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

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

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.

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

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

The effects of L-arginine on cerebral hemodynamics after controlled cortical impact injury in the mouse.

PubMed

Liu, Hao; Goodman, J Clay; Robertson, Claudia S

2002-03-01

Traumatic brain injury (TBI) induces vascular changes that may influence neurological outcome by causing the brain to be more susceptible to secondary ischemic insults. In rat models of TBI, L-arginine administration has been shown to restore cerebral blood flow and improve neurological outcome. The purpose of this study was to determine if hypoperfusion occurs in a mouse model of TBI and if L-arginine administration has the same beneficial effects after injury in the mouse. C57BL6 mice were anesthetized with isoflurane, intubated and mechanically ventilated, and underwent a 3-m/sec, 1.5-mm deformation cortical impact injury. Five minutes after injury, L-arginine, 300 mg/kg, or saline were administered. Arterial blood pressure, intracranial pressure, and laser Doppler flow at the impact site were monitored for 3 h after the injury. The cerebral hemodynamic effects of the TBI induced by cortical impact injury were similar to that previously observed in rats. Intracranial hypertension, with ICP peaking at 46+/-2 mm Hg, and systemic hypotension both contributed to a reduction in CPP. In addition, LDF decreased significantly at the impact site. L-Arginine administration restored LDF to near baseline levels without increasing ICP. These studies demonstrate that cerebral hemodynamics can be measured in mouse models of TBI. The changes in cerebral hemodynamics are relatively simlar to those see in the rat model of cortical impact injury and suggest an important role for nitric oxide metabolism in the maintenance of cerebral blood flow following TBI.

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.

The impact of systemic cortical alterations on perception

NASA Astrophysics Data System (ADS)

Zhang, Zheng

2011-12-01

Perception is the process of transmitting and interpreting sensory information, and the primary somatosensory (SI) area in the human cortex is the main sensory receptive area for the sensation of touch. The elaborate neuroanatomical connectivity that subserves the neuronal communication between adjacent and near-adjacent regions within sensory cortex has been widely recognized to be essential to normal sensory function. As a result, systemic cortical alterations that impact the cortical regional interaction, as associated with many neurological disorders, are expected to have significant impact on sensory perception. Recently, our research group has developed a novel sensory diagnostic system that employs quantitative sensory testing methods and is able to non-invasively assess central nervous system healthy status. The intent of this study is to utilize quantitative sensory testing methods that were designed to generate discriminable perception to objectively and quantitatively assess the impacts of different conditions on human sensory information processing capacity. The correlation between human perceptions with observations from animal research enables a better understanding of the underlying neurophysiology of human perception. Additional findings on different subject populations provide valuable insight of the underlying mechanisms for the development and maintenance of different neurological diseases. During the course of the study, several protocols were designed and utilized. And this set of sensory-based perceptual metrics was employed to study the effects of different conditions (non-noxious thermal stimulation, chronic pain stage, and normal aging) on sensory perception. It was found that these conditions result in significant deviations of the subjects' tactile information processing capacities from normal values. Although the observed shift of sensory detection sensitivity could be a result of enhanced peripheral activity, the changes in the effects

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

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

Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains

PubMed Central

Lörinczi, Éva; Gómez-Posada, Juan Camilo; de la Peña, Pilar; Tomczak, Adam P.; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A.

2015-01-01

Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4–S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4–S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules. PMID:25818916

Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.

PubMed

Lörinczi, Éva; Gómez-Posada, Juan Camilo; de la Peña, Pilar; Tomczak, Adam P; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A

2015-03-30

Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.

Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains

NASA Astrophysics Data System (ADS)

Lörinczi, Éva; Gómez-Posada, Juan Camilo; de La Peña, Pilar; Tomczak, Adam P.; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A.

2015-03-01

Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.

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

PubMed

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

2010-09-01

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

The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions

PubMed Central

Osier, Nicole D.; Dixon, C. Edward

2016-01-01

Controlled cortical impact (CCI) is a mechanical model of traumatic brain injury (TBI) that was developed nearly 30 years ago with the goal of creating a testing platform to determine the biomechanical properties of brain tissue exposed to direct mechanical deformation. Initially used to model TBIs produced by automotive crashes, the CCI model rapidly transformed into a standardized technique to study TBI mechanisms and evaluate therapies. CCI is most commonly produced using a device that rapidly accelerates a rod to impact the surgically exposed cortical dural surface. The tip of the rod can be varied in size and geometry to accommodate scalability to difference species. Typically, the rod is actuated by a pneumatic piston or electromagnetic actuator. With some limits, CCI devices can control the velocity, depth, duration, and site of impact. The CCI model produces morphologic and cerebrovascular injury responses that resemble certain aspects of human TBI. Commonly observed are graded histologic and axonal derangements, disruption of the blood–brain barrier, subdural and intra-parenchymal hematoma, edema, inflammation, and alterations in cerebral blood flow. The CCI model also produces neurobehavioral and cognitive impairments similar to those observed clinically. In contrast to other TBI models, the CCI device induces a significantly pronounced cortical contusion, but is limited in the extent to which it models the diffuse effects of TBI; a related limitation is that not all clinical TBI cases are characterized by a contusion. Another perceived limitation is that a non-clinically relevant craniotomy is performed. Biomechanically, this is irrelevant at the tissue level. However, craniotomies are not atraumatic and the effects of surgery should be controlled by including surgical sham control groups. CCI devices have also been successfully used to impact closed skulls to study mild and repetitive TBI. Future directions for CCI research surround continued

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.

Crumbs 2 prevents cortical abnormalities in mouse dorsal telencephalon.

PubMed

Dudok, Jacobus J; Murtaza, Mariyam; Henrique Alves, C; Rashbass, Pen; Wijnholds, Jan

2016-07-01

The formation of a functionally integrated nervous system is dependent on a highly organized sequence of events that includes timely division and differentiation of progenitors. Several apical polarity proteins have been shown to play crucial roles during neurogenesis, however, the role of Crumbs 2 (CRB2) in cortical development has not previously been reported. Here, we show that conditional ablation of Crb2 in the murine dorsal telencephalon leads to defects in the maintenance of the apical complex. Furthermore, within the mutant dorsal telencephalon there is premature expression of differentiation proteins. We examined the physiological function of Crb2 on wild type genetic background as well as on background lacking Crb1. Telencephalon lacking CRB2 resulted in reduced levels of PALS1 and CRB3 from the apical complex, an increased number of mitotic cells and expanded neuronal domain. These defects are transient and therefore only result in rather mild cortical abnormalities. We show that CRB2 is required for maintenance of the apical polarity complex during development of the cortex and regulation of cell division, and that loss of CRB2 results in cortical abnormalities. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Multigenerational Inheritance of Long QT Syndrome Type 2 in a Japanese Family.

PubMed

Ichikawa, Mari; Ohno, Seiko; Fujii, Yusuke; Ozawa, Junichi; Sonoda, Keiko; Fukuyama, Megumi; Kato, Koichi; Kimura, Hiromi; Itoh, Hideki; Hayashi, Hideki; Horie, Minoru

2016-01-01

Congenital long QT syndrome (LQTS) is an important cause of sudden cardiac death in young people without any other structural disease. Mutations in the genes encoding the cardiac ion channels or associated proteins have been shown to result in ion channel dysfunction and thereby causing LQTS. We investigated a Japanese family with LQTS for four generations, with the female family members showing severe symptoms. We performed genetic tests for LQTS-related genes and identified a heterozygous KCNH2 mutation (p.K638del). In the family, the KCNH2 mutation had a very high multigenerational inheritance, and female genotype positives showed more severe phenotypes.

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.

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.

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

PubMed Central

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

2015-01-01

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

Cortical thinning in type 2 diabetes mellitus and recovering effects of insulin therapy.

PubMed

Chen, Zhiye; Sun, Jie; Yang, Yang; Lou, Xin; Wang, Yulin; Wang, Yan; Ma, Lin

2015-02-01

The purpose of this study was to explore the brain structural changes in type 2 diabetes and the effect of insulin on the brain using a surface-based cortical thickness analysis. High-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI were obtained from 11 patients with type 2 diabetes before and after insulin therapy. The cortical thickness over the entire brain was calculated, and cross-sectional and longitudinal surface-based cortical thickness analyses were also performed. Regional cortical thinning was demonstrated in the middle temporal gyrus, posterior cingulate gyrus, precuneus, right lateral occipital gyrus and entorhinal cortex bilaterally for patients with type 2 diabetes mellitus compared with normal controls. Cortical thickening was seen in the middle temporal gyrus, entorhinal cortex and left inferior temporal gyrus bilaterally after patients underwent 1 year of insulin therapy. These findings suggest that insulin therapy may have recovering effects on the brain cortex in type 2 diabetes mellitus. The precise mechanism should be investigated further. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mapping longitudinal development of local cortical gyrification in infants from birth to 2 years of age.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Lin, Weili; Gilmore, John H; Shen, Dinggang

2014-03-19

Human cortical folding is believed to correlate with cognitive functions. This likely correlation may have something to do with why abnormalities of cortical folding have been found in many neurodevelopmental disorders. However, little is known about how cortical gyrification, the cortical folding process, develops in the first 2 years of life, a period of dynamic and regionally heterogeneous cortex growth. In this article, we show how we developed a novel infant-specific method for mapping longitudinal development of local cortical gyrification in infants. By using this method, via 219 longitudinal 3T magnetic resonance imaging scans from 73 healthy infants, we systemically and quantitatively characterized for the first time the longitudinal cortical global gyrification index (GI) and local GI (LGI) development in the first 2 years of life. We found that the cortical GI had age-related and marked development, with 16.1% increase in the first year and 6.6% increase in the second year. We also found marked and regionally heterogeneous cortical LGI development in the first 2 years of life, with the high-growth regions located in the association cortex, whereas the low-growth regions located in sensorimotor, auditory, and visual cortices. Meanwhile, we also showed that LGI growth in most cortical regions was positively correlated with the brain volume growth, which is particularly significant in the prefrontal cortex in the first year. In addition, we observed gender differences in both cortical GIs and LGIs in the first 2 years, with the males having larger GIs than females at 2 years of age. This study provides valuable information on normal cortical folding development in infancy and early childhood.

Distinct cortical and sub-cortical neurogenic domains for GABAergic interneuron precursor transcription factors NKX2.1, OLIG2 and COUP-TFII in early fetal human telencephalon.

PubMed

Alzu'bi, Ayman; Lindsay, Susan; Kerwin, Janet; Looi, Shi Jie; Khalil, Fareha; Clowry, Gavin J

2017-07-01

The extent of similarities and differences between cortical GABAergic interneuron generation in rodent and primate telencephalon remains contentious. We examined expression of three interneuron precursor transcription factors, alongside other markers, using immunohistochemistry on 8-12 post-conceptional weeks (PCW) human telencephalon sections. NKX2.1, OLIG2, and COUP-TFII expression occupied distinct (although overlapping) neurogenic domains which extended into the cortex and revealed three CGE compartments: lateral, medial, and ventral. NKX2.1 expression was very largely confined to the MGE, medial CGE, and ventral septum confirming that, at this developmental stage, interneuron generation from NKX2.1+ precursors closely resembles the process observed in rodents. OLIG2 immunoreactivity was observed in GABAergic cells of the proliferative zones of the MGE and septum, but not necessarily co-expressed with NKX2.1, and OLIG2 expression was also extensively seen in the LGE, CGE, and cortex. At 8 PCW, OLIG2+ cells were only present in the medial and anterior cortical wall suggesting a migratory pathway for interneuron precursors via the septum into the medial cortex. By 12 PCW, OLIG2+ cells were present throughout the cortex and many were actively dividing but without co-expressing cortical progenitor markers. Dividing COUP-TFII+ progenitor cells were localized to ventral CGE as previously described but were also numerous in adjacent ventral cortex; in both the cases, COUP-TFII was co-expressed with PAX6 in proliferative zones and TBR1 or calretinin in post-mitotic cortical neurons. Thus COUP-TFII+ progenitors gave rise to pyramidal cells, but also interneurons which not only migrated posteriorly into the cortex from ventral CGE but also anteriorly via the LGE.

A direct translaminar inhibitory circuit tunes cortical output

PubMed Central

Pluta, Scott; Naka, Alexander; Veit, Julia; Telian, Gregory; Yao, Lucille; Hakim, Richard; Taylor, David; Adesnik, Hillel

2015-01-01

Summary Anatomical and physiological experiments have outlined a blueprint for the feed-forward flow of activity in cortical circuits: signals are thought to propagate primarily from the middle cortical layer, L4, up to L2/3, and down to the major cortical output layer, L5. Pharmacological manipulations, however, have contested this model and suggested that L4 may not be critical for sensory responses of neurons in either superficial or deep layers. To address these conflicting models we reversibly manipulated L4 activity in awake, behaving mice using cell-type specific optogenetics. In contrast to both prevailing models, we show that activity in L4 directly suppresses L5, in part by activating deep, fast spiking inhibitory neurons. Our data suggest that the net impact of L4 activity is to sharpen the spatial representations of L5 neurons. Thus we establish a novel translaminar inhibitory circuit in the sensory cortex that acts to enhance the feature selectivity of cortical output. PMID:26414615

Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons

PubMed Central

Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew CN; Swindale, Nicholas V; Murphy, Timothy H

2017-01-01

Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps. DOI: http://dx.doi.org/10.7554/eLife.19976.001 PMID:28160463

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.

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

Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

PubMed Central

Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

2014-01-01

Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563

Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons.

PubMed

Canali, Giorgia; Garcia, Marta; Hivert, Bruno; Pinatel, Delphine; Goullancourt, Aline; Oguievetskaia, Ksenia; Saint-Martin, Margaux; Girault, Jean-Antoine; Faivre-Sarrailh, Catherine; Goutebroze, Laurence

2018-06-01

The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro. Loss of one Cntnap2 allele is sufficient to elicit axonal growth alteration, revealing a situation that may be relevant for CNTNAP2 heterozygosity in ASD patients. Then, we show that the two ASD variants I869T and G731S, which present impaired binding to Contactin2/TAG-1, do not rescue axonal growth deficits. We find that the variant R1119H leading to protein trafficking defects and retention in the endoplasmic reticulum has a dominant-negative effect on heterozygous Cntnap2 cortical neuron axon growth, through oligomerization with wild-type Caspr2. Finally, we identify an additional variant (N407S) with a dominant-negative effect on axon growth although it is well-localized at the membrane and properly binds to Contactin2. Thus, our data identify a new neurodevelopmental function for Caspr2, the dysregulation of which may contribute to clinical manifestations of ASD, and provide evidence that CNTNAP2 heterozygous missense variants may contribute to pathogenicity in ASD, through selective mechanisms.

NMDA Receptor Regulation Prevents Regression of Visual Cortical Function in the Absence of Mecp2

PubMed Central

Durand, Severine; Patrizi, Annarita; Quast, Kathleen B.; Hachigian, Lea; Pavlyuk, Roman; Saxena, Alka; Carninci, Piero; Hensch, Takao K.; Fagiolini, Michela

2012-01-01

SUMMARY Brain function is shaped by postnatal experience and vulnerable to disruption of Methyl-CpG-binding protein, Mecp2, in multiple neurodevelopmental disorders. How Mecp2 contributes to the experience-dependent refinement of specific cortical circuits and their impairment remains unknown. We analyzed vision in gene-targeted mice and observed an initial normal development in the absence of Mecp2. Visual acuity then rapidly regressed after postnatal day P35–40 and cortical circuits largely fell silent by P55-60. Enhanced inhibitory gating and an excess of parvalbumin-positive, perisomatic input preceded the loss of vision. Both cortical function and inhibitory hyperconnectivity were strikingly rescued independent of Mecp2 by early sensory deprivation or genetic deletion of the excitatory NMDA receptor subunit, NR2A. Thus, vision is a sensitive biomarker of progressive cortical dysfunction and may guide novel, circuit-based therapies for Mecp2 deficiency. PMID:23259945

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

DMRTA2 (DMRT5) is mutated in a novel cortical brain malformation.

PubMed

Urquhart, J E; Beaman, G; Byers, H; Roberts, N A; Chervinsky, E; O'Sullivan, J; Pilz, D; Fry, A; Williams, S G; Bhaskar, S S; Khayat, M; Simanovsky, N; Shachar, I B; Shalev, S A; Newman, W G

2016-06-01

Lissencephaly is a phenotypically and genetically heterogeneous group of cortical brain malformations due to abnormal neuronal migration. The identification of many causative genes has increased the understanding of normal brain development. A consanguineous family was ascertained with three siblings affected by a severe prenatal neurodevelopmental disorder characterised by fronto-parietal pachygyria, agenesis of the corpus callosum and progressive severe microcephaly. Autozygosity mapping and exome sequencing identified a homozygous novel single base pair deletion, c.1197delT in DMRTA2, predicted to result in a frameshift variant p.(Pro400Leufs*33). DMRTA2 encodes doublesex and mab-3-related transcription factor a2, a transcription factor key to the development of the dorsal telencephalon. Data from murine and zebrafish knockout models are consistent with the variant of DMTRA2 (DMRT5) as responsible for the cortical brain phenotype. Our study suggests that loss of function of DMRTA2 leads to a novel disorder of cortical development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Longitudinal development of cortical thickness, folding, and fiber density networks in the first 2 years of life.

PubMed

Nie, Jingxin; Li, Gang; Wang, Li; Shi, Feng; Lin, Weili; Gilmore, John H; Shen, Dinggang

2014-08-01

Quantitatively characterizing the development of cortical anatomical networks during the early stage of life plays an important role in revealing the relationship between cortical structural connection and high-level functional development. The development of correlation networks of cortical-thickness, cortical folding, and fiber-density is systematically analyzed in this article to study the relationship between different anatomical properties during the first 2 years of life. Specifically, longitudinal MR images of 73 healthy subjects from birth to 2 year old are used. For each subject at each time point, its measures of cortical thickness, cortical folding, and fiber density are projected to its cortical surface that has been partitioned into 78 cortical regions. Then, the correlation matrices for cortical thickness, cortical folding, and fiber density at each time point can be constructed, respectively, by computing the inter-regional Pearson correlation coefficient (of any pair of ROIs) across all 73 subjects. Finally, the presence/absence pattern (i.e., binary pattern) of the connection network is constructed from each inter-regional correlation matrix, and its statistical and anatomical properties are adopted to analyze the longitudinal development of anatomical networks. The results show that the development of anatomical network could be characterized differently by using different anatomical properties (i.e., using cortical thickness, cortical folding, or fiber density). Copyright © 2013 Wiley Periodicals, Inc.

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.

A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

PubMed Central

Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

2013-01-01

Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

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

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

Genotype-phenotype aspects of type 2 long QT syndrome.

PubMed

Shimizu, Wataru; Moss, Arthur J; Wilde, Arthur A M; Towbin, Jeffrey A; Ackerman, Michael J; January, Craig T; Tester, David J; Zareba, Wojciech; Robinson, Jennifer L; Qi, Ming; Vincent, G Michael; Kaufman, Elizabeth S; Hofman, Nynke; Noda, Takashi; Kamakura, Shiro; Miyamoto, Yoshihiro; Shah, Samit; Amin, Vinit; Goldenberg, Ilan; Andrews, Mark L; McNitt, Scott

2009-11-24

The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Previous studies were limited by population size in their ability to examine phenotypic effect of location, type, and topology. Study subjects included 858 type 2 LQTS patients with 162 different KCNH2 mutations in 213 proband-identified families. The Cox proportional-hazards survivorship model was used to evaluate independent contributions of clinical and genetic factors to the first cardiac events. For patients with missense mutations, the transmembrane pore (S5-loop-S6) and N-terminus regions were a significantly greater risk than the C-terminus region (hazard ratio [HR]: 2.87 and 1.86, respectively), but the transmembrane nonpore (S1-S4) region was not (HR: 1.19). Additionally, the transmembrane pore region was significantly riskier than the N-terminus or transmembrane nonpore regions (HR: 1.54 and 2.42, respectively). However, for nonmissense mutations, these other regions were no longer riskier than the C-terminus (HR: 1.13, 0.77, and 0.46, respectively). Likewise, subjects with nonmissense mutations were at significantly higher risk than were subjects with missense mutations in the C-terminus region (HR: 2.00), but that was not the case in other regions. This mutation location-type interaction was significant (p = 0.008). A significantly higher risk was found in subjects with mutations located in alpha-helical domains than in subjects with mutations in beta-sheet domains or other locations (HR: 1.74 and 1.33, respectively). Time-dependent beta-blocker use was associated with a significant 63% reduction in the risk of first cardiac events (p < 0.001). The KCNH2 missense mutations located in the transmembrane S5-loop-S6 region are associated with the greatest risk.

Prostaglandin E2 Increased Rat Cortical Bone Mass When Administered Immediately Following Ovariectomy

NASA Technical Reports Server (NTRS)

Ke, Hua Zhu; Jee, Webster S.S.; Zeng, Qing Qiang; Li, Mei; Lin, Bai Yun

1993-01-01

To investigate the effects of ovariectomy and the simultaneous administration of prostaglandin E2 (PGE2) on rat tibial shaft cortical bone histomorphometry, thirty-five 3 month-old female Sprague-Dawley rats were either ovariectomized (OVX), or sham ovariectomy (sham-OVX). The OVX rats were divided into three groups and treated with 0, 1 and 6 mg PGE2/kg/day for 90 days. The double fluorescent labeled undecalcified tibial shaft cross sections (proximal to the tibiofibular junction) of all the subjects were used for histomorphometry analysis. No differences in cross-sectional area and cortical bone area were found between sham-OVX and OVX controls, but OVX increased marrow area, intracortical porosity area and endocortical eroded perimeter. Periosteal and endocortical bone formation rates decreased with aging yet OVX prevented these changes. These OVX-induced increases in marrow area and endocortical eroded perimeter were prevented by 1 mg PGE2/kg/day treatment and added bone to periosteal and endocortical surfaces and to the marrow cavity. At the 6 mg/kg/day dose level, PGE2-treated OVX rats increased total tissue area, cortical bone area, marrow trabmular bone area, minimal cortical width and intracortical porosity area, and decreased marrow area compared to basal, sham-OVX and OVX controls. In addition, periosteal bone formation was elevated in the 6 mg PGE2/kg/day-treated OVX rats compared to OVX controls. Endocortical eroded perimeter increased from basal and sham-OVX control levels, but decreased from OVX control levels in the 6 mg PGE2/kg/day-treated OVX rats. Our study confirmed that ovariectomy does not cause osteopenia in tibial shaft cortical bone in rats, but it does stimulate endocortical bone resorption and enlarges marrow area. The new findings from the present study demonstrate that PGE2 prevents the OVX-induced increases in endocortical bone resorption and marrow area and adds additional bone to periosteal and endocortical surfaces and to marrow

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.

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.

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity.

PubMed

Osima, Marit; Kral, Rita; Borgen, Tove T; Høgestøl, Ingvild K; Joakimsen, Ragnar M; Eriksen, Erik F; Bjørnerem, Åshild

2017-04-01

Increased cortical porosity has been suggested as a possible factor increasing fracture propensity in patients with type 2 diabetes mellitus (T2DM). This is a paradox because cortical porosity is generally associated with high bone turnover, while bone turnover is reduced in patients with T2DM. We therefore wanted to test the hypothesis that women with T2DM have lower bone turnover markers (BTM) and lower cortical porosity than those without diabetes, and that higher serum glucose and body mass index (BMI) are associated with lower BTM, and with lower cortical porosity. This cross-sectional study is based on a prior nested case-control study including 443 postmenopausal women aged 54-94years from the Tromsø Study, 211 with non-vertebral fracture and 232 fracture-free controls. Of those 443 participants, 22 women exhibited T2DM and 421 women did not have diabetes. All had fasting blood samples assayed for procollagen type I N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX) and glucose, and femoral subtrochanteric architecture was quantified using low-resolution clinical CT and StrAx1.0 software. Women with T2DM had higher serum glucose (7.2 vs. 5.3mmol/L), BMI (29.0 vs. 26.4kg/m 2 ), and higher femoral subtrochanteric total volumetric bone mineral density (vBMD) (783 vs. 715mgHA/cm 3 ), but lower cortical porosity (40.9 vs. 42.8%) than nondiabetic women (all p<0.05). Each standard deviation (SD) increment in glucose was associated with 0.10-0.12 SD lower PINP and CTX, and 0.13 SD lower cortical porosity (all p<0.05). Each SD increment in BMI was associated with 0.10-0.18 SD lower serum PINP and CTX, and 0.19 SD thicker cortices (all p<0.05). Increasing glucose and BMI were associated with lower bone turnover suggesting that reduced intracortical and endocortical remodeling leads to reduced porosity and thicker cortices. Using low-resolution clinical CT, cortical porosity was lower in women with T2DM compared to women

Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch Between Cortical and Striatal Interneurons

PubMed Central

McKinsey, Gabriel L.; Lindtner, Susan; Trzcinski, Brett; Visel, Axel; Pennacchio, Len A.; Huylebroeck, Danny; Higashi, Yujiro; Rubenstein, John L. R.

2013-01-01

Summary Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform towards a subtype of GABAeric striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome). PMID:23312518

Longitudinal development of cortical and subcortical gray matter from birth to 2 years.

PubMed

Gilmore, John H; Shi, Feng; Woolson, Sandra L; Knickmeyer, Rebecca C; Short, Sarah J; Lin, Weili; Zhu, Hongtu; Hamer, Robert M; Styner, Martin; Shen, Dinggang

2012-11-01

Very little is known about cortical development in the first years of life, a time of rapid cognitive development and risk for neurodevelopmental disorders. We studied regional cortical and subcortical gray matter volume growth in a group of 72 children who underwent magnetic resonance scanning after birth and at ages 1 and 2 years using a novel longitudinal registration/parcellation approach. Overall, cortical gray matter volumes increased substantially (106%) in the first year of life and less so in the second year (18%). We found marked regional differences in developmental rates, with primary motor and sensory cortices growing slower in the first year of life with association cortices growing more rapidly. In the second year of life, primary sensory regions continued to grow more slowly, while frontal and parietal regions developed relatively more quickly. The hippocampus grew less than other subcortical structures such as the amygdala and thalamus in the first year of life. It is likely that these patterns of regional gray matter growth reflect maturation and development of underlying function, as they are consistent with cognitive and functional development in the first years of life.

Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

PubMed

Cheng, A V; Ferrier, I N; Morris, C M; Jabeen, S; Sahgal, A; McKeith, I G; Edwardson, J A; Perry, R H; Perry, E K

1991-11-01

The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.

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

NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development.

PubMed

Piper, Michael; Barry, Guy; Harvey, Tracey J; McLeay, Robert; Smith, Aaron G; Harris, Lachlan; Mason, Sharon; Stringer, Brett W; Day, Bryan W; Wray, Naomi R; Gronostajski, Richard M; Bailey, Timothy L; Boyd, Andrew W; Richards, Linda J

2014-02-19

Epigenetic mechanisms are essential in regulating neural progenitor cell self-renewal, with the chromatin-modifying protein Enhancer of zeste homolog 2 (EZH2) emerging as a central player in promoting progenitor cell self-renewal during cortical development. Despite this, how Ezh2 is itself regulated remains unclear. Here, we demonstrate that the transcription factor nuclear factor IB (NFIB) plays a key role in this process. Nfib(-/-) mice exhibit an increased number of proliferative ventricular zone cells that express progenitor cell markers and upregulation of EZH2 expression within the neocortex and hippocampus. NFIB binds to the Ezh2 promoter and overexpression of NFIB represses Ezh2 transcription. Finally, key downstream targets of EZH2-mediated epigenetic repression are misregulated in Nfib(-/-) mice. Collectively, these results suggest that the downregulation of Ezh2 transcription by NFIB is an important component of the process of neural progenitor cell differentiation during cortical development.

Hierarchical genetic interactions between FOXG1 and LHX2 regulate the formation of the cortical hem in the developing telencephalon.

PubMed

Godbole, Geeta; Shetty, Ashwin S; Roy, Achira; D'Souza, Leora; Chen, Bin; Miyoshi, Goichi; Fishell, Gordon; Tole, Shubha

2018-01-09

During forebrain development, a telencephalic organizer called the cortical hem is crucial for inducing hippocampal fate in adjacent cortical neuroepithelium. How the hem is restricted to its medial position is therefore a fundamental patterning issue. Here, we demonstrate that Foxg1 - Lhx2 interactions are crucial for the formation of the hem. Loss of either gene causes a region of the cortical neuroepithelium to transform into hem. We show that FOXG1 regulates Lhx2 expression in the cortical primordium. In the absence of Foxg1 , the presence of Lhx2 is sufficient to suppress hem fate, and hippocampal markers appear selectively in Lhx2 -expressing regions. FOXG1 also restricts the temporal window in which loss of Lhx2 results in a transformation of cortical primordium into hem. Therefore, Foxg1 and Lhx2 form a genetic hierarchy in the spatiotemporal regulation of cortical hem specification and positioning, and together ensure the normal development of this hippocampal organizer. © 2018. Published by The Company of Biologists Ltd.

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

PubMed Central

Combs, Hannah L.; Jones, Theresa A.; Kozlowski, Dorothy A.

2016-01-01

Abstract Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI. PMID:26421759

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

PubMed

Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

PubMed

Liu, Bing; Zhang, Xiaolong; Cui, Yue; Qin, Wen; Tao, Yan; Li, Jin; Yu, Chunshui; Jiang, Tianzi

2017-05-01

Schizophrenia is highly heritable, whereas the effect of each genetic variant is very weak. Since clinical heterogeneity and complexity of schizophrenia is high, considerable effort has been made to relate genetic variants to underlying neurobiological aspects of schizophrenia (endophenotypes). Given the polygenic nature of schizophrenia, our goal was to form a measure of additive genetic risk and explore its relationship to cortical morphology. Utilizing the data from a recent genome-wide association study that included nearly 37 000 cases of schizophrenia, we computed a polygenic risk score (PGRS) for each subject in 2 independent and healthy general populations. We then investigated the effect of polygenic risk for schizophrenia on cortical gyrification calculated from 3.0T structural imaging data in the discovery dataset (N = 315) and replication dataset (N = 357). We found a consistent effect of the polygenic risk for schizophrenia on cortical gyrification in the inferior parietal lobules in 2 independent general-population samples. A higher PGRS was significantly associated with a lower local gyrification index in the bilateral inferior parietal lobles, where case-control differences have been reported in previous studies on schizophrenia. Our findings strongly support the effectiveness of both PGRSs and endophenotypes in establishing the genetic architecture of psychiatry. Our findings may provide some implications regarding individual differences in the genetic risk for schizophrenia to cortical morphology and brain development. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The 2007 AASM recommendations for EEG electrode placement in polysomnography: impact on sleep and cortical arousal scoring.

PubMed

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

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. Prospective, non-blinded, randomized comparison. Three Australian tertiary-care hospital clinical sleep laboratories. 30 PSGs from consecutive patients investigated for obstructive sleep apnea (OSA) during December 2007 and January 2008. N/A. 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. 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

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%).

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

PubMed Central

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

2011-01-01

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

Alteration of the Cortical Actin Cytoskeleton Deregulates Ca2+ Signaling, Monospermic Fertilization, and Sperm Entry

PubMed Central

Puppo, A.; Chun, Jong T.; Gragnaniello, Giovanni; Garante, Ezio; Santella, Luigia

2008-01-01

Background When preparing for fertilization, oocytes undergo meiotic maturation during which structural changes occur in the endoplasmic reticulum (ER) that lead to a more efficient calcium response. During meiotic maturation and subsequent fertilization, the actin cytoskeleton also undergoes dramatic restructuring. We have recently observed that rearrangements of the actin cytoskeleton induced by actin-depolymerizing agents, or by actin-binding proteins, strongly modulate intracellular calcium (Ca2+) signals during the maturation process. However, the significance of the dynamic changes in F-actin within the fertilized egg has been largely unclear. Methodology/Principal Findings We have measured changes in intracellular Ca2+ signals and F-actin structures during fertilization. We also report the unexpected observation that the conventional antagonist of the InsP3 receptor, heparin, hyperpolymerizes the cortical actin cytoskeleton in postmeiotic eggs. Using heparin and other pharmacological agents that either hypo- or hyperpolymerize the cortical actin, we demonstrate that nearly all aspects of the fertilization process are profoundly affected by the dynamic restructuring of the egg cortical actin cytoskeleton. Conclusions/Significance Our findings identify important roles for subplasmalemmal actin fibers in the process of sperm-egg interaction and in the subsequent events related to fertilization: the generation of Ca2+ signals, sperm penetration, cortical granule exocytosis, and the block to polyspermy. PMID:18974786

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

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.

Spatial heterogeneity of cortical receptive fields and its impact on multisensory interactions.

PubMed

Carriere, Brian N; Royal, David W; Wallace, Mark T

2008-05-01

Investigations of multisensory processing at the level of the single neuron have illustrated the importance of the spatial and temporal relationship of the paired stimuli and their relative effectiveness in determining the product of the resultant interaction. Although these principles provide a good first-order description of the interactive process, they were derived by treating space, time, and effectiveness as independent factors. In the anterior ectosylvian sulcus (AES) of the cat, previous work hinted that the spatial receptive field (SRF) architecture of multisensory neurons might play an important role in multisensory processing due to differences in the vigor of responses to identical stimuli placed at different locations within the SRF. In this study the impact of SRF architecture on cortical multisensory processing was investigated using semichronic single-unit electrophysiological experiments targeting a multisensory domain of the cat AES. The visual and auditory SRFs of AES multisensory neurons exhibited striking response heterogeneity, with SRF architecture appearing to play a major role in the multisensory interactions. The deterministic role of SRF architecture was tightly coupled to the manner in which stimulus location modulated the responsiveness of the neuron. Thus multisensory stimulus combinations at weakly effective locations within the SRF resulted in large (often superadditive) response enhancements, whereas combinations at more effective spatial locations resulted in smaller (additive/subadditive) interactions. These results provide important insights into the spatial organization and processing capabilities of cortical multisensory neurons, features that may provide important clues as to the functional roles played by this area in spatially directed perceptual processes.

Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells

PubMed Central

Baird, Michelle A.; Billington, Neil; Wang, Aibing; Adelstein, Robert S.; Sellers, James R.; Fischer, Robert S.; Waterman, Clare M.

2017-01-01

The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A “pulses” occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell–cell or cell–ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase– or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. PMID:27881665

Cortical GluN2B deletion attenuates punished suppression of food reward-seeking.

PubMed

Radke, Anna K; Nakazawa, Kazu; Holmes, Andrew

2015-10-01

Compulsive behavior, which is a hallmark of psychiatric disorders such as addiction and obsessive-compulsive disorder, engages corticostriatal circuits. Previous studies indicate a role for corticostriatal N-methyl-D-aspartate receptors (NMDARs) in mediating compulsive-like responding for drugs of abuse, but the specific receptor subunits controlling reward-seeking in the face of punishment remain unclear. The current study assessed the involvement of corticostriatal GluN2B-containing NMDARs in measures of persistent and punished food reward-seeking. Mice with genetic deletion of GluN2B in one of three distinct neuronal populations, cortical principal neurons, forebrain interneurons, or striatal medium spiny neurons, were tested for (1) sustained food reward-seeking when reward was absent, (2) reward-seeking under a progressive ratio schedule of reinforcement, and (3) persistent reward-seeking after a footshock punishment. Mutant mice with genetic deletion of GluN2B in cortical principal neurons demonstrated attenuated suppression of reward-seeking during punishment. These mice performed normally on other behavioral measures, including an assay for pain sensitivity. Mutants with interneuronal or striatal GluN2B deletions were normal on all behavioral assays. Current findings offer novel evidence that loss of GluN2B-containing NMDARs expressed on principal neurons in the cortex results in reduced punished food reward-seeking. These data support the involvement of GluN2B subunit in cortical circuits regulating cognitive flexibility in a variety of settings, with implications for understanding the basis of inflexible behavior in neuropsychiatric disorders including obsessive-compulsive disorders (OCD) and addictions.

EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages

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

Gu, Da-min; Lu, Pei-Hua, E-mail: lphty1_1@163.com; Zhang, Ke

In this study, we tested the potential role of astragaloside IV (AS-IV) against oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damages in murine cortical neurons, and studied the associated signaling mechanisms. AS-IV exerted significant neuroprotective effects against OGD/R by reducing reactive oxygen species (ROS) accumulation, thereby attenuating oxidative stress and neuronal cell death. We found that AS-IV treatment in cortical neurons resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by Nrf2 Ser-40 phosphorylation, and its nuclear localization, as well as transcription of antioxidant-responsive element (ARE)-regulated genes: heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and sulphiredoxin 1 (SRXN-1). Knockdown of Nrf2 throughmore » lentiviral shRNAs prevented AS-IV-induced ARE genes transcription, and abolished its anti-oxidant and neuroprotective activities. Further, we discovered that AS-IV stimulated heparin-binding-epidermal growth factor (HB-EGF) release to trans-activate epidermal growth factor receptor (EGFR) in cortical neurons. Blockage or silencing EGFR prevented Nrf2 activation by AS-IV, thus inhibiting AS-IV-mediated anti-oxidant and neuroprotective activities against OGD/R. In summary, AS-IV protects cortical neurons against OGD/R damages through activating of EGFR-Nrf2 signaling. - Highlights: • Pre-treatment of astragaloside IV (AS-IV) protects murine cortical neurons from OGD/R. • AS-IV activates Nrf2-ARE signaling in murine cortical neurons. • Nrf2 is required for AS-IV-mediated anti-oxidant and neuroprotective activities. • AS-IV stimulates HB-EGF release to trans-activate EGFR in murine cortical neurons. • EGFR mediates AS-IV-induced Nrf2 activation and neuroprotection against OGD/R.« less

Improved autologous cortical bone harvest and viability with 2Flute otologic burs.

PubMed

Roth, Adam A; Tang, Pei-Ciao; Ye, Michael J; Mohammad, Khalid S; Nelson, Rick F

2018-01-01

To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration. Institutional review board-approved prospective cohort study. Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified. Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm 2 vs. 66 ± 8 μm 2 ; P < 0.05) and 4 mm diameter (70 ± 8 μm 2 vs. 50 ± 3 μm 2 ; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips. Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing. NA. Laryngoscope, 128:E41-E46, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

SKA2 Methylation is associated with Decreased Prefrontal Cortical Thickness and Greater PTSD Severity among Trauma-Exposed Veterans

PubMed Central

Sadeh, Naomi; Spielberg, Jeffrey M.; Logue, Mark W.; Wolf, Erika J.; Smith, Alicia K.; Lusk, Joanna; Hayes, Jasmeet P.; Sperbeck, Emily; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.; Carter, Weleetka C.; Stone, Annjanette; Schichman, Steven A.; Humphries, Donald E.; Miller, Mark W.

2015-01-01

Methylation of the SKA2 gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness, and psychiatric phenotypes linked to suicide in trauma-exposed veterans. 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the CpG locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated SNP (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD), and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylationadj). Specifically, DNA methylationadj was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylationadj and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylationadj of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility. PMID:26324104

The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol.

PubMed

Osier, Nicole; Dixon, C Edward

2016-01-01

Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details-that should be reported in CCI studies-will be noted.

Differential Impact of Multiple Sclerosis on Cortical and Deep Gray Matter Structures in African Americans and Caucasian Americans.

PubMed

Al-Kawaz, Mais; Monohan, Elizabeth; Morris, Eric; Perumal, Jai S; Nealon, Nancy; Vartanian, Timothy; Gauthier, Susan A

2017-05-01

African Americans with multiple sclerosis (AAwMS) have different disease phenotypes when compared to Caucasians Americans with MS (CAwMS). The pathologic basis of this difference in disease presentation is unknown. Fifty-Four AAwMS and 54 CAwMS were appropriately matched for age, gender, treatment duration, and disease duration. FreeSurfer was used to segment brain white matter and gray matter from T1 images and compute thalamic volume. Regional cortical thickness was calculated using QDEC. The 2 matched cohorts differed in disability, with AAwMS demonstrating significantly higher EDSS scores (2.3±2.2 vs. 1.3±1.5, P < .009), yet the 2 populations had similar T2 hyperintense lesion volumes (P = .35). AAwMS had a significantly lower total global cortical thickness when compared to CAwMS (P = .03). Controlling for EDSS, AAwMS showed multiple cortical regions to be significantly thinner than CAwMS; these included areas within the temporal, parietal and occipital lobes, as well as the precentral and postcentral gyrus. Middletemporal cortex was most affected in AAwMS in the left hemisphere (P = .009), while the superiortemporal cortex was most affected in the right hemisphere (P = .0001). In contrast, thalamic volume was significantly reduced in CAwMS when compared to AAwMS (P = .01). In both groups, worse disability was associated with lower total thalamic volume percentage. AAwMS and CAwMS patients differ with regard to global and regional cortical thickness and thalamic volume. This diverging pattern of gray matter volumetrics among otherwise matched patients suggests that racial-specific disease differences may exist. Copyright © 2016 by the American Society of Neuroimaging.

Electrical remodelling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents.

PubMed

Nerbonne, Jeanne M; Gerber, Benjamin R; Norris, Aaron; Burkhalter, Andreas

2008-03-15

Considerable experimental evidence has accumulated demonstrating a role for voltage-gated K(+) (Kv) channel pore-forming (alpha) subunits of the Kv4 subfamily in the generation of fast transient outward K(+), I(A), channels. Immunohistochemical data suggest that I(A) channels in hippocampal and cortical pyramidal neurons reflect the expression of homomeric Kv4.2 channels. The experiments here were designed to define directly the role of Kv4.2 in the generation of I(A) in cortical pyramidal neurons and to determine the functional consequences of the targeted deletion of Kv4.2 on the resting and active membrane properties of these cells. Whole-cell voltage-clamp recordings, obtained from visual cortical pyramidal neurons isolated from mice in which the KCND2 (Kv4.2) locus was disrupted (Kv4.2-/- mice), revealed that I(A) is indeed eliminated. In addition, the densities of other Kv current components, specifically I(K) and I(ss), are increased significantly (P < 0.001) in most ( approximately 80%) Kv4.2-/- cells. The deletion of KCND2 (Kv4.2) and the elimination of I(A) is also accompanied by the loss of the Kv4 channel accessory protein KChIP3, suggesting that in the absence of Kv4.2, the KChIP3 protein is targeted for degradation. The expression levels of several Kv alpha subunits (Kv4.3, Kv1.4, Kv2.1, Kv2.2), however, are not measurably altered in Kv4.2-/- cortices. Although I(A) is eliminated in Kv4.2-/- pyramidal neurons, the mean +/- s.e.m. current threshold for action potential generation and the waveforms of action potentials are indistinguishable from those recorded from wild-type cells. Repetitive firing is also maintained in Kv4.2-/- cortical pyramidal neurons, suggesting that the increased densities of I(K) and I(ss) compensate for the in vivo loss of I(A).

Cortical-basal ganglionic degeneration.

PubMed

Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

1990-08-01

We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

PubMed

Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

2014-01-01

Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

PubMed

Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

2014-06-18

Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

Right frontal pole cortical thickness and executive functioning in children with traumatic brain injury: the impact on social problems.

PubMed

Levan, Ashley; Black, Garrett; Mietchen, Jonathan; Baxter, Leslie; Brock Kirwan, C; Gale, Shawn D

2016-12-01

Cognitive and social outcomes may be negatively affected in children with a history of traumatic brain injury (TBI). We hypothesized that executive function would mediate the association between right frontal pole cortical thickness and problematic social behaviors. Child participants with a history of TBI were recruited from inpatient admissions for long-term follow-up (n = 23; average age = 12.8, average time post-injury =3.2 years). Three measures of executive function, the Trail Making Test, verbal fluency test, and the Conners' Continuous Performance Test-Second edition (CPT-II), were administered to each participant while caregivers completed the Childhood Behavior Checklist (CBCL). All participants underwent brain magnetic resonance imaging following cognitive testing. Regression analysis demonstrated right frontal pole cortical thickness significantly predicted social problems. Measures of executive functioning also significantly predicted social problems; however, the mediation model testing whether executive function mediated the relationship between cortical thickness and social problems was not statistically significant. Right frontal pole cortical thickness and omission errors on the CPT-II predicted Social Problems on the CBCL. Results did not indicate that the association between cortical thickness and social problems was mediated by executive function.

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

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

The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol

PubMed Central

Osier, Nicole; Dixon, C. Edward

2017-01-01

Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details—that should be reported in CCI studies—will be noted. PMID:27604719

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.

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

Parvalbumin-producing cortical interneurons receive inhibitory inputs on proximal portions and cortical excitatory inputs on distal dendrites.

PubMed

Kameda, Hiroshi; Hioki, Hiroyuki; Tanaka, Yasuyo H; Tanaka, Takuma; Sohn, Jaerin; Sonomura, Takahiro; Furuta, Takahiro; Fujiyama, Fumino; Kaneko, Takeshi

2012-03-01

To examine inputs to parvalbumin (PV)-producing interneurons, we generated transgenic mice expressing somatodendritic membrane-targeted green fluorescent protein specifically in the interneurons, and completely visualized their dendrites and somata. Using immunolabeling for vesicular glutamate transporter (VGluT)1, VGluT2, and vesicular GABA transporter, we found that VGluT1-positive terminals made contacts 4- and 3.1-fold more frequently with PV-producing interneurons than VGluT2-positive and GABAergic terminals, respectively, in the primary somatosensory cortex. Even in layer 4, where VGluT2-positive terminals were most densely distributed, VGluT1-positive inputs to PV-producing interneurons were 2.4-fold more frequent than VGluT2-positive inputs. Furthermore, although GABAergic inputs to PV-producing interneurons were as numerous as VGluT2-positive inputs in most cortical layers, GABAergic inputs clearly preferred the proximal dendrites and somata of the interneurons, indicating that the sites of GABAergic inputs were more optimized than those of VGluT2-positive inputs. Simulation analysis with a PV-producing interneuron model compatible with the present morphological data revealed a plausible reason for this observation, by showing that GABAergic and glutamatergic postsynaptic potentials evoked by inputs to distal dendrites were attenuated to 60 and 87%, respectively, of those evoked by somatic inputs. As VGluT1-positive and VGluT2-positive axon terminals were presumed to be cortical and thalamic glutamatergic inputs, respectively, cortical excitatory inputs to PV-producing interneurons outnumbered the thalamic excitatory and intrinsic inhibitory inputs more than two-fold in any cortical layer. Although thalamic inputs are known to evoke about two-fold larger unitary excitatory postsynaptic potentials than cortical ones, the present results suggest that cortical inputs control PV-producing interneurons at least as strongly as thalamic inputs. © 2012 The

Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells.

PubMed

Baird, Michelle A; Billington, Neil; Wang, Aibing; Adelstein, Robert S; Sellers, James R; Fischer, Robert S; Waterman, Clare M

2017-01-15

The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A "pulses" occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell-cell or cell-ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase- or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. © 2017 Baird et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

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

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

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.

LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11.

PubMed

Muralidharan, Bhavana; Khatri, Zeba; Maheshwari, Upasana; Gupta, Ritika; Roy, Basabdatta; Pradhan, Saurabh J; Karmodiya, Krishanpal; Padmanabhan, Hari; Shetty, Ashwin S; Balaji, Chinthapalli; Kolthur-Seetharam, Ullas; Macklis, Jeffrey D; Galande, Sanjeev; Tole, Shubha

2017-01-04

In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity. The functional complexity of the cerebral cortex arises from an array of distinct neuronal subtypes with unique connectivity patterns that are produced from common progenitors. This study reveals that transcription factor LHX2 regulates the numbers of specific cortical output neuron subtypes by controlling the genes that are required to produce them. Loss or increase in LHX2 during neurogenesis is sufficient to increase or decrease, respectively, a particular subcerebrally projecting population. Mechanistically, LHX2 interacts with chromatin modifying protein complexes to edit the chromatin landscape of its targets Fezf2 and Sox11, which regulates their expression and consequently the identities of the neurons produced. Thus, LHX2 is a key component of the control network for producing neurons that will participate in cortical circuitry. Copyright © 2017 Muralidharan et al.

High-resolution 2-deoxyglucose mapping of functional cortical columns in mouse barrel cortex.

PubMed

McCasland, J S; Woolsey, T A

1988-12-22

Cortical columns associated with barrels in layer IV of the somatosensory cortex were characterized by high-resolution 2-deoxy-D-glucose (2DG) autoradiography in freely behaving mice. The method demonstrates a more exact match between columnar labeling and cytoarchitectonic barrel boundaries than previously reported. The pattern of cortical activation seen with stimulation of a single whisker (third whisker in the middle row of large hairs--C3) was compared with the patterns from two control conditions--normal animals with all whiskers present ("positive control")--and with all large whiskers clipped ("negative control"). Two types of measurements were made from 2DG autoradiograms of tangential cortical sections: 1) labeled cells were identified by eye and tabulated with a computer, and 2) grain densities were obtained automatically with a computer-controlled microscope and image processor. We studied the fine-grained patterns of 2DG labeling in a nine-barrel grid with the C3 barrel in the center. From the analysis we draw five major conclusions. 1. Approximately 30-40% of the total number of neurons in the C3 barrel column are activated when only the C3 whisker is stimulated. This is about twice the number of neurons labeled in the C3 column when all whiskers are stimulated and about ten times the number of neurons labeled when all large whiskers are clipped. 2. There is evidence for a vertical functional organization within a barrel-related whisker column which has smaller dimensions in the tangential direction than a barrel. There are densely labeled patches within a barrel which are unique to an individual cortex. The same patchy pattern is found in the appropriate regions of sections above and below the barrels through the full thickness of the cortex. This functional arrangement could be considered to be a "minicolumn" or more likely a group of "minicolumns" (Mountcastle: In G.M. Edelman and U.B. Mountcastle (eds): The Material Brain: Cortical Organization

Cortical tremor: a variant of cortical reflex myoclonus.

PubMed

Ikeda, A; Kakigi, R; Funai, N; Neshige, R; Kuroda, Y; Shibasaki, H

1990-10-01

Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit.

PubMed

Wang, Chia-Fang; Hsing, Hsiang-Wei; Zhuang, Zi-Hui; Wen, Meng-Hsuan; Chang, Wei-Jen; Briz, Carlos G; Nieto, Marta; Shyu, Bai Chuang; Chou, Shen-Ju

2017-01-24

Cortical neurons must be specified and make the correct connections during development. Here, we examine a mechanism initiating neuronal circuit formation in the barrel cortex, a circuit comprising thalamocortical axons (TCAs) and layer 4 (L4) neurons. When Lhx2 is selectively deleted in postmitotic cortical neurons using conditional knockout (cKO) mice, L4 neurons in the barrel cortex are initially specified but fail to form cellular barrels or develop polarized dendrites. In Lhx2 cKO mice, TCAs from the thalamic ventral posterior nucleus reach the barrel cortex but fail to further arborize to form barrels. Several activity-regulated genes and genes involved in regulating barrel formation are downregulated in the Lhx2 cKO somatosensory cortex. Among them, Btbd3, an activity-regulated gene controlling dendritic development, is a direct downstream target of Lhx2. We find that Lhx2 confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of Btbd3. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Disruption of neurogenesis and cortical development in transgenic mice misexpressing Olig2, a gene in the Down syndrome critical region.

