonstrated a frequency dependent damping on tremor, which may prevent tremor above 8 Hz to occur.

Corticomuscular Transmission of Tremor Signals by Propriospinal Neurons in Parkinson's Disease

PubMed Central

Hao, Manzhao; He, Xin; Xiao, Qin; Alstermark, Bror; Lan, Ning

2013-01-01

Cortical oscillatory signals of single and double tremor frequencies act together to cause tremor in the peripheral limbs of patients with Parkinson's disease (PD). But the corticospinal pathway that transmits the tremor signals has not been clarified, and how alternating bursts of antagonistic muscle activations are generated from the cortical oscillatory signals is not well understood. This paper investigates the plausible role of propriospinal neurons (PN) in C3–C4 in transmitting the cortical oscillatory signals to peripheral muscles. Kinematics data and surface electromyogram (EMG) of tremor in forearm were collected from PD patients. A PN network model was constructed based on known neurophysiological connections of PN. The cortical efferent signal of double tremor frequencies were integrated at the PN network, whose outputs drove the muscles of a virtual arm (VA) model to simulate tremor behaviors. The cortical efferent signal of single tremor frequency actuated muscle spindles. By comparing tremor data of PD patients and the results of model simulation, we examined two hypotheses regarding the corticospinal transmission of oscillatory signals in Parkinsonian tremor. Hypothesis I stated that the oscillatory cortical signals were transmitted via the mono-synaptic corticospinal pathways bypassing the PN network. The alternative hypothesis II stated that they were transmitted by way of PN multi-synaptic corticospinal pathway. Simulations indicated that without the PN network, the alternating burst patterns of antagonistic muscle EMGs could not be reliably generated, rejecting the first hypothesis. However, with the PN network, the alternating burst patterns of antagonist EMGs were naturally reproduced under all conditions of cortical oscillations. The results suggest that cortical commands of single and double tremor frequencies are further processed at PN to compute the alternating burst patterns in flexor and extensor muscles, and the neuromuscular dynamics demonstrated a frequency dependent damping on tremor, which may prevent tremor above 8 Hz to occur. PMID:24278189

Colour or shape: examination of neural processes underlying mental flexibility in posttraumatic stress disorder.

PubMed

Pang, E W; Sedge, P; Grodecki, R; Robertson, A; MacDonald, M J; Jetly, R; Shek, P N; Taylor, M J

2014-08-05

Posttraumatic stress disorder (PTSD) is a mental disorder that stems from exposure to one or more traumatic events. While PTSD is thought to result from a dysregulation of emotional neurocircuitry, neurocognitive difficulties are frequently reported. Mental flexibility is a core executive function that involves the ability to shift and adapt to new information. It is essential for appropriate social-cognitive behaviours. Magnetoencephalography (MEG), a neuroimaging modality with high spatial and temporal resolution, has been used to track the progression of brain activation during tasks of mental flexibility called set-shifting. We hypothesized that the sensitivity of MEG would be able to capture the abnormal neurocircuitry implicated in PTSD and this would negatively impact brain regions involved in set-shifting. Twenty-two soldiers with PTSD and 24 matched control soldiers completed a colour-shape set-shifting task. MEG data were recorded and source localized to identify significant brain regions involved in the task. Activation latencies were obtained by analysing the time course of activation in each region. The control group showed a sequence of activity that involved dorsolateral frontal cortex, insula and posterior parietal cortices. The soldiers with PTSD showed these activations but they were interrupted by activations in paralimbic regions. This is consistent with models of PTSD that suggest dysfunctional neurocircuitry is driven by hyper-reactive limbic areas that are not appropriately modulated by prefrontal cortical control regions. This is the first study identifying the timing and location of atypical neural responses in PTSD with set-shifting and supports the model that hyperactive limbic structures negatively impact cognitive function.

Hepatic Expression of Serum Amyloid A1 Is Induced by Traumatic Brain Injury and Modulated by Telmisartan

PubMed Central

Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G.; Campbell, Ashley M.; Saavedra, Juan M.; Shewmaker, Frank P.; Symes, Aviva J.

2016-01-01

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. PMID:26435412

Quantitative two-dimensional ultrashort echo time magnetization transfer (2D UTE-MT) imaging of cortical bone.

PubMed

Ma, Ya-Jun; Tadros, Anthony; Du, Jiang; Chang, Eric Y

2018-04-01

To investigate quantitative 2D ultrashort echo time magnetization transfer (UTE-MT) imaging in ex vivo bovine cortical bone and in vivo human tibial cortical bone. Data were acquired from five fresh bovine cortical bone samples and five healthy volunteer tibial cortical bones using a 2D UTE-MT sequence on a clinical 3T scanner. The 2D UTE-MT sequence used four or five MT powers with five frequency offsets. Results were analyzed with a two-pool quantitative MT model, providing measurements of macromolecular fraction (f), macromolecular proton transverse relaxation times (T 2m ), proton exchange rates from water/macromolecular to the macromolecular/water pool (RM 0m /RM 0w ), and spin-lattice relaxation rate of water pool (R 1w ). A sequential air-drying study for a small bovine cortical bone chip was used to investigate whether above MT modeling parameters were sensitive to the water loss. Mean fresh bovine cortical bone values for f, T 2m , R 1w , RM 0m , and RM 0w were 59.9 ± 7.3%, 14.6 ± 0.3 μs, 9.9 ± 2.4 s -1 , 17.9 ± 3.6 s -1 , and 11.8 ± 2.0 s -1 , respectively. Mean in vivo human cortical bone values for f, T 2m , R 1w , RM 0m and RM 0w were 54.5 ± 4.9%, 15.4 ± 0.6 μs, 8.9 ± 1.1 s -1 , 11.5 ± 3.5 s -1 , and 9.5 ± 1.9 s -1 , respectively. The sequential air-drying study shows that f, RM 0m , and R 1w were increased with longer drying time. UTE-MT two-pool modeling provides novel and useful quantitative information for cortical bone. Magn Reson Med 79:1941-1949, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

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

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.

Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration

PubMed Central

Yip, Ping Kei; Carrillo-Jimenez, Alejandro; King, Paul; Vilalta, Anna; Nomura, Koji; Chau, Chi Cheng; Egerton, Alexander Michael Scott; Liu, Zhuo-Hao; Shetty, Ashray Jayaram; Tremoleda, Jordi L.; Davies, Meirion; Deierborg, Tomas; Priestley, John V.; Brown, Guy Charles; Michael-Titus, Adina Teodora; Venero, Jose Luis; Burguillos, Miguel Angel

2017-01-01

Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galectin-3. In this study, using a controlled cortical impact (CCI) model of head injury, we show a large increase in the expression of galectin-3 in microglia and also an increase in the released form of galectin-3 in the cerebrospinal fluid (CSF) 24 h after head injury. We report that galectin-3 can bind to TLR-4, and that administration of a neutralizing antibody against galectin-3 decreases the expression of IL-1β, IL-6, TNFα and NOS2 and promotes neuroprotection in the cortical and hippocampal cell populations after head injury. Long-term analysis demonstrated a significant neuroprotection in the cortical region in the galectin-3 knockout animals in response to TBI. These results suggest that following head trauma, released galectin-3 may act as an alarmin, binding, among other proteins, to TLR-4 and promoting inflammation and neuronal loss. Taking all together, galectin-3 emerges as a clinically relevant target for TBI therapy. PMID:28128358

Dissociation of neural mechanisms underlying orientation processing in humans

PubMed Central

Ling, Sam; Pearson, Joel; Blake, Randolph

2009-01-01

Summary Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and discovery of that property [1, 2] dramatically shaped how we conceptualize visual processing [3–6]. However, much remains unknown about the neural substrates of these basic building blocks of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS) to attenuate neural responses evoked by stimuli presented within a local region of the visual field. Previous physiological studies have shown that rTMS can significantly suppress the neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region [7, 8]. By suppressing neural activity with rTMS, we were able to dissociate components of the neural circuitry underlying two distinct aspects of orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened following rTMS. This dissociation implies that orientation processing relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is largely governed by the patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses contained within those orientation-selective cortical neurons. PMID:19682905

Firing-rate based network modeling of the dLGN circuit: Effects of cortical feedback on spatiotemporal response properties of relay cells.

PubMed

Mobarhan, Milad Hobbi; Halnes, Geir; Martínez-Cañada, Pablo; Hafting, Torkel; Fyhn, Marianne; Einevoll, Gaute T

2018-05-01

Visually evoked signals in the retina pass through the dorsal geniculate nucleus (dLGN) on the way to the visual cortex. This is however not a simple feedforward flow of information: there is a significant feedback from cortical cells back to both relay cells and interneurons in the dLGN. Despite four decades of experimental and theoretical studies, the functional role of this feedback is still debated. Here we use a firing-rate model, the extended difference-of-Gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells. For this model the responses are found by direct evaluation of two- or three-dimensional integrals allowing for fast and comprehensive studies of putative effects of different candidate organizations of the cortical feedback. Our analysis identifies a special mixed configuration of excitatory and inhibitory cortical feedback which seems to best account for available experimental data. This configuration consists of (i) a slow (long-delay) and spatially widespread inhibitory feedback, combined with (ii) a fast (short-delayed) and spatially narrow excitatory feedback, where (iii) the excitatory/inhibitory ON-ON connections are accompanied respectively by inhibitory/excitatory OFF-ON connections, i.e. following a phase-reversed arrangement. The recent development of optogenetic and pharmacogenetic methods has provided new tools for more precise manipulation and investigation of the thalamocortical circuit, in particular for mice. Such data will expectedly allow the eDOG model to be better constrained by data from specific animal model systems than has been possible until now for cat. We have therefore made the Python tool pyLGN which allows for easy adaptation of the eDOG model to new situations.

Wavelet decomposition of transmitted ultrasound wave through a 1-D muscle-bone system.

PubMed

Buchanan, James L; Gilbert, Robert P; Ou, Miao-jung Y

2011-01-11

In the attempt for using ultrasound as a diagnostic device for osteoporosis, several authors have described the result of the in vitro experiment in which ultrasound is passed through a cancellous bone specimen placed in a water tank. However, in the in vivo setting, a patient's cancellous bone is surrounded by cortical and muscle layers. This paper considers in the one-dimensional case (1) what effect the cortical bone segments surrounding the cancellous segment would have on the received signal and (2) what the received signal would be when a source and receiver are placed on opposite sides of a structure consisting of a cancellous segment surrounded by cortical and muscle layers. Mathematically this is accomplished by representing the received signal as a sum of wavelets which go through different reflection-transmission histories at the muscle-cortical bone and cortical-cancellous bone interfaces. The muscle and cortical bone are modeled as elastic materials and the cancellous bone as a poroelastic material described by the Biot-Johnson-Koplik-Dashen model. The approach presented here permits the assessment of which possible paths of transmission and reflection through the cortical-cancellous or muscle-cortical-cancellous complex will result in significant contributions to the received waveform. This piece of information can be useful for solving the inverse problem of non-destructive assessment of material properties of bone. Our methodology can be generalized to three-dimensional parallelly layered structure by first applying Fourier transform in the directions perpendicular to the transverse direction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cortical circuitry implementing graphical models.

PubMed

Litvak, Shai; Ullman, Shimon

2009-11-01

In this letter, we develop and simulate a large-scale network of spiking neurons that approximates the inference computations performed by graphical models. Unlike previous related schemes, which used sum and product operations in either the log or linear domains, the current model uses an inference scheme based on the sum and maximization operations in the log domain. Simulations show that using these operations, a large-scale circuit, which combines populations of spiking neurons as basic building blocks, is capable of finding close approximations to the full mathematical computations performed by graphical models within a few hundred milliseconds. The circuit is general in the sense that it can be wired for any graph structure, it supports multistate variables, and it uses standard leaky integrate-and-fire neuronal units. Following previous work, which proposed relations between graphical models and the large-scale cortical anatomy, we focus on the cortical microcircuitry and propose how anatomical and physiological aspects of the local circuitry may map onto elements of the graphical model implementation. We discuss in particular the roles of three major types of inhibitory neurons (small fast-spiking basket cells, large layer 2/3 basket cells, and double-bouquet neurons), subpopulations of strongly interconnected neurons with their unique connectivity patterns in different cortical layers, and the possible role of minicolumns in the realization of the population-based maximum operation.

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

Feature-Selective Attentional Modulations in Human Frontoparietal Cortex.

PubMed

Ester, Edward F; Sutterer, David W; Serences, John T; Awh, Edward

2016-08-03

Control over visual selection has long been framed in terms of a dichotomy between "source" and "site," where top-down feedback signals originating in frontoparietal cortical areas modulate or bias sensory processing in posterior visual areas. This distinction is motivated in part by observations that frontoparietal cortical areas encode task-level variables (e.g., what stimulus is currently relevant or what motor outputs are appropriate), while posterior sensory areas encode continuous or analog feature representations. Here, we present evidence that challenges this distinction. We used fMRI, a roving searchlight analysis, and an inverted encoding model to examine representations of an elementary feature property (orientation) across the entire human cortical sheet while participants attended either the orientation or luminance of a peripheral grating. Orientation-selective representations were present in a multitude of visual, parietal, and prefrontal cortical areas, including portions of the medial occipital cortex, the lateral parietal cortex, and the superior precentral sulcus (thought to contain the human homolog of the macaque frontal eye fields). Additionally, representations in many-but not all-of these regions were stronger when participants were instructed to attend orientation relative to luminance. Collectively, these findings challenge models that posit a strict segregation between sources and sites of attentional control on the basis of representational properties by demonstrating that simple feature values are encoded by cortical regions throughout the visual processing hierarchy, and that representations in many of these areas are modulated by attention. Influential models of visual attention posit a distinction between top-down control and bottom-up sensory processing networks. These models are motivated in part by demonstrations showing that frontoparietal cortical areas associated with top-down control represent abstract or categorical stimulus information, while visual areas encode parametric feature information. Here, we show that multivariate activity in human visual, parietal, and frontal cortical areas encode representations of a simple feature property (orientation). Moreover, representations in several (though not all) of these areas were modulated by feature-based attention in a similar fashion. These results provide an important challenge to models that posit dissociable top-down control and sensory processing networks on the basis of representational properties. Copyright © 2016 the authors 0270-6474/16/368188-12$15.00/0.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

A cooperation and competition based simple cell receptive field model and study of feed-forward linear and nonlinear contributions to orientation selectivity.

PubMed

Bhaumik, Basabi; Mathur, Mona

2003-01-01

We present a model for development of orientation selectivity in layer IV simple cells. Receptive field (RF) development in the model, is determined by diffusive cooperation and resource limited competition guided axonal growth and retraction in geniculocortical pathway. The simulated cortical RFs resemble experimental RFs. The receptive field model is incorporated in a three-layer visual pathway model consisting of retina, LGN and cortex. We have studied the effect of activity dependent synaptic scaling on orientation tuning of cortical cells. The mean value of hwhh (half width at half the height of maximum response) in simulated cortical cells is 58 degrees when we consider only the linear excitatory contribution from LGN. We observe a mean improvement of 22.8 degrees in tuning response due to the non-linear spiking mechanisms that include effects of threshold voltage and synaptic scaling factor.

Neurodevelopmental origins of abnormal cortical morphology in dissociative identity disorder.

PubMed

Reinders, A A T S; Chalavi, S; Schlumpf, Y R; Vissia, E M; Nijenhuis, E R S; Jäncke, L; Veltman, D J; Ecker, C

2018-02-01

To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of gaining important novel insights into the underlying neurobiological mechanisms mediating DID. This study included 32 female patients with DID and 43 matched healthy controls. Between-group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex-wise approach. Whole-brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization. Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found. In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of gap junctions on synchronization in human neocortical networks.

PubMed

Gigout, S; Deisz, R A; Dehnicke, C; Turak, B; Devaux, B; Pumain, R; Louvel, J

2016-04-15

Gap junctions (GJ) have been implicated in the synchronization of epileptiform activities induced by 4-aminopyrine (4AP) in slices from human epileptogenic cortex. Previous evidence implicated glial GJ to govern the frequency of these epileptiform events. The synchrony of these events (evaluated by the phase unlocking index, PUI) in adjacent areas however was attributed to neuronal GJ. In the present study, we have investigated the effects of GAP-134, a recently developed specific activator of glial GJ, on both the PUI and the frequency of the 4AP-induced epileptiform activities in human neocortical slices of temporal lobe epilepsy tissue. To delineate the impact of GJ on spatial spread of synchronous activity we evaluated the effects of carbenoxolone (CBX, a non-selective GJ blocker) on the spread in three axes 1. vertically in a given cortical column, 2. laterally within the deep cortical layers and 3. laterally within the upper cortical layers. GAP-134 slightly increased the frequency of the 4AP-induced spontaneous epileptiform activities while leaving the PUI unaffected. CBX had no effect on the PUI within a cortical column or on the PUI in the deep cortical layers. CBX increased the PUI for long interelectrodes distances in the upper cortical layers. In conclusion we provide new arguments toward the role played by glial GJ to maintain the frequency of spontaneous activities. We show that neuronal GJ control the PUI only in upper cortical layers. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Including long-range dependence in integrate-and-fire models of the high interspike-interval variability of cortical neurons.

PubMed

Jackson, B Scott

2004-10-01

Many different types of integrate-and-fire models have been designed in order to explain how it is possible for a cortical neuron to integrate over many independent inputs while still producing highly variable spike trains. Within this context, the variability of spike trains has been almost exclusively measured using the coefficient of variation of interspike intervals. However, another important statistical property that has been found in cortical spike trains and is closely associated with their high firing variability is long-range dependence. We investigate the conditions, if any, under which such models produce output spike trains with both interspike-interval variability and long-range dependence similar to those that have previously been measured from actual cortical neurons. We first show analytically that a large class of high-variability integrate-and-fire models is incapable of producing such outputs based on the fact that their output spike trains are always mathematically equivalent to renewal processes. This class of models subsumes a majority of previously published models, including those that use excitation-inhibition balance, correlated inputs, partial reset, or nonlinear leakage to produce outputs with high variability. Next, we study integrate-and-fire models that have (nonPoissonian) renewal point process inputs instead of the Poisson point process inputs used in the preceding class of models. The confluence of our analytical and simulation results implies that the renewal-input model is capable of producing high variability and long-range dependence comparable to that seen in spike trains recorded from cortical neurons, but only if the interspike intervals of the inputs have infinite variance, a physiologically unrealistic condition. Finally, we suggest a new integrate-and-fire model that does not suffer any of the previously mentioned shortcomings. By analyzing simulation results for this model, we show that it is capable of producing output spike trains with interspike-interval variability and long-range dependence that match empirical data from cortical spike trains. This model is similar to the other models in this study, except that its inputs are fractional-gaussian-noise-driven Poisson processes rather than renewal point processes. In addition to this model's success in producing realistic output spike trains, its inputs have long-range dependence similar to that found in most subcortical neurons in sensory pathways, including the inputs to cortex. Analysis of output spike trains from simulations of this model also shows that a tight balance between the amounts of excitation and inhibition at the inputs to cortical neurons is not necessary for high interspike-interval variability at their outputs. Furthermore, in our analysis of this model, we show that the superposition of many fractional-gaussian-noise-driven Poisson processes does not approximate a Poisson process, which challenges the common assumption that the total effect of a large number of inputs on a neuron is well represented by a Poisson process.

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.

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

PubMed Central

Krajewska, Maryla; You, Zerong; Rong, Juan; Kress, Christina; Huang, Xianshu; Yang, Jinsheng; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Hu, Yue; Sze, Chia-Hung; Whalen, Michael J.; Salmena, Leonardo; Hakem, Razqallah; Head, Brian P.; Reed, John C.; Krajewski, Stan

2011-01-01

Background Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8 −/−), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Methodology/Principal Findings Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8 −/− mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. Conclusions Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma. PMID:21957448

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.

Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

PubMed Central

Dahlem, Markus A.; Schmidt, Bernd; Bojak, Ingo; Boie, Sebastian; Kneer, Frederike; Hadjikhani, Nouchine; Kurths, Jürgen

2015-01-01

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation. PMID:25798103

Developing guinea pig brain as a model for cortical folding.

PubMed

Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

2017-05-01

The cerebral cortex in mammals, the neocortex specifically, is highly diverse among species with respect to its size and morphology, likely reflecting the immense adaptiveness of this lineage. In particular, the pattern and number of convoluted ridges and fissures, called gyri and sulci, respectively, on the surface of the cortex are variable among species and even individuals. However, little is known about the mechanism of cortical folding, although there have been several hypotheses proposed. Recent studies on embryonic neurogenesis revealed the differences in cortical progenitors as a critical factor of the process of gyrification. Here, we investigated the gyrification processes using developing guinea pig brains that form a simple but fundamental pattern of gyri. In addition, we established an electroporation-mediated gene transfer method for guinea pig embryos. We introduce the guinea pig brain as a useful model system to understand the mechanisms and basic principle of cortical folding. © 2017 Japanese Society of Developmental Biologists.

The impact of early-onset cannabis use on functional brain correlates of working memory.

PubMed

Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

2010-08-16

Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Neocortical dynamics due to axon propagation delays in cortico-cortical fibers: EEG traveling and standing waves with implications for top-down influences on local networks and white matter disease

PubMed Central

Nunez, Paul L.; Srinivasan, Ramesh

2013-01-01

The brain is treated as a nested hierarchical complex system with substantial interactions across spatial scales. Local networks are pictured as embedded within global fields of synaptic action and action potentials. Global fields may act top-down on multiple networks, acting to bind remote networks. Because of scale-dependent properties, experimental electrophysiology requires both local and global models that match observational scales. Multiple local alpha rhythms are embedded in a global alpha rhythm. Global models are outlined in which cm-scale dynamic behaviors result largely from propagation delays in cortico-cortical axons and cortical background excitation level, controlled by neuromodulators on long time scales. The idealized global models ignore the bottom-up influences of local networks on global fields so as to employ relatively simple mathematics. The resulting models are transparently related to several EEG and steady state visually evoked potentials correlated with cognitive states, including estimates of neocortical coherence structure, traveling waves, and standing waves. The global models suggest that global oscillatory behavior of self-sustained (limit-cycle) modes lower than about 20 Hz may easily occur in neocortical/white matter systems provided: Background cortical excitability is sufficiently high; the strength of long cortico-cortical axon systems is sufficiently high; and the bottom-up influence of local networks on the global dynamic field is sufficiently weak. The global models provide "entry points" to more detailed studies of global top-down influences, including binding of weakly connected networks, modulation of gamma oscillations by theta or alpha rhythms, and the effects of white matter deficits. PMID:24505628

Cortical network models of impulse firing in the resting and active states predict cortical energetics

PubMed Central

Bennett, Maxwell R.; Farnell, Les; Gibson, William G.; Lagopoulos, Jim

2015-01-01

Measurements of the cortical metabolic rate of glucose oxidation [CMRglc(ox)] have provided a number of interesting and, in some cases, surprising observations. One is the decline in CMRglc(ox) during anesthesia and non-rapid eye movement (NREM) sleep, and another, the inverse relationship between the resting-state CMRglc(ox) and the transient following input from the thalamus. The recent establishment of a quantitative relationship between synaptic and action potential activity on the one hand and CMRglc(ox) on the other allows neural network models of such activity to probe for possible mechanistic explanations of these phenomena. We have carried out such investigations using cortical models consisting of networks of modules with excitatory and inhibitory neurons, each receiving excitatory inputs from outside the network in addition to intermodular connections. Modules may be taken as regions of cortical interest, the inputs from outside the network as arising from the thalamus, and the intermodular connections as long associational fibers. The model shows that the impulse frequency of different modules can differ from each other by less than 10%, consistent with the relatively uniform CMRglc(ox) observed across different regions of cortex. The model also shows that, if correlations of the average impulse rate between different modules decreases, there is a concomitant decrease in the average impulse rate in the modules, consistent with the observed drop in CMRglc(ox) in NREM sleep and under anesthesia. The model also explains why a transient thalamic input to sensory cortex gives rise to responses with amplitudes inversely dependent on the resting-state frequency, and therefore resting-state CMRglc(ox). PMID:25775588

Cortical atrophy patterns in early Parkinson's disease patients using hierarchical cluster analysis.

PubMed

Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Campabadal, Anna; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Tolosa, Eduard; Junque, Carme

2018-05-01

Cortical brain atrophy detectable with MRI in non-demented advanced Parkinson's disease (PD) is well characterized, but its presence in early disease stages is still under debate. We aimed to investigate cortical atrophy patterns in a large sample of early untreated PD patients using a hypothesis-free data-driven approach. Seventy-seven de novo PD patients and 50 controls from the Parkinson's Progression Marker Initiative database with T1-weighted images in a 3-tesla Siemens scanner were included in this study. Mean cortical thickness was extracted from 360 cortical areas defined by the Human Connectome Project Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was performed using Ward's linkage method. A general linear model with cortical thickness data was then used to compare clustering groups using FreeSurfer software. We identified two patterns of cortical atrophy. Compared with controls, patients grouped in pattern 1 (n = 33) were characterized by cortical thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left postcentral gyrus, and they showed neuropsychological impairment in memory and other cognitive domains. Even in the early stages of PD, there is evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to detect two subgroups of cortical thinning, one with mainly anterior atrophy, and the other with posterior predominance and worse cognitive performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

PubMed

Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

2012-08-22

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Visual detection following retinal damage: predictions of an inhomogeneous retino-cortical model

NASA Astrophysics Data System (ADS)

Arnow, Thomas L.; Geisler, Wilson S.

1996-04-01

A model of human visual detection performance has been developed, based on available anatomical and physiological data for the primate visual system. The inhomogeneous retino- cortical (IRC) model computes detection thresholds by comparing simulated neural responses to target patterns with responses to a uniform background of the same luminance. The model incorporates human ganglion cell sampling distributions; macaque monkey ganglion cell receptive field properties; macaque cortical cell contrast nonlinearities; and a optical decision rule based on ideal observer theory. Spatial receptive field properties of cortical neurons were not included. Two parameters were allowed to vary while minimizing the squared error between predicted and observed thresholds. One parameter was decision efficiency, the other was the relative strength of the ganglion-cell center and surround. The latter was only allowed to vary within a small range consistent with known physiology. Contrast sensitivity was measured for sinewave gratings as a function of spatial frequency, target size and eccentricity. Contrast sensitivity was also measured for an airplane target as a function of target size, with and without artificial scotomas. The results of these experiments, as well as contrast sensitivity data from the literature were compared to predictions of the IRC model. Predictions were reasonably good for grating and airplane targets.

Nonlinear hierarchical multiscale modeling of cortical bone considering its nanoscale microstructure.

PubMed

Ghanbari, J; Naghdabadi, R

2009-07-22

We have used a hierarchical multiscale modeling scheme for the analysis of cortical bone considering it as a nanocomposite. This scheme consists of definition of two boundary value problems, one for macroscale, and another for microscale. The coupling between these scales is done by using the homogenization technique. At every material point in which the constitutive model is needed, a microscale boundary value problem is defined using a macroscopic kinematical quantity and solved. Using the described scheme, we have studied elastic properties of cortical bone considering its nanoscale microstructural constituents with various mineral volume fractions. Since the microstructure of bone consists of mineral platelet with nanometer size embedded in a protein matrix, it is similar to the microstructure of soft matrix nanocomposites reinforced with hard nanostructures. Considering a representative volume element (RVE) of the microstructure of bone as the microscale problem in our hierarchical multiscale modeling scheme, the global behavior of bone is obtained under various macroscopic loading conditions. This scheme may be suitable for modeling arbitrary bone geometries subjected to a variety of loading conditions. Using the presented method, mechanical properties of cortical bone including elastic moduli and Poisson's ratios in two major directions and shear modulus is obtained for different mineral volume fractions.

Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets

PubMed Central

Quebeda-Clerkin, Patricia B.; Dodge, Carter P.; Harris, Brent T.; Hillier, Simon C.; Duhaime, Ann-Christine

2012-01-01

Abstract A peripheral indicator of the presence and magnitude of brain injury has been a sought-after tool by clinicians. We measured neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, prior to and after scaled cortical impact in immature pigs, to determine if these purported markers increase after injury, correlate with the resulting lesion volume, and if these relationships vary with maturation. Scaled cortical impact resulted in increased lesion volume with increasing age. Concentrations of NSE, but not S100B or MBP, increased after injury in all age groups. The high variability of S100B concentrations prior to injury may have precluded detection of an increase due to injury. Total serum markers were estimated, accounting for the allometric growth of blood volume, and resulted in a positive correlation of both NSE and S100B with lesion volume. Even with allometric scaling of blood volume and a uniform mechanism of injury, NSE had only a fair to poor predictive value. In a clinical setting, where the types of injuries are varied, more investigation is required to yield a panel of serum markers that can reliably predict the extent of injury. Allometric scaling may improve estimation of serum marker release in pediatric populations. PMID:22867012

Quantification of Human Cortical Bone Bound and Free Water in Vivo with Ultrashort Echo Time MR Imaging: A Model-based Approach.

PubMed

Abbasi-Rad, Shahrokh; Saligheh Rad, Hamidreza

2017-06-01

Purpose To quantify free and bound water components of cortical bone with a model-based numeric approach with use of ultrashort echo time (UTE) magnetic resonance (MR) imaging in vivo in order to introduce a new predictor for age-related deterioration of cortical bone structure. Materials and Methods Human studies were compliant with HIPAA and approved by the institutional review board. Dual-repetition time three-dimensional hybrid-radial UTE imaging was performed, followed by the application of postprocessing algorithms, to quantify free and bound water parameters (concentration [ρ] and longitudinal relaxation time [T1]) of human cortical bone in vivo. The postprocessing algorithms included the decomposition of bulk equations into free- and bound-associated equations and solving resulted inverse problem by using evolutionary strategy methods. To test the validity of the introduced biomarker, it was measured in 40 healthy women by using the proposed method, and associations among parameters were evaluated with the Pearson correlation coefficient. Results The mean free water concentration, bound water concentration, free water T1, and bound water T1 in the recruited population were 5.9%, 19.6%, 306.79 msec, and 162.47 msec, respectively. All reported values were in good agreement with those in the literature. Cortical bone free water T1 (R 2 = 0.72) and cortical bone free water concentration (R 2 = 0.62) showed strong positive correlations with age. Conclusion The cortical bone free water concentration and free water T1 derived with UTE imaging are good predictors of age-related deterioration of cortical bone structure and are potentially superior to previously introduced measures such as bone water concentration and suppression ratio. © RSNA, 2017.

Technical Note: Cortical thickness and density estimation from clinical CT using a prior thickness-density relationship

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

Humbert, Ludovic, E-mail: ludohumberto@gmail.com; Hazrati Marangalou, Javad; Rietbergen, Bert van

Purpose: Cortical thickness and density are critical components in determining the strength of bony structures. Computed tomography (CT) is one possible modality for analyzing the cortex in 3D. In this paper, a model-based approach for measuring the cortical bone thickness and density from clinical CT images is proposed. Methods: Density variations across the cortex were modeled as a function of the cortical thickness and density, location of the cortex, density of surrounding tissues, and imaging blur. High resolution micro-CT data of cadaver proximal femurs were analyzed to determine a relationship between cortical thickness and density. This thickness-density relationship was usedmore » as prior information to be incorporated in the model to obtain accurate measurements of cortical thickness and density from clinical CT volumes. The method was validated using micro-CT scans of 23 cadaver proximal femurs. Simulated clinical CT images with different voxel sizes were generated from the micro-CT data. Cortical thickness and density were estimated from the simulated images using the proposed method and compared with measurements obtained using the micro-CT images to evaluate the effect of voxel size on the accuracy of the method. Then, 19 of the 23 specimens were imaged using a clinical CT scanner. Cortical thickness and density were estimated from the clinical CT images using the proposed method and compared with the micro-CT measurements. Finally, a case-control study including 20 patients with osteoporosis and 20 age-matched controls with normal bone density was performed to evaluate the proposed method in a clinical context. Results: Cortical thickness (density) estimation errors were 0.07 ± 0.19 mm (−18 ± 92 mg/cm{sup 3}) using the simulated clinical CT volumes with the smallest voxel size (0.33 × 0.33 × 0.5 mm{sup 3}), and 0.10 ± 0.24 mm (−10 ± 115 mg/cm{sup 3}) using the volumes with the largest voxel size (1.0 × 1.0 × 3.0 mm{sup 3}). A trend for the cortical thickness and density estimation errors to increase with voxel size was observed and was more pronounced for thin cortices. Using clinical CT data for 19 of the 23 samples, mean errors of 0.18 ± 0.24 mm for the cortical thickness and 15 ± 106 mg/cm{sup 3} for the density were found. The case-control study showed that osteoporotic patients had a thinner cortex and a lower cortical density, with average differences of −0.8 mm and −58.6 mg/cm{sup 3} at the proximal femur in comparison with age-matched controls (p-value < 0.001). Conclusions: This method might be a promising approach for the quantification of cortical bone thickness and density using clinical routine imaging techniques. Future work will concentrate on investigating how this approach can improve the estimation of mechanical strength of bony structures, the prevention of fracture, and the management of osteoporosis.« less

Excitatory neuronal connectivity in the barrel cortex

PubMed Central

Feldmeyer, Dirk

2012-01-01

Neocortical areas are believed to be organized into vertical modules, the cortical columns, and the horizontal layers 1–6. In the somatosensory barrel cortex these columns are defined by the readily discernible barrel structure in layer 4. Information processing in the neocortex occurs along vertical and horizontal axes, thereby linking individual barrel-related columns via axons running through the different cortical layers of the barrel cortex. Long-range signaling occurs within the neocortical layers but also through axons projecting through the white matter to other neocortical areas and subcortical brain regions. Because of the ease of identification of barrel-related columns, the rodent barrel cortex has become a prototypical system to study the interactions between different neuronal connections within a sensory cortical area and between this area and other cortical as well subcortical regions. Such interactions will be discussed specifically for the feed-forward and feedback loops between the somatosensory and the somatomotor cortices as well as the different thalamic nuclei. In addition, recent advances concerning the morphological characteristics of excitatory neurons and their impact on the synaptic connectivity patterns and signaling properties of neuronal microcircuits in the whisker-related somatosensory cortex will be reviewed. In this context, their relationship between the structural properties of barrel-related columns and their function as a module in vertical synaptic signaling in the whisker-related cortical areas will be discussed. PMID:22798946

In vivo studies of low level laser (light) therapy for traumatic brain injury

NASA Astrophysics Data System (ADS)

Xuan, Weijun; Wu, Qiuhe; Huang, Ying-Ying; Ando, Takahiro; Huang, Liyi; Hamblin, Michael R.

2012-03-01

Low-level laser (or light) therapy (LLLT) is attracting growing interest to treat both stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain allows non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. It is proposed that red and NIR light is absorbed by chromophores in the mitochondria of cells leading to changes in gene transcription and upregulation of proteins involved in cell survival, antioxidant production, collagen synthesis, reduction of chronic inflammation and cell migration and proliferation. We developed a mouse model of controlled cortical impact (CCI) TBI and examined the effect of 0, 1, 3, and 14 daily 810-nm CW laser treatments in the CCI model as measured by neurological severity score and wire grip and motion test. 1 laser Tx gave a significant improvement while 3 laser Tx was even better. Surprisingly 14 laser Tx was no better than no treatment. Histological studies at necropsy suggested that the neurodegeneration was reduced at 14 days and that the cortical lesion was repaired by BrdU+ve neural progenitor (stem) cells at 28 days. Transcranial laser therapy is a promising treatment for acute (and chronic TBI) and the lack of side-effects and paucity of alternative treatments encourages early clinical trials.

Anatomy of aphasia revisited.

PubMed

Fridriksson, Julius; den Ouden, Dirk-Bart; Hillis, Argye E; Hickok, Gregory; Rorden, Chris; Basilakos, Alexandra; Yourganov, Grigori; Bonilha, Leonardo

2018-01-17

In most cases, aphasia is caused by strokes involving the left hemisphere, with more extensive damage typically being associated with more severe aphasia. The classical model of aphasia commonly adhered to in the Western world is the Wernicke-Lichtheim model. The model has been in existence for over a century, and classification of aphasic symptomatology continues to rely on it. However, far more detailed models of speech and language localization in the brain have been formulated. In this regard, the dual stream model of cortical brain organization proposed by Hickok and Poeppel is particularly influential. Their model describes two processing routes, a dorsal stream and a ventral stream, that roughly support speech production and speech comprehension, respectively, in normal subjects. Despite the strong influence of the dual stream model in current neuropsychological research, there has been relatively limited focus on explaining aphasic symptoms in the context of this model. Given that the dual stream model represents a more nuanced picture of cortical speech and language organization, cortical damage that causes aphasic impairment should map clearly onto the dual processing streams. Here, we present a follow-up study to our previous work that used lesion data to reveal the anatomical boundaries of the dorsal and ventral streams supporting speech and language processing. Specifically, by emphasizing clinical measures, we examine the effect of cortical damage and disconnection involving the dorsal and ventral streams on aphasic impairment. The results reveal that measures of motor speech impairment mostly involve damage to the dorsal stream, whereas measures of impaired speech comprehension are more strongly associated with ventral stream involvement. Equally important, many clinical tests that target behaviours such as naming, speech repetition, or grammatical processing rely on interactions between the two streams. This latter finding explains why patients with seemingly disparate lesion locations often experience similar impairments on given subtests. Namely, these individuals' cortical damage, although dissimilar, affects a broad cortical network that plays a role in carrying out a given speech or language task. The current data suggest this is a more accurate characterization than ascribing specific lesion locations as responsible for specific language deficits.awx363media15705668782001. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

GABAA Receptor-Mediated Activity in a Model of Cortical Dysplasia

DTIC Science & Technology

2012-06-29

epilepsy, autism and schizophrenia, and results from failure of immature neurons to appropriately migrate to their cortical targets. We developed a...schizophrenia, and autism , and results from failure of immature neurons to appropriately migrate and reach their cortical targets (Taylor et al., 1971; Choi and...2012) autism (Fatemi et al., 2006 , 2009; Chao et al., 2010; Oblak et al., 2010; Chattopaddhyaya and Di Cristo, 2012; Kang and Barnes; 2012), and X

Cortical bone drilling: An experimental and numerical study.

PubMed

Alam, Khurshid; Bahadur, Issam M; Ahmed, Naseer

2014-12-16

Bone drilling is a common surgical procedure in orthopedics, dental and neurosurgeries. In conventional bone drilling process, the surgeon exerts a considerable amount of pressure to penetrate the drill into the bone tissue. Controlled penetration of drill in the bone is necessary for safe and efficient drilling. Development of a validated Finite Element (FE) model of cortical bone drilling. Drilling experiments were conducted on bovine cortical bone. The FE model of the bone drilling was based on mechanical properties obtained from literature data and additionally conducted microindentation tests on the cortical bone. The magnitude of stress in bone was found to decrease exponentially away from the lips of the drill in simulations. Feed rate was found to be the main influential factor affecting the force and torque in the numerical simulations and experiments. The drilling thrust force and torque were found to be unaffected by the drilling speed in numerical simulations. Simulated forces and torques were compared with experimental results for similar drilling conditions and were found in good agreement.CONCLUSIONS: FE schemes may be successfully applied to model complex kinematics of bone drilling process.

Cortical microtubule nucleation can organise the cytoskeleton of Drosophila oocytes to define the anteroposterior axis

PubMed Central

Khuc Trong, Philipp; Doerflinger, Hélène; Dunkel, Jörn; St Johnston, Daniel; Goldstein, Raymond E

2015-01-01

Many cells contain non-centrosomal arrays of microtubules (MTs), but the assembly, organisation and function of these arrays are poorly understood. We present the first theoretical model for the non-centrosomal MT cytoskeleton in Drosophila oocytes, in which bicoid and oskar mRNAs become localised to establish the anterior-posterior body axis. Constrained by experimental measurements, the model shows that a simple gradient of cortical MT nucleation is sufficient to reproduce the observed MT distribution, cytoplasmic flow patterns and localisation of oskar and naive bicoid mRNAs. Our simulations exclude a major role for cytoplasmic flows in localisation and reveal an organisation of the MT cytoskeleton that is more ordered than previously thought. Furthermore, modulating cortical MT nucleation induces a bifurcation in cytoskeletal organisation that accounts for the phenotypes of polarity mutants. Thus, our three-dimensional model explains many features of the MT network and highlights the importance of differential cortical MT nucleation for axis formation. DOI: http://dx.doi.org/10.7554/eLife.06088.001 PMID:26406117

Accelerated Changes in Cortical Thickness Measurements with Age in Military Service Members with Traumatic Brain Injury.

PubMed

Savjani, Ricky R; Taylor, Brian A; Acion, Laura; Wilde, Elisabeth A; Jorge, Ricardo E

2017-11-15

Finding objective and quantifiable imaging markers of mild traumatic brain injury (TBI) has proven challenging, especially in the military population. Changes in cortical thickness after injury have been reported in animals and in humans, but it is unclear how these alterations manifest in the chronic phase, and it is difficult to characterize accurately with imaging. We used cortical thickness measures derived from Advanced Normalization Tools (ANTs) to predict a continuous demographic variable: age. We trained four different regression models (linear regression, support vector regression, Gaussian process regression, and random forests) to predict age from healthy control brains from publicly available datasets (n = 762). We then used these models to predict brain age in military Service Members with TBI (n = 92) and military Service Members without TBI (n = 34). Our results show that all four models overpredicted age in Service Members with TBI, and the predicted age difference was significantly greater compared with military controls. These data extend previous civilian findings and show that cortical thickness measures may reveal an association of accelerated changes over time with military TBI.

Variability of magnetoencephalographic sensor sensitivity measures as a function of age, brain volume and cortical area

PubMed Central

Irimia, Andrei; Erhart, Matthew J.; Brown, Timothy T.

2014-01-01

Objective To assess the feasibility and appropriateness of magnetoencephalography (MEG) for both adult and pediatric studies, as well as for the developmental comparison of these factors across a wide range of ages. Methods For 45 subjects with ages from 1 to 24 years (infants, toddlers, school-age children and young adults), lead fields (LFs) of MEG sensors are computed using anatomically realistic boundary element models (BEMs) and individually-reconstructed cortical surfaces. Novel metrics are introduced to quantify MEG sensor focality. Results The variability of MEG focality is graphed as a function of brain volume and cortical area. Statistically significant differences in total cerebral volume, cortical area, MEG global sensitivity and LF focality are found between age groups. Conclusions Because MEG focality and sensitivity differ substantially across the age groups studied, the cortical LF maps explored here can provide important insights for the examination and interpretation of MEG signals from early childhood to young adulthood. Significance This is the first study to (1) investigate the relationship between MEG cortical LFs and brain volume as well as cortical area across development, and (2) compare LFs between subjects with different head sizes using detailed cortical reconstructions. PMID:24589347

Lateral Spread of Orientation Selectivity in V1 is Controlled by Intracortical Cooperativity

PubMed Central

Chavane, Frédéric; Sharon, Dahlia; Jancke, Dirk; Marre, Olivier; Frégnac, Yves; Grinvald, Amiram

2011-01-01

Neurons in the primary visual cortex receive subliminal information originating from the periphery of their receptive fields (RF) through a variety of cortical connections. In the cat primary visual cortex, long-range horizontal axons have been reported to preferentially bind to distant columns of similar orientation preferences, whereas feedback connections from higher visual areas provide a more diverse functional input. To understand the role of these lateral interactions, it is crucial to characterize their effective functional connectivity and tuning properties. However, the overall functional impact of cortical lateral connections, whatever their anatomical origin, is unknown since it has never been directly characterized. Using direct measurements of postsynaptic integration in cat areas 17 and 18, we performed multi-scale assessments of the functional impact of visually driven lateral networks. Voltage-sensitive dye imaging showed that local oriented stimuli evoke an orientation-selective activity that remains confined to the cortical feedforward imprint of the stimulus. Beyond a distance of one hypercolumn, the lateral spread of cortical activity gradually lost its orientation preference approximated as an exponential with a space constant of about 1 mm. Intracellular recordings showed that this loss of orientation selectivity arises from the diversity of converging synaptic input patterns originating from outside the classical RF. In contrast, when the stimulus size was increased, we observed orientation-selective spread of activation beyond the feedforward imprint. We conclude that stimulus-induced cooperativity enhances the long-range orientation-selective spread. PMID:21629708

Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

PubMed

Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G; Campbell, Ashley M; Saavedra, Juan M; Shewmaker, Frank P; Symes, Aviva J

2015-10-01

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

PubMed Central

Proudfoot, Malcolm; Rohenkohl, Gustavo; Quinn, Andrew; Colclough, Giles L.; Wuu, Joanne; Talbot, Kevin; Woolrich, Mark W.; Benatar, Michael

2016-01-01

Abstract Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15–30 Hz) power. Cortical beta‐band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven “classical” ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS‐associated gene mutations were compared with age‐similar healthy control groups. Augmented beta desynchronization was observed in both contra‐ and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237–254, 2017. © 2016 Wiley Periodicals, Inc. PMID:27623516

Emergent Spatial Patterns of Excitatory and Inhibitory Synaptic Strengths Drive Somatotopic Representational Discontinuities and their Plasticity in a Computational Model of Primary Sensory Cortical Area 3b

PubMed Central

Grajski, Kamil A.

2016-01-01

Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers), boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties. PMID:27504086

Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders.

PubMed

Kana, Rajesh K; Libero, Lauren E; Moore, Marie S

2011-12-01

Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to 'disrupted cortical connectivity' to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills such as Theory-of-Mind, cognitive flexibility, and information processing; and 2) how connection abnormalities relate to, and may determine, behavioral symptoms hallmarked by the triad of Impairments in ASD. Furthermore, we will relate the disrupted cortical connectivity model to existing cognitive and neural models of ASD. Published by Elsevier B.V.

Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders

NASA Astrophysics Data System (ADS)

Kana, Rajesh K.; Libero, Lauren E.; Moore, Marie S.

2011-12-01

Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to ‘disrupted cortical connectivity’ to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills such as Theory-of-Mind, cognitive flexibility, and information processing; and 2) how connection abnormalities relate to, and may determine, behavioral symptoms hallmarked by the triad of Impairments in ASD. Furthermore, we will relate the disrupted cortical connectivity model to existing cognitive and neural models of ASD.

Polyamine catabolism is enhanced after traumatic brain injury.

PubMed

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A; Strauss, Kenneth I

2010-03-01

Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N(1)-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6-24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6-24 h), then increased by approximately 50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6-72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24-72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies.

Local Immediate versus Long-Range Delayed Changes in Functional Connectivity Following rTMS on the Visual Attention Network.

PubMed

Battelli, Lorella; Grossman, Emily D; Plow, Ela B

The interhemispheric competition hypothesis attributes the distribution of selective attention to a balance of mutual inhibition between homotopic, interhemispheric connections in parietal cortex (Kinsbourne 1977; Battelli et al., 2009). In support of this hypothesis, repetitive inhibitory TMS over right parietal cortex in healthy individuals rapidly induces interhemispheric imbalance in cortical activity that spreads beyond the site of stimulation (Plow et al., 2014). Behaviorally, the impacts of inhibitory rTMS may be long delayed from the onset of stimulation, as much as 30 minutes (Agosta et al., 2014; Hubl et al., 2008). In this study, we examine the temporal dynamics of inhibitory rTMS on cortical network integrity that supports sustained visual attention. Healthy individuals received 15 min of 1 Hz offline, inhibitory rTMS (or sham) over left parietal cortex, and then immediately engaged in a bilateral visual tracking task while we recorded brain activity with fMRI. We computed functional connectivity (FC) between three nodes of the attention network engaged by visual tracking: the intraparietal sulcus (IPS), frontal eye fields (FEF) and human MT+ (hMT+). FC immediately and significantly decreased between the stimulation site (left IPS) and all other regions, then recovered to normal levels within 30 minutes. rTMS increased FC between left and right FEF at approximately 36 min following stimulation, and between sites in the unstimulated hemisphere approximately 48 min after stimulation. These findings demonstrate large-scale changes in cortical organization following inhibitory rTMS. The immediate impact of rTMS on connectivity to the stimulation site dovetails with the putative role of interhemispheric balance for bilateral visual sustained attention. The delayed, compensatory increases in functional connectivity have implications for models of dynamic reorganization in networks supporting spatial and nonspatial selective attention, and compensatory mechanisms within these networks that may be stabilized in chronic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Response of the Hippocampal Transcriptome Following Mild Traumatic Brain Injury After Controlled Cortical Impact in the Rat.

PubMed

Samal, Babru B; Waites, Cameron K; Almeida-Suhett, Camila; Li, Zheng; Marini, Ann M; Samal, Nihar R; Elkahloun, Abdel; Braga, Maria F M; Eiden, Lee E

2015-10-01

We have previously demonstrated that mild controlled cortical impact (mCCI) injury to rat cortex causes indirect, concussive injury to underlying hippocampus and other brain regions, providing a reproducible model for mild traumatic brain injury (mTBI) and its neurochemical, synaptic, and behavioral sequelae. Here, we extend a preliminary gene expression study of the hippocampus-specific events occurring after mCCI and identify 193 transcripts significantly upregulated, and 21 transcripts significantly downregulated, 24 h after mCCI. Fifty-three percent of genes altered by mCCI within 24 h of injury are predicted to be expressed only in the non-neuronal/glial cellular compartment, with only 13% predicted to be expressed only in neurons. The set of upregulated genes following mCCI was interrogated using Ingenuity Pathway Analysis (IPA) augmented with manual curation of the literature (190 transcripts accepted for analysis), revealing a core group of 15 first messengers, mostly inflammatory cytokines, predicted to account for >99% of the transcript upregulation occurring 24 h after mCCI. Convergent analysis of predicted transcription factors (TFs) regulating the mCCI target genes, carried out in IPA relative to the entire Affymetrix-curated transcriptome, revealed a high concordance with TFs regulated by the cohort of 15 cytokines/cytokine-like messengers independently accounting for upregulation of the mCCI transcript cohort. TFs predicted to regulate transcription of the 193-gene mCCI cohort also displayed a high degree of overlap with TFs predicted to regulate glia-, rather than neuron-specific genes in cortical tissue. We conclude that mCCI predominantly affects transcription of non-neuronal genes within the first 24 h after insult. This finding suggests that early non-neuronal events trigger later permanent neuronal changes after mTBI, and that early intervention after mTBI could potentially affect the neurochemical cascade leading to later reported synaptic and behavioral dysfunction.

Localized Cortical Thinning in Patients with Obstructive Sleep Apnea Syndrome

PubMed Central

Joo, Eun Yeon; Jeon, Seun; Kim, Sung Tae; Lee, Jong-Min; Hong, Seung Bong

2013-01-01

Study Objectives: To investigate differences in cortical thickness in patients with obstructive sleep apnea (OSA) syndrome and healthy controls. Design: Cortical thickness was measured using a three-dimensional surface-based method that enabled more accurate measurement in deep sulci and localized regional mapping. Setting: University hospital. Patients: Thirty-eight male patients with severe OSA (mean apnea-hypopnea index > 30/h) and 36 age-matched male healthy controls were enrolled. Interventions: Cortical thickness was obtained at 81,924 vertices across the entire brain by reconstructing inner and outer cortical surfaces using an automated anatomical pipeline. Measurements: Group difference in cortical thickness and correlation between patients' data and thickness were analyzed by a general linear model. Results: Localized cortical thinning in patients was found in the orbitorectal gyri, dorsolateral/ventromedial prefrontal regions, pericentral gyri, anterior cingulate, insula, inferior parietal lobule, uncus, and basolateral temporal regions at corrected P < 0.05. Patients with OSA showed impaired attention and learning difficulty in memory tests compared to healthy controls. Higher number of respiratory arousals was related to cortical thinning of the anterior cingulate and inferior parietal lobule. A significant correlation was observed between the longer apnea maximum duration and the cortical thinning of the dorsolateral prefrontal regions, pericentral gyri, and insula. Retention scores in visual memory tests were associated with cortical thickness of parahippocampal gyrus and uncus. Conclusions: Brain regions with cortical thinning may provide elucidations for prefrontal cognitive dysfunction, upper airway sensorimotor dysregulation, and cardiovascular disturbances in OSA patients, that experience sleep disruption including sleep fragmentation and oxygen desaturation. Citation: Joo EY; Jeon S; Kim ST; Lee JM; Hong SB. Localized cortical thinning in patients with obstructive sleep apnea syndrome. SLEEP 2013;36(8):1153-1162. PMID:23904675

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

Phase Difference between Model Cortical Areas Determines Level of Information Transfer

PubMed Central

ter Wal, Marije; Tiesinga, Paul H.

2017-01-01

Communication between cortical sites is mediated by long-range synaptic connections. However, these connections are relatively static, while everyday cognitive tasks demand a fast and flexible routing of information in the brain. Synchronization of activity between distant cortical sites has been proposed as the mechanism underlying such a dynamic communication structure. Here, we study how oscillatory activity affects the excitability and input-output relation of local cortical circuits and how it alters the transmission of information between cortical circuits. To this end, we develop model circuits showing fast oscillations by the PING mechanism, of which the oscillatory characteristics can be altered. We identify conditions for synchronization between two brain circuits and show that the level of intercircuit coherence and the phase difference is set by the frequency difference between the intrinsic oscillations. We show that the susceptibility of the circuits to inputs, i.e., the degree of change in circuit output following input pulses, is not uniform throughout the oscillation period and that both firing rate, frequency and power are differentially modulated by inputs arriving at different phases. As a result, an appropriate phase difference between the circuits is critical for the susceptibility windows of the circuits in the network to align and for information to be efficiently transferred. We demonstrate that changes in synchrony and phase difference can be used to set up or abolish information transfer in a network of cortical circuits. PMID:28232796

Joint Prediction of Longitudinal Development of Cortical Surfaces and White Matter Fibers from Neonatal MRI

PubMed Central

Rekik, Islem; Li, Gang; Yap, Pew-Thian; Chen, Geng; Lin, Weili; Shen, Dinggang

2017-01-01

The human brain can be modeled as multiple interrelated shapes (or a multishape), each for characterizing one aspect of the brain, such as the cortex and white matter pathways. Predicting the developing multishape is a very challenging task due to the contrasting nature of the developmental trajectories of the constituent shapes: smooth for the cortical surface and non-smooth for white matter tracts due to changes such as bifurcation. We recently addressed this problem and proposed an approach for predicting the multishape developmental spatiotemporal trajectories of infant brains based only on neonatal MRI data using a set of geometric, dynamic, and fiber-to-surface connectivity features. In this paper, we propose two key innovations to further improve the prediction of multishape evolution. First, for a more accurate cortical surface prediction, instead of simply relying on one neonatal atlas to guide the prediction of the multishape, we propose to use multiple neonatal atlases to build a spatially heterogeneous atlas using the multidirectional varifold representation. This individualizes the atlas by locally maximizing its similarity to the testing baseline cortical shape for each cortical region, thereby better representing the baseline testing cortical surface, which founds the multishape prediction process. Second, for temporally consistent fiber prediction, we propose to reliably estimate spatiotemporal connectivity features using low-rank tensor completion, thereby capturing the variability and richness of the temporal development of fibers. Experimental results confirm that the proposed variants significantly improve the prediction performance of our original multishape prediction framework for both cortical surfaces and fiber tracts shape at 3, 6, and 9 months of age. Our pioneering model will pave the way for learning how to predict the evolution of anatomical shapes with abnormal changes. Ultimately, devising accurate shape evolution prediction models that can help quantify and predict the severity of a brain disorder as it progresses will be of great aid in individualized treatment planning. PMID:28284800

Joint prediction of longitudinal development of cortical surfaces and white matter fibers from neonatal MRI.

PubMed

Rekik, Islem; Li, Gang; Yap, Pew-Thian; Chen, Geng; Lin, Weili; Shen, Dinggang

2017-05-15

The human brain can be modeled as multiple interrelated shapes (or a multishape), each for characterizing one aspect of the brain, such as the cortex and white matter pathways. Predicting the developing multishape is a very challenging task due to the contrasting nature of the developmental trajectories of the constituent shapes: smooth for the cortical surface and non-smooth for white matter tracts due to changes such as bifurcation. We recently addressed this problem and proposed an approach for predicting the multishape developmental spatiotemporal trajectories of infant brains based only on neonatal MRI data using a set of geometric, dynamic, and fiber-to-surface connectivity features. In this paper, we propose two key innovations to further improve the prediction of multishape evolution. First, for a more accurate cortical surface prediction, instead of simply relying on one neonatal atlas to guide the prediction of the multishape, we propose to use multiple neonatal atlases to build a spatially heterogeneous atlas using the multidirectional varifold representation. This individualizes the atlas by locally maximizing its similarity to the testing baseline cortical shape for each cortical region, thereby better representing the baseline testing cortical surface, which founds the multishape prediction process. Second, for temporally consistent fiber prediction, we propose to reliably estimate spatiotemporal connectivity features using low-rank tensor completion, thereby capturing the variability and richness of the temporal development of fibers. Experimental results confirm that the proposed variants significantly improve the prediction performance of our original multishape prediction framework for both cortical surfaces and fiber tracts shape at 3, 6, and 9 months of age. Our pioneering model will pave the way for learning how to predict the evolution of anatomical shapes with abnormal changes. Ultimately, devising accurate shape evolution prediction models that can help quantify and predict the severity of a brain disorder as it progresses will be of great aid in individualized treatment planning. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of cortical oscillations in a spiking neural network model of the basal ganglia

PubMed Central

Fountas, Zafeirios; Shanahan, Murray

2017-01-01

Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8–12Hz) and beta (13–30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus—globus pallidus loop. In contrast, gamma (30–90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders. PMID:29236724

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.

Neural and cognitive plasticity: from maps to minds.

PubMed

Mercado, Eduardo

2008-01-01

Some species and individuals are able to learn cognitive skills more flexibly than others. Learning experiences and cortical function are known to contribute to such differences, but the specific factors that determine an organism's intellectual capacities remain unclear. Here, an integrative framework is presented suggesting that variability in cognitive plasticity reflects neural constraints on the precision and extent of an organism's stimulus representations. Specifically, it is hypothesized that cognitive plasticity depends on the number and diversity of cortical modules that an organism has available as well as the brain's capacity to flexibly reconfigure and customize networks of these modules. The author relates this framework to past proposals on the neural mechanisms of intelligence, including (a) the relationship between brain size and intellectual capacity; (b) the role of prefrontal cortex in cognitive control and the maintenance of stimulus representations; and (c) the impact of neural plasticity and efficiency on the acquisition and performance of cognitive skills. The proposed framework provides a unified account of variability in cognitive plasticity as a function of species, age, and individual, and it makes specific predictions about how manipulations of cortical structure and function will impact intellectual capacity. Copyright (c) 2008 APA.

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.

A Mechanistic Link from GABA to Cortical Architecture and Perception.

PubMed

Kolasinski, James; Logan, John P; Hinson, Emily L; Manners, Daniel; Divanbeighi Zand, Amir P; Makin, Tamar R; Emir, Uzay E; Stagg, Charlotte J

2017-06-05

Understanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the maintenance of cortical receptive fields [2]; however, it is unclear how this fine-grain inhibition relates to measurable patterns of perception [3, 4]. Based on perceptual changes following perturbation of the GABAergic system, it is conceivable that the resting level of cortical GABAergic tone directly relates to the spatial specificity of activation in response to a given input [5-7]. The specificity of cortical activation can be considered in terms of cortical tuning: greater cortical tuning yields more localized recruitment of cortical territory in response to a given input. We applied a combination of fMRI, MR spectroscopy, and psychophysics to substantiate the link between the cortical neurochemical milieu, the tuning of cortical activity, and variability in perceptual acuity, using human somatosensory cortex as a model. We provide data that explain human perceptual acuity in terms of both the underlying cellular and metabolic processes. Specifically, higher concentrations of sensorimotor GABA are associated with more selective cortical tuning, which in turn is associated with enhanced perception. These results show anatomical and neurochemical specificity and are replicated in an independent cohort. The mechanistic link from neurochemistry to perception provides a vital step in understanding population variability in sensory behavior, informing metabolic therapeutic interventions to restore perceptual abilities clinically. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Increased pCREB expression and the spontaneous epileptiform activity in a BCNU-treated rat model of cortical dysplasia.