PubMed

Liu, Wei; Zhou, Hui; Liu, Lei; Zhao, Chuntao; Deng, Yaqi; Chen, Lina; Wu, Laiman; Mandrycky, Nicole; McNabb, Christopher T; Peng, Yuanbo; Fuchs, Perry N; Lu, Jie; Sheen, Volney; Qiu, Mengsheng; Mao, Meng; Lu, Q Richard

2015-05-01

The basic helix-loop-helix (bHLH) transcription factor Olig2 is crucial for mammalian central nervous system development. Human ortholog OLIG2 is located in the Down syndrome critical region in trisomy 21. To investigate the effect of Olig2 misexpression on brain development, we generated a developmentally regulated Olig2-overexpressing transgenic line with a Cre/loxP system. The transgenic mice with Olig2 misexpression in cortical neural stem/progenitor cells exhibited microcephaly, cortical dyslamination, hippocampus malformation, and profound motor deficits. Ectopic misexpression of Olig2 impaired cortical progenitor proliferation and caused precocious cell cycle exit. Massive neuronal cell death was detected in the developing cortex of Olig2-misexpressing mice. In addition, Olig2 misexpression led to a significant downregulation of neuronal specification factors including Ngn1, Ngn2 and Pax6, and a defect in cortical neurogenesis. Chromatin-immunoprecipitation and sequencing (ChIP-Seq) analysis indicates that Olig2 directly targets the promoter and/or enhancer regions of Nfatc4, Dscr1/Rcan1 and Dyrk1a, the critical neurogenic genes that contribute to Down syndrome phenotypes, and inhibits their expression. Together, our study suggests that Olig2 misexpression in neural stem cells elicits neurogenesis defects and neuronal cell death, which may contribute to developmental disorders including Down syndrome, where OLIG2 is triplicated on chromosomal 21. Copyright © 2015 Elsevier Inc. 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

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.

Elastic Properties of Chimpanzee Craniofacial Cortical Bone

PubMed Central

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

2017-01-01

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

Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function

PubMed Central

Castejon, Carlos; Barros-Zulaica, Natali; Nuñez, Angel

2016-01-01

Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas. PMID:26820514

INTERFRAGMENTARY SURFACE AREA AS AN INDEX OF COMMINUTION SEVERITY IN CORTICAL BONE IMPACT

PubMed Central

Beardsley, Christina L.; Anderson, Donald D.; Marsh, J. Lawrence; Brown, Thomas D.

2008-01-01

Summary A monotonic relationship is expected between energy absorption and fracture surface area generation for brittle solids, based on fracture mechanics principles. It was hypothesized that this relationship is demonstrable in bone, to the point that on a continuous scale, comminuted fractures created with specific levels of energy delivery could be discriminated from one another. Using bovine cortical bone segments in conjunction with digital image analysis of CT fracture data, the surface area freed by controlled impact fracture events was measured. The results demonstrated a statistically significant (p<0.0001) difference in measured de novo surface area between three specimen groups, over a range of input energies from 0.423 to 0.702 J/g. Local material properties were also incorporated into these measurements via CT Hounsfield intensities. This study confirms that comminution severity of bone fractures can indeed be measured on a continuous scale, based on energy absorption. This lays a foundation for similar assessments in human injuries. PMID:15885492

Cortical afferents onto the nucleus Reticularis thalami promote plasticity of low-threshold excitability through GluN2C-NMDARs.

PubMed

Fernandez, Laura M J; Pellegrini, Chiara; Vantomme, Gil; Béard, Elidie; Lüthi, Anita; Astori, Simone

2017-09-25

Thalamus and cortex represent a highly integrated processing unit that elaborates sensory representations. Interposed between cortex and thalamus, the nucleus Reticularis thalami (nRt) receives strong cortical glutamatergic input and mediates top-down inhibitory feedback to thalamus. Despite growing appreciation that the nRt is integral for thalamocortical functions from sleep to attentional wakefulness, we still face considerable gaps in the synaptic bases for cortico-nRt communication and plastic regulation. Here, we examined modulation of nRt excitability by cortical synaptic drive in Ntsr1-Cre x ChR2 tg/+ mice expressing Channelrhodopsin2 in layer 6 corticothalamic cells. We found that cortico-nRt synapses express a major portion of NMDA receptors containing the GluN2C subunit (GluN2C-NMDARs). Upon repetitive photoactivation (10 Hz trains), GluN2C-NMDARs induced a long-term increase in nRt excitability involving a potentiated recruitment of T-type Ca 2+ channels. In anaesthetized mice, analogous stimulation of cortical afferents onto nRt produced long-lasting changes in cortical local field potentials (LFPs), with delta oscillations being augmented at the expense of slow oscillations. This shift in LFP spectral composition was sensitive to NMDAR blockade in the nRt. Our data reveal a novel mechanism involving plastic modification of synaptically recruited T-type Ca 2+ channels and nRt bursting and indicate a critical role for GluN2C-NMDARs in thalamocortical rhythmogenesis.

FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology.

PubMed

Yasuda-Yamahara, M; Rogg, M; Frimmel, J; Trachte, P; Helmstaedter, M; Schroder, P; Schiffer, M; Schell, C; Huber, T B

2018-01-11

Simplification and retraction of podocyte protrusions, generally termed as foot process effacement, is a uniform pathological pattern observed in the majority of glomerular disease, including focal segmental glomerulosclerosis. However, it is still incompletely understood how the interaction of cortical actin structures, actomyosin contractility and focal adhesions, is being orchestrated to control foot process morphology in health and disease. By uncovering the functional role of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now evidence, how cell-extracellular matrix (ECM) interactions modulate membrane tension and actomyosin contractility. A genetic modeling approach was applied by deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified human podocytes. Loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization associated with plasma membrane blebbing and a remodeling of focal adhesions. We further show that FERMT2 knockout podocytes have high levels of RhoA activation and concomitantly increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype. Thus, our findings establish a direct link between cell-matrix adhesions, cortical actin structures and plasma membrane tension allowing to better explain cell morphological changes in foot process effacement. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis.

PubMed

Padula, Maria Carmela; Schaer, Marie; Armando, Marco; Sandini, Corrado; Zöller, Daniela; Scariati, Elisa; Schneider, Maude; Eliez, Stephan

2018-01-17

Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile. In this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach. Our results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS. These results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.

Cellular organization of cortical barrel columns is whisker-specific

PubMed Central

Meyer, Hanno S.; Egger, Robert; Guest, Jason M.; Foerster, Rita; Reissl, Stefan; Oberlaender, Marcel

2013-01-01

The cellular organization of the cortex is of fundamental importance for elucidating the structural principles that underlie its functions. It has been suggested that reconstructing the structure and synaptic wiring of the elementary functional building block of mammalian cortices, the cortical column, might suffice to reverse engineer and simulate the functions of entire cortices. In the vibrissal area of rodent somatosensory cortex, whisker-related “barrel” columns have been referred to as potential cytoarchitectonic equivalents of functional cortical columns. Here, we investigated the structural stereotypy of cortical barrel columns by measuring the 3D neuronal composition of the entire vibrissal area in rat somatosensory cortex and thalamus. We found that the number of neurons per cortical barrel column and thalamic “barreloid” varied substantially within individual animals, increasing by ∼2.5-fold from dorsal to ventral whiskers. As a result, the ratio between whisker-specific thalamic and cortical neurons was remarkably constant. Thus, we hypothesize that the cellular architecture of sensory cortices reflects the degree of similarity in sensory input and not columnar and/or cortical uniformity principles. PMID:24101458

Interdigitated Color- and Disparity-Selective Columns within Human Visual Cortical Areas V2 and V3

PubMed Central

Polimeni, Jonathan R.; Tootell, Roger B.H.

2016-01-01

In nonhuman primates (NHPs), secondary visual cortex (V2) is composed of repeating columnar stripes, which are evident in histological variations of cytochrome oxidase (CO) levels. Distinctive “thin” and “thick” stripes of dark CO staining reportedly respond selectively to stimulus variations in color and binocular disparity, respectively. Here, we first tested whether similar color-selective or disparity-selective stripes exist in human V2. If so, available evidence predicts that such stripes should (1) radiate “outward” from the V1–V2 border, (2) interdigitate, (3) differ from each other in both thickness and length, (4) be spaced ∼3.5–4 mm apart (center-to-center), and, perhaps, (5) have segregated functional connections. Second, we tested whether analogous segregated columns exist in a “next-higher” tier area, V3. To answer these questions, we used high-resolution fMRI (1 × 1 × 1 mm3) at high field (7 T), presenting color-selective or disparity-selective stimuli, plus extensive signal averaging across multiple scan sessions and cortical surface-based analysis. All hypotheses were confirmed. V2 stripes and V3 columns were reliably localized in all subjects. The two stripe/column types were largely interdigitated (e.g., nonoverlapping) in both V2 and V3. Color-selective stripes differed from disparity-selective stripes in both width (thickness) and length. Analysis of resting-state functional connections (eyes closed) showed a stronger correlation between functionally alike (compared with functionally unlike) stripes/columns in V2 and V3. These results revealed a fine-scale segregation of color-selective or disparity-selective streams within human areas V2 and V3. Together with prior evidence from NHPs, this suggests that two parallel processing streams extend from visual subcortical regions through V1, V2, and V3. SIGNIFICANCE STATEMENT In current textbooks and reviews, diagrams of cortical visual processing highlight two distinct neural

Discovering Cortical Folding Patterns in Neonatal Cortical Surfaces Using Large-Scale Dataset

PubMed Central

Meng, Yu; Li, Gang; Wang, Li; Lin, Weili; Gilmore, John H.

2017-01-01

The cortical folding of the human brain is highly complex and variable across individuals. Mining the major patterns of cortical folding from modern large-scale neuroimaging datasets is of great importance in advancing techniques for neuroimaging analysis and understanding the inter-individual variations of cortical folding and its relationship with cognitive function and disorders. As the primary cortical folding is genetically influenced and has been established at term birth, neonates with the minimal exposure to the complicated postnatal environmental influence are the ideal candidates for understanding the major patterns of cortical folding. In this paper, for the first time, we propose a novel method for discovering the major patterns of cortical folding in a large-scale dataset of neonatal brain MR images (N = 677). In our method, first, cortical folding is characterized by the distribution of sulcal pits, which are the locally deepest points in cortical sulci. Because deep sulcal pits are genetically related, relatively consistent across individuals, and also stable during brain development, they are well suitable for representing and characterizing cortical folding. Then, the similarities between sulcal pit distributions of any two subjects are measured from spatial, geometrical, and topological points of view. Next, these different measurements are adaptively fused together using a similarity network fusion technique, to preserve their common information and also catch their complementary information. Finally, leveraging the fused similarity measurements, a hierarchical affinity propagation algorithm is used to group similar sulcal folding patterns together. The proposed method has been applied to 677 neonatal brains (the largest neonatal dataset to our knowledge) in the central sulcus, superior temporal sulcus, and cingulate sulcus, and revealed multiple distinct and meaningful folding patterns in each region. PMID:28229131

Increased Cortical Porosity in Type-2 Diabetic Postmenopausal Women with Fragility Fractures

PubMed Central

Patsch, Janina M.; Burghardt, Andrew J.; Yap, Samuel P.; Baum, Thomas; Schwartz, Ann V.; Joseph, Gabby B.; Link, Thomas M.

2012-01-01

The primary goal of this study was to assess peripheral bone microarchitecture and strength in diabetic postmenopausal women with fragility fractures (DMFx) and to compare them with diabetic women without fracture (DM). Secondary goals were to assess differences in non-diabetic women with (Fx) and without fragility fractures (Co) and in women with (DM) and without diabetes (Co). Eighty women (mean age 61.3±5.7 yrs) were recruited into these groups (n=20 per group). Participants underwent DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density, cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro-finite element analysis (μFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p=0.009; +95.4%, p=0.020), relative porosity (+58.1%; p=0.005; +87.9%, p=0.011) and endocortical bone surface (+10.9%, p=0.031; +11.5%, 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p=0.000) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p=0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius; +36.8%, p=0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p=0.031; −6.8%, p=0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing non-diabetic Fx and Co, we only found a non-significant trend with increase in pore volume (+38.9%, p=0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in

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.

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

PubMed

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

2010-11-01

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

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

Elastic Properties of Chimpanzee Craniofacial Cortical Bone.

PubMed

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

2016-12-01

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

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

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.

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.

Effect of vitamin K2 on cortical and cancellous bone mass and hepatic lipids in rats with combined methionine-choline deficiency.

PubMed

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

2011-05-01

The present study examined changes of cancellous and cortical bone in rats with combined methionine-choline deficiency (MCD). In addition, the effects of vitamin K2 on cortical and cancellous bone mass and hepatic lipids were investigated in rats with MCD. Six-week-old male Sprague-Dawley rats were randomized into three groups of ten, including an age-matched control (standard diet) group, an MCD diet group, and an MCD diet+vitamin K2 (menatetrenone at 30mg/kg/d orally, 5 times a week) group. After the one-month experimental period, histomorphometric analysis was performed on cortical and cancellous bone from the tibial diaphysis and proximal metaphysis, respectively, while histological examination of the liver was performed after staining with hematoxylin and eosin and Oil Red O. MCD rats displayed weight loss, diffuse and centrilobular fatty changes of the liver, and a decrease of the cancellous bone volume per tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular, periosteal, and endocortical bone formation along with increased trabecular and endocortical bone resorption. Administration of vitamin K2 to rats with MCD attenuated weight loss, accelerated the decrease of cancellous BV/TV due to an increase of bone remodeling, and ameliorated the decrease of percent Ct Ar by increasing periosteal and endocortical bone formation. Vitamin K2 administration also prevented MCD-induced diffuse fatty change of the liver. These findings suggest a beneficial effect of vitamin K2 on cortical bone mass and hepatic lipid metabolism in rats with MCD. The loss of cancellous bone mass could possibly have been due to re-distribution of minerals to cortical bone. Copyright © 2011 Elsevier Inc. All rights reserved.

Up-regulated neuronal COX-2 expression after cortical spreading depression is involved in non-REM sleep induction in rats.

PubMed

Cui, Yilong; Kataoka, Yosky; Inui, Takashi; Mochizuki, Takatoshi; Onoe, Hirotaka; Matsumura, Kiyoshi; Urade, Yoshihiro; Yamada, Hisao; Watanabe, Yasuyoshi

2008-03-01

Cortical spreading depression is an excitatory wave of depolarization spreading throughout cerebral cortex at a rate of 2-5 mm/min and has been implicated in various neurological disorders, such as epilepsy, migraine aura, and trauma. Although sleepiness or sleep is often induced by these neurological disorders, the cellular and molecular mechanism has remained unclear. To investigate whether and how the sleep-wake behavior is altered by such aberrant brain activity, we induced cortical spreading depression in freely moving rats, monitoring REM and non-REM (NREM) sleep and sleep-associated changes in cyclooxygenase (COX)-2 and prostaglandins (PGs). In such a model for aberrant neuronal excitation in the cerebral cortex, the amount of NREM sleep, but not of REM sleep, increased subsequently for several hours, with an up-regulated expression of COX-2 in cortical neurons and considerable production of PGs. A specific inhibitor of COX-2 completely arrested the increase in NREM sleep. These results indicate that up-regulated neuronal COX-2 would be involved in aberrant brain excitation-induced NREM sleep via production of PGs. (c) 2007 Wiley-Liss, Inc.

Store-depletion and hyperforin activate distinct types of Ca(2+)-conducting channels in cortical neurons.

PubMed

Gibon, Julien; Tu, Peng; Bouron, Alexandre

2010-06-01

Cortical neurons embryos (E13) from murine brain have a wide diversity of plasma membrane Ca(2+)-conducting channels. For instance, they express several types of transient receptor potential channels of C-type (TRPC) and hyperforin, a potent TRPC6-channel activator, controls the activity of TRPC6-like channels. In addition, E13 cortical neurons possess plasma membrane channels activated in response to the depletion of internal Ca(2+) pools. Since some TRPC channels seem to be involved in the activity of store-depletion-activated channels, we investigated whether hyperforin and the depletion of the Ca(2+) stores control similar or distinct Ca(2+) routes. Calcium imaging experiments performed with the fluorescent Ca(2+) indicator Fluo-4 showed that the TRPC3 channel blocker Pyr3 potently inhibits with an IC(50) of 0.5microM the entry of Ca(2+) triggered in response to the thapsigargin-dependent depletion of the Ca(2+) stores. On the other hand, Pyr3 does not block the hyperforin-sensitive Ca(2+) entry. In contrast to the hyperforin responses, the Ca(2+) entry through the store-depletion-activated channels is down-regulated by the competitive tyrosine kinase inhibitors genistein and PP2. In addition, the immunosuppressant FK506, known to modulate several classes of Ca(2+)-conducting channels, strongly attenuates the entry of Ca(2+) through the store-depletion-activated channels, leaving the hyperforin-sensitive responses unaffected. Hence, the Zn(2+) chelator TPEN markedly attenuated the hyperforin-sensitive responses without modifying the thapsigargin-dependent Ca(2+) signals. Pyr3-insensitive channels are key components of the hyperforin-sensitive channels, whereas the thapsigargin-dependent depletion of the Ca(2+) stores of the endoplasmic reticulum activates Pyr3-sensitive channels. Altogether, these data support the notion that hyperforin and the depletion of the Ca(2+) pools control distinct plasma membrane Ca(2+)-conducting channels. This report further

Renal Cortical Pyruvate Depletion during AKI

PubMed Central

Johnson, Ali C.M.; Becker, Kirsten

2014-01-01

Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15–60 minutes; 0–18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury. PMID:24385590

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.

Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

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

Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de

Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blotmore » analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a

FoxP2 regulates neurogenesis during embryonic cortical development.

PubMed

Tsui, David; Vessey, John P; Tomita, Hideaki; Kaplan, David R; Miller, Freda D

2013-01-02

The transcription factor FoxP2 has been associated with the development of human speech but the underlying cellular function of FoxP2 is still unclear. Here we provide evidence that FoxP2 regulates genesis of some intermediate progenitors and neurons in the mammalian cortex, one of the key centers for human speech. Specifically, knockdown of FoxP2 in embryonic cortical precursors inhibits neurogenesis, at least in part by inhibiting the transition from radial glial precursors to neurogenic intermediate progenitors. Moreover, overexpression of human, but not mouse, FoxP2 enhances the genesis of intermediate progenitors and neurons. In contrast, expression of a human FoxP2 mutant that causes vocalization deficits decreases neurogenesis, suggesting that in the murine system human FoxP2 acts as a gain-of-function protein, while a human FoxP2 mutant acts as a dominant-inhibitory protein. These results support the idea that FoxP2 regulates the transition from neural precursors to transit-amplifying progenitors and ultimately neurons, and shed light upon the molecular changes that might contribute to evolution of the mammalian cortex.

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.

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

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.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

PubMed

Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

2014-05-01

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

Gravitropism of Arabidopsis thaliana roots requires the polarization of PIN2 toward the root tip in meristematic cortical cells.

PubMed

Rahman, Abidur; Takahashi, Maho; Shibasaki, Kyohei; Wu, Shuang; Inaba, Takehito; Tsurumi, Seiji; Baskin, Tobias I

2010-06-01

In the root, the transport of auxin from the tip to the elongation zone, referred to here as shootward, governs gravitropic bending. Shootward polar auxin transport, and hence gravitropism, depends on the polar deployment of the PIN-FORMED auxin efflux carrier PIN2. In Arabidopsis thaliana, PIN2 has the expected shootward localization in epidermis and lateral root cap; however, this carrier is localized toward the root tip (rootward) in cortical cells of the meristem, a deployment whose function is enigmatic. We use pharmacological and genetic tools to cause a shootward relocation of PIN2 in meristematic cortical cells without detectably altering PIN2 polarization in other cell types or PIN1 polarization. This relocation of cortical PIN2 was negatively regulated by the membrane trafficking factor GNOM and by the regulatory A1 subunit of type 2-A protein phosphatase (PP2AA1) but did not require the PINOID protein kinase. When GNOM was inhibited, PINOID abundance increased and PP2AA1 was partially immobilized, indicating both proteins are subject to GNOM-dependent regulation. Shootward PIN2 specifically in the cortex was accompanied by enhanced shootward polar auxin transport and by diminished gravitropism. These results demonstrate that auxin flow in the root cortex is important for optimal gravitropic response.

Chemical induced demineralization study in cortical bone

NASA Astrophysics Data System (ADS)

Sales, E.; da Silva, C. E. R.; Letichevsky, S.; dos Santos, R.; Leitao, R.; dos Santos, C. T.; de Oliveira, L. F.; de Avillez, R.; Monteiro, M.; Costa-Felix, R.; Paciornik, S.; dos Anjos, M.

2018-05-01

In this work we present a study of demineralization in bovine cortical bone. We selected 9 fresh cortical bone samples from 2 diaphyseal femurs for analysis. Samples were demineralized for 24 h, 48 h, 72 h and 96 h using two concentrations of EDTA with different pH: EDTA 0.1 M (pH 10, alkaline) and EDTA 0.5 M (pH 7.4, neutral). We have employed μ-X-ray fluorescence (μ-XRF) and X-ray diffraction (XRD) to assess the degree of demineralization. EDTA solutions were analyzed for Calcium (Ca) and Phosphorous (P) extractions by Atomic Absorption Spectrophotometry (AAS) and Ion Chromatography (IC), respectively. Results from AAS and IC showed that EDTA 0.5 M (pH 7.4) removed two times more Ca and 3 times more P than EDTA 0.1 M (pH 10) in the first 24 hours. μ-XRF results presented that EDTA has a high capacity to bind Calcium and Phosphorus. On the other hand, despite the differences in concentration and pH, EDTA did not bind Zn and Sr. Results from XRD showed that EDTA with high concentration had a greater impact to the samples' crystallinity causing a severe damage.

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.

Cortical relapses in multiple sclerosis.

PubMed

Puthenparampil, Marco; Poggiali, Davide; Causin, Francesco; Rolma, Giuseppe; Rinaldi, Francesca; Perini, Paola; Gallo, Paolo

2016-08-01

Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS. © The Author(s), 2015.

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.

Visualizing Mutation-Specific Differences in the Trafficking-Deficient Phenotype of Kv11.1 Proteins Linked to Long QT Syndrome Type 2.

PubMed

Hall, Allison R; Anderson, Corey L; Smith, Jennifer L; Mirshahi, Tooraj; Elayi, Claude S; January, Craig T; Delisle, Brian P

2018-01-01

KCNH2 encodes the Kv11.1 α-subunit that underlies the rapidly activating delayed-rectifier K + current in the heart. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channel protein to the cell surface membrane. Several trafficking-deficient LQT2 mutations (e.g., G601S) generate Kv11.1 proteins that are sequestered in a microtubule-dependent quality control (QC) compartment in the transitional endoplasmic reticulum (ER). We tested the hypothesis that the QC mechanisms that regulate LQT2-linked Kv11.1 protein trafficking are mutation-specific. Confocal imaging analyses of HEK293 cells stably expressing the trafficking-deficient LQT2 mutation F805C showed that, unlike G601S-Kv11.1 protein, F805C-Kv11.1 protein was concentrated in several transitional ER subcompartments. The microtubule depolymerizing drug nocodazole differentially affected G601S- and F805C-Kv11.1 protein immunostaining. Nocodazole caused G601S-Kv11.1 protein to distribute into peripheral reticular structures, and it increased the diffuse immunostaining of F805C-Kv11.1 protein around the transitional ER subcompartments. Proteasome inhibition also affected the immunostaining of G601S- and F805C-Kv11.1 protein differently. Incubating cells in MG132 minimally impacted G601S-Kv11.1 immunostaining, but it dramatically increased the diffuse immunostaining of F805C-Kv11.1 protein in the transitional ER. Similar results were seen after incubating cells in the proteasome inhibitor lactacystin. Differences in the cellular distribution of G601S-Kv11.1 and F805C-Kv11.1 protein persisted in transfected human inducible pluripotent stem cell derived cardiomyocytes. These are the first data to visually demonstrate mutation-specific differences in the trafficking-deficient LQT2 phenotype, and this study has identified a novel way to categorize trafficking-deficient LQT2 mutations based on differences in intracellular

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.

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

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.

TONNEAU2/FASS Regulates the Geometry of Microtubule Nucleation and Cortical Array Organization in Interphase Arabidopsis Cells[C][W

PubMed Central

Kirik, Angela; Ehrhardt, David W.; Kirik, Viktor

2012-01-01

Organization of microtubules into ordered arrays involves spatial and temporal regulation of microtubule nucleation. Here, we show that acentrosomal microtubule nucleation in plant cells involves a previously unknown regulatory step that determines the geometry of microtubule nucleation. Dynamic imaging of interphase cortical microtubules revealed that the ratio of branching to in-bundle microtubule nucleation on cortical microtubules is regulated by the Arabidopsis thaliana B′′ subunit of protein phosphatase 2A, which is encoded by the TONNEAU2/FASS (TON2) gene. The probability of nucleation from γ-tubulin complexes localized at the cell cortex was not affected by a loss of TON2 function, suggesting a specific role of TON2 in regulating the nucleation geometry. Both loss of TON2 function and ectopic targeting of TON2 to the plasma membrane resulted in defects in cell shape, suggesting the importance of TON2-mediated regulation of the microtubule cytoskeleton in cell morphogenesis. Loss of TON2 function also resulted in an inability for cortical arrays to reorient in response to light stimulus, suggesting an essential role for TON2 and microtubule branching nucleation in reorganization of microtubule arrays. Our data establish TON2 as a regulator of interphase microtubule nucleation and provide experimental evidence for a novel regulatory step in the process of microtubule-dependent nucleation. PMID:22395485

Epilepsy surgery in children and adolescents with malformations of cortical development--outcome and impact of the new ILAE classification on focal cortical dysplasia.