PubMed

Pennacchio, Paolo; Noé, Francesco; Gnatkovsky, Vadym; Moroni, Ramona Frida; Zucca, Ileana; Regondi, Maria Cristina; Inverardi, Francesca; de Curtis, Marco; Frassoni, Carolina

2015-09-01

Cortical dysplasias (CDs) represent a wide range of cortical abnormalities that closely correlate with intractable epilepsy. Rats prenatally exposed to 1-3-bis-chloroethyl-nitrosurea (BCNU) represent an injury-based model that reproduces many histopathologic features of human CD. Previous studies reported in vivo hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. To determine whether cortical and hippocampal lesions lead to epileptiform discharges and/or seizures in the BCNU model, rats at three different ages (3, 5, and 9 months old) were implanted for long-term video electroencephalographic recording. At the end of the recording session, brain tissue was processed for histologic and immunohistochemical investigation including cAMP response element binding protein (CREB) phosphorylation, as a biomarker of epileptogenicity. BCNU-treated rats showed spontaneous epileptiform activity (67%) in the absence of a second seizure-provoking hit. Such activity originated mainly from one hippocampus and propagated to the ipsilateral neocortex. No epileptiform activity was found in age-matched control rats. The histopathologic investigation revealed that all BCNU rats with epileptiform activity showed neocortical and hippocampal abnormalities; the presence and the severity of these lesions did not correlate consistently with the propensity to generate epileptiform discharges. Epileptiform activity was found only in cortical areas of BCNU-treated rats in which a correlation between brain abnormalities and increased pCREB expression was observed. This study demonstrates the in vivo occurrence of spontaneous epileptiform discharges in the BCNU model and shows that increased pCREB expression can be utilized as a reliable biomarker of epileptogenicity. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Ube3a loss increases excitability and blunts orientation tuning in the visual cortex of Angelman syndrome model mice.

PubMed

Wallace, Michael L; van Woerden, Geeske M; Elgersma, Ype; Smith, Spencer L; Philpot, Benjamin D

2017-07-01

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A Ube3a STOP/p+ mice recapitulate major features of AS in humans and allow conditional reinstatement of maternal Ube3a with the expression of Cre recombinase. We have recently shown that AS model mice exhibit reduced inhibitory drive onto layer (L)2/3 pyramidal neurons of visual cortex, which contributes to a synaptic excitatory/inhibitory imbalance. However, it remains unclear how this loss of inhibitory drive affects neural circuits in vivo. Here we examined visual cortical response properties in individual neurons to explore the consequences of Ube3a loss on intact cortical circuits and processing. Using in vivo patch-clamp electrophysiology, we measured the visually evoked responses to square-wave drifting gratings in L2/3 regular-spiking (RS) neurons in control mice, Ube3a -deficient mice, and mice in which Ube3a was conditionally reinstated in GABAergic neurons. We found that Ube3a -deficient mice exhibited enhanced pyramidal neuron excitability in vivo as well as weaker orientation tuning. These observations are the first to show alterations in cortical computation in an AS model, and they suggest a basis for cortical dysfunction in AS. NEW & NOTEWORTHY Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of the gene UBE3A Using electrophysiological recording in vivo, we describe visual cortical dysfunctions in a mouse model of AS. Aberrant cellular properties in AS model mice could be improved by reinstating Ube3a in inhibitory neurons. These findings suggest that inhibitory neurons play a substantial role in the pathogenesis of AS. Copyright © 2017 the American Physiological Society.

Deficits in novelty exploration after controlled cortical impact.

PubMed

Wagner, Amy K; Postal, Brett A; Darrah, Shaun D; Chen, Xiangbai; Khan, Amina S

2007-08-01

Experimental models of traumatic brain injury (TBI) have been utilized to characterize the behavioral derangements associated with brain trauma. Several studies exist characterizing motor function in the controlled cortical impact (CCI) injury model of TBI, but less research has focused on how CCI affects exploratory behavior. The goal of this study was to characterize deficits in three novelty exploration tasks after the CCI. Under anesthesia, 37 adult male Sprague Dawley rats received CCI (2.7 mm and 2.9 mm; 4 m/sec) over the right parietal cortex or sham surgery. For days 1-6 post-surgery, the beam balance and beam walking tasks were used to assess motor deficits. The Open Field, Y-Maze, and Free Choice Novelty (FCN) tasks were used to measure exploratory deficits from days 7-14 post-surgery. Injured rats displayed a significant, but transient, deficit on each motor task (p < 0.0001). Open Field results showed that injured rats had lower activity levels than shams (p < 0.0001), displayed less habituation to the task, and had more anxiety related behaviors (thigmotaxis) across days (p < 0.0001). Y-maze results suggest that injured rats spent less time in the novel arm versus the familiar arms when compared to shams (p < 0.0001). For FCN, injured rats were less active (p < 0.05) and spent less time and had fewer interactions with objects in the novel environment compared to shams (p < 0.05). These results suggest that several ethological factors contribute to exploratory deficits after CCI and can be effectively characterized with the behavioral tasks described. Future work will utilize these tasks to evaluate the neural substrates underlying exploratory deficits after TBI.

Model for the orientational ordering of the plant microtubule cortical array

NASA Astrophysics Data System (ADS)

Hawkins, Rhoda J.; Tindemans, Simon H.; Mulder, Bela M.

2010-07-01

The plant microtubule cortical array is a striking feature of all growing plant cells. It consists of a more or less homogeneously distributed array of highly aligned microtubules connected to the inner side of the plasma membrane and oriented transversely to the cell growth axis. Here, we formulate a continuum model to describe the origin of orientational order in such confined arrays of dynamical microtubules. The model is based on recent experimental observations that show that a growing cortical microtubule can interact through angle dependent collisions with pre-existing microtubules that can lead either to co-alignment of the growth, retraction through catastrophe induction or crossing over the encountered microtubule. We identify a single control parameter, which is fully determined by the nucleation rate and intrinsic dynamics of individual microtubules. We solve the model analytically in the stationary isotropic phase, discuss the limits of stability of this isotropic phase, and explicitly solve for the ordered stationary states in a simplified version of the model.

Bilateral sensory disturbance after cortical spreading depression revealed by fluorescence imaging of voltage-sensitive dye.

PubMed

Huang, Qin; Liu, Rui; Gui, Shen; Lu, Jinling; Li, Pengcheng

2018-03-07

Cortical spreading depression (CSD), a propagation wave of transient neuronal and glial depolarization followed by suppression of spontaneous brain activity, has been hypothesized to be the underlying mechanism of migraine aura and triggers the headache attack. Evidence from various animal models accumulates since its first discovery in 1944 and provides support for this hypothesis. In this paper, alterations of bilateral cortical responses are investigated in a mice migrainous model of CSD using voltage-sensitive dye imaging under hindlimb and cortical stimulation. After CSD induction in the right hemisphere, bilateral sensory responses evoked by left hindlimb stimulation dramatically decreases, whereas right hindlimb stimulation can still activate bilateral responses with an increased response of the left hemisphere and a well-preserved response of the right hemisphere. In addition, cortical neural excitability remains after CSD assessed by direct activation of the right hemisphere in spite of the sensory deficit under contralateral hindlimb stimulation. These results depict the sensory disturbance of bilateral hemispheres after CSD, which may be helpful in understanding how sensory disturbance occur during migraine aura. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The cytokine temporal profile in rat cortex after controlled cortical impact

PubMed Central

Dalgard, Clifton L.; Cole, Jeffrey T.; Kean, William S.; Lucky, Jessica J.; Sukumar, Gauthaman; McMullen, David C.; Pollard, Harvey B.; Watson, William D.

2012-01-01

Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury (TBI). Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact (CCI) on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12, and 24 hours) and extended (3 and 7 days) time points post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemiluminescence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFN-γ, TNF-α levels significantly peaked at four hours post-injury compared to levels found in naïve or contralateral tissue. CXCL1, IFN-γ, and TNF-α levels were then observed to decrease at least 3-fold by 12 hours post-injury. IL-1β, IL-4, and IL-13 levels were also significantly elevated at four hours post-injury although their expression did not decrease more than 3-fold for up to 24 hours post-injury. Additionally, IL-1β and IL-4 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in adaptive immune responses. Interestingly, peak levels of CCL2 and CCL20 were not observed until after four hours post-injury. CCL2 levels in injured cortical tissue were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses. PMID:22291617

The cytokine temporal profile in rat cortex after controlled cortical impact.

PubMed

Dalgard, Clifton L; Cole, Jeffrey T; Kean, William S; Lucky, Jessica J; Sukumar, Gauthaman; McMullen, David C; Pollard, Harvey B; Watson, William D

2012-01-01

Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury (TBI). Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact (CCI) on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12, and 24 hours) and extended (3 and 7 days) time points post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemiluminescence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFN-γ, TNF-α levels significantly peaked at four hours post-injury compared to levels found in naïve or contralateral tissue. CXCL1, IFN-γ, and TNF-α levels were then observed to decrease at least 3-fold by 12 hours post-injury. IL-1β, IL-4, and IL-13 levels were also significantly elevated at four hours post-injury although their expression did not decrease more than 3-fold for up to 24 hours post-injury. Additionally, IL-1β and IL-4 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in adaptive immune responses. Interestingly, peak levels of CCL2 and CCL20 were not observed until after four hours post-injury. CCL2 levels in injured cortical tissue were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses.

Healthy and pathological cerebellar Spiking Neural Networks in Vestibulo-Ocular Reflex.

PubMed

Antonietti, Alberto; Casellato, Claudia; Geminiani, Alice; D'Angelo, Egidio; Pedrocchi, Alessandra

2015-01-01

Since the Marr-Albus model, computational neuroscientists have been developing a variety of models of the cerebellum, with different approaches and features. In this work, we developed and tested realistic artificial Spiking Neural Networks inspired to this brain region. We tested in computational simulations of the Vestibulo-Ocular Reflex protocol three different models: a network equipped with a single plasticity site, at the cortical level; a network equipped with a distributed plasticity, at both cortical and nuclear levels; a network with a pathological plasticity mechanism at the cortical level. We analyzed the learning performance of the three different models, highlighting the behavioral differences among them. We proved that the model with a distributed plasticity produces a faster and more accurate cerebellar response, especially during a second session of acquisition, compared with the single plasticity model. Furthermore, the pathological model shows an impaired learning capability in Vestibulo-Ocular Reflex acquisition, as found in neurophysiological studies. The effect of the different plasticity conditions, which change fast and slow dynamics, memory consolidation and, in general, learning capabilities of the cerebellar network, explains differences in the behavioral outcome.

Estimation of cortical magnification from positional error in normally sighted and amblyopic subjects

PubMed Central

Hussain, Zahra; Svensson, Carl-Magnus; Besle, Julien; Webb, Ben S.; Barrett, Brendan T.; McGraw, Paul V.

2015-01-01

We describe a method for deriving the linear cortical magnification factor from positional error across the visual field. We compared magnification obtained from this method between normally sighted individuals and amblyopic individuals, who receive atypical visual input during development. The cortical magnification factor was derived for each subject from positional error at 32 locations in the visual field, using an established model of conformal mapping between retinal and cortical coordinates. Magnification of the normally sighted group matched estimates from previous physiological and neuroimaging studies in humans, confirming the validity of the approach. The estimate of magnification for the amblyopic group was significantly lower than the normal group: by 4.4 mm deg−1 at 1° eccentricity, assuming a constant scaling factor for both groups. These estimates, if correct, suggest a role for early visual experience in establishing retinotopic mapping in cortex. We discuss the implications of altered cortical magnification for cortical size, and consider other neural changes that may account for the amblyopic results. PMID:25761341

Pathophysiological analyses of cortical malformation using gyrencephalic mammals

PubMed Central

Masuda, Kosuke; Toda, Tomohisa; Shinmyo, Yohei; Ebisu, Haruka; Hoshiba, Yoshio; Wakimoto, Mayu; Ichikawa, Yoshie; Kawasaki, Hiroshi

2015-01-01

One of the most prominent features of the cerebral cortex of higher mammals is the presence of gyri. Because malformations of the cortical gyri are associated with severe disability in brain function, the mechanisms underlying malformations of the cortical gyri have been of great interest. Combining gyrencephalic carnivore ferrets and genetic manipulations using in utero electroporation, here we successfully recapitulated the cortical phenotypes of thanatophoric dysplasia (TD) by expressing fibroblast growth factor 8 in the ferret cerebral cortex. Strikingly, in contrast to TD mice, our TD ferret model showed not only megalencephaly but also polymicrogyria. We further uncovered that outer radial glial cells (oRGs) and intermediate progenitor cells (IPs) were markedly increased. Because it has been proposed that increased oRGs and/or IPs resulted in the appearance of cortical gyri during evolution, it seemed possible that increased oRGs and IPs underlie the pathogenesis of polymicrogyria. Our findings should help shed light on the molecular mechanisms underlying the formation and malformation of cortical gyri in higher mammals. PMID:26482531

The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update.

PubMed

Harmon-Jones, Eddie; Gable, Philip A; Peterson, Carly K

2010-07-01

Conceptual and empirical approaches to the study of the role of asymmetric frontal cortical activity in emotional processes are reviewed. Although early research suggested that greater left than right frontal cortical activity was associated with positive affect, more recent research, primarily on anger, suggests that greater left than right frontal cortical activity is associated with approach motivation, which can be positive (e.g., enthusiasm) or negative in valence (e.g., anger). In addition to reviewing this research on anger, research on guilt, bipolar disorder, and various types of positive affect is reviewed with relation to their association with asymmetric frontal cortical activity. The reviewed research not only contributes to a more complete understanding of the emotive functions of asymmetric frontal cortical activity, but it also points to the importance of considering motivational direction as separate from affective valence in psychological models of emotional space. Copyright © 2009 Elsevier B.V. All rights reserved.

Prediction of brain maturity based on cortical thickness at different spatial resolutions.

PubMed

Khundrakpam, Budhachandra S; Tohka, Jussi; Evans, Alan C

2015-05-01

Several studies using magnetic resonance imaging (MRI) scans have shown developmental trajectories of cortical thickness. Cognitive milestones happen concurrently with these structural changes, and a delay in such changes has been implicated in developmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Accurate estimation of individuals' brain maturity, therefore, is critical in establishing a baseline for normal brain development against which neurodevelopmental disorders can be assessed. In this study, cortical thickness derived from structural magnetic resonance imaging (MRI) scans of a large longitudinal dataset of normally growing children and adolescents (n=308), were used to build a highly accurate predictive model for estimating chronological age (cross-validated correlation up to R=0.84). Unlike previous studies which used kernelized approach in building prediction models, we used an elastic net penalized linear regression model capable of producing a spatially sparse, yet accurate predictive model of chronological age. Upon investigating different scales of cortical parcellation from 78 to 10,240 brain parcels, we observed that the accuracy in estimated age improved with increased spatial scale of brain parcellation, with the best estimations obtained for spatial resolutions consisting of 2560 and 10,240 brain parcels. The top predictors of brain maturity were found in highly localized sensorimotor and association areas. The results of our study demonstrate that cortical thickness can be used to estimate individuals' brain maturity with high accuracy, and the estimated ages relate to functional and behavioural measures, underscoring the relevance and scope of the study in the understanding of biological maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

Cortical functional hyperconnectivity in a mouse model of depression and selective network effects of ketamine.

PubMed

McGirr, Alexander; LeDue, Jeffrey; Chan, Allen W; Xie, Yicheng; Murphy, Timothy H

2017-08-01

See Huang and Liston (doi:10.1093/awx166) for a scientific commentary on this article.Human depression is associated with glutamatergic dysfunction and alterations in resting state network activity. However, the indirect nature of human in vivo glutamate and activity assessments obscures mechanistic details. Using the chronic social defeat mouse model of depression, we determine how mesoscale glutamatergic networks are altered after chronic stress, and in response to the rapid acting antidepressant, ketamine. Transgenic mice (Ai85) expressing iGluSnFR (a recombinant protein sensor) permitted real-time in vivo selective characterization of extracellular glutamate and longitudinal imaging of mesoscale cortical glutamatergic functional circuits. Mice underwent chronic social defeat or a control condition, while spontaneous cortical activity was longitudinally sampled. After chronic social defeat, we observed network-wide glutamate functional hyperconnectivity in defeated animals, which was confirmed with voltage sensitive dye imaging in an independent cohort. Subanaesthetic ketamine has unique effects in defeated animals. Acutely, subanaesthetic ketamine induces large global cortical glutamate transients in defeated animals, and an elevated subanaesthetic dose resulted in sustained global increase in cortical glutamate. Local cortical inhibition of glutamate transporters in naïve mice given ketamine produced a similar extracellular glutamate phenotype, with both glutamate transients and a dose-dependent accumulation of glutamate. Twenty-four hours after ketamine, normalization of depressive-like behaviour in defeated animals was accompanied by reduced glutamate functional connectivity strength. Altered glutamate functional connectivity in this animal model confirms the central role of glutamate dynamics as well as network-wide changes after chronic stress and in response to ketamine. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combining MRI and VEP imaging to isolate the temporal response of visual cortical areas

NASA Astrophysics Data System (ADS)

Carney, Thom; Ales, Justin; Klein, Stanley A.

2008-02-01

The human brain has well over 30 cortical areas devoted to visual processing. Classical neuro-anatomical as well as fMRI studies have demonstrated that early visual areas have a retinotopic organization whereby adjacent locations in visual space are represented in adjacent areas of cortex within a visual area. At the 2006 Electronic Imaging meeting we presented a method using sprite graphics to obtain high resolution retinotopic visual evoked potential responses using multi-focal m-sequence technology (mfVEP). We have used this method to record mfVEPs from up to 192 non overlapping checkerboard stimulus patches scaled such that each patch activates about 12 mm2 of cortex in area V1 and even less in V2. This dense coverage enables us to incorporate cortical folding constraints, given by anatomical MRI and fMRI results from the same subject, to isolate the V1 and V2 temporal responses. Moreover, the method offers a simple means of validating the accuracy of the extracted V1 and V2 time functions by comparing the results between left and right hemispheres that have unique folding patterns and are processed independently. Previous VEP studies have been contradictory as to which area responds first to visual stimuli. This new method accurately separates the signals from the two areas and demonstrates that both respond with essentially the same latency. A new method is introduced which describes better ways to isolate cortical areas using an empirically determined forward model. The method includes a novel steady state mfVEP and complex SVD techniques. In addition, this evolving technology is put to use examining how stimulus attributes differentially impact the response in different cortical areas, in particular how fast nonlinear contrast processing occurs. This question is examined using both state triggered kernel estimation (STKE) and m-sequence "conditioned kernels". The analysis indicates different contrast gain control processes in areas V1 and V2. Finally we show that our m-sequence multi-focal stimuli have advantages for integrating EEG and MEG for improved dipole localization.

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

PubMed

Sun, Daqiang; Ching, Christopher R K; Lin, Amy; Forsyth, Jennifer K; Kushan, Leila; Vajdi, Ariana; Jalbrzikowski, Maria; Hansen, Laura; Villalon-Reina, Julio E; Qu, Xiaoping; Jonas, Rachel K; van Amelsvoort, Therese; Bakker, Geor; Kates, Wendy R; Antshel, Kevin M; Fremont, Wanda; Campbell, Linda E; McCabe, Kathryn L; Daly, Eileen; Gudbrandsen, Maria; Murphy, Clodagh M; Murphy, Declan; Craig, Michael; Vorstman, Jacob; Fiksinski, Ania; Koops, Sanne; Ruparel, Kosha; Roalf, David R; Gur, Raquel E; Schmitt, J Eric; Simon, Tony J; Goodrich-Hunsaker, Naomi J; Durdle, Courtney A; Bassett, Anne S; Chow, Eva W C; Butcher, Nancy J; Vila-Rodriguez, Fidel; Doherty, Joanne; Cunningham, Adam; van den Bree, Marianne B M; Linden, David E J; Moss, Hayley; Owen, Michael J; Murphy, Kieran C; McDonald-McGinn, Donna M; Emanuel, Beverly; van Erp, Theo G M; Turner, Jessica A; Thompson, Paul M; Bearden, Carrie E

2018-06-13

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

PubMed

Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

2017-09-01

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN. Copyright © 2017 the American Physiological Society.

Cortical Transformation of Spatial Processing for Solving the Cocktail Party Problem: A Computational Model123

PubMed Central

Dong, Junzi; Colburn, H. Steven

2016-01-01

In multisource, “cocktail party” sound environments, human and animal auditory systems can use spatial cues to effectively separate and follow one source of sound over competing sources. While mechanisms to extract spatial cues such as interaural time differences (ITDs) are well understood in precortical areas, how such information is reused and transformed in higher cortical regions to represent segregated sound sources is not clear. We present a computational model describing a hypothesized neural network that spans spatial cue detection areas and the cortex. This network is based on recent physiological findings that cortical neurons selectively encode target stimuli in the presence of competing maskers based on source locations (Maddox et al., 2012). We demonstrate that key features of cortical responses can be generated by the model network, which exploits spatial interactions between inputs via lateral inhibition, enabling the spatial separation of target and interfering sources while allowing monitoring of a broader acoustic space when there is no competition. We present the model network along with testable experimental paradigms as a starting point for understanding the transformation and organization of spatial information from midbrain to cortex. This network is then extended to suggest engineering solutions that may be useful for hearing-assistive devices in solving the cocktail party problem. PMID:26866056

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.

Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

PubMed

Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

2016-05-01

Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. Copyright © 2016 Elsevier Inc. All rights reserved.

Cortical Transformation of Spatial Processing for Solving the Cocktail Party Problem: A Computational Model(1,2,3).

PubMed

Dong, Junzi; Colburn, H Steven; Sen, Kamal

2016-01-01

In multisource, "cocktail party" sound environments, human and animal auditory systems can use spatial cues to effectively separate and follow one source of sound over competing sources. While mechanisms to extract spatial cues such as interaural time differences (ITDs) are well understood in precortical areas, how such information is reused and transformed in higher cortical regions to represent segregated sound sources is not clear. We present a computational model describing a hypothesized neural network that spans spatial cue detection areas and the cortex. This network is based on recent physiological findings that cortical neurons selectively encode target stimuli in the presence of competing maskers based on source locations (Maddox et al., 2012). We demonstrate that key features of cortical responses can be generated by the model network, which exploits spatial interactions between inputs via lateral inhibition, enabling the spatial separation of target and interfering sources while allowing monitoring of a broader acoustic space when there is no competition. We present the model network along with testable experimental paradigms as a starting point for understanding the transformation and organization of spatial information from midbrain to cortex. This network is then extended to suggest engineering solutions that may be useful for hearing-assistive devices in solving the cocktail party problem.

Frontal cortical mitochondrial dysfunction and mitochondria-related β-amyloid accumulation by chronic sleep restriction in mice.

PubMed

Zhao, Hongyi; Wu, Huijuan; He, Jialin; Zhuang, Jianhua; Liu, Zhenyu; Yang, Yang; Huang, Liuqing; Zhao, Zhongxin

2016-08-17

Mitochondrial dysfunction induced by mitochondria-related β-amyloid (Aβ) accumulation is increasingly being considered a novel risk factor for sporadic Alzheimer's disease pathophysiology. The close relationship between chronic sleep restriction (CSR) and cortical Aβ elevation was confirmed recently. By assessing frontal cortical mitochondrial function (electron microscopy manifestation, cytochrome C oxidase concentration, ATP level, and mitochondrial membrane potential) and the levels of mitochondria-related Aβ in 9-month-old adult male C57BL/6J mice subjected to CSR and as an environmental control (CO) group, we aimed to evaluate the association of CSR with mitochondrial dysfunction and mitochondria-related Aβ accumulation. In this study, frontal cortical mitochondrial dysfunction was significantly more severe in CSR mice compared with CO animals. Furthermore, CSR mice showed higher mitochondria-associated Aβ, total Aβ, and mitochondria-related β-amyloid protein precursor (AβPP) levels compared with CO mice. In the CSR model, mouse frontal cortical mitochondrial dysfunction was correlated with mitochondria-associated Aβ and mitochondria-related AβPP levels. However, frontal cortical mitochondria-associated Aβ levels showed no significant association with cortical total Aβ and mitochondrial AβPP concentrations. These findings indicated that CSR-induced frontal cortical mitochondrial dysfunction and mitochondria-related Aβ accumulation, which was closely related to mitochondrial dysfunction under CSR.

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study.

PubMed

Rijken, Marcus J; de Wit, Merel Charlotte; Mulder, Eduard J H; Kiricharoen, Suporn; Karunkonkowit, Noaeni; Paw, Tamalar; Visser, Gerard H A; McGready, Rose; Nosten, François H; Pistorius, Lourens R

2012-07-02

Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound. Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses. Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies. The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.

Cortical thickness in adolescent marijuana and alcohol users: A three-year prospective study from adolescence to young adulthood.

PubMed

Jacobus, Joanna; Squeglia, Lindsay M; Meruelo, Alejandro D; Castro, Norma; Brumback, Ty; Giedd, Jay N; Tapert, Susan F

2015-12-01

Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls (CON, n=38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ+ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (ps<.05). More cumulative marijuana use was associated with increased thickness estimates by 3-year follow-up (ps<.05). Heavy marijuana use during adolescence and into young adulthood may be associated with altered neural tissue development and interference with neuromaturation that can have neurobehavioral consequences. Continued follow-up of adolescent marijuana users will help understand ongoing neural changes that are associated with development of problematic use into adulthood, as well as potential for neural recovery with cessation of use. Published by Elsevier Ltd.

Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia–Ischemia

PubMed Central

Jantzie, Lauren L.; Corbett, Christopher J.; Firl, Daniel J.; Robinson, Shenandoah

2015-01-01

Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia–ischemia (TSHI) in Sprague–Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants. PMID:24722771

Signal propagation in cortical networks: a digital signal processing approach.

PubMed

Rodrigues, Francisco Aparecido; da Fontoura Costa, Luciano

2009-01-01

This work reports a digital signal processing approach to representing and modeling transmission and combination of signals in cortical networks. The signal dynamics is modeled in terms of diffusion, which allows the information processing undergone between any pair of nodes to be fully characterized in terms of a finite impulse response (FIR) filter. Diffusion without and with time decay are investigated. All filters underlying the cat and macaque cortical organization are found to be of low-pass nature, allowing the cortical signal processing to be summarized in terms of the respective cutoff frequencies (a high cutoff frequency meaning little alteration of signals through their intermixing). Several findings are reported and discussed, including the fact that the incorporation of temporal activity decay tends to provide more diversified cutoff frequencies. Different filtering intensity is observed for each community in those networks. In addition, the brain regions involved in object recognition tend to present the highest cutoff frequencies for both the cat and macaque networks.

Cortical dipole imaging using truncated total least squares considering transfer matrix error.

PubMed

Hori, Junichi; Takeuchi, Kosuke

2013-01-01

Cortical dipole imaging has been proposed as a method to visualize electroencephalogram in high spatial resolution. We investigated the inverse technique of cortical dipole imaging using a truncated total least squares (TTLS). The TTLS is a regularization technique to reduce the influence from both the measurement noise and the transfer matrix error caused by the head model distortion. The estimation of the regularization parameter was also investigated based on L-curve. The computer simulation suggested that the estimation accuracy was improved by the TTLS compared with Tikhonov regularization. The proposed method was applied to human experimental data of visual evoked potentials. We confirmed the TTLS provided the high spatial resolution of cortical dipole imaging.

Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

NASA Astrophysics Data System (ADS)

Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

2014-03-01

Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

Linear transformation of the encoding mechanism for light intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane.

PubMed

Arena, Alessandro; Lamanna, Jacopo; Gemma, Marco; Ripamonti, Maddalena; Ravasio, Giuliano; Zimarino, Vincenzo; De Vitis, Assunta; Beretta, Luigi; Malgaroli, Antonio

2017-01-01

The mechanisms of action of anaesthetics on the living brain are still poorly understood. In this respect, the analysis of the differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity might provide important and novel cues. Here we show that the anaesthetic sevoflurane strongly silences the brain but potentiates in a dose- and frequency-dependent manner the cortical visual response. Such enhancement arises from a linear scaling by sevoflurane of the power-law relation between light intensity and the cortical response. The fingerprint of sevoflurane action suggests that circuit silencing can boost linearly synaptic responsiveness presumably by scaling the number of responding units and/or their correlation following a sensory stimulation. General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and the bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light intensity. To the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 to 1 Hz. Overall, our results support the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

DTIC Science & Technology

2013-07-01

injury (FPI), in which injury is produced by the impact of a pendulum onto a fluid reservoir, or controlled cortical impact (CCI), in which a rigid...algorithm, and the MSigDB Web site in Table 3 allows users to run GSEA on up- loaded data. One drawback to GSEA and the hypergeometric test is that

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.

The Unique Brain Anatomy of Meditation Practitioners: Alterations in Cortical Gyrification

PubMed Central

Luders, Eileen; Kurth, Florian; Mayer, Emeran A.; Toga, Arthur W.; Narr, Katherine L.; Gaser, Christian

2012-01-01

Several cortical regions are reported to vary in meditation practitioners. However, prior analyses have focused primarily on examining gray matter or cortical thickness. Thus, additional effects with respect to other cortical features might have remained undetected. Gyrification (the pattern and degree of cortical folding) is an important cerebral characteristic related to the geometry of the brain’s surface. Thus, exploring cortical gyrification in long-term meditators may provide additional clues with respect to the underlying anatomical correlates of meditation. This study examined cortical gyrification in a large sample (n = 100) of meditators and controls, carefully matched for sex and age. Cortical gyrification was established by calculating mean curvature across thousands of vertices on individual cortical surface models. Pronounced group differences indicating larger gyrification in meditators were evident within the left precentral gyrus, right fusiform gyrus, right cuneus, as well as left and right anterior dorsal insula (the latter representing the global significance maximum). Positive correlations between gyrification and the number of meditation years were similarly pronounced in the right anterior dorsal insula. Although the exact functional implications of larger cortical gyrification remain to be established, these findings suggest the insula to be a key structure involved in aspects of meditation. For example, variations in insular complexity could affect the regulation of well-known distractions in the process of meditation, such as daydreaming, mind-wandering, and projections into past or future. Moreover, given that meditators are masters in introspection, awareness, and emotional control, increased insular gyrification may reflect an integration of autonomic, affective, and cognitive processes. Due to the cross-sectional nature of this study, further research is necessary to determine the relative contribution of nature and nurture to links between cortical gyrification and meditation. PMID:22393318

Altered cortical beta-band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis.