PubMed

Mühlebner, Angelika; Gröppel, Gudrun; Dressler, Anastasia; Reiter-Fink, Edith; Kasprian, Gregor; Prayer, Daniela; Dorfer, Christian; Czech, Thomas; Hainfellner, Johannes A; Coras, Roland; Blümcke, Ingmar; Feucht, Martha

2014-11-01

To determine long-term efficacy and safety of epilepsy surgery in children and adolescents with malformations of cortical development (MCD) and to identify differences in seizure outcome of the various MCD subgroups. Special focus was set on the newly introduced International League Against Epilepsy (ILAE) classification of focal cortical dysplasia (FCD). This is a single center retrospective cross-sectional analysis of prospectively collected data. age at surgery <18 years, pre-surgical evaluation and epilepsy surgery performed at the Vienna pediatric epilepsy center, histologically proven MCD, complete follow-up data for at least 12 months. Clinical variables evaluated: type and localization of MCD, type of surgery and a variety of clinical characteristics reported to be associated with (un-)favorable outcomes. MCD were classified following the existing classification schemes (Barkovich et al., 2012. Brain. 135, 1348-1369; Palmini et al., 2004. Neurology. 62, S2-S8) and the ILAE classification for FCD recently proposed by Blümcke in 2011. Seizure outcome was classified using the ILAE classification proposed by Wieser in 2001. 60 Patients (51.7% male) were included. Follow up was up to 14 (mean 4.4 ± 3.2) years. Mean age at surgery was 8.0 ± 6.0 (median 6.0) years; mean age at epilepsy onset was 2.9 ± 3.2 (median 2.0) years; duration of epilepsy before surgery was 4.8 ± 4.4 (median 3.0) years. 80% of the patients were seizure free at last follow-up. AEDs were successfully withdrawn in 56.7% of all patients. Extended surgery, lesion localization in the temporal lobes and absence of inter-ictal spikes in postsurgical EEG recordings were predictive of favorable seizure outcomes after surgery. However, no association was found between outcome and MCD sub-types. Epilepsy surgery is highly effective in carefully selected drug-resistant children with MCD. Surrogate markers for complete resection of the epileptogenic zone remain the only significant predictors for

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

Stability of the Cortical Sensory Waveforms, the P1-N1-P2 Complex and T-Complex, of Auditory Evoked Potentials

ERIC Educational Resources Information Center

Wagner, Monica; Shafer, Valerie L.; Haxhari, Evis; Kiprovski, Kevin; Behrmann, Katherine; Griffiths, Tara

2017-01-01

Purpose: Atypical cortical sensory waveforms reflecting impaired encoding of auditory stimuli may result from inconsistency in cortical response to the acoustic feature changes within spoken words. Thus, the present study assessed intrasubject stability of the P1-N1-P2 complex and T-complex to multiple productions of spoken nonwords in 48 adults…

NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin.

PubMed

Chiasson-MacKenzie, Christine; Morris, Zachary S; Baca, Quentin; Morris, Brett; Coker, Joanna K; Mirchev, Rossen; Jensen, Anne E; Carey, Thomas; Stott, Shannon L; Golan, David E; McClatchey, Andrea I

2015-10-26

The proliferation of normal cells is inhibited at confluence, but the molecular basis of this phenomenon, known as contact-dependent inhibition of proliferation, is unclear. We previously identified the neurofibromatosis type 2 (NF2) tumor suppressor Merlin as a critical mediator of contact-dependent inhibition of proliferation and specifically found that Merlin inhibits the internalization of, and signaling from, the epidermal growth factor receptor (EGFR) in response to cell contact. Merlin is closely related to the membrane-cytoskeleton linking proteins Ezrin, Radixin, and Moesin, and localization of Merlin to the cortical cytoskeleton is required for contact-dependent regulation of EGFR. We show that Merlin and Ezrin are essential components of a mechanism whereby mechanical forces associated with the establishment of cell-cell junctions are transduced across the cell cortex via the cortical actomyosin cytoskeleton to control the lateral mobility and activity of EGFR, providing novel insight into how cells inhibit mitogenic signaling in response to cell contact. © 2015 Chiassson-MacKenzie et al.

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.

Clinical, functional, and neurophysiologic assessment of dysplastic cortical networks: Implications for cortical functioning and surgical management.

PubMed

Duchowny, Michael

2009-10-01

Cortical malformations are highly epileptogenic lesions associated with complex, unanticipated, and often aberrant electrophysiologic and functional relationships. These relationships are inextricably linked to widespread cortical networks subserving eloquent functions, particularly language and motor ability. Cytomegalic neurons but not balloon cells in Palmini type 2 dysplastic cortex are intrinsically hyperexcitable and contribute to local epileptogenesis and functional responsiveness. However, there is much evidence that focal cortical dysplasia is rarely a localized or even regional process, and is a functionally, electrophysiologically, and ultimately clinically integrated neural network disorder. Not surprisingly, malformed cortex is implicated in cognitive dysfunction, particularly disturbances of linguistic processing. An understanding of these relationships is critical for successful epilepsy surgery. Gains in surgical prognosis rely on multiple diagnostic modalities to delineate complex anatomic, electrophysiologic, and functional relationships in magnetic resonance imaging (MRI)-negative patients with rates of seizure-freedom roughly comparable to lesional patients.

Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly.

PubMed

Inoue, Takashi; Ogawa, Masaharu; Mikoshiba, Katsuhiko; Aruga, Jun

2008-04-30

The formation of the highly organized cortical structure depends on the production and correct placement of the appropriate number and types of neurons. The Zic family of zinc-finger transcription factors plays essential roles in regulating the proliferation and differentiation of neuronal progenitors in the medial forebrain and the cerebellum. Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells. Immunohistochemical studies have revealed that Zic proteins were abundantly expressed in the meningeal cells and that the majority of the CR cells distributed in the medial and dorsal cortex also expressed Zic proteins in the mid-late embryonic and postnatal cortical marginal zones. During embryonic cortical development, Zic1/Zic3 double-mutant and hypomorphic Zic2 mutant mice showed a reduction in the number of CR cells in the rostral cortex, whereas the cell number remained unaffected in the caudal cortex. These mutants also showed mislocalization of the CR cells and cortical lamination defects, resembling the changes noted in type II (cobblestone) lissencephaly, throughout the brain. In the Zic1/3 mutant, reduced proliferation of the meningeal cells was observed before the thinner and disrupted organization of the pial basement membrane (BM) with reduced expression of the BM components and the meningeal cell-derived secretory factor. These defects correlated with the changes in the end feet morphology of the radial glial cells. These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly.

Unusual association of SCN2A epileptic encephalopathy with severe cortical dysplasia detected by prenatal MRI.

PubMed

Bernardo, Silvia; Marchionni, Enrica; Prudente, Sabrina; De Liso, Paola; Spalice, Alberto; Giancotti, Antonella; Manganaro, Lucia; Pizzuti, Antonio

2017-05-01

We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the α II -subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

30-Second bound and pore water concentration mapping of cortical bone using 2D UTE with optimized half-pulses.

PubMed

Manhard, Mary Kate; Harkins, Kevin D; Gochberg, Daniel F; Nyman, Jeffry S; Does, Mark D

2017-03-01

MRI of cortical bone has the potential to offer new information about fracture risk. Current methods are typically performed with 3D acquisitions, which suffer from long scan times and are generally limited to extremities. This work proposes using 2D UTE with half pulses for quantitatively mapping bound and pore water in cortical bone. Half-pulse 2D UTE methods were implemented on a 3T Philips Achieva scanner using an optimized slice-select gradient waveform, with preparation pulses to selectively image bound or pore water. The 2D methods were quantitatively compared with previously implemented 3D methods in the tibia in five volunteers. The mean difference between bound and pore water concentration acquired from 3D and 2D sequences was 0.6 and 0.9 mol 1 H/L bone (3 and 12%, respectively). While 2D pore water methods tended to slightly overestimate concentrations relative to 3D methods, differences were less than scan-rescan uncertainty and expected differences between healthy and fracture-prone bones. Quantitative bound and pore water concentration mapping in cortical bone can be accelerated by 2 orders of magnitude using 2D protocols with optimized half-pulse excitation. Magn Reson Med 77:945-950, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

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

Censoring distances based on labeled cortical distance maps in cortical morphometry.

PubMed

Ceyhan, Elvan; Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D; Botteron, Kelly N; Miller, Michael I; Ratnanather, J Tilak

2013-01-01

It has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (WM) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

Cortical layers: Cyto-, myelo-, receptor- and synaptic architecture in human cortical areas.

PubMed

Palomero-Gallagher, Nicola; Zilles, Karl

2017-08-12

Cortical layers have classically been identified by their distinctive and prevailing cell types and sizes, as well as the packing densities of cell bodies or myelinated fibers. The densities of multiple receptors for classical neurotransmitters also vary across the depth of the cortical ribbon, and thus determine the neurochemical properties of cyto- and myeloarchitectonic layers. However, a systematic comparison of the correlations between these histologically definable layers and the laminar distribution of transmitter receptors is currently lacking. We here analyze the densities of 17 different receptors of various transmitter systems in the layers of eight cytoarchitectonically identified, functionally (motor, sensory, multimodal) and hierarchically (primary and secondary sensory, association) distinct areas of the human cerebral cortex. Maxima of receptor densities are found in different layers when comparing different cortical regions, i.e. laminar receptor densities demonstrate differences in receptorarchitecture between isocortical areas, notably between motor and primary sensory cortices, specifically the primary visual and somatosensory cortices, as well as between allocortical and isocortical areas. Moreover, considerable differences are found between cytoarchitectonical and receptor architectonical laminar patterns. Whereas the borders of cyto- and myeloarchitectonic layers are well comparable, the laminar profiles of receptor densities rarely coincide with the histologically defined borders of layers. Instead, highest densities of most receptors are found where the synaptic density is maximal, i.e. in the supragranular layers, particularly in layers II-III. The entorhinal cortex as an example of the allocortex shows a peculiar laminar organization, which largely deviates from that of all the other cortical areas analyzed here. Copyright © 2017. Published by Elsevier Inc.

An automated tool for cortical feature analysis: Application to differences on 7 Tesla T2* -weighted images between young and older healthy subjects.

PubMed

Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; Buijs, Mathijs; Webb, Andrew G; van der Grond, Jeroen; van Buchem, Mark A; Reiber, Johan H C; Milles, Julien

2015-07-01

High field T 2 * -weighted MR images of the cerebral cortex are increasingly used to study tissue susceptibility changes related to aging or pathologies. This paper presents a novel automated method for the computation of quantitative cortical measures and group-wise comparison using 7 Tesla T 2 * -weighted magnitude and phase images. The cerebral cortex was segmented using a combination of T 2 * -weighted magnitude and phase information and subsequently was parcellated based on an anatomical atlas. Local gray matter (GM)/white matter (WM) contrast and cortical profiles, which depict the magnitude or phase variation across the cortex, were computed from the magnitude and phase images in each parcellated region and further used for group-wise comparison. Differences in local GM/WM contrast were assessed using linear regression analysis. Regional cortical profiles were compared both globally and locally using permutation testing. The method was applied to compare a group of 10 young volunteers with a group of 15 older subjects. Using local GM/WM contrast, significant differences were revealed in at least 13 of 17 studied regions. Highly significant differences between cortical profiles were shown in all regions. The proposed method can be a useful tool for studying cortical changes in normal aging and potentially in neurodegenerative diseases. Magn Reson Med 74:240-248, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

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.

Isolated Cortical Vein Thrombosis - The Cord Sign

PubMed Central

Sharma, Vijay K.; Teoh, Hock L

2009-01-01

Isolated cortical vein thrombosis is an uncommon condition and often difficult to diagnose, both clinically and radiologically. We report a case of a 38 years old man who presented with headache of new onset and clinical examination was unremarkable. The unenhanced brain CT did not reveal any abnormality. In view of unrelenting headache and partial seizures, we performed magnetic resonance imaging (with axial T1, T2 and gradient echo sequences, coronal FLAIR, diffusion weighted imaging as well as Gadolinium contrast-enhanced images) and magnetic resonance venography of the brain that revealed an isolated parietal cortical vein thrombosis with the rarely reported 'cord sign'. We report the clinical and radiological findings in our patient with isolated parietal cortical vein thrombosis. PMID:22470649

Post-adolescent developmental changes in cortical complexity.

PubMed

Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

2014-11-27

Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 14 young adults (mean age 24.24 ± 2.76, 7 women) for measures of brain complexity (fractal dimension--FD), grey matter (GM) volume and surface-area of cortical ribbon. FD was calculated using box-counting and Minkowski-Bouligand methods; FD and GM volume were measured for the whole brain, each hemisphere and lobes: frontal, occipital, parietal and temporal. The results show that the adults have a lower cortical complexity than the adolescents, which was significant for whole brain, left and right hemisphere, frontal and parietal lobes for both genders; and only for males in left temporal lobe. The GM volume was smaller in men than in boys for almost all measurements, and smaller in women than in girls just for right parietal lobe. A significant Pearson correlation was found between FD and GM volume for whole brain and each hemisphere in both genders. The decrease of the GM surface-area was significant in post-adolescence for males, not for females. During post-adolescence there are common changes in cortical complexity in the same regions for both genders, but there are also gender specific changes in some cortical areas. The sex differences from different cortical measurements (FD, GM volume and surface-area of cortical ribbon) could suggest a maturation delay in specific brain regions for each gender in relation to the other and might be explained through the functional role of the corresponding regions reflected in gender difference of developed abilities.

Trade-off of cerebello-cortical and cortico-cortical functional networks for planning in 6-year-old children.

PubMed

Kipping, Judy A; Margulies, Daniel S; Eickhoff, Simon B; Lee, Annie; Qiu, Anqi

2018-08-01

Childhood is a critical period for the development of cognitive planning. There is a lack of knowledge on its neural mechanisms in children. This study aimed to examine cerebello-cortical and cortico-cortical functional connectivity in association with planning skills in 6-year-olds (n = 76). We identified the cerebello-cortical and cortico-cortical functional networks related to cognitive planning using activation likelihood estimation (ALE) meta-analysis on existing functional imaging studies on spatial planning, and data-driven independent component analysis (ICA) of children's resting-state functional MRI (rs-fMRI). We investigated associations of cerebello-cortical and cortico-cortical functional connectivity with planning ability in 6-year-olds, as assessed using the Stockings of Cambridge task. Long-range functional connectivity of two cerebellar networks (lobules VI and lateral VIIa) with the prefrontal and premotor cortex were greater in children with poorer planning ability. In contrast, cortico-cortical association networks were not associated with the performance of planning in children. These results highlighted the key contribution of the lateral cerebello-frontal functional connectivity, but not cortico-cortical association functional connectivity, for planning ability in 6-year-olds. Our results suggested that brain adaptation to the acquisition of planning ability during childhood is partially achieved through the engagement of the cerebello-cortical functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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

Impact of Spinal Manipulation on Cortical Drive to Upper and Lower Limb Muscles

PubMed Central

Haavik, Heidi; Niazi, Imran Khan; Jochumsen, Mads; Sherwin, Diane; Flavel, Stanley; Türker, Kemal S.

2016-01-01

This study investigates whether spinal manipulation leads to changes in motor control by measuring the recruitment pattern of motor units in both an upper and lower limb muscle and to see whether such changes may at least in part occur at the cortical level by recording movement related cortical potential (MRCP) amplitudes. In experiment one, transcranial magnetic stimulation input–output (TMS I/O) curves for an upper limb muscle (abductor pollicus brevis; APB) were recorded, along with F waves before and after either spinal manipulation or a control intervention for the same subjects on two different days. During two separate days, lower limb TMS I/O curves and MRCPs were recorded from tibialis anterior muscle (TA) pre and post spinal manipulation. Dependent measures were compared with repeated measures analysis of variance, with p set at 0.05. Spinal manipulation resulted in a 54.5% ± 93.1% increase in maximum motor evoked potential (MEPmax) for APB and a 44.6% ± 69.6% increase in MEPmax for TA. For the MRCP data following spinal manipulation there were significant difference for amplitude of early bereitschafts-potential (EBP), late bereitschafts potential (LBP) and also for peak negativity (PN). The results of this study show that spinal manipulation leads to changes in cortical excitability, as measured by significantly larger MEPmax for TMS induced input–output curves for both an upper and lower limb muscle, and with larger amplitudes of MRCP component post manipulation. No changes in spinal measures (i.e., F wave amplitudes or persistence) were observed, and no changes were shown following the control condition. These results are consistent with previous findings that have suggested increases in strength following spinal manipulation were due to descending cortical drive and could not be explained by changes at the level of the spinal cord. Spinal manipulation may therefore be indicated for the patients who have lost tonus of their muscle and/or are

Mental stress test: a rapid, simple, and efficient test to unmask long QT syndrome.

PubMed

Etienne, Pauline; Huchet, François; Gaborit, Nathalie; Barc, Julien; Thollet, Aurélie; Kyndt, Florence; Guyomarch, Béatrice; Le Marec, Hervé; Charpentier, Flavien; Schott, Jean-Jacques; Redon, Richard; Probst, Vincent; Gourraud, Jean-Baptiste

2018-04-20

QT prolongation during mental stress test (MST) has been associated with familial idiopathic ventricular fibrillation. In long QT syndrome (LQTS), up to 30% of mutation carriers have normal QT duration. Our aim was to assess the QT response during MST, and its accuracy in the diagnosis of concealed LQTS. All patients who are carrier of a KCNQ1 or KCNH2 mutations without QT prolongation were enrolled. A control group was constituted of patients with negative exercise and epinephrine tests. Electrocardiogram were recorded at rest and at the maximum heart rate during MST and reviewed by two physicians. Among the 70 patients enrolled (median age 41±2.1 years, 46% male), 36 were mutation carrier for LQTS (20 KCNQ1 and 16 KCNH2), and 34 were controls. KCNQ1 and KCNH2 mutation carriers presented a longer QT interval at baseline [405(389; 416) and 421 (394; 434) ms, respectively] compared with the controls [361(338; 375)ms; P < 0.0001]. QT duration during MST varied by 9 (4; 18) ms in KCNQ1, 3 (-6; 16) ms in KCNH2, and by -22 (-29; -17) ms in controls (P < 0.0001). These QT variations were independent of heart rate (P < 0.3751). Receiver operating characteristic curve analysis identified a cut-off value of QT variation superior to -11 ms as best predictor of LQTS. It provided 97% sensitivity and 97% specificity of QT prolongation in the diagnosis of LQTS. We identified a paradoxical response of the QT interval during MST in LQTS. Easy to assess, MST may be efficient to unmask concealed LQTS in patients at risk of this pathology.

Spatial integration and cortical dynamics.

PubMed

Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

1996-01-23

Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning.

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.

Postpartum cortical blindness.

PubMed

Faiz, Shakeel Ahmed

2008-09-01

A 30-years-old third gravida with previous normal pregnancies and an unremarkable prenatal course had an emergency lower segment caesarean section at a periphery hospital for failure of labour to progress. She developed bilateral cortical blindness immediately after recovery from anesthesia due to cerebral angiopathy shown by CT and MR scan as cortical infarct cerebral angiopathy, which is a rare complication of a normal pregnancy.

Localization of the kinesin adaptor proteins trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal and cortical neurons.

PubMed

Loss, Omar; Stephenson, F Anne

2015-07-01

Neuronal function requires regulated anterograde and retrograde trafficking of mitochondria along microtubules by using the molecular motors kinesin and dynein. Previous work has established that trafficking kinesin proteins (TRAKs),TRAK1 and TRAK2, are kinesin adaptor proteins that link mitochondria to kinesin motor proteins via an acceptor protein in the mitochondrial outer membrane, etc. the Rho GTPase Miro. Recent studies have shown that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons by virtue of its binding to both kinesin and dynein motor proteins, whereas TRAK2 controls mitochondrial transport in dendrites resulting from its binding to dynein. This study further investigates the subcellular localization of TRAK1 and TRAK2 in primary cultures of hippocampal and cortical neurons by using both commercial antibodies and anti-TRAK1 and anti-TRAK2 antibodies raised in our own laboratory (in-house). Whereas TRAK1 was prevalently localized in axons of hippocampal and cortical neurons, TRAK2 was more prevalent in dendrites of hippocampal neurons. In cortical neurons, TRAK2 was equally distributed between axons and dendrites. Some qualitative differences were observed between commercial and in-house-generated antibody immunostaining. © 2015 Wiley Periodicals, Inc.

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.

Actin kinetics shapes cortical network structure and mechanics

PubMed Central

Fritzsche, Marco; Erlenkämper, Christoph; Moeendarbary, Emad; Charras, Guillaume; Kruse, Karsten

2016-01-01

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs. PMID:27152338

Actin kinetics shapes cortical network structure and mechanics.

PubMed

Fritzsche, Marco; Erlenkämper, Christoph; Moeendarbary, Emad; Charras, Guillaume; Kruse, Karsten

2016-04-01

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs.

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

Is cortical bone hip? What determines cortical bone properties?

PubMed

Epstein, Sol

2007-07-01

Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

Consistent cortical reconstruction and multi-atlas brain segmentation.

PubMed

Huo, Yuankai; Plassard, Andrew J; Carass, Aaron; Resnick, Susan M; Pham, Dzung L; Prince, Jerry L; Landman, Bennett A

2016-09-01

Whole brain segmentation and cortical surface reconstruction are two essential techniques for investigating the human brain. Spatial inconsistences, which can hinder further integrated analyses of brain structure, can result due to these two tasks typically being conducted independently of each other. FreeSurfer obtains self-consistent whole brain segmentations and cortical surfaces. It starts with subcortical segmentation, then carries out cortical surface reconstruction, and ends with cortical segmentation and labeling. However, this "segmentation to surface to parcellation" strategy has shown limitations in various cohorts such as older populations with large ventricles. In this work, we propose a novel "multi-atlas segmentation to surface" method called Multi-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. A modification called MaCRUISE(+) is designed to perform well when white matter lesions are present. Comparing to the benchmarks CRUISE and FreeSurfer, the surface accuracy of MaCRUISE and MaCRUISE(+) is validated using two independent datasets with expertly placed cortical landmarks. A third independent dataset with expertly delineated volumetric labels is employed to compare segmentation performance. Finally, 200MR volumetric images from an older adult sample are used to assess the robustness of MaCRUISE and FreeSurfer. The advantages of MaCRUISE are: (1) MaCRUISE constructs self-consistent voxelwise segmentations and cortical surfaces, while MaCRUISE(+) is robust to white matter pathology. (2) MaCRUISE achieves more accurate whole brain segmentations than independently conducting the multi-atlas segmentation. (3) MaCRUISE is comparable in accuracy to FreeSurfer (when FreeSurfer does not exhibit global failures) while achieving greater robustness across an older adult population. MaCRUISE has been made freely

Dendritic Na+ spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons

PubMed Central

Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

2014-01-01

Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na+ spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow. DOI: http://dx.doi.org/10.7554/eLife.04551.001 PMID:25390033

Gravitropism of Arabidopsis thaliana Roots Requires the Polarization of PIN2 toward the Root Tip in Meristematic Cortical Cells[C][W

PubMed Central

Rahman, Abidur; Takahashi, Maho; Shibasaki, Kyohei; Wu, Shuang; Inaba, Takehito; Tsurumi, Seiji; Baskin, Tobias I.

2010-01-01

In the root, the transport of auxin from the tip to the elongation zone, referred to here as shootward, governs gravitropic bending. Shootward polar auxin transport, and hence gravitropism, depends on the polar deployment of the PIN-FORMED auxin efflux carrier PIN2. In Arabidopsis thaliana, PIN2 has the expected shootward localization in epidermis and lateral root cap; however, this carrier is localized toward the root tip (rootward) in cortical cells of the meristem, a deployment whose function is enigmatic. We use pharmacological and genetic tools to cause a shootward relocation of PIN2 in meristematic cortical cells without detectably altering PIN2 polarization in other cell types or PIN1 polarization. This relocation of cortical PIN2 was negatively regulated by the membrane trafficking factor GNOM and by the regulatory A1 subunit of type 2-A protein phosphatase (PP2AA1) but did not require the PINOID protein kinase. When GNOM was inhibited, PINOID abundance increased and PP2AA1 was partially immobilized, indicating both proteins are subject to GNOM-dependent regulation. Shootward PIN2 specifically in the cortex was accompanied by enhanced shootward polar auxin transport and by diminished gravitropism. These results demonstrate that auxin flow in the root cortex is important for optimal gravitropic response. PMID:20562236

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.

Timeframe of socket cortication after tooth extraction: A retrospective radiographic study.

PubMed

Bertl, Kristina; Kukla, Edmund Benjamin; Albugami, Rajaa; Beck, Florian; Gahleitner, André; Stavropoulos, Andreas

2018-01-01

To assess the timeframe between tooth extraction and radiographically detectable socket cortication in humans. Two hundred and fifty patients with a CT scan ≤36 months after tooth extraction were included. First, three orthoradial multiplanar reconstruction slices, representing the major part of the extraction socket, were scored regarding the degree of bone healing as (i) healed, that is, complete/continuous cortication of the socket entrance, or (ii) non-healed. Thereafter, based on the results of all three slices, the stage of cortication of the extraction socket, as one unit, was classified as (i) non-corticated, that is, all three slices judged as non-healed, (ii) partially corticated, that is, 1 or 2 slices judged as non-healed, or (iii) completely corticated, that is, all three slices judged as healed. The possible effect of several independent parameters, that is, age, gender, timeframe between tooth extraction and CT scan, tooth type, extent of radiographic bone loss of the extracted tooth, tooth-gap type, smoking status, presence of any systemic disease, and medication intake, on cortication status was statistically evaluated. Three to 6 months after tooth extraction, 27% of the sockets were judged as non-corticated and 53% were judged as partially corticated. After 9-12 months, >80% of the sockets were corticated, while some incompletely corticated sockets were detected up to 15 months after extraction. Each additional month after tooth extraction contributed significantly to a higher likelihood of a more advanced stage of cortication, while radiographic bone loss ≥75% significantly prolonged cortication time; no other independent variable had a significant effect. The results indicate a considerably long timeframe until complete cortication of an extraction socket, that is, 3-6 months after tooth extraction 3 of 4 sockets were still not completely corticated, and only after 9-12 months, complete cortication was observed in about 80% of the

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy

PubMed Central

Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J.; Yong, Keir X.X.; Paterson, Ross W.; Slattery, Catherine F.; Foulkes, Alexander J.M.; Rabinovici, Gil D.; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M.; Fox, Nick C.; Crutch, Sebastian J.

2016-01-01

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer’s disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. PMID:27318138

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

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

PubMed

Numbenjapon, N; Costin, G; Pitukcheewanont, P

2012-09-01

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

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

In vivo imaging of cortical pathology in multiple sclerosis using ultra-high field MRI

PubMed Central

Mainero, C; Benner, T; Radding, A; van der Kouwe, A; Jensen, R; Rosen, B R.; Kinkel, R P.

2009-01-01

Objective: We used ultra-high field MRI to visualize cortical lesion types described by neuropathology in 16 patients with multiple sclerosis (MS) compared with 8 age-matched controls; to characterize the contrast properties of cortical lesions including T2*, T2, T1, and phase images; and to investigate the relationship between cortical lesion types and clinical data. Methods: We collected, on a 7-T scanner, 2-dimensional fast low-angle shot (FLASH)-T2*-weighted spoiled gradient-echo, T2-weighted turbo spin-echo (TSE) images (0.33 × 033 × 1 mm3), and a 3-dimensional magnetization-prepared rapid gradient echo. Results: Overall, 199 cortical lesions were detected in patients on both FLASH-T2* and T2-TSE scans. Seven-tesla MRI allowed for characterization of cortical plaques into type I (leukocortical), type II (intracortical), and type III/IV (subpial extending partly or completely through the cortical width) lesions as described histopathologically. Types III and IV were the most frequent type of cortical plaques (50.2%), followed by type I (36.2%) and type II (13.6%) lesions. Each lesion type was more frequent in secondary progressive than in relapsing–remitting MS. This difference, however, was significant only for type III/IV lesions. T2*-weighted images showed the highest, while phase images showed the lowest, contrast-to-noise ratio for all cortical lesion types. In patients, the number of type III/IV lesions was associated with greater disability (p < 0.02 by Spearman test) and older age (p < 0.04 by Spearman test). Conclusions: Seven-tesla MRI detected different histologic cortical lesion types in our small multiple sclerosis (MS) sample, suggesting, if validated in a larger population, that it may prove a valuable tool to assess the contribution of cortical MS pathology to clinical disability. GLOSSARY ANOVA = analysis of variance; BN = background noise; CNR = contrast-to-noise ratio; DIR = double-inversion recovery; EDSS = Expanded Disability Status

The Changing Roles of Neurons in the Cortical Subplate

PubMed Central

Friedlander, Michael J.; Torres-Reveron, Juan

2009-01-01

Neurons may serve different functions over the course of an organism's life. Recent evidence suggests that cortical subplate (SP) neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the SP. While the cortical plate neurons form most of the cortical layers (layers 2–6), the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10–20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving SP cells' axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer 6. This suggests that they participate in local synaptic networks, as well. Moreover, they receive excitatory and inhibitory synaptic inputs, potentially monitoring outputs from axon collaterals of cortical efferents, from cortical afferents and/or from each other. We explore our understanding of the functional connectivity of these cells at different

Cortical gray and subcortical white matter associations in Parkinson's disease.

PubMed

Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

2017-01-01

Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

Cortical inhibition and excitation by bilateral transcranial alternating current stimulation.

PubMed

Cancelli, Andrea; Cottone, Carlo; Zito, Giancarlo; Di Giorgio, Marina; Pasqualetti, Patrizio; Tecchio, Franca

2015-01-01

Transcranial electric stimulations (tES) with amplitude-modulated currents are promising tools to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. We aimed at assessing the dependence of cortical excitability changes on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) over the bilateral primary motor cortex. We chose two amplitude ranges of the stimulations, around 25 μA/cm2 and 63 μA/cm2 from peak to peak, with three values (at steps of about 2.5%) around each, to generate, respectively, inhibitory and excitatory effects of the primary motor cortex. We checked such changes online through transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). Cortical excitability changes depended upon current density (p = 0.001). Low current densities decreased MEP amplitudes (inhibition) while high current densities increased them (excitation). tACS targeting bilateral homologous cortical areas can induce online inhibition or excitation as a function of the current density.

Cortical thickness in neuropsychologically near-normal schizophrenia.

PubMed

Cobia, Derin J; Csernansky, John G; Wang, Lei

2011-12-01

Schizophrenia is a severe psychiatric illness with widespread impairments of cognitive functioning; however, a certain percentage of subjects are known to perform in the normal range on neuropsychological measures. While the cognitive profiles of these individuals have been examined, there has been relatively little attention to the neuroanatomical characteristics of this important subgroup. The aims of this study were to statistically identify schizophrenia subjects with relatively normal cognition, examine their neuroanatomical characteristics relative to their more impaired counterparts using cortical thickness mapping, and to investigate relationships between these characteristics and demographic variables to better understand the nature of cognitive heterogeneity in schizophrenia. Clinical, neuropsychological, and MRI data were collected from schizophrenia (n = 79) and healthy subjects (n = 65). A series of clustering algorithms on neuropsychological scores was examined, and a 2-cluster solution that separated subjects into neuropsychologically near-normal (NPNN) and neuropsychologically impaired (NPI) groups was determined most appropriate. Surface-based cortical thickness mapping was utilized to examine differences in thinning among schizophrenia subtypes compared with the healthy participants. A widespread cortical thinning pattern characteristic of schizophrenia emerged in the NPI group, while NPNN subjects demonstrated very limited thinning relative to healthy comparison subjects. Analysis of illness duration indicated minimal effects on subtype classification and cortical thickness results. Findings suggest a strong link between cognitive impairment and cortical thinning in schizophrenia, where subjects with near-normal cognitive abilities also demonstrate near-normal cortical thickness patterns. While generally supportive of distinct etiological processes for cognitive subtypes, results provide direction for further examination of additional

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

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

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

Interaction between DRD2 and lead exposure on the cortical thickness of the frontal lobe in youth with attention-deficit/hyperactivity disorder.

PubMed

Kim, Johanna Inhyang; Kim, Jae-Won; Lee, Jong-Min; Yun, Hyuk Jin; Sohn, Chul-Ho; Shin, Min-Sup; Kim, Bongseog; Chae, Jonghee; Roh, Jaewoo; Kim, Bung-Nyun

2018-03-02

The dopamine receptor D2 receptor (DRD2) gene and lead exposure are both thought to contribute to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). ADHD is characterized by delay in brain maturation, most prominent in the prefrontal cortex (PFC). The D2 receptor is also mainly located in the PFC, and animal studies show that lead exposure affects the dopaminergic system of the frontal lobe, indicating an overlap in neural correlates of ADHD, DRD2, and lead exposure. We examined the interaction effects of DRD2 rs1800497 and lead exposure on the cortical thickness of the frontal lobe in patients with ADHD. A 1:1 age- and gender-matched sample of 75 participants with ADHD and 75 healthy participants was included in the analysis. The interaction effects of DRD2 and lead exposure on the cortical thickness of 12 regions of interest in the frontal lobe were examined by multivariable linear regression analyses. When we investigated the DRD2×lead effects in the ADHD and HC groups separately, significant DRD2×lead effects were found in the ADHD group, but not in the healthy control group in multiple ROIs of the frontal lobe. There was a significant negative correlation between the cortical thickness of the right superior frontal gyrus and inattention scores. The present findings demonstrated significant interaction effects of DRD2 and lead exposure on the cortical thickness of the frontal lobe in ADHD. Replication studies with larger sample sizes, using a prospective design, are warranted to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Communication and wiring in the cortical connectome

PubMed Central

Budd, Julian M. L.; Kisvárday, Zoltán F.

2012-01-01

In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimize communication there is a trade-off between spatial (construction) and temporal (routing) costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fiber tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for cortical wiring patterns

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

Perceptual learning and adult cortical plasticity.

PubMed

Gilbert, Charles D; Li, Wu; Piech, Valentin

2009-06-15

The visual cortex retains the capacity for experience-dependent changes, or plasticity, of cortical function and cortical circuitry, throughout life. These changes constitute the mechanism of perceptual learning in normal visual experience and in recovery of function after CNS damage. Such plasticity can be seen at multiple stages in the visual pathway, including primary visual cortex. The manifestation of the functional changes associated with perceptual learning involve both long term modification of cortical circuits during the course of learning, and short term dynamics in the functional properties of cortical neurons. These dynamics are subject to top-down influences of attention, expectation and perceptual task. As a consequence, each cortical area is an adaptive processor, altering its function in accordance to immediate perceptual demands.

Basic visual function and cortical thickness patterns in posterior cortical atrophy.

PubMed

Lehmann, Manja; Barnes, Josephine; Ridgway, Gerard R; Wattam-Bell, John; Warrington, Elizabeth K; Fox, Nick C; Crutch, Sebastian J

2011-09-01

Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

PubMed Central

2010-01-01

Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist) and parecoxib (a selective cyclooxygenase-2 inhibitor) on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals) were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG) desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity), while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect. PMID:20089200

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

PubMed

Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Foulkes, Alexander J M; Rabinovici, Gil D; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M; Fox, Nick C; Crutch, Sebastian J

2016-08-01

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Mapping Cortical Morphology in Youth with Velo-Cardio-Facial (22q11.2 Deletion) Syndrome

PubMed Central

Kates, Wendy R.; Bansal, Ravi; Fremont, Wanda; Antshel, Kevin M.; Hao, Xuejun; Higgins, Anne Marie; Liu, Jun; Shprintzen, Robert J.; Peterson, Bradley S.

2010-01-01

Objective Velo-cardio-facial syndrome (VCFS; 22q11.2 deletion syndrome) represents one of the highest known risk factors for schizophrenia. Insofar as up to thirty percent of individuals with this genetic disorder develop schizophrenia, VCFS constitutes a unique, etiologically homogeneous model for understanding the pathogenesis of schizophrenia. Method Using a longitudinal, case-control design, we acquired anatomic magnetic resonance images to investigate both cross-sectional and longitudinal alterations in surface cortical morphology in a cohort of adolescents with VCFS and age-matched typical controls. All participants were scanned at two time points. Results Relative to controls, youth with VCFS exhibited alterations in inferior frontal, dorsal frontal, occipital, and cerebellar brain regions at both time points. We observed little change over time in surface morphology of either study group. However, within the VCFS group only, worsening psychosocial functioning over time was associated with Time 2 surface contractions in left middle and inferior temporal gyri. Further, prodromal symptoms at Time 2 were associated with surface contractions in left and right orbitofrontal, temporal and cerebellar regions, as well as surface protrusions of supramarginal gyrus. Conclusions These findings advance our understanding of cortical disturbances in VCFS that produce vulnerability for psychosis in this high risk population. PMID:21334567

Ultrashort echo time magnetization transfer (UTE-MT) imaging of cortical bone.

PubMed

Chang, Eric Y; Bae, Won C; Shao, Hongda; Biswas, Reni; Li, Shihong; Chen, Jun; Patil, Shantanu; Healey, Robert; D'Lima, Darryl D; Chung, Christine B; Du, Jiang

2015-07-01

Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T2 tissues such as cortical bone. Ultrashort echo time (UTE) sequences with TE values as low as 8 µs can detect signals from different water components in cortical bone. In this study we aim to evaluate two-dimensional UTE-MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by micro-computed tomography (μCT) and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE-MT MR imaging, μCT, and biomechanical testing. Off-resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with μCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderately strong negative correlation was observed between OSR and μCT porosity (R(2)  = 0.46-0.51), while a moderate positive correlation was observed between OSR and yield stress (R(2)  = 0.25-0.30) and failure stress (R(2)  = 0.31-0.35), and a weak positive correlation (R(2)  = 0.09-0.12) between OSR and Young's modulus at all off-resonance saturation frequencies. OSR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function. Copyright © 2015 John Wiley & Sons, Ltd.

Spontaneous cortical activity alternates between motifs defined by regional axonal projections

PubMed Central

Mohajerani, Majid H.; Chan, Allen W.; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A.; Boyd, Jamie D.; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H.

2014-01-01

In lightly anaesthetized or awake adult mice using millisecond timescale voltage sensitive dye imaging, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing including vision, audition, and touch. Similar cortical networks were found with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality specific sources such as primary sensory areas, and a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area, and a secondary anterior medial sink within the cingulate/secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range mono-synaptic connections between cortical regions. Maps of intracortical mono-synaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

PubMed Central

Getachew, Bruk; Hauser, Sheketha R.; Csoka, Antonei B.; Taylor, Robert E.; Tizabi, Yousef

2017-01-01

Introduction Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available. Methods In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3 h daily for 10 days (blood alcohol concentration ~150 mg%) followed by daily injection of 10 mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2 h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand. Results Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains. Conclusions The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity. PMID:28414989

Cortical Correlates of Fitts’ Law

PubMed Central

Ifft, Peter J.; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2011-01-01

Fitts’ law describes the fundamental trade-off between movement accuracy and speed: it states that the duration of reaching movements is a function of target size (TS) and distance. While Fitts’ law has been extensively studied in ergonomics and has guided the design of human–computer interfaces, there have been few studies on its neuronal correlates. To elucidate sensorimotor cortical activity underlying Fitts’ law, we implanted two monkeys with multielectrode arrays in the primary motor (M1) and primary somatosensory (S1) cortices. The monkeys performed reaches with a joystick-controlled cursor toward targets of different size. The reaction time (RT), movement time, and movement velocity changed with TS, and M1 and S1 activity reflected these changes. Moreover, modifications of cortical activity could not be explained by changes of movement parameters alone, but required TS as an additional parameter. Neuronal representation of TS was especially prominent during the early RT period where it influenced the slope of the firing rate rise preceding movement initiation. During the movement period, cortical activity was correlated with movement velocity. Neural decoders were applied to simultaneously decode TS and motor parameters from cortical modulations. We suggest that sensorimotor cortex activity reflects the characteristics of both the movement and the target. Classifiers that extract these parameters from cortical ensembles could improve neuroprosthetic control. PMID:22275888

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.

Changes in cortical thickness during the course of illness in schizophrenia.

PubMed

van Haren, Neeltje E M; Schnack, Hugo G; Cahn, Wiepke; van den Heuvel, Martijn P; Lepage, Claude; Collins, Louis; Evans, Alan C; Hulshoff Pol, Hilleke E; Kahn, René S

2011-09-01

Whether cortical thickness changes in schizophrenia over time are more pronounced relative to the changes that can be attributed to normal aging has not been studied. To compare patients with schizophrenia and healthy control participants on cortical thickness change. A 5-year longitudinal study comparing schizophrenic patients and healthy controls using 2 magnetic resonance images of the brain. Patients were recruited from the Department of Psychiatry at the University Medical Centre Utrecht and from other psychiatric hospitals in the Netherlands. Healthy controls were recruited via advertisement in newspapers and notice boards. Ninety-six schizophrenic patients and 113 healthy controls aged 16 to 56 years. Cortical thickness and change in cortical thickness on a vertex-by-vertex basis across the cortical mantle, measures of functional and symptomatic outcome, and cumulative intake of antipsychotics during the scan interval. At baseline, the schizophrenic patients had thinner left orbitofrontal and right parahippocampal and superior temporal cortices and a thicker superior parietal lobule and occipital pole compared with the controls. Mean cortical thickness did not differ between the groups. Over time, excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal cortex and in the left frontal area. Poor outcome in patients was associated with more pronounced cortical thinning. Higher cumulative intake of typical antipsychotics during the scan interval was associated with more pronounced cortical thinning, whereas higher cumulative intake of atypical antipsychotic medication was associated with less pronounced cortical thinning. In schizophrenia, the cortex shows excessive thinning over time in widespread areas of the brain, most pronounced in the frontal and temporal areas, and progresses across the entire course of the illness. The excessive thinning of the cortex appears related to outcome and

Wireless Cortical Brain-Machine Interface for Whole-Body Navigation in Primates

NASA Astrophysics Data System (ADS)

Rajangam, Sankaranarayani; Tseng, Po-He; Yin, Allen; Lehew, Gary; Schwarz, David; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2016-03-01

Several groups have developed brain-machine-interfaces (BMIs) that allow primates to use cortical activity to control artificial limbs. Yet, it remains unknown whether cortical ensembles could represent the kinematics of whole-body navigation and be used to operate a BMI that moves a wheelchair continuously in space. Here we show that rhesus monkeys can learn to navigate a robotic wheelchair, using their cortical activity as the main control signal. Two monkeys were chronically implanted with multichannel microelectrode arrays that allowed wireless recordings from ensembles of premotor and sensorimotor cortical neurons. Initially, while monkeys remained seated in the robotic wheelchair, passive navigation was employed to train a linear decoder to extract 2D wheelchair kinematics from cortical activity. Next, monkeys employed the wireless BMI to translate their cortical activity into the robotic wheelchair’s translational and rotational velocities. Over time, monkeys improved their ability to navigate the wheelchair toward the location of a grape reward. The navigation was enacted by populations of cortical neurons tuned to whole-body displacement. During practice with the apparatus, we also noticed the presence of a cortical representation of the distance to reward location. These results demonstrate that intracranial BMIs could restore whole-body mobility to severely paralyzed patients in the future.

The genetics underlying acquired long QT syndrome: impact for genetic screening

PubMed Central

Itoh, Hideki; Crotti, Lia; Aiba, Takeshi; Spazzolini, Carla; Denjoy, Isabelle; Fressart, Véronique; Hayashi, Kenshi; Nakajima, Tadashi; Ohno, Seiko; Makiyama, Takeru; Wu, Jie; Hasegawa, Kanae; Mastantuono, Elisa; Dagradi, Federica; Pedrazzini, Matteo; Yamagishi, Masakazu; Berthet, Myriam; Murakami, Yoshitaka; Shimizu, Wataru; Guicheney, Pascale; Schwartz, Peter J.; Horie, Minoru

2016-01-01

Aims Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors. Methods and results We screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated ‘true aLQTS’ (QTc within normal limits) or ‘unmasked cLQTS’ (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in ‘true aLQTS’, KCNQ1 mutations were much less frequent than KCNH2 (20% [95% CI 7–41%] vs. 64% [95% CI 43–82%], P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations. Conclusion A third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members. PMID:26715165

Cortical Development Requires Mesodermal Expression of Tbx1, a Gene Haploinsufficient in 22q11.2 Deletion Syndrome.

PubMed

Flore, Gemma; Cioffi, Sara; Bilio, Marchesa; Illingworth, Elizabeth

2017-03-01

In mammals, proper temporal control of neurogenesis and neural migration during embryonic development ensures correct formation of the cerebral cortex. Changes in the distribution of cortical projection neurons and interneurons are associated with behavioral disorders and psychiatric diseases, including schizophrenia and autism, suggesting that disrupted cortical connectivity contributes to the brain pathology. TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS), a chromosomal deletion disorder characterized by a greatly increased risk for schizophrenia. We have previously shown that Tbx1 heterozygous mice have reduced prepulse inhibition, a behavioral abnormality that is associated with 22q11.2DS and nonsyndromic schizophrenia. Here, we show that loss of Tbx1 disrupts corticogenesis in mice by promoting premature neuronal differentiation in the medio-lateral embryonic cortex, which gives rise to the somatosensory cortex (S1). In addition, we found altered polarity in both radially migrating excitatory neurons and tangentially migrating inhibitory interneurons. Together, these abnormalities lead to altered lamination in the S1 at the terminal stages of corticogenesis in Tbx1 null mice and similar anomalies in Tbx1 heterozygous adult mice. Finally, we show that mesoderm-specific inactivation of Tbx1 is sufficient to recapitulate the brain phenotype indicating that Tbx1 exerts a cell nonautonomous role in cortical development from the mesoderm. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Reduced Cortical Thickness in Mental Retardation

PubMed Central

Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

2011-01-01

Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

[Schizophrenia and cortical GABA neurotransmission].

PubMed

Hashimoto, Takanori; Matsubara, Takuro; Lewis, David A

2010-01-01

Individuals with schizophrenia show disturbances in a number of brain functions that regulate cognitive, affective, motor, and sensory processing. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related molecules. First, mRNA levels for the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67), an enzyme principally responsible for GABA synthesis, and the GABA membrane transporter GAT1, which regulates the reuptake of synaptically released GABA, are decreased in a subset of GABA neurons. Second, affected GABA neurons include those that express the calcium-binding protein parvalbumin (PV), because PV mRNA levels are decreased in the prefrontal cortex of subjects with schizophrenia and GAD67 mRNA is undetectable in almost half of PV-containing neurons. These changes are accompanied by decreased GAT1 expression in the presynaptic terminals of PV-containing neurons and by increased postsynaptic GABA-A receptor alpha2 subunit expression at the axon initial segments of pyramidal neurons. These findings indicate decreased GABA synthesis/release by PV-containing GABA neurons and compensatory changes at synapses formed by these neurons. Third, another subset of GABA neurons that express the neuropeptide somatostatin (SST) also appear to be affected because their specific markers, SST and neuropeptide Y mRNAs, are decreased in a manner highly correlated with the decreases in GAD67 mRNA. Finally, mRNA levels for GABA-A receptor subunits for synaptic (alpha1 and gamma2) and extra-synaptic (delta) receptors are decreased, indicating alterations in both synaptic and extra-synaptic GABA neurotransmission. Together, this pattern of changes indicates that the altered GABA neurotransmission is specific to PV-containing and SST-containing GABA neuron subsets and involves both synaptic and extra

Association between heart rhythm and cortical sound processing.

PubMed

Marcomini, Renata S; Frizzo, Ana Claúdia F; de Góes, Viviane B; Regaçone, Simone F; Garner, David M; Raimundo, Rodrigo D; Oliveira, Fernando R; Valenti, Vitor E

2018-04-26

Sound signal processing signifies an important factor for human conscious communication and it may be assessed through cortical auditory evoked potentials (CAEP). Heart rate variability (HRV) provides information about heart rate autonomic regulation. We investigated the association between resting HRV and CAEP. We evaluated resting HRV in the time and frequency domain and the CAEP components. The subjects remained at rest for 10 minutes for HRV recording, then they performed the CAEP examinations through frequency and duration protocols in both ears. Linear regression indicated that the amplitude of the N2 wave of the CAEP in the left ear (not right ear) was significantly influenced by standard deviation of normal-to-normal RR-intervals (17.7%) and percentage of adjacent RR-intervals with a difference of duration greater than 50 milliseconds (25.3%) time domain HRV indices in the frequency protocol. In the duration protocol and in the left ear the latency of the P2 wave was significantly influenced by low (LF) (20.8%) and high frequency (HF) bands in normalized units (21%) and LF/HF ratio (22.4%) indices of HRV spectral analysis. The latency of the N2 wave was significantly influenced by LF (25.8%), HF (25.9%) and LF/HF (28.8%). In conclusion, we promote the supposition that resting heart rhythm is associated with thalamo-cortical, cortical-cortical and auditory cortex pathways involved with auditory processing in the right hemisphere.

Embedding of Cortical Representations by the Superficial Patch System

PubMed Central

Da Costa, Nuno M. A.; Girardin, Cyrille C.; Naaman, Shmuel; Omer, David B.; Ruesch, Elisha; Grinvald, Amiram; Douglas, Rodney J.

2011-01-01

Pyramidal cells in layers 2 and 3 of the neocortex of many species collectively form a clustered system of lateral axonal projections (the superficial patch system—Lund JS, Angelucci A, Bressloff PC. 2003. Anatomical substrates for functional columns in macaque monkey primary visual cortex. Cereb Cortex. 13:15–24. or daisy architecture—Douglas RJ, Martin KAC. 2004. Neuronal circuits of the neocortex. Annu Rev Neurosci. 27:419–451.), but the function performed by this general feature of the cortical architecture remains obscure. By comparing the spatial configuration of labeled patches with the configuration of responses to drifting grating stimuli, we found the spatial organizations both of the patch system and of the cortical response to be highly conserved between cat and monkey primary visual cortex. More importantly, the configuration of the superficial patch system is directly reflected in the arrangement of function across monkey primary visual cortex. Our results indicate a close relationship between the structure of the superficial patch system and cortical responses encoding a single value across the surface of visual cortex (self-consistent states). This relationship is consistent with the spontaneous emergence of orientation response–like activity patterns during ongoing cortical activity (Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A. 2003. Spontaneously emerging cortical representations of visual attributes. Nature. 425:954–956.). We conclude that the superficial patch system is the physical encoding of self-consistent cortical states, and that a set of concurrently labeled patches participate in a network of mutually consistent representations of cortical input. PMID:21383233

Influences of brain development and ageing on cortical interactive networks.

PubMed

Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

2011-02-01

To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2016-11-01

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

Cortical oscillations related to processing congruent and incongruent grapheme-phoneme pairs.

PubMed

Herdman, Anthony T; Fujioka, Takako; Chau, Wilkin; Ross, Bernhard; Pantev, Christo; Picton, Terence W

2006-05-15

In this study, we investigated changes in cortical oscillations following congruent and incongruent grapheme-phoneme stimuli. Hiragana graphemes and phonemes were simultaneously presented as congruent or incongruent audiovisual stimuli to native Japanese-speaking participants. The discriminative reaction time was 57 ms shorter for congruent than incongruent stimuli. Analysis of MEG responses using synthetic aperture magnetometry (SAM) revealed that congruent stimuli evoked larger 2-10 Hz activity in the left auditory cortex within the first 250 ms after stimulus onset, and smaller 2-16 Hz activity in bilateral visual cortices between 250 and 500 ms. These results indicate that congruent visual input can modify cortical activity in the left auditory cortex.

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

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.

Scd5p and Clathrin Function Are Important for Cortical Actin Organization, Endocytosis, and Localization of Sla2p in Yeast

PubMed Central

Henry, Kenneth R.; D'Hondt, Kathleen; Chang, JiSuk; Newpher, Thomas; Huang, Kristen; Hudson, R. Tod; Riezman, Howard; Lemmon, Sandra K.

2002-01-01

SCD5 was identified as a multicopy suppressor of clathrin HC-deficient yeast. SCD5 is essential, but an scd5-Δ338 mutant, expressing Scd5p with a C-terminal truncation of 338 amino acids, is temperature sensitive for growth. Further studies here demonstrate that scd5-Δ338 affects receptor-mediated and fluid-phase endocytosis and normal actin organization. The scd5-Δ338 mutant contains larger and depolarized cortical actin patches and a prevalence of G-actin bars. scd5-Δ338 also displays synthetic negative genetic interactions with mutations in several other proteins important for cortical actin organization and endocytosis. Moreover, Scd5p colocalizes with cortical actin. Analysis has revealed that clathrin-deficient yeast also have a major defect in cortical actin organization and accumulate G-actin. Overexpression of SCD5 partially suppresses the actin defect of clathrin mutants, whereas combining scd5-Δ338 with a clathrin mutation exacerbates the actin and endocytic phenotypes. Both Scd5p and yeast clathrin physically associate with Sla2p, a homologue of the mammalian huntingtin interacting protein HIP1 and the related HIP1R. Furthermore, Sla2p localization at the cell cortex is dependent on Scd5p and clathrin function. Therefore, Scd5p and clathrin are important for actin organization and endocytosis, and Sla2p may provide a critical link between clathrin and the actin cytoskeleton in yeast, similar to HIP1(R) in animal cells. PMID:12181333

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

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

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

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

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.

Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells.

PubMed

Ortega, J Alberto; Sirois, Carissa L; Memi, Fani; Glidden, Nicole; Zecevic, Nada

2017-07-01

The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation. Small changes in O2 levels profoundly affected RGC survival, proliferation, and differentiation. Physiological hypoxia (3% O2) promoted neurogenesis, whereas anoxia (<1% O2) and severe hypoxia (1% O2) arrested the differentiation of human RGCs, mainly by altering the generation of glutamatergic neurons. The in vitro activation of Wnt-β-catenin signaling rescued the proliferation and neuronal differentiation of RGCs subjected to anoxia. Pathologic hypoxia (≤1% O2) also exerted negative effects on gliogenesis, by decreasing the number of O4+ preoligodendrocytes and increasing the number of reactive astrocytes derived from cortical RGCs. O2-dependent alterations in glutamatergic neurogenesis and oligodendrogenesis can lead to significant changes in cortical circuitry formation. A better understanding of the cellular effects caused by changes in O2 levels during human cortical development is essential to elucidating the etiology of numerous neurodevelopmental disorders. Published by Oxford University Press 2016.

Evaluation of Electroencephalography Source Localization Algorithms with Multiple Cortical Sources.

PubMed

Bradley, Allison; Yao, Jun; Dewald, Jules; Richter, Claus-Peter

2016-01-01

Source localization algorithms often show multiple active cortical areas as the source of electroencephalography (EEG). Yet, there is little data quantifying the accuracy of these results. In this paper, the performance of current source density source localization algorithms for the detection of multiple cortical sources of EEG data has been characterized. EEG data were generated by simulating multiple cortical sources (2-4) with the same strength or two sources with relative strength ratios of 1:1 to 4:1, and adding noise. These data were used to reconstruct the cortical sources using current source density (CSD) algorithms: sLORETA, MNLS, and LORETA using a p-norm with p equal to 1, 1.5 and 2. Precision (percentage of the reconstructed activity corresponding to simulated activity) and Recall (percentage of the simulated sources reconstructed) of each of the CSD algorithms were calculated. While sLORETA has the best performance when only one source is present, when two or more sources are present LORETA with p equal to 1.5 performs better. When the relative strength of one of the sources is decreased, all algorithms have more difficulty reconstructing that source. However, LORETA 1.5 continues to outperform other algorithms. If only the strongest source is of interest sLORETA is recommended, while LORETA with p equal to 1.5 is recommended if two or more of the cortical sources are of interest. These results provide guidance for choosing a CSD algorithm to locate multiple cortical sources of EEG and for interpreting the results of these algorithms.

Evaluation of Electroencephalography Source Localization Algorithms with Multiple Cortical Sources

PubMed Central

Bradley, Allison; Yao, Jun; Dewald, Jules; Richter, Claus-Peter

2016-01-01

Background Source localization algorithms often show multiple active cortical areas as the source of electroencephalography (EEG). Yet, there is little data quantifying the accuracy of these results. In this paper, the performance of current source density source localization algorithms for the detection of multiple cortical sources of EEG data has been characterized. Methods EEG data were generated by simulating multiple cortical sources (2–4) with the same strength or two sources with relative strength ratios of 1:1 to 4:1, and adding noise. These data were used to reconstruct the cortical sources using current source density (CSD) algorithms: sLORETA, MNLS, and LORETA using a p-norm with p equal to 1, 1.5 and 2. Precision (percentage of the reconstructed activity corresponding to simulated activity) and Recall (percentage of the simulated sources reconstructed) of each of the CSD algorithms were calculated. Results While sLORETA has the best performance when only one source is present, when two or more sources are present LORETA with p equal to 1.5 performs better. When the relative strength of one of the sources is decreased, all algorithms have more difficulty reconstructing that source. However, LORETA 1.5 continues to outperform other algorithms. If only the strongest source is of interest sLORETA is recommended, while LORETA with p equal to 1.5 is recommended if two or more of the cortical sources are of interest. These results provide guidance for choosing a CSD algorithm to locate multiple cortical sources of EEG and for interpreting the results of these algorithms. PMID:26809000

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

PubMed Central

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

2013-01-01

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

Neurogliaform cortical interneurons derive from cells in the preoptic area

PubMed Central

Cadilhac, Christelle; Prados, Julien; Holtmaat, Anthony

2018-01-01

Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3AR-expressing Hmx3+ cells located in the preoptic area (POA). Hmx3-derived 5-HT3AR+ cortical interneurons (INs) expressed the transcription factors PROX1, NR2F2, the marker reelin but not VIP and exhibited the molecular, morphological and electrophysiological profile of NGCs. Overall, these results indicate that NGCs are a distinct class of INs with a unique developmental trajectory and open the possibility to study their specific functional contribution to cortical inhibitory microcircuit motifs. PMID:29557780

Mapping cortical hubs in tinnitus

PubMed Central

2009-01-01

Background Subjective tinnitus is the perception of a sound in the absence of any physical source. It has been shown that tinnitus is associated with hyperactivity of the auditory cortices. Accompanying this hyperactivity, changes in non-auditory brain structures have also been reported. However, there have been no studies on the long-range information flow between these regions. Results Using Magnetoencephalography, we investigated the long-range cortical networks of chronic tinnitus sufferers (n = 23) and healthy controls (n = 24) in the resting state. A beamforming technique was applied to reconstruct the brain activity at source level and the directed functional coupling between all voxels was analyzed by means of Partial Directed Coherence. Within a cortical network, hubs are brain structures that either influence a great number of other brain regions or that are influenced by a great number of other brain regions. By mapping the cortical hubs in tinnitus and controls we report fundamental group differences in the global networks, mainly in the gamma frequency range. The prefrontal cortex, the orbitofrontal cortex and the parieto-occipital region were core structures in this network. The information flow from the global network to the temporal cortex correlated positively with the strength of tinnitus distress. Conclusion With the present study we suggest that the hyperactivity of the temporal cortices in tinnitus is integrated in a global network of long-range cortical connectivity. Top-down influence from the global network on the temporal areas relates to the subjective strength of the tinnitus distress. PMID:19930625

Dynamic Development of Regional Cortical Thickness and Surface Area in Early Childhood.

PubMed

Lyall, Amanda E; Shi, Feng; Geng, Xiujuan; Woolson, Sandra; Li, Gang; Wang, Li; Hamer, Robert M; Shen, Dinggang; Gilmore, John H

2015-08-01

Cortical thickness (CT) and surface area (SA) are altered in many neuropsychiatric disorders and are correlated with cognitive functioning. Little is known about how these components of cortical gray matter develop in the first years of life. We studied the longitudinal development of regional CT and SA expansion in healthy infants from birth to 2 years. CT and SA have distinct and heterogeneous patterns of development that are exceptionally dynamic; overall CT increases by an average of 36.1%, while cortical SA increases 114.6%. By age 2, CT is on average 97% of adult values, compared with SA, which is 69%. This suggests that early identification, prevention, and intervention strategies for neuropsychiatric illness need to be targeted to this period of rapid postnatal brain development, and that SA expansion is the principal driving factor in cortical volume after 2 years of age. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of Dimeric PSD-95 Inhibition on Excitotoxic Cell Death and Outcome After Controlled Cortical Impact in Rats.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Gynther, Mikko; Bjerre, Ann-Sofie; Gram, Marie Gajhede; Marschner, Linda; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-12-01

Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at 2 weeks post-trauma, and at 4 weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.

Cardiovascular fitness, cortical plasticity, and aging.

PubMed

Colcombe, Stanley J; Kramer, Arthur F; Erickson, Kirk I; Scalf, Paige; McAuley, Edward; Cohen, Neal J; Webb, Andrew; Jerome, Gerry J; Marquez, David X; Elavsky, Steriani

2004-03-02

Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

Drugs for stroke: action of nitrone (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2-amine oxide on rat cortical neurons in culture subjected to oxygen-glucose-deprivation.

PubMed

Arce, Carmen; Diaz-Castroverde, Sabela; Canales, María J; Marco-Contelles, José; Samadi, Abdelouahid; Oset-Gasque, María J; González, María P

2012-09-01

The action of (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2-amine oxide (RP6) on rat cortical neurons in culture, under oxygen-glucose-deprivation conditions, is reported. Cortical neurons in culture were treated during 1 h with OGD. After, they were placed under normal conditions during 24 h (reperfusion) in absence and presence of RP6. Different parameters were measured under each condition (control, 1 h OGD and 1 h OGD + reperfusion in absence and presence of RP6). RP6 protects neurons against ROS generation, lipid peroxidation levels, LDH release and mitochondrial membrane potential alteration, when administered during reperfusion after the OGD damage. Consequently, these results show that nitrone RP6 protects cells against ischemia injury produced during the reoxygenation, and could be a potential drug for the ictus therapy. Copyright © 2012. Published by Elsevier Masson SAS.

Cognitive Plasticity and Cortical Modules

PubMed Central

Mercado, Eduardo

2009-01-01

Some organisms learn to calculate, accumulate knowledge, and communicate in ways that others do not. What factors determine which intellectual abilities a particular species or individual can easily acquire? I propose that cognitive-skill learning capacity reflects (a) the availability of specialized cortical circuits, (b) the flexibility with which cortical activity is coordinated, and (c) the customizability of cortical networks. This framework can potentially account for differences in learning capacity across species, individuals, and developmental stages. Understanding the mechanisms that constrain cognitive plasticity is fundamental to developing new technologies and educational practices that maximize intellectual advancements. PMID:19750239

Cognitive Plasticity and Cortical Modules.

PubMed

Mercado, Eduardo

2009-06-01

Some organisms learn to calculate, accumulate knowledge, and communicate in ways that others do not. What factors determine which intellectual abilities a particular species or individual can easily acquire? I propose that cognitive-skill learning capacity reflects (a) the availability of specialized cortical circuits, (b) the flexibility with which cortical activity is coordinated, and (c) the customizability of cortical networks. This framework can potentially account for differences in learning capacity across species, individuals, and developmental stages. Understanding the mechanisms that constrain cognitive plasticity is fundamental to developing new technologies and educational practices that maximize intellectual advancements.

Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms

PubMed Central

Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

2016-01-01

Study Objectives: Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). Methods: The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Results: Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Conclusion: Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. Citation: Suh S, Kim H, Dang-Vu TT, Joo E, Shin C. Cortical thinning and altered cortico-cortical structural covariance of the default mode network in patients with

Low-Level Laser Light Therapy Improves Cognitive Deficits and Inhibits Microglial Activation after Controlled Cortical Impact in Mice

PubMed Central

Khuman, Jugta; Zhang, Jimmy; Park, Juyeon; Carroll, James D.; Donahue, Chad

2012-01-01

Abstract Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcomes after experimental traumatic brain injury (TBI), and coherent near-infrared light has been reported to improve cognitive function in patients with chronic TBI. However, the effects of LLLT on cognitive recovery in experimental TBI are unknown. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve post-injury Morris water maze (MWM) performance. Low-level laser light (800 nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60–80 min after CCI. Injured mice treated with 60 J/cm2 (500 mW/cm2×2 min) either transcranially or via an open craniotomy had modestly improved latency to the hidden platform (p<0.05 for group), and probe trial performance (p<0.01) compared to non-treated controls. The beneficial effects of LLLT in open craniotomy mice were associated with reduced microgliosis at 48 h (21.8±2.3 versus 39.2±4.2 IbA-1+ cells/200×field, p<0.05). Little or no effect of LLLT on post-injury cognitive function was observed using the other doses, a 4-h administration time point and 7-day administration of 60 J/cm2. No effect of LLLT (60 J/cm2 open craniotomy) was observed on post-injury motor function (days 1–7), brain edema (24 h), nitrosative stress (24 h), or lesion volume (14 days). Although further dose optimization and mechanism studies are needed, the data suggest that LLLT might be a therapeutic option to improve cognitive recovery and limit inflammation after TBI. PMID:21851183

Segmentation of cortical bone using fast level sets

NASA Astrophysics Data System (ADS)

Chowdhury, Manish; Jörgens, Daniel; Wang, Chunliang; Smedby, Årjan; Moreno, Rodrigo

2017-02-01

Cortical bone plays a big role in the mechanical competence of bone. The analysis of cortical bone requires accurate segmentation methods. Level set methods are usually in the state-of-the-art for segmenting medical images. However, traditional implementations of this method are computationally expensive. This drawback was recently tackled through the so-called coherent propagation extension of the classical algorithm which has decreased computation times dramatically. In this study, we assess the potential of this technique for segmenting cortical bone in interactive time in 3D images acquired through High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The obtained segmentations are used to estimate cortical thickness and cortical porosity of the investigated images. Cortical thickness and Cortical porosity is computed using sphere fitting and mathematical morphological operations respectively. Qualitative comparison between the segmentations of our proposed algorithm and a previously published approach on six images volumes reveals superior smoothness properties of the level set approach. While the proposed method yields similar results to previous approaches in regions where the boundary between trabecular and cortical bone is well defined, it yields more stable segmentations in challenging regions. This results in more stable estimation of parameters of cortical bone. The proposed technique takes few seconds to compute, which makes it suitable for clinical settings.

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

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

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.

Intraoperative Subcortical Fiber Mapping with Subcortico-Cortical Evoked Potentials.

PubMed

Enatsu, Rei; Kanno, Aya; Ohtaki, Shunya; Akiyama, Yukinori; Ochi, Satoko; Mikuni, Nobuhiro

2016-02-01

During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.

Extensive cortical rewiring after brain injury.

PubMed

Dancause, Numa; Barbay, Scott; Frost, Shawn B; Plautz, Erik J; Chen, Daofen; Zoubina, Elena V; Stowe, Ann M; Nudo, Randolph J

2005-11-02

Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

Functional Significance of Atypical Cortical Organization in Spina Bifida Myelomeningocele: Relations of Cortical Thickness and Gyrification with IQ and Fine Motor Dexterity

PubMed Central

Treble, Amery; Juranek, Jenifer; Stuebing, Karla K.; Dennis, Maureen; Fletcher, Jack M.

2013-01-01

The cortex in spina bifida myelomeningocele (SBM) is atypically organized, but it is not known how specific features of atypical cortical organization promote or disrupt cognitive and motor function. Relations of deviant cortical thickness and gyrification with IQ and fine motor dexterity were investigated in 64 individuals with SBM and 26 typically developing (TD) individuals, aged 8–28 years. Cortical thickness and 3D local gyrification index (LGI) were quantified from 33 cortical regions per hemisphere using FreeSurfer. Results replicated previous findings, showing regions of higher and lower cortical thickness and LGI in SBM relative to the TD comparison individuals. Cortical thickness and LGI were negatively associated in most cortical regions, though less consistently in the TD group. Whereas cortical thickness and LGI tended to be negatively associated with IQ and fine motor outcomes in regions that were thicker or more gyrified in SBM, associations tended to be positive in regions that were thinner or less gyrified in SBM. The more deviant the levels of cortical thickness and LGI—whether higher or lower relative to the TD group—the more impaired the IQ and fine motor outcomes, suggesting that these cortical atypicalities in SBM are functionally maladaptive, rather than adaptive. PMID:22875857

Cortical Entropy, Mutual Information and Scale-Free Dynamics in Waking Mice.

PubMed

Fagerholm, Erik D; Scott, Gregory; Shew, Woodrow L; Song, Chenchen; Leech, Robert; Knöpfel, Thomas; Sharp, David J

2016-10-01

Some neural circuits operate with simple dynamics characterized by one or a few well-defined spatiotemporal scales (e.g. central pattern generators). In contrast, cortical neuronal networks often exhibit richer activity patterns in which all spatiotemporal scales are represented. Such "scale-free" cortical dynamics manifest as cascades of activity with cascade sizes that are distributed according to a power-law. Theory and in vitro experiments suggest that information transmission among cortical circuits is optimized by scale-free dynamics. In vivo tests of this hypothesis have been limited by experimental techniques with insufficient spatial coverage and resolution, i.e., restricted access to a wide range of scales. We overcame these limitations by using genetically encoded voltage imaging to track neural activity in layer 2/3 pyramidal cells across the cortex in mice. As mice recovered from anesthesia, we observed three changes: (a) cortical information capacity increased, (b) information transmission among cortical regions increased and (c) neural activity became scale-free. Our results demonstrate that both information capacity and information transmission are maximized in the awake state in cortical regions with scale-free network dynamics. © The Author 2016. Published by Oxford University Press.

An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons

PubMed Central

Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi

2016-01-01

Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated I NMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on I NMDA-OUT. A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated I NMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of I NMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons. PMID:27298516

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

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

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.

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

Increase of cortical bone after a cementless long stem in periprosthetic fractures.

PubMed

García-Rey, Eduardo; García-Cimbrelo, Eduardo; Cruz-Pardos, Ana; Madero, Rosário

2013-12-01

Healing and functional recovery have been reported using an extensively porous-coated stem in Vancouver B2 and B3 periprosthetic fractures; however, loss of cortical bone has been observed when using these stems in revision surgery for aseptic loosening. However, it is unclear whether this bone loss influences subsequent loosening. We analyze the healing fracture rate and whether the radiographic changes observed around and extensively porous-coated stem used for periprosthetic fractures affect function or loosening. We retrospectively reviewed 35 patients with periprosthetic fractures (20 Vancouver B2 and 15 Vancouver B3). Patients' mean age at surgery was 80 years (range, 51-86 years). No cortical struts were used in this series. We evaluated radiographs for signs of loosening or subsidence. The cortical index and the femoral cortical width were measured at different levels on the immediate pre- and postoperative radiographs and at different periods of followup. The minimum followup was 3 years (mean, 8.3 years; range, 3-17 years). All fractures had healed, and all stems were clinically and radiographically stable at the end of followup. Nineteen hips showed nonprogressive radiographic subsidence during the first 3 postoperative months without clinical consequences. The cortical index and the lateral and medial cortical thickness increased over time. Increase of femoral cortex thicknesses was greater in cases with moderate preoperative osteoporosis and in cases with stems less than 16 mm in thickness. Our data suggest an extensively porous-coated stem for Vancouver B2 and B3 periprosthetic fractures leads to a high rate of union and stable fixation. Cortical index and lateral cortex thickness increased in these patients with periprosthetic fractures. Patients with moderate osteoporosis and those using thin stems showed a major increase in femoral cortex thickness over time.

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.

Surgical treatment of pectoralis major muscle rupture with adjustable cortical button.

PubMed

Pochini, Alberto de Castro; Rodrigues, Marcus de Souza Barbosa; Yamashita, Larissa; Belangero, Paulo Santoro; Andreoli, Carlos Vicente; Ejnisman, Benno

2018-01-01

To assess the tendon reconstruction technique for total rupture of the pectoralis major muscle using an adjustable cortical button. Prospective study of 27 male patients with a mean age of 29.9 (SD = 5.3 years) and follow-up of 2.3 years. The procedure consisted of autologous grafts taken from the semitendinosus and gracilis tendons and an adjustable cortical button. Patients were evaluated functionally by the Bak criteria. The surgical treatment of pectoralis major muscle tendon reconstruction was performed in the early stages (three weeks) in six patients (22.2%) and in 21 patients (77.8%), in the late stages. Patients operated with the adjustable cortical button technique obtained 96.3% excellent or good results, with only 3.7% having poor results (Bak criteria). Of the total, 85.2% were injured while performing bench press exercises and 14.8%, during the practice of Brazilian jiu-jitsu or wrestling. All weight-lifting athletes had history of anabolic steroid use. The early or delayed reconstruction of ruptured pectoralis major muscle tendons with considerable muscle retraction, using an adjustable cortical button and autologous knee flexor grafts, showed a high rate of good results.

Measurement of cortical functional activation in awake mice using two-photon microscopy and a novel pO2-sensitive probe(Conference Presentation)

NASA Astrophysics Data System (ADS)

Sencan, Ikbal; Esipova, Tatiana V.; Kilic, Kivilcim; Li, Baoqiang; Desjardins, Michèle; Yaseen, Mohammad A.; Wang, Hui; Jaswal, Rajeshwer S.; Kura, Sreekanth; Fu, Buyin; Boas, David A.; Devor, Anna; Sakadžić, Sava; Vinogradov, Sergei A.

2017-02-01

We characterized cortical microvascular PO2 and blood flow changes in response to whisker stimulation in awake mice. The measurements were performed by combining two-photon microscopy imaging of the cortical oxygenation and optical coherence tomography imaging of the cerebral blood flow. In order to perform fast spatio-temporally resolved measurements of PO2, we used a newly-developed oxygen-sensitive probe PtG-2P, which has significantly higher brightness than the established two-photon-enhanced oxygen sensor PtP-C343. We characterized the performance of the new probe in vivo and mapped the amplitudes and shapes (e.g. initial dip, overshoot, and post stimulus undershoot) of the PO2 changes as a function of the vessel type (e.g., arterioles, capillaries, and venules) and a distance from the activation center. The measurements in the awake mice are not affected by the confounding factors of anesthesia on the animal physiology, including the level of cerebral metabolism and the amplitude and speed of neuronal and vascular responses. Our results will help to understand changes in oxygenation and blood flow on the cortical microvascular scale, will lead to improved understanding of the cerebral physiology, pathophysiology and will improve quantitative interpretation of fMRI signals.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

PubMed

Lockwood Estrin, G; Kyriakopoulou, V; Makropoulos, A; Ball, G; Kuhendran, L; Chew, A; Hagberg, B; Martinez-Biarge, M; Allsop, J; Fox, M; Counsell, S J; Rutherford, M A

2016-01-01

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis.

PubMed

Schuster, Christina; Kasper, Elisabeth; Machts, Judith; Bittner, Daniel; Kaufmann, Jörn; Benecke, Reiner; Teipel, Stefan; Vielhaber, Stefan; Prudlo, Johannes

2014-10-01

To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p < 0.001). The LMN ALS variants demonstrated the highest rates of cortical thinning in the precentral gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.

Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.

PubMed

Fiddes, Ian T; Lodewijk, Gerrald A; Mooring, Meghan; Bosworth, Colleen M; Ewing, Adam D; Mantalas, Gary L; Novak, Adam M; van den Bout, Anouk; Bishara, Alex; Rosenkrantz, Jimi L; Lorig-Roach, Ryan; Field, Andrew R; Haeussler, Maximilian; Russo, Lotte; Bhaduri, Aparna; Nowakowski, Tomasz J; Pollen, Alex A; Dougherty, Max L; Nuttle, Xander; Addor, Marie-Claude; Zwolinski, Simon; Katzman, Sol; Kriegstein, Arnold; Eichler, Evan E; Salama, Sofie R; Jacobs, Frank M J; Haussler, David

2018-05-31

Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals that different alleles of NOTCH2NL have varying potencies to enhance Notch signaling by interacting directly with NOTCH receptors. Consistent with a role in Notch signaling, NOTCH2NL ectopic expression delays differentiation of neuronal progenitors, while deletion accelerates differentiation into cortical neurons. Furthermore, NOTCH2NL genes provide the breakpoints in 1q21.1 distal deletion/duplication syndrome, where duplications are associated with macrocephaly and autism and deletions with microcephaly and schizophrenia. Thus, the emergence of human-specific NOTCH2NL genes may have contributed to the rapid evolution of the larger human neocortex, accompanied by loss of genomic stability at the 1q21.1 locus and resulting recurrent neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

"The mute who can sing": a cortical stimulation study on singing.

PubMed

Roux, Franck-Emmanuel; Borsa, Stefano; Démonet, Jean-François

2009-02-01

In an attempt to identify cortical areas involved in singing in addition to language areas, the authors used a singing task during direct cortical mapping in 5 patients who were amateur singers and had undergone surgery for brain tumors. The organization of the cortical areas involved in language and singing was analyzed in relation with these surgical data. One left-handed and 4 right-handed patients with brain tumors in left (2 cases) and right (3 cases) hemispheres and no significant language or singing deficits underwent surgery with the "awake surgery" technique. All patients had a special interest in singing and were involved in amateur singing activities. They were tested using naming, reading, and singing tasks. Outside primary sensorimotor areas, singing interferences were rare and were exclusively localized in small cortical areas (< 1 cm(2)). A clear distinction was found between speech and singing in the Broca region. In the Broca region, no singing interference was found in areas in which interference in naming and reading tasks were detected. Conversely, a specific singing interference was found in nondominant middle frontal gyri in one patient. This interference consisted of abrupt singing arrest without apparent face, mouth, and tongue contraction. Finally, nonspecific singing interferences were found in the right and left precentral gyri in all patients (probably by interference in final articulatory mechanisms of singing). Dissociations between speech and singing found outside primary sensorimotor areas showed that these 2 functions use, in some cortical stages, different cerebral pathways.

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

Bilateral ECT induces bilateral increases in regional cortical thickness.

PubMed

van Eijndhoven, P; Mulders, P; Kwekkeboom, L; van Oostrom, I; van Beek, M; Janzing, J; Schene, A; Tendolkar, I

2016-08-23

Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.

Spatiotemporal characteristics of sleep spindles depend on cortical location.

PubMed

Piantoni, Giovanni; Halgren, Eric; Cash, Sydney S

2017-02-01

Since their discovery almost one century ago, sleep spindles, 0.5-2s long bursts of oscillatory activity at 9-16Hz during NREM sleep, have been thought to be global and relatively uniform throughout the cortex. Recent work, however, has brought this concept into question but it remains unclear to what degree spindles are global or local and if their properties are uniform or location-dependent. We addressed this question by recording sleep in eight patients undergoing evaluation for epilepsy with intracranial electrocorticography, which combines high spatial resolution with extensive cortical coverage. We find that spindle characteristics are not uniform but are strongly influenced by the underlying cortical regions, particularly for spindle density and fundamental frequency. We observe both highly isolated and spatially distributed spindles, but in highly skewed proportions: while most spindles are restricted to one or very few recording channels at any given time, there are spindles that occur over widespread areas, often involving lateral prefrontal cortices and superior temporal gyri. Their co-occurrence is affected by a subtle but significant propagation of spindles from the superior prefrontal regions and the temporal cortices towards the orbitofrontal cortex. This work provides a brain-wide characterization of sleep spindles as mostly local graphoelements with heterogeneous characteristics that depend on the underlying cortical area. We propose that the combination of local characteristics and global organization reflects the dual properties of the thalamo-cortical generators and provides a flexible framework to support the many functions ascribed to sleep in general and spindles specifically. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomized placebo-controlled study of noninvasive cortical electrostimulation in the treatment of fibromyalgia patients.