PubMed

Proudfoot, Malcolm; Rohenkohl, Gustavo; Quinn, Andrew; Colclough, Giles L; Wuu, Joanne; Talbot, Kevin; Woolrich, Mark W; Benatar, Michael; Nobre, Anna C; Turner, Martin R

2017-01-01

Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15-30 Hz) power. Cortical beta-band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven "classical" ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS-associated gene mutations were compared with age-similar healthy control groups. Augmented beta desynchronization was observed in both contra- and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237-254, 2017. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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.

Assessing the Effect of Dental Implants Thread Design on Distribution of Stress in Impact Loadings Using Three Dimensional Finite Element Method

PubMed Central

I, Zarei; S, Khajehpour; A, Sabouri; AZ, Haghnegahdar; K, Jafari

2016-01-01

Statement of Problem: Impacts and accidents are considered as the main fac- tors in losing the teeth, so the analysis and design of the implants that they can be more resistant against impacts is very important. One of the important nu- merical methods having widespread application in various fields of engineering sciences is the finite element method. Among its wide applications, the study of distribution of power in complex structures can be noted. Objectives: The aim of this research was to assess the geometric effect and the type of implant thread on its performance; we also made an attempt to determine the created stress using finite element method. Materials and Methods: In this study, the three dimensional model of bone by using Cone Beam Computerized Tomography (CBCT) of the patient has been provided. The implants in this study are designed by Solid Works software. Loading is simulated in explicit dynamic, by struck of a rigid body with the speed of 1 mm/s to implant vertically and horizontally; and the maximum level of induced stress for the cortical and trabecular bone in the ANSYS Workbench software was calculated. Results: By considering the results of this study, it was identified that, among the designed samples, the maximum imposed stress in the cortical bone layer occurred in the first group (straight threads) and the maximum stress value in the trabecular bone layer and implant occurred in the second group (tapered threads). Conclusions: Due to the limitations of this study, the implants with more depth thread, because of the increased contact surface of the implant with the bone, caused more stability; also, the implant with smaller thread and shorter pitch length caused more stress to the bone. PMID:28959748

Assessing the Effect of Dental Implants Thread Design on Distribution of Stress in Impact Loadings Using Three Dimensional Finite Element Method.

PubMed

I, Zarei; S, Khajehpour; A, Sabouri; Az, Haghnegahdar; K, Jafari

2016-06-01

Impacts and accidents are considered as the main fac- tors in losing the teeth, so the analysis and design of the implants that they can be more resistant against impacts is very important. One of the important nu- merical methods having widespread application in various fields of engineering sciences is the finite element method. Among its wide applications, the study of distribution of power in complex structures can be noted. The aim of this research was to assess the geometric effect and the type of implant thread on its performance; we also made an attempt to determine the created stress using finite element method. In this study, the three dimensional model of bone by using Cone Beam Computerized Tomography (CBCT) of the patient has been provided. The implants in this study are designed by Solid Works software. Loading is simulated in explicit dynamic, by struck of a rigid body with the speed of 1 mm/s to implant vertically and horizontally; and the maximum level of induced stress for the cortical and trabecular bone in the ANSYS Workbench software was calculated. By considering the results of this study, it was identified that, among the designed samples, the maximum imposed stress in the cortical bone layer occurred in the first group (straight threads) and the maximum stress value in the trabecular bone layer and implant occurred in the second group (tapered threads). Due to the limitations of this study, the implants with more depth thread, because of the increased contact surface of the implant with the bone, caused more stability; also, the implant with smaller thread and shorter pitch length caused more stress to the bone.

Developmental Thyroid Hormone Insufficiency Induces Cortical Brain Malformation and Learning Impairments: A Cross-Fostering Study

EPA Science Inventory

Thyroid hormones (TH) are essential for brain development, but animal models of well-defined and sensitive downstream apical neurotoxic outcomes associated with developmental TH disruption are lacking. A structural anomaly, a cortical heterotopia, in the brains of hypothyroid rat...

Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer's disease.

PubMed

Zhang, Xiuming; Mormino, Elizabeth C; Sun, Nanbo; Sperling, Reisa A; Sabuncu, Mert R; Yeo, B T Thomas

2016-10-18

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer's disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

Three-Dimensional Finite Element Analysis of Varying Diameter and Connection Type in Implants with High Crown-Implant Ratio.

PubMed

Moraes, Sandra Lúcia Dantas de; Verri, Fellippo Ramos; Santiago, Joel Ferreira; Almeida, Daniel Augusto de Faria; Lemos, Cleidiel Aparecido Araujo; Gomes, Jéssica Marcela de Luna; Pellizzer, Eduardo Piza

2018-01-01

The aim of this study was to evaluate the effect of varying the diameter, connection type and loading on stress distribution in the cortical bone for implants with a high crown-implant ratio. Six 3D models were simulated with the InVesalius, Rhinoceros 3D 4.0 and SolidWorks 2011 software programs. Models were composed of bone from the posterior mandibular region; they included an implant of 8.5 mm length, diameter Ø 3.75 mm or Ø 5.00 mm and connection types such as external hexagon (EH), internal hexagon (IH) and Morse taper (MT). Models were processed using the Femap 11.2 and NeiNastran 11.0 programs and by using an axial force of 200 N and oblique force of 100 N. Results were recorded in terms of the maximum principal stress. Oblique loading showed high stress in the cortical bone compared to that shown by axial loading. The results showed that implants with a wide diameter showed more favorable stress distribution in the cortical bone region than regular diameter, regardless of the connection type. Morse taper implants showed better stress distribution compared to other connection types, especially in the oblique loading. Thus, oblique loading showed higher stress concentration in cortical bone tissue when compared with axial loading. Wide diameter implant was favorable for improved stress distribution in the cortical bone region, while Morse taper implants showed lower stress concentration than other connections.

Characterization of Femoral Component Initial Stability and Cortical Strain in a Reduced Stem-Length Design.

PubMed

Small, Scott R; Hensley, Sarah E; Cook, Paige L; Stevens, Rebecca A; Rogge, Renee D; Meding, John B; Berend, Michael E

2017-02-01

Short-stemmed femoral components facilitate reduced exposure surgical techniques while preserving native bone. A clinically successful stem should ideally reduce risk for stress shielding while maintaining adequate primary stability for biological fixation. We asked (1) how stem-length changes cortical strain distribution in the proximal femur in a fit-and-fill geometry and (2) if short-stemmed components exhibit primary stability on par with clinically successful designs. Cortical strain was assessed via digital image correlation in composite femurs implanted with long, medium, and short metaphyseal fit-and-fill stem designs in a single-leg stance loading model. Strain was compared to a loaded, unimplanted femur. Bone-implant micromotion was then compared with reduced lateral shoulder short stem and short tapered-wedge designs in cyclic axial and torsional testing. Femurs implanted with short-stemmed components exhibited cortical strain response most closely matching that of the intact femur model, theoretically reducing the potential for proximal stress shielding. In micromotion testing, no difference in primary stability was observed as a function of reduced stem length within the same component design. Our findings demonstrate that within this fit-and-fill stem design, reduction in stem length improved proximal cortical strain distribution and maintained axial and torsional stability on par with other stem designs in a composite femur model. Short-stemmed implants may accommodate less invasive surgical techniques while facilitating more physiological femoral loading without sacrificing primary implant stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Linear summation of outputs in a balanced network model of motor cortex.

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

Predicting Cortical Dark/Bright Asymmetries from Natural Image Statistics and Early Visual Transforms

PubMed Central

Cooper, Emily A.; Norcia, Anthony M.

2015-01-01

The nervous system has evolved in an environment with structure and predictability. One of the ubiquitous principles of sensory systems is the creation of circuits that capitalize on this predictability. Previous work has identified predictable non-uniformities in the distributions of basic visual features in natural images that are relevant to the encoding tasks of the visual system. Here, we report that the well-established statistical distributions of visual features -- such as visual contrast, spatial scale, and depth -- differ between bright and dark image components. Following this analysis, we go on to trace how these differences in natural images translate into different patterns of cortical input that arise from the separate bright (ON) and dark (OFF) pathways originating in the retina. We use models of these early visual pathways to transform natural images into statistical patterns of cortical input. The models include the receptive fields and non-linear response properties of the magnocellular (M) and parvocellular (P) pathways, with their ON and OFF pathway divisions. The results indicate that there are regularities in visual cortical input beyond those that have previously been appreciated from the direct analysis of natural images. In particular, several dark/bright asymmetries provide a potential account for recently discovered asymmetries in how the brain processes visual features, such as violations of classic energy-type models. On the basis of our analysis, we expect that the dark/bright dichotomy in natural images plays a key role in the generation of both cortical and perceptual asymmetries. PMID:26020624

Analysis of the independent power of age-related, anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study.

PubMed

Reina, P; Cointry, G R; Nocciolino, L; Feldman, S; Ferretti, J L; Rittweger, J; Capozza, R F

2015-03-01

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles' areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue 'quality' (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.

Neurodevelopmental origins of lifespan changes in brain and cognition

PubMed Central

Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.

2016-01-01

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992

Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone.

PubMed

Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D; Weinstein, Robert S; Manolagas, Stavros C; O'Brien, Charles A

2015-06-01

Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. Published by Elsevier Inc.

Suppression of Autophagy in Osteocytes Does Not Modify the Adverse Effects of Glucocorticoids on Cortical Bone

PubMed Central

Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2015-01-01

Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. PMID:25700544

Neurodevelopmental origins of lifespan changes in brain and cognition.

PubMed

Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J; Håberg, Asta K; Kremen, William S; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S; Rohani, Darius A; Skranes, Jon; Storsve, Andreas B; Sølsnes, Anne Elisabeth; Tamnes, Christian K; Thompson, Wesley K; Reuter, Chase; Dale, Anders M; Fjell, Anders M

2016-08-16

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

PubMed

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R

2016-10-15

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields

PubMed Central

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E.; Cohen, Leonardo G.; Birbaumer, Niels; Soekadar, Surjo R.

2016-01-01

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. PMID:26455796

Regional cortical thinning predicts worsening apathy and hallucinations across the Alzheimer disease spectrum.

PubMed

Donovan, Nancy J; Wadsworth, Lauren P; Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A

2014-11-01

To examine regions of cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers associated with apathy and hallucinations in a continuum of individuals including clinically normal elderly, mild cognitive impairment, and mild AD dementia. Cross-sectional and longitudinal studies. Fifty-seven research sites across North America. Eight-hundred twelve community-dwelling volunteers; 413 participants in the CSF sub-study. Structural magnetic resonance imaging data and CSF concentrations of amyloid-β 1-42, total tau, and phosphorylated tau derived from the Alzheimer Disease Neuroimaging Initiative database were analyzed. Apathy and hallucinations were measured at baseline and over 3 years using the Neuropsychiatric Inventory-Questionnaire. General linear models and mixed effects models were used to evaluate the relationships among baseline cortical thickness in seven regions, and baseline CSF biomarkers, apathy, and hallucinations at baseline and longitudinally. Covariates included diagnosis, sex, age, apolipoprotein E genotype, premorbid intelligence, memory performance, processing speed, antidepressant use, and AD duration. Reduced baseline inferior temporal cortical thickness was predictive of increasing apathy over time, and reduced supramarginal cortical thickness was predictive of increasing hallucinations over time. There was no association with cortical thickness at baseline. CSF biomarkers were not related to severity of apathy or hallucinations in cross-sectional or longitudinal analyses. These results suggest that greater baseline temporal and parietal atrophy is associated with worsening apathy and hallucinations in a large AD spectrum cohort, while adjusting for multiple disease-related variables. Localized cortical neurodegeneration may contribute to the pathophysiology of apathy and hallucinations and their adverse consequences in AD. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Attention Induced Gain Stabilization in Broad and Narrow-Spiking Cells in the Frontal Eye-Field of Macaque Monkeys

PubMed Central

Brandt, Christian; Dasilva, Miguel; Gotthardt, Sascha; Chicharro, Daniel; Panzeri, Stefano; Distler, Claudia

2016-01-01

Top-down attention increases coding abilities by altering firing rates and rate variability. In the frontal eye field (FEF), a key area enabling top-down attention, attention induced firing rate changes are profound, but its effect on different cell types is unknown. Moreover, FEF is the only cortical area investigated in which attention does not affect rate variability, as assessed by the Fano factor, suggesting that task engagement affects cortical state nonuniformly. We show that putative interneurons in FEF of Macaca mulatta show stronger attentional rate modulation than putative pyramidal cells. Partitioning rate variability reveals that both cell types reduce rate variability with attention, but more strongly so in narrow-spiking cells. The effects are captured by a model in which attention stabilizes neuronal excitability, thereby reducing the expansive nonlinearity that links firing rate and variance. These results show that the effect of attention on different cell classes and different coding properties are consistent across the cortical hierarchy, acting through increased and stabilized neuronal excitability. SIGNIFICANCE STATEMENT Cortical processing is critically modulated by attention. A key feature of this influence is a modulation of “cortical state,” resulting in increased neuronal excitability and resilience of the network against perturbations, lower rate variability, and an increased signal-to-noise ratio. In the frontal eye field (FEF), an area assumed to control spatial attention in human and nonhuman primates, firing rate changes with attention occur, but rate variability, quantified by the Fano factor, appears to be unaffected by attention. Using recently developed analysis tools and models to quantify attention effects on narrow- and broad-spiking cell activity, we show that attention alters cortical state strongly in the FEF, demonstrating that its effect on the neuronal network is consistent across the cortical hierarchy. PMID:27445139

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

NASA Technical Reports Server (NTRS)

Krukowski, A. E.; Miller, K. D.

2001-01-01

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

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.

Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex

PubMed Central

Coppola, David; White, Leonard E.; Wolf, Fred

2015-01-01

The architecture of iso-orientation domains in the primary visual cortex (V1) of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants. This might indicate that V1’s intrinsic connectome and its functional architecture adhere to a single optimization principle with high precision and robustness. To validate this hypothesis, it is critical to closely examine the quantitative predictions of alternative candidate theories. Random feedforward wiring within the retino-cortical pathway represents a conceptually appealing alternative to dynamical circuit optimization because random dimension-expanding projections are believed to generically exhibit computationally favorable properties for stimulus representations. Here, we ask whether the quantitative invariants of V1 architecture can be explained as a generic emergent property of random wiring. We generalize and examine the stochastic wiring model proposed by Ringach and coworkers, in which iso-orientation domains in the visual cortex arise through random feedforward connections between semi-regular mosaics of retinal ganglion cells (RGCs) and visual cortical neurons. We derive closed-form expressions for cortical receptive fields and domain layouts predicted by the model for perfectly hexagonal RGC mosaics. Including spatial disorder in the RGC positions considerably changes the domain layout properties as a function of disorder parameters such as position scatter and its correlations across the retina. However, independent of parameter choice, we find that the model predictions substantially deviate from the layout laws of iso-orientation domains observed experimentally. Considering random wiring with the currently most realistic model of RGC mosaic layouts, a pairwise interacting point process, the predicted layouts remain distinct from experimental observations and resemble Gaussian random fields. We conclude that V1 layout invariants are specific quantitative signatures of visual cortical optimization, which cannot be explained by generic random feedforward-wiring models. PMID:26575467

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

The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans

PubMed Central

2013-01-01

Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized. PMID:23689830

Principles for the dynamic maintenance of cortical polarity

PubMed Central

Marco, Eugenio; Wedlich-Soldner, Roland; Li, Rong; Altschuler, Steven J.; Wu, Lani F.

2007-01-01

Summary Diverse cell types require the ability to dynamically maintain polarized membrane protein distributions through balancing transport and diffusion. However, design principles underlying dynamically maintained cortical polarity are not well understood. Here we constructed a mathematical model for characterizing the morphology of dynamically polarized protein distributions. We developed analytical approaches for measuring all model parameters from single-cell experiments. We applied our methods to a well-characterized system for studying polarized membrane proteins: budding yeast cells expressing activated Cdc42. We found that balanced diffusion and colocalized transport to and from the plasma membrane were sufficient for accurately describing polarization morphologies. Surprisingly, the model predicts that polarized regions are defined with a precision that is nearly optimal for measured transport rates, and that polarity can be dynamically stabilized through positive feedback with directed transport. Our approach provides a step towards understanding how biological systems shape spatially precise, unambiguous cortical polarity domains using dynamic processes. PMID:17448998

Establishing the 3-D finite element solid model of femurs in partial by volume rendering.

PubMed

Zhang, Yinwang; Zhong, Wuxue; Zhu, Haibo; Chen, Yun; Xu, Lingjun; Zhu, Jianmin

2013-01-01

It remains rare to report three-dimensional (3-D) finite element solid model of femurs in partial by volume rendering method, though several methods of femoral 3-D finite element modeling are already available. We aim to analyze the advantages of the modeling method by establishing the 3-D finite element solid model of femurs in partial by volume rendering. A 3-D finite element model of the normal human femurs, made up of three anatomic structures: cortical bone, cancellous bone and pulp cavity, was constructed followed by pretreatment of the CT original image. Moreover, the finite-element analysis was carried on different material properties, three types of materials given for cortical bone, six assigned for cancellous bone, and single for pulp cavity. The established 3-D finite element of femurs contains three anatomical structures: cortical bone, cancellous bone, and pulp cavity. The compressive stress primarily concentrated in the medial surfaces of femur, especially in the calcar femorale. Compared with whole modeling by volume rendering method, the 3-D finite element solid model created in partial is more real and fit for finite element analysis. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

NASA Astrophysics Data System (ADS)

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2015-08-01

Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new understanding of the factors by which TMS induces cortical activation necessary for predictive and repeatable use of this noninvasive stimulation modality.

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

In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

PubMed

De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

2014-01-01

Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

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.

Estimation of Thalamocortical and Intracortical Network Models from Joint Thalamic Single-Electrode and Cortical Laminar-Electrode Recordings in the Rat Barrel System

PubMed Central

Blomquist, Patrick; Devor, Anna; Indahl, Ulf G.; Ulbert, Istvan; Einevoll, Gaute T.; Dale, Anders M.

2009-01-01

A new method is presented for extraction of population firing-rate models for both thalamocortical and intracortical signal transfer based on stimulus-evoked data from simultaneous thalamic single-electrode and cortical recordings using linear (laminar) multielectrodes in the rat barrel system. Time-dependent population firing rates for granular (layer 4), supragranular (layer 2/3), and infragranular (layer 5) populations in a barrel column and the thalamic population in the homologous barreloid are extracted from the high-frequency portion (multi-unit activity; MUA) of the recorded extracellular signals. These extracted firing rates are in turn used to identify population firing-rate models formulated as integral equations with exponentially decaying coupling kernels, allowing for straightforward transformation to the more common firing-rate formulation in terms of differential equations. Optimal model structures and model parameters are identified by minimizing the deviation between model firing rates and the experimentally extracted population firing rates. For the thalamocortical transfer, the experimental data favor a model with fast feedforward excitation from thalamus to the layer-4 laminar population combined with a slower inhibitory process due to feedforward and/or recurrent connections and mixed linear-parabolic activation functions. The extracted firing rates of the various cortical laminar populations are found to exhibit strong temporal correlations for the present experimental paradigm, and simple feedforward population firing-rate models combined with linear or mixed linear-parabolic activation function are found to provide excellent fits to the data. The identified thalamocortical and intracortical network models are thus found to be qualitatively very different. While the thalamocortical circuit is optimally stimulated by rapid changes in the thalamic firing rate, the intracortical circuits are low-pass and respond most strongly to slowly varying inputs from the cortical layer-4 population. PMID:19325875

Reduced modulation of scanpaths in response to task demands in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Pertzov, Yoni; Yong, Keir X X; Nicholas, Jennifer; Crutch, Sebastian J

2015-02-01

A difficulty in perceiving visual scenes is one of the most striking impairments experienced by patients with the clinico-radiological syndrome posterior cortical atrophy (PCA). However whilst a number of studies have investigated perception of relatively simple experimental stimuli in these individuals, little is known about multiple object and complex scene perception and the role of eye movements in posterior cortical atrophy. We embrace the distinction between high-level (top-down) and low-level (bottom-up) influences upon scanning eye movements when looking at scenes. This distinction was inspired by Yarbus (1967), who demonstrated how the location of our fixations is affected by task instructions and not only the stimulus' low level properties. We therefore examined how scanning patterns are influenced by task instructions and low-level visual properties in 7 patients with posterior cortical atrophy, 8 patients with typical Alzheimer's disease, and 19 healthy age-matched controls. Each participant viewed 10 scenes under four task conditions (encoding, recognition, search and description) whilst eye movements were recorded. The results reveal significant differences between groups in the impact of test instructions upon scanpaths. Across tasks without a search component, posterior cortical atrophy patients were significantly less consistent than typical Alzheimer's disease patients and controls in where they were looking. By contrast, when comparing search and non-search tasks, it was controls who exhibited lowest between-task similarity ratings, suggesting they were better able than posterior cortical atrophy or typical Alzheimer's disease patients to respond appropriately to high-level needs by looking at task-relevant regions of a scene. Posterior cortical atrophy patients had a significant tendency to fixate upon more low-level salient parts of the scenes than controls irrespective of the viewing task. The study provides a detailed characterisation of scene perception abilities in posterior cortical atrophy and offers insights into the mechanisms by which high-level cognitive schemes interact with low-level perception. Copyright © 2015 Elsevier Ltd. All rights reserved.

Women Build Long Bones With Less Cortical Mass Relative to Body Size and Bone Size Compared With Men.

PubMed

Jepsen, Karl J; Bigelow, Erin M R; Schlecht, Stephen H

2015-08-01

The twofold greater lifetime risk of fracturing a bone for white women compared with white men and black women has been attributed in part to differences in how the skeletal system accumulates bone mass during growth. On average, women build more slender long bones with less cortical area compared with men. Although slender bones are known to have a naturally lower cortical area compared with wider bones, it remains unclear whether the relatively lower cortical area of women is consistent with their increased slenderness or is reduced beyond that expected for the sex-specific differences in bone size and body size. Whether this sexual dimorphism is consistent with ethnic background and is recapitulated in the widely used mouse model also remains unclear. We asked (1) do black women build bones with reduced cortical area compared with black men; (2) do white women build bones with reduced cortical area compared with white men; and (3) do female mice build bones with reduced cortical area compared with male mice? Bone strength and cross-sectional morphology of adult human and mouse bone were calculated from quantitative CT images of the femoral midshaft. The data were tested for normality and regression analyses were used to test for differences in cortical area between men and women after adjusting for body size and bone size by general linear model (GLM). Linear regression analysis showed that the femurs of black women had 11% lower cortical area compared with those of black men after adjusting for body size and bone size (women: mean=357.7 mm2; 95% confidence interval [CI], 347.9-367.5 mm2; men: mean=400.1 mm2; 95% CI, 391.5-408.7 mm2; effect size=1.2; p<0.001, GLM). Likewise, the femurs of white women had 12% less cortical area compared with those of white men after adjusting for body size and bone size (women: mean=350.1 mm2; 95% CI, 340.4-359.8 mm2; men: mean=394.3 mm2; 95% CI, 386.5-402.1 mm2; effect size=1.3; p<0.001, GLM). In contrast, female and male femora from recombinant inbred mouse strains showed the opposite trend; femurs from female mice had a 4% larger cortical area compared with those of male mice after adjusting for body size and bone size (female: mean=0.73 mm2; 95% CI, 0.71-0.74 mm2; male: mean=0.70 mm2; 95% CI, 0.68-0.71 mm2; effect size=0.74; p=0.04, GLM). Female femurs are not simply a more slender version of male femurs. Women acquire substantially less mass (cortical area) for their body size and bone size compared with men. Our analysis questions whether mouse long bone is a suitable model to study human sexual dimorphism. Identifying differences in the way bones are constructed may be clinically important for developing sex-specific diagnostics and treatment strategies to reduce fragility fractures.

Influence of slow oscillation on hippocampal activity and ripples through cortico-hippocampal synaptic interactions, analyzed by a cortical-CA3-CA1 network model.

PubMed

Taxidis, Jiannis; Mizuseki, Kenji; Mason, Robert; Owen, Markus R

2013-01-01

Hippocampal sharp wave-ripple complexes (SWRs) involve the synchronous discharge of thousands of cells throughout the CA3-CA1-subiculum-entorhinal cortex axis. Their strong transient output affects cortical targets, rendering SWRs a possible means for memory transfer from the hippocampus to the neocortex for long-term storage. Neurophysiological observations of hippocampal activity modulation by the cortical slow oscillation (SO) during deep sleep and anesthesia, and correlations between ripples and UP states, support the role of SWRs in memory consolidation through a cortico-hippocampal feedback loop. We couple a cortical network exhibiting SO with a hippocampal CA3-CA1 computational network model exhibiting SWRs, in order to model such cortico-hippocampal correlations and uncover important parameters and coupling mechanisms controlling them. The cortical oscillatory output entrains the CA3 network via connections representing the mossy fiber input, and the CA1 network via the temporoammonic pathway (TA). The spiking activity in CA3 and CA1 is shown to depend on the excitation-to-inhibition ratio, induced by combining the two hippocampal inputs, with mossy fiber input controlling the UP-state correlation of CA3 population bursts and corresponding SWRs, whereas the temporoammonic input affects the overall CA1 spiking activity. Ripple characteristics and pyramidal spiking participation to SWRs are shaped by the strength of the Schaffer collateral drive. A set of in vivo recordings from the rat hippocampus confirms a model-predicted segregation of pyramidal cells into subgroups according to the SO state where they preferentially fire and their response to SWRs. These groups can potentially play distinct functional roles in the replay of spike sequences.

Cortical Dynamics in Presence of Assemblies of Densely Connected Weight-Hub Neurons

PubMed Central

Setareh, Hesam; Deger, Moritz; Petersen, Carl C. H.; Gerstner, Wulfram

2017-01-01

Experimental measurements of pairwise connection probability of pyramidal neurons together with the distribution of synaptic weights have been used to construct randomly connected model networks. However, several experimental studies suggest that both wiring and synaptic weight structure between neurons show statistics that differ from random networks. Here we study a network containing a subset of neurons which we call weight-hub neurons, that are characterized by strong inward synapses. We propose a connectivity structure for excitatory neurons that contain assemblies of densely connected weight-hub neurons, while the pairwise connection probability and synaptic weight distribution remain consistent with experimental data. Simulations of such a network with generalized integrate-and-fire neurons display regular and irregular slow oscillations akin to experimentally observed up/down state transitions in the activity of cortical neurons with a broad distribution of pairwise spike correlations. Moreover, stimulation of a model network in the presence or absence of assembly structure exhibits responses similar to light-evoked responses of cortical layers in optogenetically modified animals. We conclude that a high connection probability into and within assemblies of excitatory weight-hub neurons, as it likely is present in some but not all cortical layers, changes the dynamics of a layer of cortical microcircuitry significantly. PMID:28690508

Preferred Tempo and Low-Audio-Frequency Bias Emerge From Simulated Sub-cortical Processing of Sounds With a Musical Beat

PubMed Central

Zuk, Nathaniel J.; Carney, Laurel H.; Lalor, Edmund C.

2018-01-01

Prior research has shown that musical beats are salient at the level of the cortex in humans. Yet below the cortex there is considerable sub-cortical processing that could influence beat perception. Some biases, such as a tempo preference and an audio frequency bias for beat timing, could result from sub-cortical processing. Here, we used models of the auditory-nerve and midbrain-level amplitude modulation filtering to simulate sub-cortical neural activity to various beat-inducing stimuli, and we used the simulated activity to determine the tempo or beat frequency of the music. First, irrespective of the stimulus being presented, the preferred tempo was around 100 beats per minute, which is within the range of tempi where tempo discrimination and tapping accuracy are optimal. Second, sub-cortical processing predicted a stronger influence of lower audio frequencies on beat perception. However, the tempo identification algorithm that was optimized for simple stimuli often failed for recordings of music. For music, the most highly synchronized model activity occurred at a multiple of the beat frequency. Using bottom-up processes alone is insufficient to produce beat-locked activity. Instead, a learned and possibly top-down mechanism that scales the synchronization frequency to derive the beat frequency greatly improves the performance of tempo identification. PMID:29896080

Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

PubMed Central

Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

2015-01-01

The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging

PubMed Central

Louapre, Céline; Govindarajan, Sindhuja T.; Giannì, Costanza; Nielsen, A. Scott; Cohen-Adad, Julien; Sloane, Jacob; Kinkel, Revere P.

2015-01-01

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients’ normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10−10 and P < 10−7), and mean cortical T2* in controls (P < 10−5 and P < 10−6). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface. PMID:25681411

Enhanced Burst-Suppression and Disruption of Local Field Potential Synchrony in a Mouse Model of Focal Cortical Dysplasia Exhibiting Spike-Wave Seizures.

PubMed

Williams, Anthony J; Zhou, Chen; Sun, Qian-Quan

2016-01-01

Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are often associated with intractable epilepsy. Here we evaluated aberrant brain neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode arrays were used to record extracellular potentials from cortical and subcortical brain regions near the FL in anesthetized mice (5-13 months old) followed by 24 h cortical electroencephalogram (EEG) recordings. Results indicated that FL animals exhibit a high prevalence of spontaneous spike-wave discharges (SWDs), predominately during sleep (EEG), and an increase in the incidence of hyper-excitable burst/suppression activity under general anesthesia (extracellular recordings, 0.5%-3.0% isoflurane). Brief periods of burst activity in the local field potential (LFP) typically presented as an arrhythmic pattern of increased theta-alpha spectral peaks (4-12 Hz) on a background of low-amplitude delta activity (1-4 Hz), were associated with an increase in spontaneous spiking of cortical neurons, and were highly synchronized in control animals across recording sites in both cortical and subcortical layers (average cross-correlation values ranging from +0.73 to +1.0) with minimal phase shift between electrodes. However, in FL animals, cortical vs. subcortical burst activity was strongly out of phase with significantly lower cross-correlation values compared to controls (average values of -0.1 to +0.5, P < 0.05 between groups). In particular, a marked reduction in the level of synchronous burst activity was observed, the closer the recording electrodes were to the malformation (Pearson's Correlation = 0.525, P < 0.05). In a subset of FL animals (3/9), burst activity also included a spike or spike-wave pattern similar to the SWDs observed in unanesthetized animals. In summary, neonatal FLs increased the hyperexcitable pattern of burst activity induced by anesthesia and disrupted field potential synchrony between cortical and subcortical brain regions near the site of the cortical malformation. Monitoring the altered electrophysiology of burst activity under general anesthesia with multi-dimensional micro-electrode arrays may serve to define distinct neurophysiological biomarkers of epileptogenesis in human brain and improve techniques for surgical resection of epileptogenic malformed brain tissue.

Using modern human cortical bone distribution to test the systemic robusticity hypothesis.

PubMed

Baab, Karen L; Copes, Lynn E; Ward, Devin L; Wells, Nora; Grine, Frederick E

2018-06-01

The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial vault thickness has been measured. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

PubMed Central

Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

2015-01-01

Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune encephalomyelitis (EAE) represents a reliable model of the chronic-progressive variant of MS. fMRI studies in EAE have not been performed extensively up to now. This paper reports fMRI studies in a rat model of MS with somatosensory stimulation of the forepaw. We demonstrated modifications in the recruitment of cortical areas consistent with data from MS patients. To the best of our knowledge, this is the first report of cortical remodeling in a preclinical in vivo model of MS. PMID:26157006

Abnormalities of P300 cortical current density in unmedicated depressed patients revealed by LORETA analysis of event-related potentials.

PubMed

Kawasaki, Toshihiko; Tanaka, Shin; Wang, Jijun; Hokama, Hiroto; Hiramatsu, Kenichi

2004-02-01

The purpose of the present study was to investigate the neural substrates underlying event-related potential (ERP) abnormalities, with respect to the generators of the ERP components in depressed patients. Using an oddball paradigm, ERP from auditory stimuli were recorded from 22 unmedicated patients with current depressive episodes and compared with those from 22 age- and gender-matched normal controls. Cortical current densities of the N100 and P300 components were analyzed using low-resolution electromagnetic tomography (LORETA). Group differences in cortical current density were mapped on a 3-D cortex model. The results revealed that N100 cortical current densities did not differ between the two groups, while P300 cortical current densities were significantly lower in depressed patients over the bilateral temporal lobes, the left frontal region, and the right temporal-parietal area. Furthermore, the cortical area in which the group difference in P300 current density had been identified was remarkably larger over the right than the left hemisphere, thus supporting the hypothesis of right hemisphere dysfunction in depression.

Visual cortical activity reflects faster accumulation of information from cortically blind fields

PubMed Central

Martin, Tim; Das, Anasuya; Huxlin, Krystel R.

2012-01-01

Brain responses (from functional magnetic resonance imaging) and components of information processing were investigated in nine cortically blind observers performing a global direction discrimination task. Three of these subjects had responses in perilesional cortex in response to blind field stimulation, whereas the others did not. We used the EZ-diffusion model of decision making to understand how cortically blind subjects make a perceptual decision on stimuli presented within their blind field. We found that these subjects had slower accumulation of information in their blind fields as compared with their good fields and to intact controls. Within cortically blind subjects, activity in perilesional tissue, V3A and hMT+ was associated with a faster accumulation of information for deciding direction of motion of stimuli presented in the blind field. This result suggests that the rate of information accumulation is a critical factor in the degree of impairment in cortical blindness and varies greatly among affected individuals. Retraining paradigms that seek to restore visual functions might benefit from focusing on increasing the rate of information accumulation. PMID:23169923

2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

PubMed

Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

2016-04-07

Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Combining Microdialysis and Electrophysiology in Cerebral Cortex to Delineate Functional Implications of Acetylcholine Gradients

NASA Astrophysics Data System (ADS)

Nelson, Kari L.

The neuronal network in cerebral cortex is a dynamic system that can undergo changes in collective neural activity as the organism changes its behavior. For example, during sleep and quiet restful awake state, many neurons tend to fire together in synchrony. In contrast, during alert awake states, firing patterns of neurons tend to be more asynchronous, firing more independently. These changes in population-level synchrony are defined as changes in cortical state. Response to sensory input is state-dependent, i.e., change in cortical state can impact the sensory information processing in cortex and introduce trial-to-trial variability in response to the same repeated stimuli. How the brain maintains reliable perception in spite of such trial-to-trial variability is a longstanding important question in neuroscience research. This dissertation is centered on two hypotheses. The first hypothesis is that different parts of the cortex can be in different states simultaneously. The second hypothesis is that inhomogeneity in cortical states can benefit the system by enabling the cortical network to maintain reliable sensory detection. If one part of the system is in a state that is not good for detection, then another part of the system could be in a different state that is good for detection, thus compensating and maintaining good detection for the system as a whole. These hypotheses were tested on anesthetized rats and awake mice. In anesthetized rats, cholinergic neuromodulation via microdialysis (muD) probes was used to induce cortical state changes in the somatosensory barrel cortex. Changes in cortical state and response to whisker stimulus was recorded with a microelectrode array (MEA). In awake mice, nucleus basalis was optogenetically stimulated by inserting an optic fiber in basal forebrain and response to visual stimulus was analyzed. The results demonstrated heterogeneity in cortical state across the spatial extent of cortical network. Changes in sensory response followed this heterogeneity and sensory detection was not reliable at the level of single neurons or small regions of cortex. The greater population of neurons, on the other hand, maintained reliable sensory detection, suggesting that heterogeneous state can be functionally beneficial for the cortical network.

Early development of synchrony in cortical activations in the human.

PubMed

Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

2016-05-13

Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuronal correlates of decisions to speak and act: Spontaneous emergence and dynamic topographies in a computational model of frontal and temporal areas

PubMed Central

Garagnani, Max; Pulvermüller, Friedemann

2013-01-01

The neural mechanisms underlying the spontaneous, stimulus-independent emergence of intentions and decisions to act are poorly understood. Using a neurobiologically realistic model of frontal and temporal areas of the brain, we simulated the learning of perception–action circuits for speech and hand-related actions and subsequently observed their spontaneous behaviour. Noise-driven accumulation of reverberant activity in these circuits leads to their spontaneous ignition and partial-to-full activation, which we interpret, respectively, as model correlates of action intention emergence and action decision-and-execution. Importantly, activity emerged first in higher-association prefrontal and temporal cortices, subsequently spreading to secondary and finally primary sensorimotor model-areas, hence reproducing the dynamics of cortical correlates of voluntary action revealed by readiness-potential and verb-generation experiments. This model for the first time explains the cortical origins and topography of endogenous action decisions, and the natural emergence of functional specialisation in the cortex, as mechanistic consequences of neurobiological principles, anatomical structure and sensorimotor experience. PMID:23489583

Optogenetic stimulation of a meso-scale human cortical model

NASA Astrophysics Data System (ADS)

Selvaraj, Prashanth; Szeri, Andrew; Sleigh, Jamie; Kirsch, Heidi

2015-03-01

Neurological phenomena like sleep and seizures depend not only on the activity of individual neurons, but on the dynamics of neuron populations as well. Meso-scale models of cortical activity provide a means to study neural dynamics at the level of neuron populations. Additionally, they offer a safe and economical way to test the effects and efficacy of stimulation techniques on the dynamics of the cortex. Here, we use a physiologically relevant meso-scale model of the cortex to study the hypersynchronous activity of neuron populations during epileptic seizures. The model consists of a set of stochastic, highly non-linear partial differential equations. Next, we use optogenetic stimulation to control seizures in a hyperexcited cortex, and to induce seizures in a normally functioning cortex. The high spatial and temporal resolution this method offers makes a strong case for the use of optogenetics in treating meso scale cortical disorders such as epileptic seizures. We use bifurcation analysis to investigate the effect of optogenetic stimulation in the meso scale model, and its efficacy in suppressing the non-linear dynamics of seizures.

Functional evolution of new and expanded attention networks in humans

PubMed Central

Patel, Gaurav H.; Yang, Danica; Jamerson, Emery C.; Snyder, Lawrence H.; Corbetta, Maurizio; Ferrera, Vincent P.

2015-01-01

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks. PMID:26170314

Functional evolution of new and expanded attention networks in humans.

PubMed

Patel, Gaurav H; Yang, Danica; Jamerson, Emery C; Snyder, Lawrence H; Corbetta, Maurizio; Ferrera, Vincent P

2015-07-28

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

A comparison of different models of stroke on behaviour and brain morphology.

PubMed

Gonzalez, C L R; Kolb, B

2003-10-01

We compared the effects of three models of permanent ischemia, as well as cortical aspiration, on behaviour and brain morphology. Rats received a stroke either by devascularization or by two different procedures of medial cerebral artery occlusion (MCAO; small vs. large). Animals were trained in a reaching task, forepaw asymmetry, forepaw inhibition, sunflower seed task and tongue extension. Behaviour was assessed 1 week after the lesion and at 2-week intervals for a total of 9 weeks. One week after the surgery all animals were severely impaired on all tasks and although they improved over time they only reached preoperative base lines on tongue extension. Animals with small MCAOs performed better in reaching and sunflower tasks; no other behavioural differences were detected among the groups. Pyramidal cells in forelimb and cingulate areas as well as spiny neurons of the striatum were examined for dendritic branching and spine density using a Golgi-Cox procedure. Each lesion type had a different impact on cell morphology. Overall, different changes (atrophy or hypertrophy) were observed with each kind of lesion and these changes were specific for the region (forelimb, cingulate, striatum) and the condition (intact vs. damaged hemisphere). These results suggest that: (i) different lesions to the motor cortex produce subtle differences in behaviour, and (ii) the method used to induce the lesion produces striking differences in cortical and subcortical plasticity.

Functional Magnetic Resonance Imaging to Assess the Neurobehavioral Impact of Dysphotopsia with Multifocal Intraocular Lenses.

PubMed

Rosa, Andreia M; Miranda, Ângela C; Patrício, Miguel; McAlinden, Colm; Silva, Fátima L; Murta, Joaquim N; Castelo-Branco, Miguel

2017-09-01

To investigate the association between dysphotopsia and neural responses in visual and higher-level cortical regions in patients who recently received multifocal intraocular lens (IOL) implants. Cross-sectional study. Thirty patients 3 to 4 weeks after bilateral cataract surgery with diffractive IOL implantation and 15 age- and gender-matched control subjects. Functional magnetic resonance imaging (fMRI) was performed when participants viewed low-contrast grating stimuli. A light source surrounded the stimuli in half of the runs to induce disability glare. Visual acuity, wavefront analysis, Quality of Vision (QoV) questionnaire, and psychophysical assessment were performed. Cortical activity (blood oxygen level dependent [BOLD] signal) in the primary visual cortex and in higher-level brain areas, including the attention network. When viewing low-contrast stimuli under glare, patients showed significant activation of the effort-related attention network in the early postoperative period, involving the frontal, middle frontal, parietal frontal, and postcentral gyrus (multisubject random-effects general linear model (GLM), P < 0.03). In contrast, controls showed only relative deactivation (due to lower visibility) of visual areas (occipital lobe and middle occipital gyrus, P < 0.03). Patients also had relatively stronger recruitment of cortical areas involved in learning (anterior cingulate gyrus), task planning, and solving (caudate body). Patients reporting greater symptoms induced by dysphotic symptoms showed significantly increased activity in several regions in frontoparietal circuits, as well as cingulate gyrus and caudate nucleus (q < 0.05). We found no correlation between QoV questionnaire scores and optical properties (total and higher order aberration, modulation transfer function, and Strehl ratio). This study shows the association between patient-reported subjective difficulties and fMRI outcomes, independent of optical parameters and psychophysical performance. The increased activity of cortical areas dedicated to attention (frontoparietal circuits), to learning and cognitive control (cingulate), and to task goals (caudate) likely represents the beginning of the neuroadaptation process to multifocal IOLs. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

PKBγ/AKT3 loss-of-function causes learning and memory deficits and deregulation of AKT/mTORC2 signaling: Relevance for schizophrenia

PubMed Central

Floyd, Kirsten; Law, Amanda J.

2017-01-01

Psychiatric genetic studies have identified genome-wide significant loci for schizophrenia. The AKT3/1q44 locus is a principal risk region and gene-network analyses identify AKT3 polymorphisms as a constituent of several neurobiological pathways relevant to psychiatric risk; the neurobiological mechanisms remain unknown. AKT3 shows prenatal enrichment during human neocortical development and recurrent copy number variations involving the 1q43-44 locus are associated with cortical malformations and intellectual disability, implicating an essential role in early brain development. Here, we investigated the role of AKT3 as it relates to aspects of learning and memory and behavioral function, relevant to schizophrenia and cognitive disability, utilizing a novel murine model of Akt3 genetic deficiency. Akt3 heterozygous (Akt3-/+) or null mice (Akt3-/-) were assessed in a comprehensive test battery. Brain biochemical studies were conducted to assess the impact of Akt3 deficiency on cortical Akt/mTOR signaling. Akt3-/+ and Akt3-/- mice exhibited selective deficits of temporal order discrimination and spatial memory, tasks critically dependent on intact prefrontal-hippocampal circuitry, but showed normal prepulse inhibition, fear conditioned learning, memory for novel objects and social function. Akt3 loss-of-function, reduced brain size and dramatically impaired cortical Akt Ser473 activation in an allele-dose dependent manner. Such changes were observed in the absence of altered Akt1 or Akt2 protein expression. Concomitant reduction of the mTORC2 complex proteins, Rictor and Sin1 identifies a potential mechanism. Our findings provide novel insight into the neurodevelopmental role of Akt3, identify a non-redundant role for Akt3 in the development of prefrontal cortical-mediated cognitive function and show that Akt3 is potentially the dominant regulator of AKT/mTOR signaling in brain. PMID:28467426

Control of Chaos: New Perspectives in Experimental and Theoretical Science. International Journal of Bifurcation and Chaos in Applied Sciences and Engineering. Theme Issue. Part 2, Volume 8, Number 9, September 1998.

DTIC Science & Technology

1998-09-01

discharges in the Onchidium pacemaker neu- "Episodic multiregional cortical coherence at multiple ron," J. Theor. Biol. 156, 269-291. frequencies during...with delay: A model of synchronization of Sepulchre, J. A. & Babloyantz, A. [1993] "Controlling cortical tissue," Neural Comput. 6, 1141-1154...generating circuit of different 363, 411 417. networks," Nature 351, 60-63. Singer, W. [1993] "Synchronization of cortical activity Mpitsos, G. J., Burton, R

Modeling bicortical screws under a cantilever bending load.

PubMed

James, Thomas P; Andrade, Brendan A

2013-12-01

Cyclic loading of surgical plating constructs can precipitate bone screw failure. As the frictional contact between the plate and the bone is lost, cantilever bending loads are transferred from the plate to the head of the screw, which over time causes fatigue fracture from cyclic bending. In this research, analytical models using beam mechanics theory were developed to describe the elastic deflection of a bicortical screw under a statically applied load. Four analytical models were developed to simulate the various restraint conditions applicable to bicortical support of the screw. In three of the models, the cortical bone near the tip of the screw was simulated by classical beam constraints (1) simply supported, (2) cantilever, and (3) split distributed load. In the final analytical model, the cortices were treated as an elastic foundation, whereby the response of the constraint was proportional to screw deflection. To test the predictive ability of the new analytical models, 3.5 mm cortical bone screws were tested in a synthetic bone substitute. A novel instrument was developed to measure the bending deflection of screws under radial loads (225 N, 445 N, and 670 N) applied by a surrogate surgical plate at the head of the screw. Of the four cases considered, the analytical model utilizing an elastic foundation most accurately predicted deflection at the screw head, with an average difference of 19% between the measured and predicted results. Determination of the bending moments from the elastic foundation model revealed that a maximum moment of 2.3 N m occurred near the middle of the cortical wall closest to the plate. The location of the maximum bending moment along the screw axis was consistent with the fracture location commonly observed in clinical practice.

Spatial and Feature-Based Attention in a Layered Cortical Microcircuit Model

PubMed Central

Wagatsuma, Nobuhiko; Potjans, Tobias C.; Diesmann, Markus; Sakai, Ko; Fukai, Tomoki

2013-01-01

Directing attention to the spatial location or the distinguishing feature of a visual object modulates neuronal responses in the visual cortex and the stimulus discriminability of subjects. However, the spatial and feature-based modes of attention differently influence visual processing by changing the tuning properties of neurons. Intriguingly, neurons' tuning curves are modulated similarly across different visual areas under both these modes of attention. Here, we explored the mechanism underlying the effects of these two modes of visual attention on the orientation selectivity of visual cortical neurons. To do this, we developed a layered microcircuit model. This model describes multiple orientation-specific microcircuits sharing their receptive fields and consisting of layers 2/3, 4, 5, and 6. These microcircuits represent a functional grouping of cortical neurons and mutually interact via lateral inhibition and excitatory connections between groups with similar selectivity. The individual microcircuits receive bottom-up visual stimuli and top-down attention in different layers. A crucial assumption of the model is that feature-based attention activates orientation-specific microcircuits for the relevant feature selectively, whereas spatial attention activates all microcircuits homogeneously, irrespective of their orientation selectivity. Consequently, our model simultaneously accounts for the multiplicative scaling of neuronal responses in spatial attention and the additive modulations of orientation tuning curves in feature-based attention, which have been observed widely in various visual cortical areas. Simulations of the model predict contrasting differences between excitatory and inhibitory neurons in the two modes of attentional modulations. Furthermore, the model replicates the modulation of the psychophysical discriminability of visual stimuli in the presence of external noise. Our layered model with a biologically suggested laminar structure describes the basic circuit mechanism underlying the attention-mode specific modulations of neuronal responses and visual perception. PMID:24324628

Sleeping of a Complex Brain Networks with Hierarchical Organization

NASA Astrophysics Data System (ADS)

Zhang, Ying-Yue; Yang, Qiu-Ying; Chen, Tian-Lun

2009-01-01

The dynamical behavior in the cortical brain network of macaque is studied by modeling each cortical area with a subnetwork of interacting excitable neurons. We characterize the system by studying how to perform the transition, which is now topology-dependent, from the active state to that with no activity. This could be a naive model for the wakening and sleeping of a brain-like system, i.e., a multi-component system with two different dynamical behavior.

Impaired Cognition in Rats with Cortical Dysplasia: Additional Impact of Early-Life Seizures

ERIC Educational Resources Information Center

Lucas, Marcella M.; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L.; Scott, Rod C.

2011-01-01

One of the most common and serious co-morbidities in patients with epilepsy is cognitive impairment. While early-life seizures are considered a major cause for cognitive impairment, it is not known whether it is the seizures, the underlying neurological substrate or a combination that has the largest impact on eventual learning and memory. Teasing…

Time-dependent in-vivo effects of interleukin-2 on neurotransmitters in various cortices: relationships with depressive-related and anxiety-like behaviour.

PubMed

Karrenbauer, B D; Müller, C P; Ho, Y J; Spanagel, R; Huston, J P; Schwarting, R K W; Pawlak, C R

2011-08-15

We investigated the impact of systemically injected IL-2 (2.5 μg/kg, i.p.) on serotonergic and dopaminergic neurotransmission in various cortical areas by in-vivo microdialysis. IL-2 lastingly reduced extracellular 5-HT levels in the medial prefrontal (-75%), occipital (-70%), and temporal cortices (-45%), whereas dopamine was only moderately reduced in the medial prefrontal cortex. Based on the serotonergic time profile, we conducted further experiments to test for acute and delayed (2 h post injection) depressive-related effects of systemic IL-2 (0-5.0 μg/kg) in a forced swim test and delayed effects on anxiety-like behaviour in the elevated plus-maze. IL-2 had dose-dependent effects on depressive-related behaviour after delayed but not acute testing, but no effects on anxiety-like behaviour. Copyright © 2011 Elsevier B.V. All rights reserved.

Representation of memories in the cortical-hippocampal system: Results from the application of population similarity analyses

PubMed Central

McKenzie, Sam; Keene, Chris; Farovik, Anja; Blandon, John; Place, Ryan; Komorowski, Robert; Eichenbaum, Howard

2016-01-01

Here we consider the value of neural population analysis as an approach to understanding how information is represented in the hippocampus and cortical areas and how these areas might interact as a brain system to support memory. We argue that models based on sparse coding of different individual features by single neurons in these areas (e.g., place cells, grid cells) are inadequate to capture the complexity of experience represented within this system. By contrast, population analyses of neurons with denser coding and mixed selectivity reveal new and important insights into the organization of memories. Furthermore, comparisons of the organization of information in interconnected areas suggest a model of hippocampal-cortical interactions that mediates the fundamental features of memory. PMID:26748022

Amphetamine Dependence and Co-Morbid Alcohol Abuse: Associations to Brain Cortical Thickness

PubMed Central

2010-01-01

Background Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls. While all subjects were recruited to be free of alcohol dependence, structured clinical interviews revealed significant patterns of alcohol use in the patients. Structural magnetic resonance brain images were obtained from the subjects using a 1.5 Tesla GE Signa machine. Brain cortical thickness was measured with submillimeter precision at multiple finely spaced cortical locations using semi-automated post-processing (FreeSurfer). Contrast analysis of a general linear model was used to test for differences between the two groups at each cortical location. In addition to contrasting patients with controls, a number of analyses sought to identify possible confounding effects from alcohol. Results No significant cortical thickness differences were observed between the full patient group and controls, nor between non-drinking patients and controls. Patients with a history of co-morbid heavy alcohol use (n = 29) showed reductions in the superior-frontal right hemisphere and pre-central left hemisphere when compared to healthy controls (n = 40). Conclusions Amphetamine usage was associated with reduced cortical thickness only in patients co-morbid for heavy alcohol use. Since cortical thickness is but one measure of brain structure and does not capture brain function, further studies of brain structure and function in amphetamine dependence are warranted. PMID:20487539

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems.

PubMed

Schmahmann, Jeremy D; Pandya, Deepak N

2008-09-01

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions.

Using a Large-scale Neural Model of Cortical Object Processing to Investigate the Neural Substrate for Managing Multiple Items in Short-term Memory.

PubMed

Liu, Qin; Ulloa, Antonio; Horwitz, Barry

2017-11-01

Many cognitive and computational models have been proposed to help understand working memory. In this article, we present a simulation study of cortical processing of visual objects during several working memory tasks using an extended version of a previously constructed large-scale neural model [Tagamets, M. A., & Horwitz, B. Integrating electrophysiological and anatomical experimental data to create a large-scale model that simulates a delayed match-to-sample human brain imaging study. Cerebral Cortex, 8, 310-320, 1998]. The original model consisted of arrays of Wilson-Cowan type of neuronal populations representing primary and secondary visual cortices, inferotemporal (IT) cortex, and pFC. We added a module representing entorhinal cortex, which functions as a gating module. We successfully implemented multiple working memory tasks using the same model and produced neuronal patterns in visual cortex, IT cortex, and pFC that match experimental findings. These working memory tasks can include distractor stimuli or can require that multiple items be retained in mind during a delay period (Sternberg's task). Besides electrophysiology data and behavioral data, we also generated fMRI BOLD time series from our simulation. Our results support the involvement of IT cortex in working memory maintenance and suggest the cortical architecture underlying the neural mechanisms mediating particular working memory tasks. Furthermore, we noticed that, during simulations of memorizing a list of objects, the first and last items in the sequence were recalled best, which may implicate the neural mechanism behind this important psychological effect (i.e., the primacy and recency effect).

A laminar cortical model of stereopsis and 3D surface perception: closure and da Vinci stereopsis.

PubMed

Cao, Yongqiang; Grossberg, Stephen

2005-01-01

A laminar cortical model of stereopsis and 3D surface perception is developed and simulated. The model describes how monocular and binocular oriented filtering interact with later stages of 3D boundary formation and surface filling-in in the LGN and cortical areas V1, V2, and V4. It proposes how interactions between layers 4, 3B, and 2/3 in V1 and V2 contribute to stereopsis, and how binocular and monocular information combine to form 3D boundary and surface representations. The model includes two main new developments: (1) It clarifies how surface-to-boundary feedback from V2 thin stripes to pale stripes helps to explain data about stereopsis. This feedback has previously been used to explain data about 3D figure-ground perception. (2) It proposes that the binocular false match problem is subsumed under the Gestalt grouping problem. In particular, the disparity filter, which helps to solve the correspondence problem by eliminating false matches, is realized using inhibitory interneurons as part of the perceptual grouping process by horizontal connections in layer 2/3 of cortical area V2. The enhanced model explains all the psychophysical data previously simulated by Grossberg and Howe (2003), such as contrast variations of dichoptic masking and the correspondence problem, the effect of interocular contrast differences on stereoacuity, Panum's limiting case, the Venetian blind illusion, stereopsis with polarity-reversed stereograms, and da Vinci stereopsis. It also explains psychophysical data about perceptual closure and variations of da Vinci stereopsis that previous models cannot yet explain.

The independent and combined effects of respiratory events and cortical arousals on the autonomic nervous system across sleep stages.

PubMed

Liang, Jiuxing; Zhang, Xiangmin; He, Xiaomin; Ling, Li; Zeng, Chunyao; Luo, Yuxi

2018-05-10

During sleep, respiratory events readily modulate the autonomic nervous system (ANS). Whether such modulation is caused by the respiratory event itself or the cortical arousal that follows and whether these influences differ across sleep stages are not clear. Thus, we aimed to study the independent and combined effects of respiratory events and cortical arousals on the ANS across sleep stages. We recruited 22 male patients with sleep apnea-hypopnea syndrome (SAHS) and analyzed the differences in the indices of heart rate variability among normal respiration (NR), pathological respiratory events without cortical arousals (PR), cortical arousals without respiratory events (CA), and the coexistence of PR and CA (PR&CA), by sleep stage. Compared with NR, four indices of variation of the beat-to-beat interval demonstrated consistent results in all sleep stages generally: PR&CA showed the biggest difference, followed by PR and followed by CA, which exhibited the least difference. Thus, the respiratory event itself affects ANS modulation, but the cortical arousal that follows generally enhances this effect. For low-frequency power and low-frequency/high-frequency power ratio (LF/HF), PR&CA had the greatest impact. For mean beat-to-beat interval and high-frequency power (HFP), the influence of PR, CA, and PR&CA depended on sleep depth. However, PR&CA had a different influence on HFP in N2 stage vs. REM stage. Sleep stage also has an effect on this neuromodulatory mechanism. These findings may help clarify the relationship between SAHS and cardiovascular disease.

Beyond traditional approaches to understanding the functional role of neuromodulators in sensory cortices

PubMed Central

Edeline, Jean-Marc

2012-01-01

Over the last two decades, a vast literature has described the influence of neuromodulatory systems on the responses of sensory cortex neurons (review in Gu, 2002; Edeline, 2003; Weinberger, 2003; Metherate, 2004, 2011). At the single cell level, facilitation of evoked responses, increases in signal-to-noise ratio, and improved functional properties of sensory cortex neurons have been reported in the visual, auditory, and somatosensory modality. At the map level, massive cortical reorganizations have been described when repeated activation of a neuromodulatory system are associated with a particular sensory stimulus. In reviewing our knowledge concerning the way the noradrenergic and cholinergic system control sensory cortices, I will point out that the differences between the protocols used to reveal these effects most likely reflect different assumptions concerning the role of the neuromodulators. More importantly, a gap still exists between the descriptions of neuromodulatory effects and the concepts that are currently applied to decipher the neural code operating in sensory cortices. Key examples that bring this gap into focus are the concept of cell assemblies and the role played by the spike timing precision (i.e., by the temporal organization of spike trains at the millisecond time-scale) which are now recognized as essential in sensory physiology but are rarely considered in experiments describing the role of neuromodulators in sensory cortices. Thus, I will suggest that several lines of research, particularly in the field of computational neurosciences, should help us to go beyond traditional approaches and, ultimately, to understand how neuromodulators impact on the cortical mechanisms underlying our perceptual abilities. PMID:22866031

Decursinol and decursin protect primary cultured rat cortical cells from glutamate-induced neurotoxicity.

PubMed

Kang, So Young; Kim, Young Choong

2007-06-01

We previously reported six neuroprotective decursinol derivatives, coumarins from Angelica gigas (Umbelliferae) roots. To elucidate the action patterns of decursinol derivatives, we investigated the neuroprotective effects of decursinol and decursin, which showed highly significant activity and were major constituents of A. gigas, using primary cultures of rat cortical cells in-vitro. At concentrations of 0.1-10.0 microM, both decursinol and decursin exerted a significant neuroprotective activity pretreatment and throughout treatment. In addition, decursin had a neuroprotective impact in the post-treatment paradigm implying that decursin might possess different action mechanisms from that of decursinol in the protection of neurons against glutamate injury. Both decursinol and decursin effectively reduced the glutamate-induced increased intracellular calcium ([Ca(2+)](i)) in cortical cells, suggesting that these two coumarins may exert neuroprotection by reducing calcium influx by overactivation of glutamate receptors. This suggestion was supported by the result that decursinol and decursin protected neurons against kainic acid (KA)-induced neurotoxicity better than against that induced by N-methyl-D-aspartate (NMDA). Moreover, both decursinol and decursin significantly prevented glutamate-induced decreases in glutathione, a cellular antioxidant, and glutathione peroxidase activity. In addition, both compounds efficiently reduced the overproduction of cellular peroxide in glutamate-injured cortical cells. These results suggested that both decursinol and decursin protected primary cultured rat cortical cells against glutamate-induced oxidative stress by both reducing calcium influx and acting on the cellular antioxidative defence system. Moreover, decursin is considered to probably have a different action mechanism from that of decursinol in protecting cortical cells against glutamate injury.

Eye closure in darkness animates olfactory and gustatory cortical areas.