PubMed

Hargrove, Jeffrey B; Bennett, Robert M; Simons, David G; Smith, Susan J; Nagpal, Sunil; Deering, Donald E

2012-01-01

The aim of this multicenter study was to evaluate the efficacy, safety, and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia (FM). A prospective, randomized, double-blind, placebo-controlled design was used. Setting.  Subjects received therapy at two different outpatient clinical locations. There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM. Intervention.  Thirty-nine (39) active treatment (AT) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period. The primary outcome measures were the number of tender points (TePs) and pressure pain threshold (PPT). Secondary outcome measures were responses to the Fibromyalgia Impact Questionnaire (FIQ), Symptom Checklist-90 (SCL-90), Beck Depression Inventory-II, and a novel sleep questionnaire, all evaluated at baseline and at the end of treatment. Intervention provided significant improvements in TeP measures: compared with placebo, the AT patients improved in the number of positive TePs (-7.4 vs -0.2, P<0.001) and the PPT (19.6 vs -3.2, P<0.001). Most secondary outcomes also improved more in the AT group: total FIQ score (-15.5 vs -5.6, P=0.03), FIQ pain (-2.0 vs -0.6, P=0.03), FIQ fatigue (-2.0 vs -0.4, P=0.02), and FIQ refreshing sleep (-2.1 vs -0.7, P=0.02); and while FIQ function improved (-1.0 vs -0.2), the between-group change had a 14% likelihood of occurring due to chance (P=0.14). There were no significant side effects observed. Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain, TeP measures, fatigue, and sleep; and the treatment was well tolerated. This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients. Wiley Periodicals, Inc.

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

KCC2-dependent Steady-state Intracellular Chloride Concentration and pH in Cortical Layer 2/3 Neurons of Anesthetized and Awake Mice.

PubMed

Boffi, Juan C; Knabbe, Johannes; Kaiser, Michaela; Kuner, Thomas

2018-01-01

Neuronal intracellular Cl - concentration ([Cl - ] i ) influences a wide range of processes such as neuronal inhibition, membrane potential dynamics, intracellular pH (pH i ) or cell volume. Up to date, neuronal [Cl - ] i has predominantly been studied in model systems of reduced complexity. Here, we implemented the genetically encoded ratiometric Cl - indicator Superclomeleon (SCLM) to estimate the steady-state [Cl - ] i in cortical neurons from anesthetized and awake mice using 2-photon microscopy. Additionally, we implemented superecliptic pHluorin (SE-pHluorin) as a ratiometric sensor to estimate the intracellular steady-state pH (pH i ) of mouse cortical neurons in vivo . We estimated an average resting [Cl - ] i of 6 ± 2 mM with no evidence of subcellular gradients in the proximal somato-dendritic domain and an average somatic pH i of 7.1 ± 0.2. Neither [Cl - ] i nor pH i were affected by isoflurane anesthesia. We deleted the cation-Cl - co-transporter KCC2 in single identified neurons of adult mice and found an increase of [Cl - ] i to approximately 26 ± 8 mM, demonstrating that under in vivo conditions KCC2 produces low [Cl - ] i in adult mouse neurons. In summary, neurons of the brain of awake adult mice exhibit a low and evenly distributed [Cl - ] i in the proximal somato-dendritic compartment that is independent of anesthesia and requires KCC2 expression for its maintenance.

Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms.

PubMed

Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

2016-01-01

Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. © 2016 Associated Professional Sleep Societies, LLC.

SPECT in patients with cortical visual loss.

PubMed

Silverman, I E; Galetta, S L; Gray, L G; Moster, M; Atlas, S W; Maurer, A H; Alavi, A

1993-09-01

Single-photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was used to investigate changes in cerebral blood flow in seven patients with cortical visual impairment. Traumatic brain injury (TBI) was the cause of cortical damage in two patients, cerebral ischemia in two patients and carbon monoxide (CO) poisoning, status epilepticus and Alzheimer's Disease (AD) each in three separate patients. The SPECT scans of the seven patients were compared to T2-weighted magnetic resonance image (MRI) scans of the brain to determine the correlation between functional and anatomical findings. In six of the seven patients, the qualitative interpretation of the SPECT studies supported the clinical findings (i.e., the visual field defect) by revealing altered regional cerebral blood flow (rCBF) in the appropriate regions of the visual pathway. MR scans in all of the patients, on the other hand, were either normal or disclosed smaller lesions than those detected by SPECT. We conclude that SPECT may reveal altered rCBF in patients with cortical visual impairment of various etiologies, even when MRI studies are normal or nondiagnostic.

Increased Cortical Thickness in Professional On-Line Gamers

PubMed Central

Hyun, Gi Jung; Shin, Yong Wook; Kim, Bung-Nyun; Cheong, Jae Hoon; Jin, Seong Nam

2013-01-01

Objective The bulk of recent studies have tested whether video games change the brain in terms of activity and cortical volume. However, such studies are limited by several factors including cross-sectional comparisons, co-morbidity, and short-term follow-up periods. In the present study, we hypothesized that cognitive flexibility and the volume of brain cortex would be correlated with the career length of on-line pro-gamers. Methods High-resolution magnetic resonance scans were acquired in twenty-three pro-gamers recruited from StarCraft pro-game teams. We measured cortical thickness in each individual using FreeSurfer and the cortical thickness was correlated with the career length and the performance of the pro-gamers. Results Career length was positively correlated with cortical thickness in three brain regions: right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus. Additionally, increased cortical thickness in the prefrontal cortex was correlated with winning rates of the pro-game league. Increased cortical thickness in the prefrontal and parietal cortices was also associated with higher performance of Wisconsin Card Sorting Test. Conclusion Our results suggest that in individuals without pathologic conditions, regular, long-term playing of on-line games is associated with volume changes in the prefrontal and parietal cortices, which are associated with cognitive flexibility. PMID:24474988

Cortical inhibition deficits in recent onset PTSD after a single prolonged trauma exposure☆

PubMed Central

Qi, Shun; Mu, Yunfeng; Liu, Kang; Zhang, Jian; Huan, Yi; Tan, Qingrong; Shi, Mei; Wang, Qiang; Chen, Yunchun; Wang, Huaihai; Wang, Huaning; Zhang, Nanyin; Zhang, Xiaoliang; Xiong, Lize; Yin, Hong

2013-01-01

A variety of structural abnormalities have been described in post traumatic stress disorder (PTSD), but only a few studies have focused on cortical thickness alterations in recent onset PTSD. In this study, we adopted surface-based morphometry (SBM), which enables an exploration of global structural changes throughout the brain, in order to compare cortical thickness alterations in recent onset PTSD patients, trauma-exposed subjects but without PTSD, and normal controls. Moreover, we used region of interest (ROI) partial correlation analysis to evaluate the correlation among PTSD symptom severity and significant changes of cortical thickness. The widespread cortical thickness reduction relative to the normal controls were found in bilateral inferior and superior parietal lobes, frontal lobes, hippocampus, cingulate cortex, and right lateral occipital lobes in trauma survivors, whereas cortical thickness was only increased in left calcarine cortex in PTSD group. The average cortical thickness of hippocampus and cingulate cortex decreased by 10.75% and 9.09% in PTSD, 3.48% and 2.86% in non PTSD. We further demonstrated that the cortical thicknesses of bilateral ACC and PCC, superior frontal lobes, and hippocampus are negatively correlated with CAPS scores in all trauma survivors. Our study results suggest that stress widens cortical thinning regions and causes more serious effect in recent onset PTSD than non PTSD. It also shows that the cortical thinning in recent onset PTSD predicts the symptom severity. PMID:24273707

Toward more versatile and intuitive cortical brain machine interfaces

PubMed Central

Andersen, Richard A.; Kellis, Spencer; Klaes, Christian; Aflalo, Tyson

2015-01-01

Brain machine interfaces have great potential in neuroprosthetic applications to assist patients with brain injury and neurodegenerative diseases. One type of BMI is a cortical motor prosthetic which is used to assist paralyzed subjects. Motor prosthetics to date have typically used the motor cortex as a source of neural signals for controlling external devices. The review will focus on several new topics in the arena of cortical prosthetics. These include using 1) recordings from cortical areas outside motor cortex; 2) local field potentials (LFPs) as a source of recorded signals; 3) somatosensory feedback for more dexterous control of robotics; and 4) new decoding methods that work in concert to form an ecology of decode algorithms. These new advances hold promise in greatly accelerating the applicability and ease of operation of motor prosthetics. PMID:25247368

Structural analysis of cortical porosity applied to HR-pQCT data

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

Tjong, Willy, E-mail: wwtjong@gmail.com; Nirody, Jasmine, E-mail: jnirody@berkeley.edu; Burghardt, Andrew J., E-mail: andrew.burghardt@ucsf.edu

2014-01-15

Purpose: The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualizedin vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology. Methods: Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82μm) and also using μCT at amore » voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%). Results: Correlations toμCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r{sup 2} = 0.82, p < 0.001, 82: r{sup 2} = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r{sup 2} = 0.72, p < 0

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

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.

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults

PubMed Central

Williams, Victoria; Hayes, Jasmeet P.; Forman, Daniel E.; Salat, David H.; Sperling, Reisa A.; Verfaellie, Mieke; Hayes, Scott M.

2016-01-01

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy. PMID:27989841

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults.

PubMed

Williams, Victoria J; Hayes, Jasmeet P; Forman, Daniel E; Salat, David H; Sperling, Reisa A; Verfaellie, Mieke; Hayes, Scott M

2017-02-01

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO 2 ), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO 2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO 2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy. Published by Elsevier Inc.

Anterior Cortical Development During Adolescence in Bipolar Disorder.

PubMed

Najt, Pablo; Wang, Fei; Spencer, Linda; Johnston, Jennifer A Y; Cox Lippard, Elizabeth T; Pittman, Brian P; Lacadie, Cheryl; Staib, Lawrence H; Papademetris, Xenophon; Blumberg, Hilary P

2016-02-15

Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p < .05, corrected), including greater gray matter contraction and decreased white matter expansion over time, in the BD compared with the healthy group. The findings support neurodevelopmental abnormalities during adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter. Published by Elsevier Inc.

Cortical Odor Processing in Health and Disease

PubMed Central

Wilson, Donald A.; Xu, Wenjin; Sadrian, Benjamin; Courtiol, Emmanuelle; Cohen, Yaniv; Barnes, Dylan C.

2014-01-01

The olfactory system has a rich cortical representation, including a large archicortical component present in most vertebrates, and in mammals neocortical components including the entorhinal and orbitofrontal cortices. Together, these cortical components contribute to normal odor perception and memory. They help transform the physicochemical features of volatile molecules inhaled or exhaled through the nose into the perception of odor objects with rich associative and hedonic aspects. This chapter focuses on how olfactory cortical areas contribute to odor perception and begins to explore why odor perception is so sensitive to disease and pathology. Odor perception is disrupted by a wide range of disorders including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, autism, and early life exposure to toxins. This olfactory deficit often occurs despite maintained functioning in other sensory systems. Does the unusual network of olfactory cortical structures contribute to this sensitivity? PMID:24767487

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

Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

PubMed

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

2016-11-01

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

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 areas involved in Arabic number reading.

PubMed

Roux, F-E; Lubrano, V; Lauwers-Cances, V; Giussani, C; Démonet, J-F

2008-01-15

Distinct functional pathways for processing words and numbers have been hypothesized from the observation of dissociated impairments of these categories in brain-damaged patients. We aimed to identify the cortical areas involved in Arabic number reading process in patients operated on for various brain lesions. Direct cortical electrostimulation was prospectively used in 60 brain mappings. We used object naming and two reading tasks: alphabetic script (sentences and number words) and Arabic number reading. Cortical areas involved in Arabic number reading were identified according to location, type of interference, and distinctness from areas associated with other language tasks. Arabic number reading was sustained by small cortical areas, often extremely well localized (<1 cm(2)). Over 259 language sites detected, 43 (17%) were exclusively involved in Arabic number reading (no sentence or word number reading interference detected in these sites). Specific Arabic number reading interferences were mainly found in three regions: the Broca area (Brodmann area 45), the anterior part of the dominant supramarginal gyrus (Brodmann area 40; p < 0.0001), and the temporal-basal area (Brodmann area 37; p < 0.05). Diverse types of interferences were observed (reading arrest, phonemic or semantic paraphasia). Error patterns were fairly similar across temporal, parietal, and frontal stimulation sites, except for phonemic paraphasias, which were found only in supramarginal gyrus. Our findings strongly support the fact that the acquisition through education of specific symbolic entities, such as Arabic numbers, could result in the segregation and the specialization of anatomically distinct brain areas.

Cortical mechanisms of mirror therapy after stroke.

PubMed

Rossiter, Holly E; Borrelli, Mimi R; Borchert, Robin J; Bradbury, David; Ward, Nick S

2015-06-01

Mirror therapy is a new form of stroke rehabilitation that uses the mirror reflection of the unaffected hand in place of the affected hand to augment movement training. The mechanism of mirror therapy is not known but is thought to involve changes in cerebral organization. We used magnetoencephalography (MEG) to measure changes in cortical activity during mirror training after stroke. In particular, we examined movement-related changes in the power of cortical oscillations in the beta (15-30 Hz) frequency range, known to be involved in movement. Ten stroke patients with upper limb paresis and 13 healthy controls were recorded using MEG while performing bimanual hand movements in 2 different conditions. In one, subjects looked directly at their affected hand (or dominant hand in controls), and in the other, they looked at a mirror reflection of their unaffected hand in place of their affected hand. The movement-related beta desynchronization was calculated in both primary motor cortices. Movement-related beta desynchronization was symmetrical during bilateral movement and unaltered by the mirror condition in controls. In the patients, movement-related beta desynchronization was generally smaller than in controls, but greater in contralesional compared to ipsilesional motor cortex. This initial asymmetry in movement-related beta desynchronization between hemispheres was made more symmetrical by the presence of the mirror. Mirror therapy could potentially aid stroke rehabilitation by normalizing an asymmetrical pattern of movement-related beta desynchronization in primary motor cortices during bilateral movement. © The Author(s) 2014.

A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement

PubMed Central

Ramalingam, Nagendran; Franke, Christof; Jaschinski, Evelin; Winterhoff, Moritz; Lu, Yao; Brühmann, Stefan; Junemann, Alexander; Meier, Helena; Noegel, Angelika A.; Weber, Igor; Zhao, Hongxia; Merkel, Rudolf; Schleicher, Michael; Faix, Jan

2015-01-01

Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. However, how the cortical actin meshwork in the rear is generated remains elusive. Here we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum that generates a subset of filaments as the basis of a resilient cortical actin sheath in the rear. Mechanical resistance of this actin compartment is accomplished by actin crosslinkers and IQGAP-related proteins, and is mandatory to withstand the increased contractile forces in response to mechanical stress by impeding unproductive blebbing in the rear, allowing efficient cell migration in two-dimensional-confined environments. Consistently, ForA supresses the formation of lateral protrusions, rapidly relocalizes to new prospective ends in repolarizing cells and is required for cortical integrity. Finally, we show that ForA utilizes the phosphoinositide gradients in polarized cells for subcellular targeting. PMID:26415699

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.

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.

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

PubMed

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

2017-01-01

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

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

Cortical Neural Computation by Discrete Results Hypothesis

PubMed Central

Castejon, Carlos; Nuñez, Angel

2016-01-01

One of the most challenging problems we face in neuroscience is to understand how the cortex performs computations. There is increasing evidence that the power of the cortical processing is produced by populations of neurons forming dynamic neuronal ensembles. Theoretical proposals and multineuronal experimental studies have revealed that ensembles of neurons can form emergent functional units. However, how these ensembles are implicated in cortical computations is still a mystery. Although cell ensembles have been associated with brain rhythms, the functional interaction remains largely unclear. It is still unknown how spatially distributed neuronal activity can be temporally integrated to contribute to cortical computations. A theoretical explanation integrating spatial and temporal aspects of cortical processing is still lacking. In this Hypothesis and Theory article, we propose a new functional theoretical framework to explain the computational roles of these ensembles in cortical processing. We suggest that complex neural computations underlying cortical processing could be temporally discrete and that sensory information would need to be quantized to be computed by the cerebral cortex. Accordingly, we propose that cortical processing is produced by the computation of discrete spatio-temporal functional units that we have called “Discrete Results” (Discrete Results Hypothesis). This hypothesis represents a novel functional mechanism by which information processing is computed in the cortex. Furthermore, we propose that precise dynamic sequences of “Discrete Results” is the mechanism used by the cortex to extract, code, memorize and transmit neural information. The novel “Discrete Results” concept has the ability to match the spatial and temporal aspects of cortical processing. We discuss the possible neural underpinnings of these functional computational units and describe the empirical evidence supporting our hypothesis. We propose that fast

Cortical Neural Computation by Discrete Results Hypothesis.

PubMed

Castejon, Carlos; Nuñez, Angel

2016-01-01

One of the most challenging problems we face in neuroscience is to understand how the cortex performs computations. There is increasing evidence that the power of the cortical processing is produced by populations of neurons forming dynamic neuronal ensembles. Theoretical proposals and multineuronal experimental studies have revealed that ensembles of neurons can form emergent functional units. However, how these ensembles are implicated in cortical computations is still a mystery. Although cell ensembles have been associated with brain rhythms, the functional interaction remains largely unclear. It is still unknown how spatially distributed neuronal activity can be temporally integrated to contribute to cortical computations. A theoretical explanation integrating spatial and temporal aspects of cortical processing is still lacking. In this Hypothesis and Theory article, we propose a new functional theoretical framework to explain the computational roles of these ensembles in cortical processing. We suggest that complex neural computations underlying cortical processing could be temporally discrete and that sensory information would need to be quantized to be computed by the cerebral cortex. Accordingly, we propose that cortical processing is produced by the computation of discrete spatio-temporal functional units that we have called "Discrete Results" (Discrete Results Hypothesis). This hypothesis represents a novel functional mechanism by which information processing is computed in the cortex. Furthermore, we propose that precise dynamic sequences of "Discrete Results" is the mechanism used by the cortex to extract, code, memorize and transmit neural information. The novel "Discrete Results" concept has the ability to match the spatial and temporal aspects of cortical processing. We discuss the possible neural underpinnings of these functional computational units and describe the empirical evidence supporting our hypothesis. We propose that fast-spiking (FS

Perceptual Learning: Use-Dependent Cortical Plasticity.

PubMed

Li, Wu

2016-10-14

Our perceptual abilities significantly improve with practice. This phenomenon, known as perceptual learning, offers an ideal window for understanding use-dependent changes in the adult brain. Different experimental approaches have revealed a diversity of behavioral and cortical changes associated with perceptual learning, and different interpretations have been given with respect to the cortical loci and neural processes responsible for the learning. Accumulated evidence has begun to put together a coherent picture of the neural substrates underlying perceptual learning. The emerging view is that perceptual learning results from a complex interplay between bottom-up and top-down processes, causing a global reorganization across cortical areas specialized for sensory processing, engaged in top-down attentional control, and involved in perceptual decision making. Future studies should focus on the interactions among cortical areas for a better understanding of the general rules and mechanisms underlying various forms of skill learning.

Alterations in Cortical Thickness and White Matter Integrity in Mild Cognitive Impairment Measured by Whole Brain Cortical Thickness Mapping and Diffusion Tensor Imaging

PubMed Central

Wang, Liya; Goldstein, Felicia C.; Veledar, Emir; Levey, Allan I.; Lah, James J.; Meltzer, Carolyn C.; Holder, Chad A.; Mao, Hui

2010-01-01

Background and Purpose Mild cognitive impairment (MCI) is a risk factor for Alzheimer's disease (AD) and can be difficult to diagnose due to the subtlety of symptoms. This work attempted to examine gray and white matter changes with cortical thickness analysis and diffusion tensor imaging (DTI) in MCI patients and demographically-matched comparison subjects in order to test these measurements as possible imaging markers for diagnosis. Materials and Methods Subjects with amnestic MCI (n=10; age 72.2±7.1) and normal cognition (n=10; age 70.1±7.7) underwent DTI and T1 weighted MRI at 3T. Fractional anisotropy, apparent diffusion coefficient and cortical thickness were measured and compared between MCI and control groups. The diagnostic accuracy of two methods, either in combination or separately, was evaluated using binary logistic regression and nonparametric statistical analyses for sensitivity, specificity and accuracy. Results Decreased FA and increased ADC in white matter regions of frontal and temporal lobes and corpus callosum were observed in MCI patients. Cortical thickness was decreased in gray matter regions of the frontal, temporal, parietal lobes in MCI patients. Changes in white matter and cortical thickness appeared to be more pronounced in the left hemisphere than in the right hemisphere. Furthermore the combination of cortical thickness and DTI measurements in left temporal areas improved the accuracy of differentiating MCI patients from controls compared to either measure alone. Conclusion DTI and cortical thickness analyses may both serve imaging markers for differentiating MCI from normal aging. Combined use of two methods may improve the accuracy of MCI diagnosis. PMID:19279272

Adrenal cortical oncocytoma mimicking pheochromocytoma.

PubMed

Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

2011-01-01

Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

Cortical Thickness and Episodic Memory Impairment in Systemic Lupus Erythematosus.

PubMed

Bizzo, Bernardo Canedo; Sanchez, Tiago Arruda; Tukamoto, Gustavo; Zimmermann, Nicolle; Netto, Tania Maria; Gasparetto, Emerson Leandro

2017-01-01

The purpose of this study was to investigate differences in brain cortical thickness of systemic lupus erythematosus (SLE) patients with and without episodic memory impairment and healthy controls. We studied 51 patients divided in 2 groups (SLE with episodic memory deficit, n = 17; SLE without episodic memory deficit, n = 34) by the Rey Auditory Verbal Learning Test and 34 healthy controls. Groups were paired based on sex, age, education, Mini-Mental State Examination score, and accumulation of disease burden. Cortical thickness from magnetic resonance imaging scans was determined using the FreeSurfer software package. SLE patients with episodic memory deficits presented reduced cortical thickness in the left supramarginal cortex and superior temporal gyrus when compared to the control group and in the right superior frontal, caudal, and rostral middle frontal and precentral gyri when compared to the SLE group without episodic memory impairment considering time since diagnosis of SLE as covaried. There were no significant differences in the cortical thickness between the SLE without episodic memory and control groups. Different memory-related cortical regions thinning were found in the episodic memory deficit group when individually compared to the groups of patients without memory impairment and healthy controls. Copyright © 2016 by the American Society of Neuroimaging.

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

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

PubMed Central

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

2010-01-01

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

Variability in Cortical Representations of Speech Sound Perception

ERIC Educational Resources Information Center

Boatman, Dana F.

2007-01-01

Recent brain mapping studies have provided new insights into the cortical systems that mediate human speech perception. Electrocortical stimulation mapping (ESM) is a brain mapping method that is used clinically to localize cortical functions in neurosurgical patients. Recent ESM studies have yielded new insights into the cortical systems that…

Visualization of Cortical Dynamics

NASA Astrophysics Data System (ADS)

Grinvald, Amiram

2003-03-01

Recent progress in studies of cortical dynamics will be reviewed including the combination of real time optical imaging based on voltage sensitive dyes, single and multi- unit recordings, LFP, intracellular recordings and microstimulation. To image the flow of neuronal activity from one cortical site to the next, in real time, we have used optical imaging based on newly designed voltage sensitive dyes and a Fuji 128x 128 fast camera which we modified. A factor of 20-40 fold improvement in the signal to noise ratio was obtained with the new dye during in vivo imaging experiments. This improvements has facilitates the exploration of cortical dynamics without signal averaging in the millisecond time domain. We confirmed that the voltage sensitive dye signal indeed reflects membrane potential changes in populations of neurons by showing that the time course of the intracellular activity recorded intracellularly from a single neuron was highly correlated in many cases with the optical signal from a small patch of cortex recorded nearby. We showed that the firing of single cortical neurons is not a random process but occurs when the on-going pattern of million of neurons is similar to the functional architecture map which correspond to the tuning properties of that neuron. Chronic optical imaging, combined with electrical recordings and microstimulation, over a long period of times of more than a year, was successfully applied also to the study of higher brain functions in the behaving macaque monkey.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

PubMed

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-11-15

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans

PubMed Central

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-01-01

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications. PMID:12949224

Mapping Cortical Laminar Structure in the 3D BigBrain.

PubMed

Wagstyl, Konrad; Lepage, Claude; Bludau, Sebastian; Zilles, Karl; Fletcher, Paul C; Amunts, Katrin; Evans, Alan C

2018-07-01

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2018-04-21

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

Gravity-induced changes in intracellular potentials in elongating cortical cells of mung bean roots

NASA Technical Reports Server (NTRS)

Ishikawa, H.; Evans, M. L.

1990-01-01

Gravity-induced changes in intracellular potentials in primary roots of 2-day-old mung bean (Vigna mungo L. cv. black matpe) seedlings were investigated using glass microelectrodes held by 3-dimensional hydraulic micro-drives. The electrodes were inserted into outer cortical cells within the elongation zone. Intracellular potentials, angle of root orientation with respect to gravity, and position within the root of the impaled cortical cell were measured simultaneously. Gravistimulation caused intracellular potential changes in cortical cells of the elongation zone. When the roots were oriented vertically, the intracellular potentials of the outer cortical cells (2 mm behind the root apex) were approximately - 115 mV. When the roots were placed horizontally cortical cells on the upper side hyperpolarized to - 154 mV within 30 s while cortical cells on the lower side depolarized to about - 62 mV. This electrical asymmetry did not occur in cells of the maturation zone. Because attempts to insert the electrode into cells of the root cap were unsuccessful, these cells were not measured. The hyperpolarization of cortical cells on the upper side was greatly reduced upon application of N,N'-dicyclohexylcarbodiimide (DCCD), an inhibitor of respiratory energy coupling. When stimulated roots were returned to the vertical, the degree of hyperpolarization of cortical cells on the previous upper side decreased within 30 s and approached that of cortical cells in non-stimulated roots. This cycle of hyperpolarization/loss of hyperpolarization was repeatable at least ten times by alternately turning the root from the vertical to the horizontal and back again. The very short (<30 s) lag period of these electrical changes indicates that they may result from stimulus-perception and transduction within the elongation zone rather than from transmission of a signal from the root cap.