PubMed

Wiesmann, M; Kopietz, R; Albrecht, J; Linn, J; Reime, U; Kara, E; Pollatos, O; Sakar, V; Anzinger, A; Fesl, G; Brückmann, H; Kobal, G; Stephan, T

2006-08-01

In two previous fMRI studies, it was reported that eyes-open and eyes-closed conditions in darkness had differential effects on brain activity, and typical patterns of cortical activity were identified. Without external stimulation, ocular motor and attentional systems were activated when the eyes were open. On the contrary, the visual, somatosensory, vestibular, and auditory systems were activated when the eyes were closed. In this study, we investigated whether cortical areas related to the olfactory and gustatory system are also animated by eye closure without any other external stimulation. In a first fMRI experiment (n = 22), we identified cortical areas including the piriform cortex activated by olfactory stimulation. In a second experiment (n = 12) subjects lying in darkness in the MRI scanner alternately opened and closed their eyes. In accordance to previous studies, we found activation clusters bilaterally in visual, somatosensory, vestibular and auditory cortical areas for the contrast eyes-closed vs. eyes-open. In addition, we were able to show that cortical areas related to the olfactory and gustatory system were also animated by eye closure. These results support the hypothesis that there are two different states of mental activity: with the eyes closed, an "interoceptive" state characterized by imagination and multisensory activity and with the eyes open, an "exteroceptive" state characterized by attention and ocular motor activity. Our study also suggests that the chosen baseline condition may have a considerable impact on activation patterns and on the interpretation of brain activation studies. This needs to be considered for studies of the olfactory and gustatory system.

Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast Cancer: The Impact of Cortical Thickness

PubMed Central

Stachs, A.; Thi, A. Tra-Ha; Dieterich, M.; Stubert, J.; Hartmann, S.; Glass, Ä.; Reimer, T.; Gerber, B.

2015-01-01

Purpose: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal metastasis in patients with early-stage breast cancer and to identify AUS features with high predictive power. Materials and Methods: Prospective single-center preliminary study in 105 patients with a primary diagnosis of breast cancer and clinically negative axilla. AUS was performed using a 12 MHz linear-array transducer before ultrasound-guided needle biopsy. Nodal characteristics (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness, hyperechoic hilum) were correlated with histopathological nodal status after SLNB or axillary lymph node dissection (ALND). Results: Nodal metastases were present in 42/105 patients (40.0%). Univariate analyses showed that absence of hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical thickness>3 mm were associated with lymph node metastasis. Multivariate logistic regression analysis revealed cortical thickness > 3 mm as an independent predictive parameter for nodal involvement. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6, 77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the criterion for AUS positivity. Axillary tumor volume was low in patients with pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic lymph nodes. Conclusion: Cortical thickness>3 mm is a reliable predictor of nodal metastatic involvement. Negative AUS does not exclude lymph node metastases, but extensive axillary tumor volume is rare. PMID:27689144

In vivo gene delivery to the postnatal ferret cerebral cortex by DNA electroporation.

PubMed

Borrell, Víctor

2010-02-15

Ferrets have been extensively used to unravel the neural mechanisms of coding and processing of visual information, and also to identify the developmental mechanisms underlying the emergence of such a complex and fine-tuned neural system. In recent years numerous tools have been generated that allow studying neural systems with unprecedented power. Unfortunately, because many of these tools are genetically encoded, they are having a limited impact on research involving "non-genetic" species, like ferret, cat and monkey. Here I show how in vivo electroporation can be performed in postnatal ferret kits to deliver genetic constructs to pyramidal neurons of the cerebral cortex. Electroporation of GFP- and DsRed-encoding plasmids results in labeling of cortical progenitors first, then migrating neurons, and finally differentiating neurons and their processes. This technique also allows for the genetic manipulation of cortical development in the ferret, as illustrated by electroporation of a dominant-negative form of Cdk5. In the mature brain of electroporated animals, expression of reporter genes reveals the detailed morphological traits of cortical pyramids, including their axonal and dendritic arborization, and dendritic spines. I also show that postnatal electroporation can be used for the transfection of a massive cortical territory, or it can be specifically directed to a subset of cortical areas, and even only to a few scattered pyramids along the cortical mantle. In vivo electroporation of postnatal ferrets is therefore an effective, rapid, simple and highly versatile method for delivering genetic constructs to this animal, optimal for both developmental studies and adult anatomical/functional studies. Copyright 2009 Elsevier B.V. All rights reserved.

Role of subdural electrocorticography in prediction of long-term seizure outcome in epilepsy surgery

PubMed Central

Juhász, Csaba; Shah, Aashit; Sood, Sandeep; Chugani, Harry T.

2009-01-01

Since prediction of long-term seizure outcome using preoperative diagnostic modalities remains suboptimal in epilepsy surgery, we evaluated whether interictal spike frequency measures obtained from extraoperative subdural electrocorticography (ECoG) recording could predict long-term seizure outcome. This study included 61 young patients (age 0.4–23.0 years), who underwent extraoperative ECoG recording prior to cortical resection for alleviation of uncontrolled focal seizures. Patient age, frequency of preoperative seizures, neuroimaging findings, ictal and interictal ECoG measures were preoperatively obtained. The seizure outcome was prospectively measured [follow-up period: 2.5–6.4 years (mean 4.6 years)]. Univariate and multivariate logistic regression analyses determined how well preoperative demographic and diagnostic measures predicted long-term seizure outcome. Following the initial cortical resection, Engel Class I, II, III and IV outcomes were noted in 35, 6, 12 and 7 patients, respectively. One child died due to disseminated intravascular coagulation associated with pseudomonas sepsis 2 days after surgery. Univariate regression analyses revealed that incomplete removal of seizure onset zone, higher interictal spike-frequency in the preserved cortex and incomplete removal of cortical abnormalities on neuroimaging were associated with a greater risk of failing to obtain Class I outcome. Multivariate logistic regression analysis revealed that incomplete removal of seizure onset zone was the only independent predictor of failure to obtain Class I outcome. The goodness of regression model fit and the predictive ability of regression model were greatest in the full regression model incorporating both ictal and interictal measures [R2 0.44; Area under the receiver operating characteristic (ROC) curve: 0.81], slightly smaller in the reduced model incorporating ictal but not interictal measures (R2 0.40; Area under the ROC curve: 0.79) and slightly smaller again in the reduced model incorporating interictal but not ictal measures (R2 0.27; Area under the ROC curve: 0.77). Seizure onset zone and interictal spike frequency measures on subdural ECoG recording may both be useful in predicting the long-term seizure outcome of epilepsy surgery. Yet, the additive clinical impact of interictal spike frequency measures to predict long-term surgical outcome may be modest in the presence of ictal ECoG and neuroimaging data. PMID:19286694

Gel-Based Hippocampal Proteomic Analysis 2 Weeks following Traumatic Brain Injury to Immature Rats Using Controlled Cortical Impact

PubMed Central

Kochanek, Ashley R.; Kline, Anthony E.; Gao, Wei-Min; Chadha, Mandeep; Lai, Yichen; Clark, Robert S.B.; Dixon, C. Edward; Jenkins, Larry W.

2009-01-01

Traumatic brain injury (TBI) to postnatal day 17 rats has been shown to produce acute changes in hippocampal global protein levels and spatial learning and memory deficits. The purpose of the present study was to analyze global hippocampal protein changes 2 weeks after a moderate ipsilateral controlled cortical impact in postnatal day 17 rats using 2-dimensional difference gel electrophoresis and mass spectrometry. Paired sham and ipsilateral injured hippocampal lysates were independently labeled with different fluorescent cyanine dyes and coseparated within the same immobilized pH gradient strips and slab gel based on isoelectric point and molecular mass. Significant changes in key proteins involved in glial and neuronal stress, oxidative metabolism, calcium uptake and neurotransmitter function were found 2 weeks after injury, and their potential roles in hippocampal plasticity and cognitive dysfunction were discussed. PMID:16943664

Parametric convergence sensitivity and validation of a finite element model of the human lumbar spine.

PubMed

Ayturk, Ugur M; Puttlitz, Christian M

2011-08-01

The primary objective of this study was to generate a finite element model of the human lumbar spine (L1-L5), verify mesh convergence for each tissue constituent and perform an extensive validation using both kinematic/kinetic and stress/strain data. Mesh refinement was accomplished via convergence of strain energy density (SED) predictions for each spinal tissue. The converged model was validated based on range of motion, intradiscal pressure, facet force transmission, anterolateral cortical bone strain and anterior longitudinal ligament deformation predictions. Changes in mesh resolution had the biggest impact on SED predictions under axial rotation loading. Nonlinearity of the moment-rotation curves was accurately simulated and the model predictions on the aforementioned parameters were in good agreement with experimental data. The validated and converged model will be utilised to study the effects of degeneration on the lumbar spine biomechanics, as well as to investigate the mechanical underpinning of the contemporary treatment strategies.

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

STIM1L traps and gates Orai1 channels without remodeling the cortical ER

PubMed Central

Saüc, Sophie; Bulla, Monica; Nunes, Paula; Orci, Lelio; Marchetti, Anna; Antigny, Fabrice; Bernheim, Laurent; Cosson, Pierre; Frieden, Maud; Demaurex, Nicolas

2015-01-01

STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca2+ entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca2+ influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca2+ imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1−/−/Stim2−/− fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca2+ elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides. PMID:25736291

Evidence for the adverse effect of starvation on bone quality: a review of the literature.

PubMed

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.

PubMed

Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt; Férézou, Isabelle; Pezet, Sophie

2016-01-01

Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.

Sex differences in thickness, and folding developments throughout the cortex.

PubMed

Mutlu, A Kadir; Schneider, Maude; Debbané, Martin; Badoud, Deborah; Eliez, Stephan; Schaer, Marie

2013-11-15

While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30 years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females. Copyright © 2013 Elsevier Inc. All rights reserved.

Multi-Scale Computational Models for Electrical Brain Stimulation

PubMed Central

Seo, Hyeon; Jun, Sung C.

2017-01-01

Electrical brain stimulation (EBS) is an appealing method to treat neurological disorders. To achieve optimal stimulation effects and a better understanding of the underlying brain mechanisms, neuroscientists have proposed computational modeling studies for a decade. Recently, multi-scale models that combine a volume conductor head model and multi-compartmental models of cortical neurons have been developed to predict stimulation effects on the macroscopic and microscopic levels more precisely. As the need for better computational models continues to increase, we overview here recent multi-scale modeling studies; we focused on approaches that coupled a simplified or high-resolution volume conductor head model and multi-compartmental models of cortical neurons, and constructed realistic fiber models using diffusion tensor imaging (DTI). Further implications for achieving better precision in estimating cellular responses are discussed. PMID:29123476

Cortical Bases of Elementary Deductive Reasoning: Inference, Memory, and Metadeduction

ERIC Educational Resources Information Center

Reverberi, Carlo; Shallice, Tim; D'Agostini, Serena; Skrap, Miran; Bonatti, Luca L.

2009-01-01

Elementary deduction is the ability of unreflectively drawing conclusions from explicit or implicit premises, on the basis of their logical forms. This ability is involved in many aspects of human cognition and interactions. To date, limited evidence exists on its cortical bases. We propose a model of elementary deduction in which logical…

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

PubMed Central

Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Cortical thickness differences between bipolar depression and major depressive disorder.

PubMed

Lan, Martin J; Chhetry, Binod Thapa; Oquendo, Maria A; Sublette, M Elizabeth; Sullivan, Gregory; Mann, J John; Parsey, Ramin V

2014-06-01

Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers. Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups. Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within the frontal and parietal lobes, and the posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6 to 9.6% (cluster-wise p-values from 1.0 e-4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5 to 8.2% (cluster-wise p-values from 1.0 e-4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group. Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dynamic patterns of cortical expansion during folding of the preterm human brain.

PubMed

Garcia, Kara E; Robinson, Emma C; Alexopoulos, Dimitrios; Dierker, Donna L; Glasser, Matthew F; Coalson, Timothy S; Ortinau, Cynthia M; Rueckert, Daniel; Taber, Larry A; Van Essen, David C; Rogers, Cynthia E; Smyser, Christopher D; Bayly, Philip V

2018-03-20

During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggest that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a unique method to estimate local growth from sequential cortical reconstructions. Using anatomically constrained multimodal surface matching (aMSM), we obtain accurate, physically guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned two to four times during the period of rapid cortical expansion (28-38 wk postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with the emergence of new folds. Furthermore, these growth patterns shift over the course of development, with noninjured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully automated surface analysis, based on tools freely available to the brain-mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.

Dopaminergic Modulation of Cortical Plasticity in Alzheimer's Disease Patients

PubMed Central

Koch, Giacomo; Di Lorenzo, Francesco; Bonnì, Sonia; Giacobbe, Viola; Bozzali, Marco; Caltagirone, Carlo; Martorana, Alessandro

2014-01-01

In animal models of Alzheimer's disease (AD), mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are impaired. In AD patients, LTP-like cortical plasticity is abolished, whereas LTD seems to be preserved. Dopaminergic transmission has been hypothesized as a new player in ruling mechanisms of cortical plasticity in AD. We aimed at investigating whether administration of the dopamine agonist rotigotine (RTG) could modulate cortical plasticity in AD patients, as measured by theta burst stimulation (TBS) protocols of repetitive transcranial stimulation applied over the primary motor cortex. Thirty mild AD patients were tested in three different groups before and after 4 weeks of treatment with RTG, rivastigmine (RVT), or placebo (PLC). Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS protocols. Short-latency afferent inhibition (SAI) protocol was performed to indirectly assess central cholinergic activity. A group of age-matched healthy controls was recruited for baseline comparisons. Results showed that at baseline, AD patients were characterized by impaired LTP-like cortical plasticity, as assessed by iTBS. These reduced levels of LTP-like cortical plasticity were increased and normalized after RTG administration. No effect was induced by RVT or PLC on LTP. LTD-like cortical plasticity was not modulated in any condition. Cholinergic activity was increased by both RTG and RVT. Our findings reveal that dopamine agonists may restore the altered mechanisms of LTP-like cortical plasticity in AD patients, thus providing novel implications for therapies based on dopaminergic stimulation. PMID:24859851

Linear summation of outputs in a balanced network model of motor cortex

PubMed Central

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis. PMID:26097452

Modeling Early Cortical Serotonergic Deficits in Autism

PubMed Central

Boylan, Carolyn B.; Blue, Mary E.; Hohmann, Christine F.

2007-01-01

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas. PMID:17034875

Modeling early cortical serotonergic deficits in autism.

PubMed

Boylan, Carolyn B; Blue, Mary E; Hohmann, Christine F

2007-01-10

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macro-scopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria

PubMed Central

Jin, Xiaoming; Jiang, Kewen

2014-01-01

A variety of major developmental cortical malformations are closely associated with clinically intractable epilepsy. Pathophysiological aspects of one such disorder, human polymicrogyria, can be modeled by making neocortical freeze lesions (FL) in neonatal rodents, resulting in the formation of microgyri. Previous studies showed enhanced excitatory and inhibitory synaptic transmission and connectivity in cortical layer V pyramidal neurons in the paramicrogyral cortex. In young adult transgenic mice that express green fluorescent protein (GFP) specifically in parvalbumin positive fast-spiking (FS) interneurons, we used laser scanning photostimulation (LSPS) of caged glutamate to map excitatory and inhibitory synaptic connectivity onto FS interneurons in layer V of paramicrogyral cortex in control and FL groups. The proportion of uncaging sites from which excitatory postsynaptic currents (EPSCs) could be evoked (hotspot ratio) increased slightly but significantly in FS cells of the FL vs. control cortex, while the mean amplitude of LSPS-evoked EPSCs at hotspots did not change. In contrast, the hotspot ratio of inhibitory postsynaptic currents (IPSCs) was significantly decreased in FS neurons of the FL cortex. These alterations in synaptic inputs onto FS interneurons may result in an enhanced inhibitory output. We conclude that alterations in synaptic connectivity to cortical layer V FS interneurons do not contribute to hyperexcitability of the FL model. Instead, the enhanced inhibitory output from these neurons may partially offset an earlier demonstrated increase in synaptic excitation of pyramidal cells and thereby maintain a relative balance between excitation and inhibition in the affected cortical circuitry. PMID:24990567

Transferring and generalizing deep-learning-based neural encoding models across subjects.

PubMed

Wen, Haiguang; Shi, Junxing; Chen, Wei; Liu, Zhongming

2018-08-01

Recent studies have shown the value of using deep learning models for mapping and characterizing how the brain represents and organizes information for natural vision. However, modeling the relationship between deep learning models and the brain (or encoding models), requires measuring cortical responses to large and diverse sets of natural visual stimuli from single subjects. This requirement limits prior studies to few subjects, making it difficult to generalize findings across subjects or for a population. In this study, we developed new methods to transfer and generalize encoding models across subjects. To train encoding models specific to a target subject, the models trained for other subjects were used as the prior models and were refined efficiently using Bayesian inference with a limited amount of data from the target subject. To train encoding models for a population, the models were progressively trained and updated with incremental data from different subjects. For the proof of principle, we applied these methods to functional magnetic resonance imaging (fMRI) data from three subjects watching tens of hours of naturalistic videos, while a deep residual neural network driven by image recognition was used to model visual cortical processing. Results demonstrate that the methods developed herein provide an efficient and effective strategy to establish both subject-specific and population-wide predictive models of cortical representations of high-dimensional and hierarchical visual features. Copyright © 2018 Elsevier Inc. All rights reserved.

Distributed Bandpass Filtering and Signal Demodulation in Cortical Network Models

NASA Astrophysics Data System (ADS)

McDonnell, Mark D.

Experimental recordings of cortical activity often exhibit narrowband oscillations, at various center frequencies ranging in the order of 1-200 Hz. Many neuronal mechanisms are known to give rise to oscillations, but here we focus on a population effect known as sparsely synchronised oscillations. In this effect, individual neurons in a cortical network fire irregularly at slow average spike rates (1-10 Hz), but the population spike rate oscillates at gamma frequencies (greater than 40 Hz) in response to spike bombardment from the thalamus. These cortical networks form recurrent (feedback) synapses. Here we describe a model of sparsely synchronized population oscillations using the language of feedback control engineering, where we treat spiking as noisy feedback. We show, using a biologically realistic model of synaptic current that includes a delayed response to inputs, that the collective behavior of the neurons in the network is like a distributed bandpass filter acting on the network inputs. Consequently, the population response has the character of narrowband random noise, and therefore has an envelope and instantaneous frequency with lowpass characteristics. Given that there exist biologically plausible neuronal mechanisms for demodulating the envelope and instantaneous frequency, we suggest there is potential for similar effects to be exploited in nanoscale electronics implementations of engineered communications receivers.

Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder.

PubMed

Zhu, Shanshan; Cordner, Zachary A; Xiong, Jiali; Chiu, Chi-Tso; Artola, Arabiye; Zuo, Yanning; Nelson, Andrew D; Kim, Tae-Yeon; Zaika, Natalya; Woolums, Brian M; Hess, Evan J; Wang, Xiaofang; Chuang, De-Maw; Pletnikov, Mikhail M; Jenkins, Paul M; Tamashiro, Kellie L; Ross, Christopher A

2017-09-26

Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition. Expression of c-fos was increased in cortical pyramidal neurons, consistent with increased neuronal activity due to disinhibition. The mice showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by antimania drugs lithium and valproate. Repeated social defeat stress resulted in repeated episodes of dramatic behavioral changes from hyperactivity to "depression-like" behavior, suggestive of some aspects of human bipolar disorder. Overall, we suggest that this Ank-G cKO mouse model recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. The model may be useful for studying disease pathophysiology and for developing experimental therapeutics.

The Upper Limit of Cerebral Blood Flow Autoregulation Is Decreased with Elevations in Intracranial Pressure.

PubMed

Pesek, Matthew; Kibler, Kathleen; Easley, R Blaine; Mytar, Jennifer; Rhee, Christopher; Andropolous, Dean; Brady, Ken

2016-01-01

The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized. We sought to delineate the ULA in a neonatal swine model. Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF; n = 10), controlled cortical impact (CCI; n = 10), or impact + infusion (CCI + INF; n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flux recordings during arterial hypertension until lethality. An increase in red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression and static rates of autoregulation (SRoRs) were determined above and below this inflection. When identified, the ULA (median [interquartile range]) was as follows: sham group: 102 mmHg (97-109), INF group: 75 mmHg (52-84), CCI group: 81 mmHg (69-101), and CCI + INF group: 61 mmHg (52-57; p = 0.01). Both groups with interventricular infusion had significantly lower ULA compared with the sham group. Neonatal piglets without intracranial pathological conditions tolerated acute hypertension, with minimal perturbation of cerebral blood flow. Piglets with acutely elevated intracranial pressure, with or without trauma, demonstrated loss of autoregulation when subjected to arterial hypertension.

Influence of Manual Screwdriver Design in Combination With and Without Predrilling on Insertion Torque of Orthodontic Mini-Implants.

PubMed

Katalinic, Andrej; Trinajstic Zrinski, Magda; Roksandic Vrancic, Zlatka; Spalj, Stjepan

2017-02-01

The study focused on the influence of screwdriver design in combination with and without predrilling a pilot hole of inner implant diameter on insertion torque of orthodontic mini-implants, controlling for cortical thickness and vertical insertion force as cofactors. One hundred twenty mini-implants (Forestadent) of 1.7 mm in diameter and 6 and 8 mm in length were manually inserted into 120 swine rib bone samples. Maximal insertion torque as a measure of primary stability and vertical force were measured. The study included procedures with and without pilot hole and different screwdriver handles and shaft length and 2 implant lengths. Design of manual screwdriver does not modify insertion torque to a significant extent. In multiple linear regression model, significant predictors of insertion torque are thicker cortical bone (explaining 16.6% of variability), higher vertical force at maximal torque (13.5%), 6-mm implant length (2.5%), and the presence of pilot hole (2.3%). Handle type and shaft length of manual screwdriver do not significantly influence insertion torque, whereas predrilling a pilot hole has low impact on torque values of manually inserted self-drilling orthodontic mini-implants.

In Vivo High-Resolution 7 Tesla MRI Shows Early and Diffuse Cortical Alterations in CADASIL

PubMed Central

De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

2014-01-01

Background and Purpose Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Methods Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. Results MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Conclusions Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined. PMID:25165824

Regional magnetic resonance imaging measures for multivariate analysis in Alzheimer's disease and mild cognitive impairment.

PubMed

Westman, Eric; Aguilar, Carlos; Muehlboeck, J-Sebastian; Simmons, Andrew

2013-01-01

Automated structural magnetic resonance imaging (MRI) processing pipelines are gaining popularity for Alzheimer's disease (AD) research. They generate regional volumes, cortical thickness measures and other measures, which can be used as input for multivariate analysis. It is not clear which combination of measures and normalization approach are most useful for AD classification and to predict mild cognitive impairment (MCI) conversion. The current study includes MRI scans from 699 subjects [AD, MCI and controls (CTL)] from the Alzheimer's disease Neuroimaging Initiative (ADNI). The Freesurfer pipeline was used to generate regional volume, cortical thickness, gray matter volume, surface area, mean curvature, gaussian curvature, folding index and curvature index measures. 259 variables were used for orthogonal partial least square to latent structures (OPLS) multivariate analysis. Normalisation approaches were explored and the optimal combination of measures determined. Results indicate that cortical thickness measures should not be normalized, while volumes should probably be normalized by intracranial volume (ICV). Combining regional cortical thickness measures (not normalized) with cortical and subcortical volumes (normalized with ICV) using OPLS gave a prediction accuracy of 91.5 % when distinguishing AD versus CTL. This model prospectively predicted future decline from MCI to AD with 75.9 % of converters correctly classified. Normalization strategy did not have a significant effect on the accuracies of multivariate models containing multiple MRI measures for this large dataset. The appropriate choice of input for multivariate analysis in AD and MCI is of great importance. The results support the use of un-normalised cortical thickness measures and volumes normalised by ICV.

Brief anesthesia, but not voluntary locomotion, significantly alters cortical temperature

PubMed Central

Shirey, Michael J.; Kudlik, D'Anne E.; Huo, Bing-Xing; Greene, Stephanie E.; Drew, Patrick J.

2015-01-01

Changes in brain temperature can alter electrical properties of neurons and cause changes in behavior. However, it is not well understood how behaviors, like locomotion, or experimental manipulations, like anesthesia, alter brain temperature. We implanted thermocouples in sensorimotor cortex of mice to understand how cortical temperature was affected by locomotion, as well as by brief and prolonged anesthesia. Voluntary locomotion induced small (∼0.1°C) but reliable increases in cortical temperature that could be described using a linear convolution model. In contrast, brief (90-s) exposure to isoflurane anesthesia depressed cortical temperature by ∼2°C, which lasted for up to 30 min after the cessation of anesthesia. Cortical temperature decreases were not accompanied by a concomitant decrease in the γ-band local field potential power, multiunit firing rate, or locomotion behavior, which all returned to baseline within a few minutes after the cessation of anesthesia. In anesthetized animals where core body temperature was kept constant, cortical temperature was still >1°C lower than in the awake animal. Thermocouples implanted in the subcortex showed similar temperature changes under anesthesia, suggesting these responses occur throughout the brain. Two-photon microscopy of individual blood vessel dynamics following brief isoflurane exposure revealed a large increase in vessel diameter that ceased before the brain temperature significantly decreased, indicating cerebral heat loss was not due to increased cerebral blood vessel dilation. These data should be considered in experimental designs recording in anesthetized preparations, computational models relating temperature and neural activity, and awake-behaving methods that require brief anesthesia before experimental procedures. PMID:25972579

Radiographic evaluation of bone adaptation adjacent to percutaneous osseointegrated prostheses in a sheep model.

PubMed

Jeyapalina, Sujee; Beck, James Peter; Bachus, Kent N; Chalayon, Ornusa; Bloebaum, Roy D

2014-10-01

Percutaneous osseointegrated prostheses (POPs) are being investigated as an alternative to conventional socket suspension and require a radiographic followup in translational studies to confirm that design objectives are being met. In this 12-month animal study, we determined (1) radiographic signs of osseointegration and (2) radiographic signs of periprosthetic bone hypertrophy and resorption (adaptation) and (3) confirmed them with the histologic evidence of host bone osseointegration and adaptation around a novel, distally porous-coated titanium POP with a collar. A POP device was designed to fit the right metacarpal bone of sheep. Amputation and implantation surgeries (n = 14) were performed, and plane-film radiographs were collected quarterly for 12 months. Radiographs were assessed for osseointegration (fixation) and bone adaptation (resorption and hypertrophy). The cortical wall and medullary canal widths were used to compute the cortical index and expressed as a percentage. Based on the cortical index changes and histologic evaluations, bone adaptation was quantified. Radiographic data showed signs of osseointegration including those with incomplete seating against the collar attachment. Cortical index data indicated distal cortical wall thinning if the collar was not seated distally. When implants were bound proximally, bone resorbed distally and the diaphyseal cortex hypertrophied. Histopathologic evidence and cortical index measurements confirmed the radiographic indications of adaptation and osseointegration. Distal bone loading, through collar attachment and porous coating, limited the distal bone resorption. Serial radiographic studies, in either animal models or preclinical trials for new POP devices, will help to determine which designs are likely to be safe over time and avoid implant failures.

Hierarchical neurocomputations underlying concurrent sound segregation: connecting periphery to percept.

PubMed

Bidelman, Gavin M; Alain, Claude

2015-02-01

Natural soundscapes often contain multiple sound sources at any given time. Numerous studies have reported that in human observers, the perception and identification of concurrent sounds is paralleled by specific changes in cortical event-related potentials (ERPs). Although these studies provide a window into the cerebral mechanisms governing sound segregation, little is known about the subcortical neural architecture and hierarchy of neurocomputations that lead to this robust perceptual process. Using computational modeling, scalp-recorded brainstem/cortical ERPs, and human psychophysics, we demonstrate that a primary cue for sound segregation, i.e., harmonicity, is encoded at the auditory nerve level within tens of milliseconds after the onset of sound and is maintained, largely untransformed, in phase-locked activity of the rostral brainstem. As then indexed by auditory cortical responses, (in)harmonicity is coded in the signature and magnitude of the cortical object-related negativity (ORN) response (150-200 ms). The salience of the resulting percept is then captured in a discrete, categorical-like coding scheme by a late negativity response (N5; ~500 ms latency), just prior to the elicitation of a behavioral judgment. Subcortical activity correlated with cortical evoked responses such that weaker phase-locked brainstem responses (lower neural harmonicity) generated larger ORN amplitude, reflecting the cortical registration of multiple sound objects. Studying multiple brain indices simultaneously helps illuminate the mechanisms and time-course of neural processing underlying concurrent sound segregation and may lead to further development and refinement of physiologically driven models of auditory scene analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress distribution of various designs of prostheses on short implants or standard implants in posterior maxilla: a three dimensional finite element analysis

PubMed Central

JOMJUNYONG, K.; RUNGSIYAKULL, P.; RUNGSIYAKULL, C.; AUNMEUNGTONG, W.; CHANTARAMUNGKORN, M.; KHONGKHUNTHIAN, P.

2017-01-01

SUMMARY Introduction. Although many previous studies have reported on the high success rate of short dental implants, prosthetic design still plays an important role in the long-term implant treatment results. This study aims to evaluate stress distribution characteristics involved with various prosthetic designs on standard implants or short implants in the posterior maxilla. Materials and methods. Six finite element models were simulated representing the missing first and second maxillary molars. A standard implant (PW+ implant: 5.0×10 mm) and a short implant (PW+ implant: 5.0×6.0 mm) were applied under the various prosthetic conditions. The peri-implant maximum bone stress (V on mises stress) was evaluated when 200 N 30° oblique load was applied. A type III bone was approximated and complete osseous integration was assumed. Results. Maximum Von mises stress was numerically located at the cortical bone around the implant neck in all models. In every standard implant model shows better stress distribution. Stress values and concentration area decreased in the cortical and cancellous bone when implants were splinted in both the standard and short implant models. With regard to the non-replacing second molar models found that the area of stress at the cortical bone around the first molar implant to be more intensive. Moreover, in the non-replacing second molar models, the stress also spread to the second pre-molar in both the standard and short implant models. Conclusions. The length of the implant and prosthetics designs both affect the stress value and distribution of stress to the cortical and cancellous bones around the implant. PMID:29682254

Traumatic injury to the immature frontal lobe: a new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits.

PubMed

Chen, Chien-Yi; Noble-Haeusslein, Linda J; Ferriero, Donna; Semple, Bridgette D

2013-01-01

Traumatic brain injury in children commonly involves the frontal lobes and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here, we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. Male C57Bl/6J mice at postnatal day (p)21, an age approximating a toddler-aged child, received a controlled cortical impact or sham surgery to the left frontal lobe and were euthanized 1 or 7 days later. A necrotic cavity and local inflammatory response were largely confined to the unilateral frontal lobe, dorsal corpus callosum and striatum anterior to the bregma. While cell death and accumulated β-amyloid precursor protein were characteristic features of the pericontusional motor cortex, corpus callosum, cingulum and dorsal striatum, underlying structures including the hippocampus showed no overt pathology. To determine the long-term functional consequences of injury at p21, two additional cohorts were subjected to a battery of behavioral tests in adolescence (p35-45) or adulthood (p70-80). In both cohorts, brain-injured mice showed normal levels of anxiety, sociability, spatial learning and memory. The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory likely reflects several variables, including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent brain development. © 2013 S. Karger AG, Basel.

INCREASING DURATION OF TYPE 1 DIABETES PERTURBS THE STRENGTH-STRUCTURE RELATIONSHIP AND INCREASES BRITTLENESS OF BONE

PubMed Central

Nyman, Jeffry S.; Even, Jesse L.; Jo, Chan-Hee; Herbert, Erik G.; Murry, Matthew R.; Cockrell, Gael E.; Wahl, Elizabeth C.; Bunn, R. Clay; Lumpkin, Charles K.; Fowlkes, John L.; Thrailkill, Kathryn M.

2011-01-01

Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (IMIN) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by microcomputed tomography and 2) biomechanical properties by three point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, IMIN, rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then IMIN would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and IMIN depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes in tissue properties that ultimately reduce the fracture resistance of bone. PMID:21185416

Traumatic injury to the immature frontal lobe: A new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits

PubMed Central

Chen, Chien-Yi; Noble-Haeusslein, Linda J; Ferriero, Donna; Semple, Bridgette D

2014-01-01

Traumatic brain injury in children commonly involves the frontal lobes, and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. Male C57Bl/6J mice at postnatal day (p) 21, an age approximating a toddler-aged child, received a controlled cortical impact or sham surgery to the left frontal lobe and were euthanized 1 and 7 d later. A necrotic cavity and local inflammatory response were largely confined to the unilateral frontal lobe, dorsal corpus callosum and striatum anterior to Bregma. While cell death and accumulated beta-amyloid precursor protein were characteristic features of the peri-contusional motor cortex, corpus callosum, cingulum and dorsal striatum, underlying structures including the hippocampus showed no overt pathology. To determine the long-term functional consequences of injury at p21, two additional cohorts were subjected to a battery of behavioral tests in adolescence (p35-45) or adulthood (p70-80). In both cohorts, brain-injured mice showed normal levels of anxiety, sociability, spatial learning and memory. The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory, likely reflect several variables including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent brain development. PMID:24247103

Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain

NASA Astrophysics Data System (ADS)

Zhou, Chao; Yu, Guoqiang; Furuya, Daisuke; Greenberg, Joel; Yodh, Arjun; Durduran, Turgut

2006-02-01

Diffuse optical correlation methods were adapted for three-dimensional (3D) tomography of cerebral blood flow (CBF) in small animal models. The image reconstruction was optimized using a noise model for diffuse correlation tomography which enabled better data selection and regularization. The tomographic approach was demonstrated with simulated data and during in-vivo cortical spreading depression (CSD) in rat brain. Three-dimensional images of CBF were obtained through intact skull in tissues(~4mm) deep below the cortex.

Cortical and subcortical predictive dynamics and learning during perception, cognition, emotion and action

PubMed Central

Grossberg, Stephen

2009-01-01

An intimate link exists between the predictive and learning processes in the brain. Perceptual/cognitive and spatial/motor processes use complementary predictive mechanisms to learn, recognize, attend and plan about objects in the world, determine their current value, and act upon them. Recent neural models clarify these mechanisms and how they interact in cortical and subcortical brain regions. The present paper reviews and synthesizes data and models of these processes, and outlines a unified theory of predictive brain processing. PMID:19528003

Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise

PubMed Central

Ioannou, Christos I.; Pereda, Ernesto; Lindsen, Job P.; Bhattacharya, Joydeep

2015-01-01

The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB). The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min) of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha) binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies. PMID:26065708

Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise.

PubMed

Ioannou, Christos I; Pereda, Ernesto; Lindsen, Job P; Bhattacharya, Joydeep

2015-01-01

The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB). The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min) of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha) binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies.

Influence of bone microstructure on the mechanical properties of skull cortical bone - A combined experimental and computational approach.

PubMed

Boruah, Sourabh; Subit, Damien L; Paskoff, Glenn R; Shender, Barry S; Crandall, Jeff R; Salzar, Robert S

2017-01-01

The strength and compliance of the dense cortical layers of the human skull have been examined since the beginning of the 20th century with the wide range in the observed mechanical properties attributed to natural biological variance. Since this variance may be explained by the difference in structural arrangement of bone tissue, micro-computed tomography (µCT) was used in conjunction with mechanical testing to study the relationship between the microstructure of human skull cortical coupons and their mechanical response. Ninety-seven bone samples were machined from the cortical tables of the calvaria of ten fresh post mortem human surrogates and tested in dynamic tension until failure. A linear response between stress and strain was observed until close to failure, which occurred at 0.6% strain on average. The effective modulus of elasticity for the coupons was 12.01 ± 3.28GPa. Porosity of the test specimens, determined from µCT, could explain only 51% of the variation of their effective elastic modulus. Finite element (FE) models of the tested specimens built from µCT images indicated that modeling the microstructural arrangement of the bone, in addition to the porosity, led to a marginal improvement of the coefficient of determination to 54%. Modulus for skull cortical bone for an element size of 50µm was estimated to be 19GPa at an average. Unlike the load bearing bones of the body, almost half of the variance in the mechanical properties of cortical bone from the skull may be attributed to differences at the sub-osteon (< 50µm) level. ANOVA tests indicated that effective failure stress and strain varied significantly between the frontal and parietal bones, while the bone phase modulus was different for the superior and inferior aspects of the calvarium. The micro FE models did not indicate any anisotropy attributable to the pores observable under µCT. Published by Elsevier Ltd.

rab3 mediates cortical granule exocytosis in the sea urchin egg.

PubMed

Conner, S; Wessel, G M

1998-11-15

Egg activation at fertilization in the sea urchin results in the exocytosis of approximately 15,000 cortical granules that are docked at the plasma membrane. Previously, we reported that several integral membrane proteins modeled in the SNARE hypothesis, synaptotagmin, VAMP, and syntaxin, in addition to a small GTPase of the ras superfamily, rab3, were present on cortical granules (Conner, S., Leaf, D., and Wessel, G., Mol. Reprod. Dev. 48, 1-13, 1997). Here we report that rab3 is associated with cortical granules throughout oogenesis, during cortical granule translocation, and while docked at the egg plasma membrane. Following cortical granule exocytosis, however, rab3 reassociates with a different population of vesicles, at least some of which are of endocytic origin. Because of its selective association with cortical granules in eggs and oocytes, we hypothesize that rab3 functions in cortical granule exocytosis. To test this hypothesis, we used a strategy of interfering with rab3 function by peptide competition with its effector domain, a conserved region within specific rab types. We first identified the effector domain sequence in Lytechinus variegatus eggs and find the sequence 94% identical to the effector domain of rab3 in Stronglocentrotus purpuratus. Then, with synthetic peptides to different regions of the rab3 protein, we find that cortical granule exocytosis is inhibited in eggs injected with effector domain peptides, but not with peptides from the hypervariable region or with a scrambled effector peptide. Additionally, effector-peptide-injected eggs injected with IP3 are blocked in their ability to exocytose cortical granules, suggesting that the inhibition is directly on the membrane fusion event and not the result of interference with the signal transduction mechanism leading to calcium release. We interpret these results to mean that rab3 functions in the regulation of cortical granule exocytosis following vesicle docking. Copyright 1998 Academic Press.

Subcortical and cortical structural central nervous system changes and attention processing deficits in preschool-aged children with prenatal methamphetamine and tobacco exposure.

PubMed

Derauf, Chris; Lester, Barry M; Neyzi, Nurunisa; Kekatpure, Minal; Gracia, Luis; Davis, James; Kallianpur, Kalpana; Efird, Jimmy T; Kosofsky, Barry

2012-01-01

To examine the independent contributions of prenatal methamphetamine exposure (PME) and prenatal tobacco exposure (PTE) on brain morphology among a sample of nonalcohol-exposed 3- to 5-year-old children followed prospectively since birth. The sample included 20 children with PME (19 with PTE) and 15 comparison children (7 with PTE), matched on race, birth weight, maternal education and type of insurance. Subcortical and cortical volumes and cortical thickness measures were derived through an automated segmentation procedure from T1-weighted structural magnetic resonance images obtained on unsedated children. Attention was assessed using the computerized Conners' Kiddie Continuous Performance Test Version 5 (K-CPT™ V.5). PME effects on subcortical and cortical brain volumes and cortical thickness were tested by general linear model with type III sum of squares, adjusting for PTE, prenatal marijuana exposure, age at time of scan, gender, handedness, pulse sequence and total intracranial volume (for volumetric outcomes). A similar analysis was done for PTE effects on subcortical and cortical brain volumes and thickness, adjusting for PME and the above covariates. Children with PME had significantly reduced caudate nucleus volumes and cortical thickness increases in perisylvian and orbital-frontal cortices. In contrast, children with PTE showed cortical thinning in perisylvian and lateral occipital cortices and volumetric increases in frontal regions and decreases in anterior cingulate. PME was positively related and caudate volume was inversely related to K-CPT reaction time by inter-stimulus interval, a measure of the ability to adjust to changing task demands, suggesting that children with PME may have subtle attentional deficits mediated by caudate volume reductions. Our results suggest that PME and PTE may have distinct differential cortical effects on the developing central nervous system. Additionally, PME may be associated with subtle deficits in attention mediated by caudate volume reductions. Copyright © 2012 S. Karger AG, Basel.

Model of Cortical Organization Embodying a Basis for a Theory of Information Processing and Memory Recall

NASA Astrophysics Data System (ADS)

Shaw, Gordon L.; Silverman, Dennis J.; Pearson, John C.

1985-04-01

Motivated by V. B. Mountcastle's organizational principle for neocortical function, and by M. E. Fisher's model of physical spin systems, we introduce a cooperative model of the cortical column incorporating an idealized substructure, the trion, which represents a localized group of neurons. Computer studies reveal that typical networks composed of a small number of trions (with symmetric interactions) exhibit striking behavior--e.g., hundreds to thousands of quasi-stable, periodic firing patterns, any of which can be selected out and enhanced with only small changes in interaction strengths by using a Hebb-type algorithm.

Stereopsis and 3D surface perception by spiking neurons in laminar cortical circuits: a method for converting neural rate models into spiking models.

PubMed

Cao, Yongqiang; Grossberg, Stephen

2012-02-01

A laminar cortical model of stereopsis and 3D surface perception is developed and simulated. The model shows how spiking neurons that interact in hierarchically organized laminar circuits of the visual cortex can generate analog properties of 3D visual percepts. The model describes how monocular and binocular oriented filtering interact with later stages of 3D boundary formation and surface filling-in in the LGN and cortical areas V1, V2, and V4. It proposes how interactions between layers 4, 3B, and 2/3 in V1 and V2 contribute to stereopsis, and how binocular and monocular information combine to form 3D boundary and surface representations. The model suggests how surface-to-boundary feedback from V2 thin stripes to pale stripes helps to explain how computationally complementary boundary and surface formation properties lead to a single consistent percept, eliminate redundant 3D boundaries, and trigger figure-ground perception. The model also shows how false binocular boundary matches may be eliminated by Gestalt grouping properties. In particular, the disparity filter, which helps to solve the correspondence problem by eliminating false matches, is realized using inhibitory interneurons as part of the perceptual grouping process by horizontal connections in layer 2/3 of cortical area V2. The 3D sLAMINART model simulates 3D surface percepts that are consciously seen in 18 psychophysical experiments. These percepts include contrast variations of dichoptic masking and the correspondence problem, the effect of interocular contrast differences on stereoacuity, Panum's limiting case, the Venetian blind illusion, stereopsis with polarity-reversed stereograms, da Vinci stereopsis, and perceptual closure. The model hereby illustrates a general method of unlumping rate-based models that use the membrane equations of neurophysiology into models that use spiking neurons, and which may be embodied in VLSI chips that use spiking neurons to minimize heat production. Copyright © 2011 Elsevier Ltd. All rights reserved.

The 2007 AASM Recommendations for EEG Electrode Placement in Polysomnography: Impact on Sleep and Cortical Arousal Scoring

PubMed Central

Ruehland, Warren R.; O'Donoghue, Fergal J.; Pierce, Robert J.; Thornton, Andrew T.; Singh, Parmjit; Copland, Janet M.; Stevens, Bronwyn; Rochford, Peter D.

2011-01-01

Study Objective: To examine the impact of using American Academy of Sleep Medicine (AASM) recommended EEG derivations (F4/M1, C4/M1, O2/M1) vs. a single derivation (C4/M1) in polysomnography (PSG) on the measurement of sleep and cortical arousals, including inter- and intra-observer variability. Design: Prospective, non-blinded, randomized comparison. Setting: Three Australian tertiary-care hospital clinical sleep laboratories. Patients or Participants: 30 PSGs from consecutive patients investigated for obstructive sleep apnea (OSA) during December 2007 and January 2008. Interventions: N/A Measurements and Results: To examine the impact of EEG derivations on PSG summary statistics, 3 scorers from different Australian clinical sleep laboratories each scored separate sets of 10 PSGs twice, once using 3 EEG derivations and once using 1 EEG derivation. To examine the impact on inter- and intra-scorer reliability, all 3 scorers scored a subset of 10 PSGs 4 times, twice using each method. All PSGs were de-identified and scored in random order according to the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Using 3 referential EEG derivations during PSG, as recommended in the AASM manual, instead of a single central EEG derivation, as originally suggested by Rechtschaffen and Kales (1968), resulted in a mean ± SE decrease in N1 sleep of 9.6 ± 3.9 min (P = 0.018) and an increase in N3 sleep of 10.6 ± 2.8 min (P = 0.001). No significant differences were observed for any other sleep or arousal scoring summary statistics; nor were any differences observed in inter-scorer or intra-scorer reliability for scoring sleep or cortical arousals. Conclusion: This study provides information for those changing practice to comply with the 2007 AASM recommendations for EEG placement in PSG, for those using portable devices that are unable to comply with the recommendations due to limited channel options, and for the development of future standards for PSG scoring and recording. As the use of multiple EEG derivations only led to small changes in the distribution of derived sleep stages and no significant differences in scoring reliability, this study calls into question the need to use multiple EEG derivations in clinical PSG as suggested in the AASM manual. Citation: Ruehland WR; O'Donoghue FJ; Pierce RJ; Thornton AT; Singh P; Copland JM; Stevens B; Rochford PD. The 2007 AASM recommendations for EEG electrode placement in polysomnography: impact on sleep and cortical arousal scoring. SLEEP 2011;34(1):73-81. PMID:21203376

Increased Prefrontal Cortical Thickness Is Associated with Enhanced Abilities to Regulate Emotions in PTSD-Free Women with Borderline Personality Disorder

PubMed Central

Bruehl, Hannah; Preißler, Sandra; Heuser, Isabella; Heekeren, Hauke R.

2013-01-01

Previous studies suggest that amygdala, insula and prefrontal cortex (PFC) disintegrity play a crucial role in the failure to adequately regulate emotions in Borderline Personality Disorder (BPD). However, prior results are confounded by the high rate of comorbidity with Posttraumatic Stress Disorder (PTSD), which itself has been associated with changes in frontolimbic circuitry. We thus scrutinized the link between PFC, amygdala, insula, and the ability to regulate emotions, contrasting 17 women with BPD without comorbid PTSD to 27 non-clinical control women and in addition to those with BPD and PTSD (n = 14). BPD women without PTSD, but not those with comorbid PTSD, had increased cortical thickness in the dorsolateral PFC (DLPFC) in comparison to control women. Furthermore, cortical thickness in the DLPFC of BPD women without PTSD positively correlated with emotion regulation scores and furthermore was positively associated with amygdala volume, as well as cortical thickness of the insula. Our findings highlight the importance of disentangling the impact of BPD and PTSD on the brain and suggest possible compensatory mechanisms for the impaired emotion regulation in BPD women without PTSD. PMID:23755254

Suberoylanilide hydroxamic acid increases progranulin production in iPSC-derived cortical neurons of frontotemporal dementia patients.

PubMed

Almeida, Sandra; Gao, Fuying; Coppola, Giovanni; Gao, Fen-Biao

2016-06-01

Mutations in the granulin (GRN) gene cause frontotemporal dementia (FTD) due to progranulin haploinsufficiency. Compounds that can increase progranulin production and secretion may be considered as potential therapeutic drugs; however, very few of them have been directly tested on human cortical neurons. To this end, we differentiated 9 induced pluripotent stem cell lines derived from a control subject, a sporadic FTD case and an FTD patient with progranulin S116X mutation. Treatment with 1 μM suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, increased the production of progranulin in cortical neurons of all subjects at both the mRNA and protein levels without affecting their viability. Microarray analysis revealed that SAHA treatment not only reversed some gene expression changes caused by progranulin haploinsufficiency but also caused massive alterations in the overall transcriptome. Thus, histone deacetylase inhibitors may be considered as therapeutic drugs for GRN mutation carriers. However, this class of drugs also causes drastic changes in overall gene expression in human cortical neurons and their side effects and potential impacts on other pathways should be carefully evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Biomechanical evaluation of implant-supported prosthesis with various tilting implant angles and bone types in atrophic maxilla: A finite element study.

PubMed

Gümrükçü, Zeynep; Korkmaz, Yavuz Tolga; Korkmaz, Fatih Mehmet

2017-07-01

The purpose of this study is to evaluate and compare bone stress that occurs as a result of using vertical implants with simultaneous sinus augmentation with bone stress generated from oblique implants without sinus augmentation in atrophic maxilla. Six, three-dimensional (3D) finite element (FE) models of atrophic maxilla were generated with SolidWorks software. The maxilla models were varied for two different bone types. Models 2a, 2b and 2c represent maxilla models with D2 bone type. Models 3a, 3b and 3c represent maxilla models with D3 bone type. Five implants were embedded in each model with different configurations for vertical implant insertion with sinus augmentation: Model 2a/Model 3a, 30° tilted insertion; Model 2b/Model 3b and 45° tilted insertion; Model 2c/Model 3c. A 150 N load was applied obliquely on the hybrid prosthesis. The maximum von Mises stress values were comparatively evaluated using color scales. The von Mises stress values predicted by the FE models were higher for all D3 bone models in both cortical and cancellous bone. For the vertical implant models, lower stress values were found in cortical bone. Tilting of the distal implants by 30° increased the stress in the cortical layer compared to vertical implant models. Tilting of the distal implant by 45° decreased the stress in the cortical bone compared to the 30° models, but higher stress values were detected in the 45° models compared to the vertical implant models. Augmentation should be the first treatment option in atrophic maxilla in terms of biomechanics. Tilted posterior implants can create higher stress values than vertical posterior implants. During tilting implant planning, the use of a 45° tilted implant results in better biomechanical performance in peri-implant bone than 30° tilted implant due to the decrease in cantilever length. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Stimulus Dependence of Correlated Variability across Cortical Areas

PubMed Central

Cohen, Marlene R.

2016-01-01

The way that correlated trial-to-trial variability between pairs of neurons in the same brain area (termed spike count or noise correlation, rSC) depends on stimulus or task conditions can constrain models of cortical circuits and of the computations performed by networks of neurons (Cohen and Kohn, 2011). In visual cortex, rSC tends not to depend on stimulus properties (Kohn and Smith, 2005; Huang and Lisberger, 2009) but does depend on cognitive factors like visual attention (Cohen and Maunsell, 2009; Mitchell et al., 2009). However, neurons across visual areas respond to any visual stimulus or contribute to any perceptual decision, and the way that information from multiple areas is combined to guide perception is unknown. To gain insight into these issues, we recorded simultaneously from neurons in two areas of visual cortex (primary visual cortex, V1, and the middle temporal area, MT) while rhesus monkeys viewed different visual stimuli in different attention conditions. We found that correlations between neurons in different areas depend on stimulus and attention conditions in very different ways than do correlations within an area. Correlations across, but not within, areas depend on stimulus direction and the presence of a second stimulus, and attention has opposite effects on correlations within and across areas. This observed pattern of cross-area correlations is predicted by a normalization model where MT units sum V1 inputs that are passed through a divisive nonlinearity. Together, our results provide insight into how neurons in different areas interact and constrain models of the neural computations performed across cortical areas. SIGNIFICANCE STATEMENT Correlations in the responses of pairs of neurons within the same cortical area have been a subject of growing interest in systems neuroscience. However, correlated variability between different cortical areas is likely just as important. We recorded simultaneously from neurons in primary visual cortex and the middle temporal area while rhesus monkeys viewed different visual stimuli in different attention conditions. We found that correlations between neurons in different areas depend on stimulus and attention conditions in very different ways than do correlations within an area. The observed pattern of cross-area correlations was predicted by a simple normalization model. Our results provide insight into how neurons in different areas interact and constrain models of the neural computations performed across cortical areas. PMID:27413163

Perspectives for computational modeling of cell replacement for neurological disorders

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

Aimone, James B.; Weick, Jason P.

Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behaviormore » in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

Cortex Inspired Model for Inverse Kinematics Computation for a Humanoid Robotic Finger

PubMed Central

Gentili, Rodolphe J.; Oh, Hyuk; Molina, Javier; Reggia, James A.; Contreras-Vidal, José L.

2013-01-01

In order to approach human hand performance levels, artificial anthropomorphic hands/fingers have increasingly incorporated human biomechanical features. However, the performance of finger reaching movements to visual targets involving the complex kinematics of multi-jointed, anthropomorphic actuators is a difficult problem. This is because the relationship between sensory and motor coordinates is highly nonlinear, and also often includes mechanical coupling of the two last joints. Recently, we developed a cortical model that learns the inverse kinematics of a simulated anthropomorphic finger. Here, we expand this previous work by assessing if this cortical model is able to learn the inverse kinematics for an actual anthropomorphic humanoid finger having its two last joints coupled and controlled by pneumatic muscles. The findings revealed that single 3D reaching movements, as well as more complex patterns of motion of the humanoid finger, were accurately and robustly performed by this cortical model while producing kinematics comparable to those of humans. This work contributes to the development of a bioinspired controller providing adaptive, robust and flexible control of dexterous robotic and prosthetic hands. PMID:23366569

Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of PTEN-associated autism.

PubMed

Garcia-Junco-Clemente, Pablo; Chow, David K; Tring, Elaine; Lazaro, Maria T; Trachtenberg, Joshua T; Golshani, Peyman

2013-11-05

De novo phosphatase and tensin homolog on chromosome ten (PTEN) mutations are a cause of sporadic autism. How single-copy loss of PTEN alters neural function is not understood. Here we report that Pten haploinsufficiency increases the expression of small-conductance calcium-activated potassium channels. The resultant augmentation of this conductance increases the amplitude of the afterspike hyperpolarization, causing a decrease in intrinsic excitability. In vivo, this change in intrinsic excitability reduces evoked firing rates of cortical pyramidal neurons but does not alter receptive field tuning. The decreased in vivo firing rate is not associated with deficits in the dendritic integration of synaptic input or with changes in dendritic complexity. These findings identify calcium-activated potassium channelopathy as a cause of cortical dysfunction in the PTEN model of autism and provide potential molecular therapeutic targets.

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.

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

PubMed Central

Hanlon, Lauren A.; Huh, Jimmy W.

2016-01-01

Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

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

Cortical Thickness Change in Autism during Early Childhood

PubMed Central

Smith, Elizabeth; Thurm, Audrey; Greenstein, Deanna; Farmer, Cristan; Swedo, Susan; Giedd, Jay; Raznahan, Armin

2016-01-01

Structural magnetic resonance imaging (MRI) scans at high spatial resolution can detect potential foci of early brain dysmaturation in children with autism spectrum disorders (ASD). In addition, comparison between MRI and behavior measures over time can identify patterns of brain change accompanying specific outcomes. We report structural MRI data from two time points for a total of 84 scans in children with ASD and 30 scans in typical controls (mean age time one=4.1 years, mean age at time two=6.6 years). Surface-based cortical morphometry and linear mixed effects models were used to link changes in cortical anatomy to both diagnostic status and individual differences in changes in language and autism severity. Compared to controls, children with ASD showed accelerated gray matter volume gain with age, which was driven by a lack of typical age-related cortical thickness (CT) decrease within ten cortical regions involved in language, social cognition and behavioral control. Greater expressive communication gains with age in children with ASD were associated with greater CT gains in a set of right hemisphere homologues to dominant language cortices, potentially identifying a compensatory system for closer translational study. PMID:27061356

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

Cortical and Hippocampal Correlates of Deliberation during Model-Based Decisions for Rewards in Humans

PubMed Central

Bornstein, Aaron M.; Daw, Nathaniel D.

2013-01-01

How do we use our memories of the past to guide decisions we've never had to make before? Although extensive work describes how the brain learns to repeat rewarded actions, decisions can also be influenced by associations between stimuli or events not directly involving reward — such as when planning routes using a cognitive map or chess moves using predicted countermoves — and these sorts of associations are critical when deciding among novel options. This process is known as model-based decision making. While the learning of environmental relations that might support model-based decisions is well studied, and separately this sort of information has been inferred to impact decisions, there is little evidence concerning the full cycle by which such associations are acquired and drive choices. Of particular interest is whether decisions are directly supported by the same mnemonic systems characterized for relational learning more generally, or instead rely on other, specialized representations. Here, building on our previous work, which isolated dual representations underlying sequential predictive learning, we directly demonstrate that one such representation, encoded by the hippocampal memory system and adjacent cortical structures, supports goal-directed decisions. Using interleaved learning and decision tasks, we monitor predictive learning directly and also trace its influence on decisions for reward. We quantitatively compare the learning processes underlying multiple behavioral and fMRI observables using computational model fits. Across both tasks, a quantitatively consistent learning process explains reaction times, choices, and both expectation- and surprise-related neural activity. The same hippocampal and ventral stream regions engaged in anticipating stimuli during learning are also engaged in proportion to the difficulty of decisions. These results support a role for predictive associations learned by the hippocampal memory system to be recalled during choice formation. PMID:24339770

The Teaching and the Learning Brain: A Cortical Hemodynamic Marker of Teacher-Student Interactions in the Socratic Dialog

ERIC Educational Resources Information Center

Holper, Lisa; Goldin, Andrea P.; Shalom, Diego E.; Battro, Antonio M.; Wolf, Martin; Sigman, Mariano

2013-01-01

The study aimed to step into two-person (teacher-student) educational neuroscience. We describe a physiological marker of cortical hemodynamic correlates involved in teacher-student interactions during performance of a classical teaching model, the Socratic dialog. We recorded prefrontal brain activity during dialog execution simultaneously in…

Advanced Restoration Therapies in Spinal Cord Injury

DTIC Science & Technology

2015-07-01

stimulation in a mouse model of chronic SCI induces cortical plasticity as measured by resting state functional magnetic resonance imaging (rs- fMRI ...that enables us to examine the dynamics of myelin formation. We will also further our imaging work by developing methodology to use rs- fMRI for examination of cortical plasticity in response to FES.

Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

PubMed

Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

2014-11-01

The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

The influence of mesoscale porosity on cortical bone anisotropy. Investigations via asymptotic homogenization

PubMed Central

Parnell, William J; Grimal, Quentin

2008-01-01

Recently, the mesoscale of cortical bone has been given particular attention in association with novel experimental techniques such as nanoindentation, micro-computed X-ray tomography and quantitative scanning acoustic microscopy (SAM). A need has emerged for reliable mathematical models to interpret the related microscopic and mesoscopic data in terms of effective elastic properties. In this work, a new model of cortical bone elasticity is developed and used to assess the influence of mesoscale porosity on the induced anisotropy of the material. Only the largest pores (Haversian canals and resorption cavities), characteristic of the mesoscale, are considered. The input parameters of the model are derived from typical mesoscale experimental data (e.g. SAM data). We use the method of asymptotic homogenization to determine the local effective elastic properties by modelling the propagation of low-frequency elastic waves through an idealized material that models the local mesostructure. We use a novel solution of the cell problem developed by Parnell & Abrahams. This solution is stable for the physiological range of variation of mesoscopic porosity and elasticity found in bone. Results are computed efficiently (in seconds) and the solutions can be implemented easily by other workers. Parametric studies are performed in order to assess the influence of mesoscopic porosity, the assumptions regarding the material inside the mesoscale pores (drained or undrained bone) and the shape of pores. Results are shown to be in good qualitative agreement with existing schemes and we describe the potential of the scheme for future use in modelling more complex microstructures for cortical bone. In particular, the scheme is shown to be a useful tool with which to predict the qualitative changes in anisotropy due to variations in the structure at the mesoscale. PMID:18628200

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.

Angiotensin II AT1 receptor blocker candesartan prevents the fast up-regulation of cerebrocortical benzodiazepine-1 receptors induced by acute inflammatory and restraint stress

PubMed Central

Sánchez-Lemus, Enrique; Honda, Masaru; Saavedra, Juan M.

2012-01-01

Centrally acting Angiotensin II AT1 receptor blockers (ARBs) protect from stress-induced disorders and decrease anxiety in a model of inflammatory stress, the systemic injection of bacterial endotoxin lipopolysaccharide (LPS). In order to better understand the anxiolytic effect of ARBs, we treated rats with LPS (50 µg/kg) with or without three days of pretreatment with the ARB candesartan (1 mg/kg/day), and studied cortical benzodiazepine (BZ) and corticotrophin-releasing factor (CRF) receptors. We compared the cortical BZ and CRF receptors expression pattern induced by LPS with that produced in restraint stress. Inflammation stress produced a generalized increase in cortical BZ1 receptors and reduced mRNA expression of the GABAA receptor γ2 subunit in cingulate cortex; changes were prevented by candesartan pretreatment. Moreover, restraint stress produced similar increases in cortical BZ1 receptor binding, and candesartan prevented these changes. Treatment with candesartan alone increased cortical BZ1 binding, and decreased γ2 subunit mRNA expression in the cingulate cortex. Conversely, we did not find changes in CRF1 receptor expression in any of the cortical areas studied, either after inflammation or restraint stress. Cortical CRF2 receptor binding was undetectable, but CRF2 mRNA expression was decreased by inflammation stress, a change prevented by candesartan. We conclude that stress promotes rapid and widespread changes in cortical BZ1 receptor expression; and that the stress-induced BZ1 receptor expression is under the control of AT1 receptor activity. The results suggest that the anti-anxiety effect of ARBs may be associated with their capacity to regulate stress-induced alterations in cortical BZ1 receptors. PMID:22503782

Macrodamage Accumulation Model for a Human Femur

PubMed Central

2017-01-01

The objective of this study was to more fully understand the mechanical behavior of bone tissue that is important to find an alternative material to be used as an implant and to develop an accurate model to predict the fracture of the bone. Predicting and preventing bone failure is an important area in orthopaedics. In this paper, the macrodamage accumulation models in the bone tissue have been investigated. Phenomenological models for bone damage have been discussed in detail. In addition, 3D finite element model of the femur prepared from imaging data with both cortical and trabecular structures is delineated using MIMICS and ANSYS® and simulated as a composite structure. The damage accumulation occurring during cyclic loading was analyzed for fatigue scenario. We found that the damage accumulates sooner in the multiaxial than in the uniaxial loading condition for the same number of cycles, and the failure starts in the cortical bone. The damage accumulation behavior seems to follow a three-stage growth: a primary phase, a secondary phase of damage growth marked by linear damage growth, and a tertiary phase that leads to failure. Finally, the stiffness of the composite bone comprising the cortical and trabecular bone was significantly different as expected. PMID:28951659

Attentional control of associative learning--a possible role of the central cholinergic system.

PubMed

Pauli, Wolfgang M; O'Reilly, Randall C

2008-04-02

How does attention interact with learning? Kruschke [Kruschke, J.K. (2001). Toward a unified Model of Attention in Associative Learning. J. Math. Psychol. 45, 812-863.] proposed a model (EXIT) that captures Mackintosh's [Mackintosh, N.J. (1975). A theory of attention: Variations in the associability of stimuli with reinforcement. Psychological Review, 82(4), 276-298.] framework for attentional modulation of associative learning. We developed a computational model that showed analogous interactions between selective attention and associative learning, but is significantly simplified and, in contrast to EXIT, is motivated by neurophysiological findings. Competition among input representations in the internal representation layer, which increases the contrast between stimuli, is critical for simulating these interactions in human behavior. Furthermore, this competition is modulated in a way that might be consistent with the phasic activation of the central cholinergic system, which modulates activity in sensory cortices. Specifically, phasic increases in acetylcholine can cause increased excitability of both pyramidal excitatory neurons in cortical layers II/III and cortical GABAergic inhibitory interneurons targeting the same pyramidal neurons. These effects result in increased attentional contrast in our model. This model thus represents an initial attempt to link human attentional learning data with underlying neural substrates.

Attentional control of associative learning—A possible role of the central cholinergic system

PubMed Central

Pauli, Wolfgang M.; O'Reilly, Randall C.

2010-01-01

How does attention interact with learning? Kruschke [Kruschke, J.K. (2001). Toward a unified Model of Attention in Associative Learning. J. Math. Psychol. 45, 812–863.] proposed a model (EXIT) that captures Mackintosh's [Mackintosh, N.J. (1975). A theory of attention: Variations in the associability of stimuli with reinforcement. Psychological Review, 82(4), 276–298.] framework for attentional modulation of associative learning. We developed a computational model that showed analogous interactions between selective attention and associative learning, but is significantly simplified and, in contrast to EXIT, is motivated by neurophysiological findings. Competition among input representations in the internal representation layer, which increases the contrast between stimuli, is critical for simulating these interactions in human behavior. Furthermore, this competition is modulated in a way that might be consistent with the phasic activation of the central cholinergic system, which modulates activity in sensory cortices. Specifically, phasic increases in acetylcholine can cause increased excitability of both pyramidal excitatory neurons in cortical layers II/III and cortical GABAergic inhibitory interneurons targeting the same pyramidal neurons. These effects result in increased attentional contrast in our model. This model thus represents an initial attempt to link human attentional learning data with underlying neural substrates. PMID:17870060

Visual Attention Model Based on Statistical Properties of Neuron Responses

PubMed Central

Duan, Haibin; Wang, Xiaohua

2015-01-01

Visual attention is a mechanism of the visual system that can select relevant objects from a specific scene. Interactions among neurons in multiple cortical areas are considered to be involved in attentional allocation. However, the characteristics of the encoded features and neuron responses in those attention related cortices are indefinite. Therefore, further investigations carried out in this study aim at demonstrating that unusual regions arousing more attention generally cause particular neuron responses. We suppose that visual saliency is obtained on the basis of neuron responses to contexts in natural scenes. A bottom-up visual attention model is proposed based on the self-information of neuron responses to test and verify the hypothesis. Four different color spaces are adopted and a novel entropy-based combination scheme is designed to make full use of color information. Valuable regions are highlighted while redundant backgrounds are suppressed in the saliency maps obtained by the proposed model. Comparative results reveal that the proposed model outperforms several state-of-the-art models. This study provides insights into the neuron responses based saliency detection and may underlie the neural mechanism of early visual cortices for bottom-up visual attention. PMID:25747859

Quantifying the Cerebral Hemodynamics of Dural Arteriovenous Fistula in Transverse Sigmoid Sinus Complicated by Sinus Stenosis: A Retrospective Cohort Study.

PubMed

Guo, W-Y; Lee, C-C J; Lin, C-J; Yang, H-C; Wu, H-M; Wu, C-C; Chung, W-Y; Liu, K-D

2017-01-01

Sinus stenosis occasionally occurs in dural arteriovenous fistulas. Sinus stenosis impedes venous outflow and aggravates intracranial hypertension by reversing cortical venous drainage. This study aimed to analyze the likelihood of sinus stenosis and its impact on cerebral hemodynamics of various types of dural arteriovenous fistulas. Forty-three cases of dural arteriovenous fistula in the transverse-sigmoid sinus were reviewed and divided into 3 groups: Cognard type I, type IIa, and types with cortical venous drainage. Sinus stenosis and the double peak sign (occurrence of 2 peaks in the time-density curve of the ipsilateral drainage of the internal jugular vein) in dural arteriovenous fistula were evaluated. "TTP" was defined as the time at which a selected angiographic point reached maximum concentration. TTP of the vein of Labbé, TTP of the ipsilateral normal transverse sinus, trans-fistula time, and trans-stenotic time were compared across the 3 groups. Thirty-six percent of type I, 100% of type IIa, and 84% of types with cortical venous drainage had sinus stenosis. All sinus stenosis cases demonstrated loss of the double peak sign that occurs in dural arteriovenous fistula. Trans-fistula time (2.09 seconds) and trans-stenotic time (0.67 seconds) in types with cortical venous drainage were the most prolonged, followed by those in type IIa and type I. TTP of the vein of Labbé was significantly shorter in types with cortical venous drainage. Six patients with types with cortical venous drainage underwent venoplasty and stent placement, and 4 were downgraded to type IIa. Sinus stenosis indicated dysfunction of venous drainage and is more often encountered in dural arteriovenous fistula with more aggressive types. Venoplasty ameliorates cortical venous drainage in dural arteriovenous fistulas and serves as a bridge treatment to stereotactic radiosurgery in most cases. © 2017 by American Journal of Neuroradiology.

Pronounced impairment of everyday skills and self-care in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Yong, Keir X X; Foxe, David; Hodges, John; Crutch, Sebastian J

2015-01-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition.

Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology.

PubMed

Hamilton, Roy; Patel, Sunil; Lee, Edward B; Jackson, Eric M; Lopinto, Joanna; Arnold, Steven E; Clark, Christopher M; Basil, Anuj; Shaw, Leslie M; Xie, Sharon X; Grady, M Sean; Trojanowski, John Q

2010-10-01

To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

PubMed Central

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-01-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life. PMID:27137745

Progesterone Sharpens Temporal Response Profiles of Sensory Cortical Neurons in Animals Exposed to Traumatic Brain Injury

PubMed Central

Allitt, Benjamin J.; Johnstone, Victoria P. A.; Richards, Katrina L.; Yan, Edwin B.

2017-01-01

Traumatic brain injury (TBI) initiates a cascade of pathophysiological changes that are both complex and difficult to treat. Progesterone (P4) is a neuroprotective treatment option that has shown excellent preclinical benefits in the treatment of TBI, but these benefits have not translated well in the clinic. We have previously shown that P4 exacerbates the already hypoactive upper cortical responses in the short-term post-TBI and does not reduce upper cortical hyperactivity in the long term, and we concluded that there is no tangible benefit to sensory cortex firing strength. Here we examined the effects of P4 treatment on temporal coding resolution in the rodent sensory cortex in both the short term (4 d) and long term (8 wk) following impact-acceleration–induced TBI. We show that in the short-term postinjury, TBI has no effect on sensory cortex temporal resolution and that P4 also sharpens the response profile in all cortical layers in the uninjured brain and all layers other than layer 2 (L2) in the injured brain. In the long term, TBI broadens the response profile in all cortical layers despite firing rate hyperactivity being localized to upper cortical layers and P4 sharpens the response profile in TBI animals in all layers other than L2 and has no long-term effect in the sham brain. These results indicate that P4 has long-term effects on sensory coding that may translate to beneficial perceptual outcomes. The effects seen here, combined with previous beneficial preclinical data, emphasize that P4 is still a potential treatment option in ameliorating TBI-induced disorders. PMID:28933224

Effects of environmental risks and polygenic loading for schizophrenia on cortical thickness.

PubMed

Neilson, Emma; Bois, Catherine; Gibson, Jude; Duff, Barbara; Watson, Andrew; Roberts, Neil; Brandon, Nicholas J; Dunlop, John; Hall, Jeremy; McIntosh, Andrew M; Whalley, Heather C; Lawrie, Stephen M

2017-06-01

There are established differences in cortical thickness (CT) in schizophrenia (SCZ) and bipolar (BD) patients when compared to healthy controls (HC). However, it is unknown to what extent environmental or genetic risk factors impact on CT in these populations. We have investigated the effect of Environmental Risk Scores (ERS) and Polygenic Risk Scores for SCZ (PGRS-SCZ) on CT. Structural MRI scans were acquired at 3T for patients with SCZ or BD (n=57) and controls (n=41). Cortical reconstructions were generated in FreeSurfer (v5.3). The ERS was created by determining exposure to cannabis use, childhood adverse events, migration, urbanicity and obstetric complications. The PGRS-SCZ were generated, for a subset of the sample (Patients=43, HC=32), based on the latest PGC GWAS findings. ANCOVAs were used to test the hypotheses that ERS and PGRS-SCZ relate to CT globally, and in frontal and temporal lobes. An increase in ERS was negatively associated with CT within temporal lobe for patients. A higher PGRS-SCZ was also related to global cortical thinning for patients. ERS effects remained significant when including PGRS-SCZ as a fixed effect. No relationship which survived FDR correction was found for ERS and PGRS-SCZ in controls. Environmental risk for SCZ was related to localised cortical thinning in patients with SCZ and BD, while increased PGRS-SCZ was associated with global cortical thinning. Genetic and environmental risk factors for SCZ appear therefore to have differential effects. This provides a mechanistic means by which different risk factors may contribute to the development of SCZ and BD. Copyright © 2016 Elsevier B.V. All rights reserved.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

PubMed

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-06-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Polyamine Catabolism Is Enhanced after Traumatic Brain Injury

PubMed Central

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A.

2010-01-01

Abstract Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N1-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6–24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6–24 h), then increased by ∼50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6–72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24–72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies. PMID:19968558

Cortical Thickness Correlates of Specific Cognitive Performance Accounted for by the General Factor of Intelligence in Healthy Children Aged 6 to 18

PubMed Central

Karama, Sherif; Colom, Roberto; Johnson, Wendy; Deary, Ian J.; Haier, Richard; Waber, Deborah P.; Lepage, Claude; Ganjavi, Hooman; Jung, Rex; Evans, Alan C.

2011-01-01

Prevailing psychometric theories of intelligence posit that individual differences in cognitive performance are attributable to three main sources of variance: the general factor of intelligence (g), cognitive ability domains, and specific test requirements and idiosyncrasies. Cortical thickness has been previously associated with g. In the present study, we systematically analyzed associations between cortical thickness and cognitive performance with and without adjusting for the effects of g in a representative sample of children and adolescents (N = 207, Mean age = 11.8; SD = 3.5; Range = 6 to 18.3 years). Seven cognitive tests were included in a measurement model that identified three first-order factors (representing cognitive ability domains) and one second-order factor representing g. Residuals of the cognitive ability domain scores were computed to represent g-independent variance for the three domains and seven tests. Cognitive domain and individual test scores as well as residualized scores were regressed against cortical thickness, adjusting for age, gender and a proxy measure of brain volume. g and cognitive domain scores were positively correlated with cortical thickness in very similar areas across the brain. Adjusting for the effects of g eliminated associations of domain and test scores with cortical thickness. Within a psychometric framework, cortical thickness correlates of cognitive performance on complex tasks are well captured by g in this demographically representative sample. PMID:21241809

Maturation of Cortico-Subcortical Structural Networks-Segregation and Overlap of Medial Temporal and Fronto-Striatal Systems in Development.

PubMed

Walhovd, Kristine B; Tamnes, Christian K; Bjørnerud, Atle; Due-Tønnessen, Paulina; Holland, Dominic; Dale, Anders M; Fjell, Anders M

2015-07-01

The brain consists of partly segregated neural circuits within which structural convergence and functional integration occurs during development. The relationship of structural cortical and subcortical maturation is largely unknown. We aimed to study volumetric development of the hippocampus and basal ganglia (caudate, putamen, pallidum, accumbens) in relation to volume changes throughout the cortex. Longitudinal MRI data were obtained across a mean interval of 2.6 years in 85 participants with an age range of 8-19 years at study start. Left and right subcortical changes were related to cortical change vertex-wise in the ipsilateral hemisphere with general linear models with age, sex, interval between scans, and mean cortical volume change as covariates. Hippocampal-cortical change relationships centered on parts of the Papez circuit, including entorhinal, parahippocampal, and isthmus cingulate areas, and lateral temporal, insular, and orbitofrontal cortices in the left hemisphere. Basal ganglia-cortical change relationships were observed in mostly nonoverlapping and more anterior cortical areas, all including the anterior cingulate. Other patterns were unique to specific basal ganglia structures, including pre-, post-, and paracentral patterns relating to putamen change. In conclusion, patterns of cortico-subcortical development as assessed by morphometric analyses in part map out segregated neural circuits at the macrostructural level. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Rhizobial infection does not require cortical expression of upstream common symbiosis genes responsible for the induction of Ca(2+) spiking.

PubMed

Hayashi, Teruyuki; Shimoda, Yoshikazu; Sato, Shusei; Tabata, Satoshi; Imaizumi-Anraku, Haruko; Hayashi, Makoto

2014-01-01

For the establishment of an effective root nodule symbiosis, a coordinated regulation of the infection processes between the epidermis and cortex is required. However, it remains unclear whether the symbiotic genes identified so far are involved in epidermal and/or cortical infection, e.g. epidermal and cortical infection thread formation or cortical cell division. To analyze the symbiotic gene requirements of the infection process, we have developed an epidermis-specific expression system (pEpi expression system) and examined the symbiotic genes NFR1, NFR5, NUP85, NUP133, CASTOR, POLLUX, CCaMK, CYCLOPS, NSP1 and NSP2 for involvement in the infection process in the epidermis and cortex. Our study shows that expression of the upstream common symbiosis genes CASTOR, POLLUX, NUP85 and NUP133 in the epidermis is sufficient to induce formation of infection threads and cortical cell division, leading to the development of fully effective nodules. Our system also shows a requirement of CCaMK, CYCLOPS, NSP1 and NSP2 for the entire nodulation process, and the different contributions of NFR1 and NFR5 to cortical infection thread formation. Based on these analyses using the pEpi expression system, we propose a functional model of symbiotic genes for epidermal and cortical infection. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Comparison of gray matter volume and thickness for analysis of cortical changes in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Liu, Jiachao; Li, Ziyi; Chen, Kewei; Yao, Li; Wang, Zhiqun; Li, Kunchen; Guo, Xiaojuan

2011-03-01

Gray matter volume and cortical thickness are two indices of concern in brain structure magnetic resonance imaging research. Gray matter volume reflects mixed-measurement information of cerebral cortex, while cortical thickness reflects only the information of distance between inner surface and outer surface of cerebral cortex. Using Scaled Subprofile Modeling based on Principal Component Analysis (SSM_PCA) and Pearson's Correlation Analysis, this study further provided quantitative comparisons and depicted both global relevance and local relevance to comprehensively investigate morphometrical abnormalities in cerebral cortex in Alzheimer's disease (AD). Thirteen patients with AD and thirteen age- and gender-matched healthy controls were included in this study. Results showed that factor scores from the first 8 principal components accounted for ~53.38% of the total variance for gray matter volume, and ~50.18% for cortical thickness. Factor scores from the fifth principal component showed significant correlation. In addition, gray matter voxel-based volume was closely related to cortical thickness alterations in most cortical cortex, especially, in some typical abnormal brain regions such as insula and the parahippocampal gyrus in AD. These findings suggest that these two measurements are effective indices for understanding the neuropathology in AD. Studies using both gray matter volume and cortical thickness can separate the causes of the discrepancy, provide complementary information and carry out a comprehensive description of the morphological changes of brain structure.

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine

PubMed Central

Andreou, Anna P.; Holland, Philip R.; Akerman, Simon; Summ, Oliver; Fredrick, Joe

2016-01-01

Abstract A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. PMID:27246325

Linking physics with physiology in TMS: a sphere field model to determine the cortical stimulation site in TMS.

PubMed

Thielscher, Axel; Kammer, Thomas

2002-11-01

A fundamental problem of transcranial magnetic stimulation (TMS) is determining the site and size of the stimulated cortical area. In the motor system, the most common procedure for this is motor mapping. The obtained two-dimensional distribution of coil positions with associated muscle responses is used to calculate a center of gravity on the skull. However, even in motor mapping the exact stimulation site on the cortex is not known and only rough estimates of its size are possible. We report a new method which combines physiological measurements with a physical model used to predict the electric field induced by the TMS coil. In four subjects motor responses in a small hand muscle were mapped with 9-13 stimulation sites at the head perpendicular to the central sulcus in order to keep the induced current direction constant in a given cortical region of interest. Input-output functions from these head locations were used to determine stimulator intensities that elicit half-maximal muscle responses. Based on these stimulator intensities the field distribution on the individual cortical surface was calculated as rendered from anatomical MR data. The region on the cortical surface in which the different stimulation sites produced the same electric field strength (minimal variance, 4.2 +/- 0.8%.) was determined as the most likely stimulation site on the cortex. In all subjects, it was located at the lateral part of the hand knob in the motor cortex. Comparisons of model calculations with the solutions obtained in this manner reveal that the stimulated cortex area innervating the target muscle is substantially smaller than the size of the electric field induced by the coil. Our results help to resolve fundamental questions raised by motor mapping studies as well as motor threshold measurements.

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.

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.

Biomechanics of the Proximal Radius Following Drilling of the Bicipital Tuberosity to Mimic Cortical Button Distal Biceps Repair Technique.

PubMed

Oak, Nikhil R; Lien, John R; Brunfeldt, Alexander; Lawton, Jeffrey N

2018-05-01

A fracture through the proximal radius is a theoretical concern after cortical button distal biceps fixation in an active patient. The permanent, nonossified cortical defect and medullary tunnel is at risk during a fall eliciting rotational and compressive forces. We hypothesized that during simulated torsion and compression, in comparison with unaltered specimens, the cortical button distal biceps repair model would have decreased torsional and compressive strength and would fracture in the vicinity of the bicipital tuberosity bone tunnel. Sixteen fourth-generation composite radius Sawbones models were used in this controlled laboratory study. A bone tunnel was created through the bicipital tuberosity to mimic the exact bone tunnel, 8 mm near cortex and 3.2 mm far cortex, made for the BicepsButton distal biceps tendon repair. The radius was then prepared and mounted on either a torsional or compression testing device and compared with undrilled control specimens. Compression tests resulted in average failure loads of 9015.2 N in controls versus 8253.25 N in drilled specimens ( P = .074). Torsional testing resulted in an average failure torque of 27.3 Nm in controls and 19.3 Nm in drilled specimens ( P = .024). Average fracture angle was 35.1° in controls versus 21.1° in drilled. Gross fracture patterns were similar in compression testing; however, in torsional testing all fractures occurred through the bone tunnel in the drilled group. There are weaknesses in the vicinity of the bone tunnel in the proximal radius during biomechanical stress testing which may not be clinically relevant in nature. In cortical button fixation, distal biceps repairs creates a permanent, nonossified cortical defect with tendon interposed in the bone tunnel, which can alter the biomechanical properties of the proximal radius during compressive and torsional loading.

The effects of cortical bone thickness and trabecular bone strength on noninvasive measures of the implant primary stability using synthetic bone models.

PubMed

Hsu, Jui-Ting; Fuh, Lih-Jyh; Tu, Ming-Gene; Li, Yu-Fen; Chen, Kuan-Ting; Huang, Heng-Li

2013-04-01

This study investigated how the primary stability of a dental implant as measured by the insertion torque value (ITV), Periotest value (PTV), and implant stability quotient (ISQ) is affected by varying thicknesses of cortical bone and strengths of trabecular bone using synthetic bone models. Four synthetic cortical shells (with thicknesses of 0, 1, 2, and 3 mm) were attached to four cellular rigid polyurethane foams (with elastic moduli of 137, 47.5, 23, and 12.4 MPa) and one open-cell rigid polyurethane foam which mimic the osteoporotic bone (with an elastic modulus 6.5 MPa), to represent the jawbones with various cortical bone thicknesses and strengths of trabecular bone. A total of 60 bone specimens accompanied with implants was examined by a torque meter, Osstell resonance frequency analyzer, and Periotest electronic device. All data were statistically analyzed by two-way analysis of variance. In addition, second-order nonlinear regression was utilized to assess the correlations of the primary implant stability with the four cortex thicknesses and five strengths of trabecular bone. ITV, ISQ, and PTV differed significantly (p < .05) and were strongly correlated with the thickness of cortical bone (R(2) > 0.9) and the elastic modulus of trabecular bone (R(2) = 0.74-0.99). The initial stability at the time of implant placement is influenced by both the cortical bone thickness and the strength of trabecular bone; however, these factors are mostly nonlinearly correlated with ITV, PTV, and ISQ. Using ITV and PTV seems more suitable for identifying the primary implant stability in osteoporotic bone with a thin cortex. © 2011 Wiley Periodicals, Inc.

Effect of Integration Patterns Around Implant Neck on Stress Distribution in Peri-Implant Bone: A Finite Element Analysis.

PubMed

Han, Jingyun; Sun, Yuchun; Wang, Chao

2017-08-01

To investigate the biomechanical performance of different osseointegration patterns between cortical bone and implants using finite element analysis. Fifteen finite element models were constructed of the mandibular fixed prosthesis supported by implants. Masticatory loads (200 N axial, 100 N oblique, 40 N horizontal) were applied. The cortical bone/implant interface was divided equally into four layers: upper, upper-middle, lower-middle, and lower. The bone stress and implant displacement were calculated for 5 degrees of uniform integration (0, 20%, 40%, 60%, and 100%) and 10 integration patterns. The stress was concentrated in the bone margin and gradually decreased as osseointegration progressed, when the integrated and nonintegrated areas were alternated on the bone-implant surface. Compared with full integration, the integration of only the lower-middle layer or lower half layers significantly decreased von Mises, tensile, and compressive stresses in cortical bone under oblique and horizontal loads, and these patterns did not induce higher stress in the cancellous bone. For the integration of only the upper or upper-middle layer, stress in the cortical and cancellous bones significantly increased and was considerably higher than in the case of nonintegration. In addition, the maximum stress in the cortical bone was sensitive to the quantity of integrated nodes at the bone margin; lower quantity was associated with higher stress. There was no significant difference in the displacement of implants among 15 models. Integration patterns of cortical bone significantly affect stress distribution in peri-implant bone. The integration of only the lower-middle or lower half layers helps to increase the load-bearing capacity of peri-implant bone and decrease the risk of overloading, while upper integration may further increase the risk of bone resorption. © 2016 by the American College of Prosthodontists.

Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

PubMed

Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

2018-02-01

Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synaptic Mechanisms of Memory Consolidation during Sleep Slow Oscillations

PubMed Central

Wei, Yina; Krishnan, Giri P.

2016-01-01

Sleep is critical for regulation of synaptic efficacy, memories, and learning. However, the underlying mechanisms of how sleep rhythms contribute to consolidating memories acquired during wakefulness remain unclear. Here we studied the role of slow oscillations, 0.2–1 Hz rhythmic transitions between Up and Down states during stage 3/4 sleep, on dynamics of synaptic connectivity in the thalamocortical network model implementing spike-timing-dependent synaptic plasticity. We found that the spatiotemporal pattern of Up-state propagation determines the changes of synaptic strengths between neurons. Furthermore, an external input, mimicking hippocampal ripples, delivered to the cortical network results in input-specific changes of synaptic weights, which persisted after stimulation was removed. These synaptic changes promoted replay of specific firing sequences of the cortical neurons. Our study proposes a neuronal mechanism on how an interaction between hippocampal input, such as mediated by sharp wave-ripple events, cortical slow oscillations, and synaptic plasticity, may lead to consolidation of memories through preferential replay of cortical cell spike sequences during slow-wave sleep. SIGNIFICANCE STATEMENT Sleep is critical for memory and learning. Replay during sleep of temporally ordered spike sequences related to a recent experience was proposed to be a neuronal substrate of memory consolidation. However, specific mechanisms of replay or how spike sequence replay leads to synaptic changes that underlie memory consolidation are still poorly understood. Here we used a detailed computational model of the thalamocortical system to report that interaction between slow cortical oscillations and synaptic plasticity during deep sleep can underlie mapping hippocampal memory traces to persistent cortical representation. This study provided, for the first time, a mechanistic explanation of how slow-wave sleep may promote consolidation of recent memory events. PMID:27076422

Tracking the time-varying cortical connectivity patterns by adaptive multivariate estimators.

PubMed

Astolfi, L; Cincotti, F; Mattia, D; De Vico Fallani, F; Tocci, A; Colosimo, A; Salinari, S; Marciani, M G; Hesse, W; Witte, H; Ursino, M; Zavaglia, M; Babiloni, F

2008-03-01

The directed transfer function (DTF) and the partial directed coherence (PDC) are frequency-domain estimators that are able to describe interactions between cortical areas in terms of the concept of Granger causality. However, the classical estimation of these methods is based on the multivariate autoregressive modelling (MVAR) of time series, which requires the stationarity of the signals. In this way, transient pathways of information transfer remains hidden. The objective of this study is to test a time-varying multivariate method for the estimation of rapidly changing connectivity relationships between cortical areas of the human brain, based on DTF/PDC and on the use of adaptive MVAR modelling (AMVAR) and to apply it to a set of real high resolution EEG data. This approach will allow the observation of rapidly changing influences between the cortical areas during the execution of a task. The simulation results indicated that time-varying DTF and PDC are able to estimate correctly the imposed connectivity patterns under reasonable operative conditions of signal-to-noise ratio (SNR) ad number of trials. An SNR of five and a number of trials of at least 20 provide a good accuracy in the estimation. After testing the method by the simulation study, we provide an application to the cortical estimations obtained from high resolution EEG data recorded from a group of healthy subject during a combined foot-lips movement and present the time-varying connectivity patterns resulting from the application of both DTF and PDC. Two different cortical networks were detected with the proposed methods, one constant across the task and the other evolving during the preparation of the joint movement.

Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury.

PubMed

Vonder Haar, Cole; Anderson, Gail D; Hoane, Michael R

2011-10-31

Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B(3)) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1 ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies. Copyright © 2011 Elsevier B.V. All rights reserved.

Rehabilitation of cortical blindness secondary to stroke.

PubMed

Gaber, Tarek A-Z K

2010-01-01

Cortical blindness is a rare complication of posterior circulation stroke. However, its complex presentation with sensory, physical, cognitive and behavioural impairments makes it one of the most challenging. Appropriate approach from a rehabilitation standpoint was never reported. Our study aims to discuss the rehabilitation methods and outcomes of a cohort of patients with cortical blindness. The notes of all patients with cortical blindness referred to a local NHS rehabilitation service in the last 6~years were examined. Patients' demographics, presenting symptoms, scan findings, rehabilitation programmes and outcomes were documented. Seven patients presented to our service, six of them were males. The mean age was 63. Patients 1, 2 and 3 had total blindness with severe cognitive and behavioural impairments, wandering and akathisia. All of them failed to respond to any rehabilitation effort and the focus was on damage limitation. Pharmacological interventions had a modest impact on behaviour and sleep pattern. The 3 patients were discharged to a nursing facility. Patients 4, 5, 6 and 7 had partial blindness with variable severity. All of them suffered from significant memory impairment. However, none suffered from any behavioural, physical or other cognitive impairment. Rehabilitation efforts on 3 patients were carried out collaboratively between brain injury occupational therapists and sensory disability officers. All patients experienced significant improvement in handicap and they all maintained community placements. This small cohort of patients suggests that the rehabilitation philosophy and outcomes of these 2 distinct groups of either total or partial cortical blindness differ significantly.