Lipids and collagen matrix restrict the hydraulic permeability within the porous compartment of adult cortical bone

PubMed Central

Wen, Demin; Androjna, Caroline; Vasanji, Amit; Belovich, Joanne; Midura, Ronald J.

2010-01-01

In vivo the hydraulic permeability of cortical bone influences the transport of nutrients, waste products and signaling molecules, thus influencing the metabolic functions of osteocytes and osteoblasts. In the current study two hypotheses were tested: the presence of (1) lipids and (2) collagen matrix in the porous compartment of cortical bone restricts its permeability. Our approach was to measure the radial permeability of adult canine cortical bone before and after extracting lipids with acetone-methanol, and before and after digesting collagen with bacterial collagenase. Our results showed that the permeability of adult canine cortical bone was below 4.0 × 10−17 m2, a value consistent with prior knowledge. After extracting lipids, permeability increased to a median value of 8.6 × 10−16 m2. After further digesting with collagenase, permeability increased to a median value of 1.4 × 10−14 m2. We conclude that the presence of both lipids and collagen matrix within the porous compartment of cortical bone restricts its radial permeability. These novel findings suggest that the chemical composition of the tissue matrix within the porous compartment of cortical bone influences the transport and exchange of nutrients and waste products, and possibly influences the metabolic functions of osteocytes and osteoblasts. PMID:19967451

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 Development and Neuroplasticity in Auditory Neuropathy Spectrum Disorder

PubMed Central

Sharma, Anu; Cardon, Garrett

2015-01-01

Cortical development is dependent to a large extent on stimulus-driven input. Auditory Neuropathy Spectrum Disorder (ANSD) is a recently described form of hearing impairment where neural dys-synchrony is the predominant characteristic. Children with ANSD provide a unique platform to examine the effects of asynchronous and degraded afferent stimulation on cortical auditory neuroplasticity and behavioral processing of sound. In this review, we describe patterns of auditory cortical maturation in children with ANSD. The disruption of cortical maturation that leads to these various patterns includes high levels of intra-individual cortical variability and deficits in cortical phase synchronization of oscillatory neural responses. These neurodevelopmental changes, which are constrained by sensitive periods for central auditory maturation, are correlated with behavioral outcomes for children with ANSD. Overall, we hypothesize that patterns of cortical development in children with ANSD appear to be markers of the severity of the underlying neural dys-synchrony, providing prognostic indicators of success of clinical intervention with amplification and/or electrical stimulation. PMID:26070426

Asymmetry of cortical decline in subtypes of primary progressive aphasia.

PubMed

Rogalski, Emily; Cobia, Derin; Martersteck, Adam; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Mesulam, M-Marsel

2014-09-23

The aim of this study was to provide quantitative measures of changes in cortical atrophy over a 2-year period associated with 3 subtypes of primary progressive aphasia (PPA) using whole-brain vertex-wise and region-of-interest (ROI) neuroimaging methods. The purpose was to quantitate disease progression, establish an empirical basis for clinical expectations, and provide outcome measures for therapeutic trials. Changes in cortical thickness and volume loss as well as neuropsychological performance were assessed at baseline and 2-year follow-up in 26 patients who fulfilled criteria for logopenic (8 patients), agrammatic (10 patients), and semantic (8 patients) PPA subtypes. Whole-brain vertex-wise and ROI imaging analysis were conducted using the FreeSurfer longitudinal pipeline. Clinical deficits and cortical atrophy patterns showed distinct patterns of change among the subtypes over 2 years. Results confirmed that progression for each of the 3 subtypes showed left greater than right hemisphere asymmetry. An ROI analysis also revealed that progression was greater within, rather than outside, the language network. Preferential neurodegeneration of the left hemisphere language network is a common denominator for all 3 PPA subtypes, even as the disease progresses. Using a focal cortical language network ROI as an outcome measure of disease progression appears to be more sensitive than whole-brain or ventricular volume measures of change and may be helpful for designing future clinical trials in PPA. © 2014 American Academy of Neurology.

Asymmetry of cortical decline in subtypes of primary progressive aphasia

PubMed Central

Cobia, Derin; Martersteck, Adam; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Mesulam, M.-Marsel

2014-01-01

Objective: The aim of this study was to provide quantitative measures of changes in cortical atrophy over a 2-year period associated with 3 subtypes of primary progressive aphasia (PPA) using whole-brain vertex-wise and region-of-interest (ROI) neuroimaging methods. The purpose was to quantitate disease progression, establish an empirical basis for clinical expectations, and provide outcome measures for therapeutic trials. Methods: Changes in cortical thickness and volume loss as well as neuropsychological performance were assessed at baseline and 2-year follow-up in 26 patients who fulfilled criteria for logopenic (8 patients), agrammatic (10 patients), and semantic (8 patients) PPA subtypes. Whole-brain vertex-wise and ROI imaging analysis were conducted using the FreeSurfer longitudinal pipeline. Results: Clinical deficits and cortical atrophy patterns showed distinct patterns of change among the subtypes over 2 years. Results confirmed that progression for each of the 3 subtypes showed left greater than right hemisphere asymmetry. An ROI analysis also revealed that progression was greater within, rather than outside, the language network. Conclusions: Preferential neurodegeneration of the left hemisphere language network is a common denominator for all 3 PPA subtypes, even as the disease progresses. Using a focal cortical language network ROI as an outcome measure of disease progression appears to be more sensitive than whole-brain or ventricular volume measures of change and may be helpful for designing future clinical trials in PPA. PMID:25165386

Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation.

PubMed

Sharma, Ashish K; Toussaint, Nigel D; Masterson, Rosemary; Holt, Stephen G; Rajapakse, Chamith S; Ebeling, Peter R; Mohanty, Sindhu T; Baldock, Paul; Elder, Grahame J

2018-05-23

Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients. By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD. © 2018 S. Karger AG, Basel.

Background noise can enhance cortical auditory evoked potentials under certain conditions

PubMed Central

Papesh, Melissa A.; Billings, Curtis J.; Baltzell, Lucas S.

2017-01-01

Objective To use cortical auditory evoked potentials (CAEPs) to understand neural encoding in background noise and the conditions under which noise enhances CAEP responses. Methods CAEPs from 16 normal-hearing listeners were recorded using the speech syllable/ba/presented in quiet and speech-shaped noise at signal-to-noise ratios of 10 and 30 dB. The syllable was presented binaurally and monaurally at two presentation rates. Results The amplitudes of N1 and N2 peaks were often significantly enhanced in the presence of low-level background noise relative to quiet conditions, while P1 and P2 amplitudes were consistently reduced in noise. P1 and P2 amplitudes were significantly larger during binaural compared to monaural presentations, while N1 and N2 peaks were similar between binaural and monaural conditions. Conclusions Methodological choices impact CAEP peaks in very different ways. Negative peaks can be enhanced by background noise in certain conditions, while positive peaks are generally enhanced by binaural presentations. Significance Methodological choices significantly impact CAEPs acquired in quiet and in noise. If CAEPs are to be used as a tool to explore signal encoding in noise, scientists must be cognizant of how differences in acquisition and processing protocols selectively shape CAEP responses. PMID:25453611

The genetics underlying acquired long QT syndrome: impact for genetic screening.

PubMed

Itoh, Hideki; Crotti, Lia; Aiba, Takeshi; Spazzolini, Carla; Denjoy, Isabelle; Fressart, Véronique; Hayashi, Kenshi; Nakajima, Tadashi; Ohno, Seiko; Makiyama, Takeru; Wu, Jie; Hasegawa, Kanae; Mastantuono, Elisa; Dagradi, Federica; Pedrazzini, Matteo; Yamagishi, Masakazu; Berthet, Myriam; Murakami, Yoshitaka; Shimizu, Wataru; Guicheney, Pascale; Schwartz, Peter J; Horie, Minoru

2016-05-07

Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors. We screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated 'true aLQTS' (QTc within normal limits) or 'unmasked cLQTS' (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in 'true aLQTS', KCNQ1 mutations were much less frequent than KCNH2 (20% [95% CI 7-41%] vs. 64% [95% CI 43-82%], P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations. A third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

PubMed

Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

2016-01-13

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN

Cortical network reorganization guided by sensory input features.

PubMed

Kilgard, Michael P; Pandya, Pritesh K; Engineer, Navzer D; Moucha, Raluca

2002-12-01

Sensory experience alters the functional organization of cortical networks. Previous studies using behavioral training motivated by aversive or rewarding stimuli have demonstrated that cortical plasticity is specific to salient inputs in the sensory environment. Sensory experience associated with electrical activation of the basal forebrain (BasF) generates similar input specific plasticity. By directly engaging plasticity mechanisms and avoiding extensive behavioral training, BasF stimulation makes it possible to efficiently explore how specific sensory features contribute to cortical plasticity. This review summarizes our observations that cortical networks employ a variety of strategies to improve the representation of the sensory environment. Different combinations of receptive-field, temporal, and spectrotemporal plasticity were generated in primary auditory cortex neurons depending on the pitch, modulation rate, and order of sounds paired with BasF stimulation. Simple tones led to map expansion, while modulated tones altered the maximum cortical following rate. Exposure to complex acoustic sequences led to the development of combination-sensitive responses. This remodeling of cortical response characteristics may reflect changes in intrinsic cellular mechanisms, synaptic efficacy, and local neuronal connectivity. The intricate relationship between the pattern of sensory activation and cortical plasticity suggests that network-level rules alter the functional organization of the cortex to generate the most behaviorally useful representation of the sensory environment.

Cortical thickness in symptomatic and asymptomatic bipolar offspring.

PubMed

Hanford, Lindsay C; Sassi, Roberto B; Minuzzi, Luciano; Hall, Geoffrey B

2016-05-30

Children of parents diagnosed with bipolar disorder are at greater risk for developing a variety of psychiatric disorders, however, the reasons remain unknown. The present study aimed to investigate gray matter integrity in high-risk bipolar offspring (HRO) and healthy offspring (HCO) using cortical thickness techniques. Here we examined healthy control offspring (HCO; n=20) and HRO with (n=17) or without (n=13) psychiatric symptoms. T1-weighted images were collected from all offspring, and cortical thickness and age-cortical thickness correlations were compared. HRO showed cortical thinning in superior and inferior temporal regions, supramarginal, and caudal and rostral middle frontal regions compared to HCO. When comparing HRO with and without psychiatric symptoms, we found cortical thinning in symptomatic offspring in the superior frontal and somatosensory related cortices. Age-thickness correlations showed a relatively consistent negative relationship in most regions in HCO, while the reverse was true for the HRO. These regions included parahippocampal, lateral orbitofrontal, and inferior temporal regions. Our study provides evidence of cortical thickness reductions among symptomatic and asymptomatic high-risk offspring during youth. Some of these alterations, found in regions of emotion processing and regulation, are evident only when associated with the presence of psychiatric symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Incomplete cortical reorganization in macular degeneration.

PubMed

Liu, Tingting; Cheung, Sing-Hang; Schuchard, Ronald A; Glielmi, Christopher B; Hu, Xiaoping; He, Sheng; Legge, Gordon E

2010-12-01

Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? Eight MD subjects-four with age-related onset (AMD) and four with juvenile onset (JMD)-and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD. Functional reorganization is more prominent

Incomplete Cortical Reorganization in Macular Degeneration

PubMed Central

Cheung, Sing-Hang; Schuchard, Ronald A.; Glielmi, Christopher B.; Hu, Xiaoping; He, Sheng; Legge, Gordon E.

2010-01-01

Purpose. Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? Methods. Eight MD subjects—four with age-related onset (AMD) and four with juvenile onset (JMD)—and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. Results. A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. Conclusions. The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD

Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes.

PubMed

Vauzour, David; Buonfiglio, Maria; Corona, Giulia; Chirafisi, Joselita; Vafeiadou, Katerina; Angeloni, Cristina; Hrelia, Silvana; Hrelia, Patrizia; Spencer, Jeremy P E

2010-04-01

The degeneration of dopaminergic neurons in the substantia nigra has been linked to the formation of the endogenous neurotoxin 5-S-cysteinyl-dopamine. Sulforaphane (SFN), an isothiocyanate derived from the corresponding precursor glucosinolate found in cruciferous vegetables has been observed to exert a range of biological activities in various cell populations. In this study, we show that SFN protects primary cortical neurons against 5-S-cysteinyl-dopamine induced neuronal injury. Pre-treatment of cortical neurons with SFN (0.01-1 microM) resulted in protection against 5-S-cysteinyl-dopamine-induced neurotoxicity, which peaked at 100 nM. This protection was observed to be mediated by the ability of SFN to modulate the extracellular signal-regulated kinase 1 and 2 and the activation of Kelch-like ECH-associated protein 1/NF-E2-related factor-2 leading to the increased expression and activity of glutathione-S-transferase (M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the NF-E2-related factor-2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of Parkinson's disease.

Enhancement of synaptic transmission induced by BDNF in cultured cortical neurons

NASA Astrophysics Data System (ADS)

He, Jun; Gong, Hui; Zeng, Shaoqun; Li, Yanling; Luo, Qingming

2005-03-01

Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation (LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca2+ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as were the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca2+]c). This effect was partially dependent on [Ca2+]o; The BDNF-induced increase in [Ca2+]c can not be completely blocked by Ca2+-free solution. It was completely blocked by K252a and partially blocked by Cd2+ and TTX. The results demonstrate that BDNF can enhances synaptic transmission and that this effect is accompanied by a rise in [Ca2+]c that requires two route: the release of Ca2+ from intracellular calcium stores and influx of extracellular Ca2+ through voltage-dependent Ca2+ channels in cultured cortical neurons.

Genetic and epigenetic contributions to the cortical phenotype in mammals☆

PubMed Central

Larsen, DeLaine D.; Krubitzer, Leah

2008-01-01

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

Prostaglandin E2 (PGE2) and risedronate was superior to PGE2 alone in maintaining newly added bone in the cortical bone site after withdrawal in older intact rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Lin, B. Y.; Jee, W. S.; Lin, C. H.; Chen, Y. Y.; Ke, H. Z.; Li, X. J.

1997-01-01

The objects of this study were (1) to determine the effects of risedronate (Ris) and prostaglandin E2 (PGE2) alone and in combination, on tibial diaphyses of older intact female rats; and (2) to observe the fate of any extra bone if formed after withdrawal of the treatment. Nine-month-old female Sprague-Dawley rats were treated with 6 mg of PGE2/kg/day, 1 or 5 micrograms of Ris/kg twice a week, or 6 mg of PGE2/kg/day plus 1 or 5 micrograms of Ris/kg twice a week for the first 60 days and followed by vehicle injections for another 60 days. Cross-sections of double fluorescent labeled, undecalcified tibial diaphyses proximal to the tibiofibular junction were processed for histomorphometry. We found that: (1) neither the 1 microgram nor the 5 micrograms of Ris treatment in the 60-day on/60-day off group showed any histomorphometric differences from age-related controls; (2) while the 60 days of PGE2 treatment added extra cortical bone (6%) on the tibial shaft (due to stimulation of periosteal, endocortical, and marrow trabecular bone formation), the new endocortical and most of the new marrow trabecular bone were lost when treatment was withdrawn; however, the new periosteal bone remained; (3) PGE2 with Ris added the same amount of new bone to tibial diaphysis as did PGE2 alone and upon withdrawal, new marrow trabecular bone was lost but new periosteal and endocortical bones were preserved in PGE2 + 1 microgram of Ris on/off group. In contrast, all the new bone was maintained in the PGE2 + 5 micrograms of Ris on/off group; (4) PGE2 + Ris cotreatment failed to block the increase in cortical bone porosity induced by PGE2; and (5) in the PGE2 alone and PGE2 + 1 microgram of Ris on/off groups bone turnover was higher than that in the PGE2 + 5 micrograms of Ris on/off group. These results indicate that on/off treatment with PGE2 and Ris is superior to PGE2 alone in that it forms the same amount of new bone during treatment, but preserves more cortical bone during

Comparison of Multidetector Computed Tomography and Flat-Panel Computed Tomography Regarding Visualization of Cortical Fractures, Cortical Defects, and Orthopedic Screws: A Phantom Study.

PubMed

Neubauer, Jakob; Benndorf, Matthias; Lang, Hannah; Lampert, Florian; Kemna, Lars; Konstantinidis, Lukas; Neubauer, Claudia; Reising, Kilian; Zajonc, Horst; Kotter, Elmar; Langer, Mathias; Goerke, Sebastian M

2015-08-01

To compare the visualization of cortical fractures, cortical defects, and orthopedic screws in a dedicated extremity flat-panel computed tomography (FPCT) scanner and a multidetector computed tomography (MDCT) scanner.We used feet of European roe deer as phantoms for cortical fractures, cortical defects, and implanted orthopedic screws. FPCT and MDCT scans were performed with equivalent dose settings. Six observers rated the scans according to number of fragments, size of defects, size of defects opposite orthopedic screws, and the length of different screws. The image quality regarding depiction of the cortical bone was assessed. The gold standard (real number of fragments) was evaluated by autopsy.The correlation of reader assessment of fragments, cortical defects, and screws with the gold standard was similar for FPCT and MDCT. Three readers rated the subjective image quality of the MDCT to be higher, whereas the others showed no preferences.Although the image quality was rated higher in the MDCT than in the FPCT by 3 out of 6 observers, both modalities proved to be comparable regarding the visualization of cortical fractures, cortical defects, and orthopedic screws and of use to musculoskeletal radiology regarding fracture detection and postsurgical evaluation in our experimental setting.

Adult Visual Cortical Plasticity

PubMed Central

Gilbert, Charles D.; Li, Wu

2012-01-01

The visual cortex has the capacity for experience dependent change, or cortical plasticity, that is retained throughout life. Plasticity is invoked for encoding information during perceptual learning, by internally representing the regularities of the visual environment, which is useful for facilitating intermediate level vision - contour integration and surface segmentation. The same mechanisms have adaptive value for functional recovery after CNS damage, such as that associated with stroke or neurodegenerative disease. A common feature to plasticity in primary visual cortex (V1) is an association field that links contour elements across the visual field. The circuitry underlying the association field includes a plexus of long range horizontal connections formed by cortical pyramidal cells. These connections undergo rapid and exuberant sprouting and pruning in response to removal of sensory input, which can account for the topographic reorganization following retinal lesions. Similar alterations in cortical circuitry may be involved in perceptual learning, and the changes observed in V1 may be representative of how learned information is encoded throughout the cerebral cortex. PMID:22841310

SNARE-dependent upregulation of KCC2 activity following metabotropic zinc receptor (mZnR/GPR39) activation in rat cortical neurons in vitro

PubMed Central

Saadi, Robert A.; He, Kai; Hartnett, Karen A.; Kandler, Karl; Hershfinkel, Michal; Aizenman, Elias

2012-01-01

The major outward chloride transporter in neurons is the potassium chloride co-transporter 2 (KCC2), critical for maintaining an inhibitory reversal potential for GABAA receptor channels. In a recent study, we showed that Zn2+ regulates GABAA reversal potentials in the hippocampus by enhancing the activity of KCC2 via an increase in its surface expression. Zn2+ initiates this process by activating the Gq-coupled metabotropic Zn2+ receptor mZnR/GPR39. Here, we first demonstrated that mZnR/GPR39 is functional in cortical neurons in culture and then tested the hypothesis that the increase in KCC2 activity is mediated through a SNARE-dependent process. We established the presence of functional mZnR in rat cultured cortical neurons by loading cells with a Ca2+ indicator and exposing cells to Zn2+, which triggered consistent Ca2+ responses that were blocked by the Gq antagonist YM-254890, but not by the metabotropic glutamate receptor antagonist MCPG. Importantly, Zn2+ treatment under these conditions did not increase the intracellular concentrations of Zn2+ itself. We then measured KCC2 activity by monitoring both the rate and relative amount of furosemide-sensitive NH4+ influx via the co-transporter using an intracellular pH sensitive fluorescent indicator. We observed that Zn2+ pretreatment induced a Ca2+-dependent increase in KCC2 activity. The effects of Zn2+ on KCC2 activity were also observed in wild-type mouse cortical neurons in culture, but not in neurons obtained from mZnR/GPR39−/− mice, suggesting that Zn2+ acts via mZnR/GPR39 activation to upregulate KCC2 activity. We next transfected rat cortical neurons with a plasmid encoding botulinum toxin C1 (Botox C1), which cleaves the SNARE proteins syntaxin 1 and SNAP-25. Basal KCC2 activity was similar in both transfected and non-transfected neurons. Non-transfected cells, or cells transfected with marker vector alone, showed a Zn2+-dependent increase in KCC2 activity. In contrast, KCC2 activity in neurons

Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice.

PubMed

Savignac, Helene M; Couch, Yvonne; Stratford, Michael; Bannerman, David M; Tzortzis, George; Anthony, Daniel C; Burnet, Philip W J

2016-02-01

The manipulation of the enteric microbiota with specific prebiotics and probiotics, has been shown to reduce the host's inflammatory response, alter brain chemistry, and modulate anxiety behaviour in both rodents and humans. However, the neuro-immune and behavioural effects of prebiotics on sickness behaviour have not been explored. Here, adult male CD1 mice were fed with a specific mix of non-digestible galacto-oligosaccharides (Bimuno®, BGOS) for 3 weeks, before receiving a single injection of lipopolysaccharide (LPS), which induces sickness behaviour and anxiety. Locomotor and marble burying activities were assessed 4h after LPS injection, and after 24h, anxiety in the light-dark box was assessed. Cytokine expression, and key components of the serotonergic (5-Hydroxytryptamine, 5-HT) and glutamatergic system were evaluated in the frontal cortex to determine the impact of BGOS administration at a molecular level. BGOS-fed mice were less anxious in the light-dark box compared to controls 24h after the LPS injection. Elevated cortical IL-1β concentrations in control mice 28 h after LPS were not observed in BGOS-fed animals. This significant BGOS×LPS interaction was also observed for 5HT2A receptors, but not for 5HT1A receptors, 5HT, 5HIAA, NMDA receptor subunits, or other cytokines. The intake of BGOS did not influence LPS-mediated reductions in marble burying behaviour, and its effect on locomotor activity was equivocal. Together, our data show that the prebiotic BGOS has an anxiolytic effect, which may be related to the modulation of cortical IL-1β and 5-HT2A receptor expression. Our data suggest a potential role for prebiotics in the treatment of neuropsychiatric disorders where anxiety and neuroinflammation are prominent clinical features. Copyright © 2015. Published by Elsevier Inc.

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.

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

Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

PubMed Central

Gulati, Srishti; Cao, Vania Y.; Otte, Stephani

2017-01-01

In vivo circuit and cellular level functional imaging is a critical tool for understanding the brain in action. High resolution imaging of mouse cortical neurons with two-photon microscopy has provided unique insights into cortical structure, function and plasticity. However, these studies are limited to head fixed animals, greatly reducing the behavioral complexity available for study. In this paper, we describe a procedure for performing chronic fluorescence microscopy with cellular-resolution across multiple cortical layers in freely behaving mice. We used an integrated miniaturized fluorescence microscope paired with an implanted prism probe to simultaneously visualize and record the calcium dynamics of hundreds of neurons across multiple layers of the somatosensory cortex as the mouse engaged in a novel object exploration task, over several days. This technique can be adapted to other brain regions in different animal species for other behavioral paradigms. PMID:28654056

Analysis of Altered Micro RNA Expression Profiles in Focal Cortical Dysplasia IIB.

PubMed

Li, Lin; Liu, Chang-Qing; Li, Tian-Fu; Guan, Yu-Guang; Zhou, Jian; Qi, Xue-Ling; Yang, Yu-Tao; Deng, Jia-Hui; Xu, Zhi-Qing David; Luan, Guo-Ming

2016-04-01

Focal cortical dysplasia type IIB is a commonly encountered subtype of developmental malformation of the cerebral cortex and is often associated with pharmacoresistant epilepsy. In this study, to investigate the molecular etiology of focal cortical dysplasia type IIB, the authors performed micro ribonucleic acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male, mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24 micro RNAs were differentially expressed in focal cortical dysplasia type IIB, and the microarray results were validated using quantitative real-time polymerase chain reaction (PCR). Then the putative target genes of the differentially expressed micro RNAs were identified by bioinformatics analysis. Moreover, biological significance of the target genes was evaluated by investigating the pathways in which the genes were enriched, and the Hippo signaling pathway was proposed to be highly related with the pathogenesis of focal cortical dysplasia type IIB. © The Author(s) 2015.

Altered behavior in experimental cortical dysplasia.

PubMed

Zhou, Fu-Wen; Rani, Asha; Martinez-Diaz, Hildabelis; Foster, Thomas C; Roper, Steven N

2011-12-01

Developmental delay and cognitive impairment are common comorbidities in people with epilepsy associated with malformations of cortical development (MCDs). We studied cognition and behavior in an animal model of diffuse cortical dysplasia (CD), in utero irradiation, using a battery of behavioral tests for neuromuscular and cognitive function. Fetal rats were exposed to 2.25 Gy external radiation on embryonic day 17 (E17). At 1 month of age they were tested using an open field task, a grip strength task, a grid walk task, inhibitory avoidance, an object recognition task, and the Morris water maze task. Rats with CD showed reduced nonlocomotor activity in the open field task and impaired motor coordination for grid walking but normal grip strength. They showed a reduced tendency to recognize novel objects and reduced retention in an inhibitory avoidance task. Water maze testing showed that learning and memory were impaired in irradiated rats for both cue discrimination and spatially oriented tasks. These results demonstrate significant deficits in cortex- and hippocampus-dependent cognitive functions associated with the diffuse abnormalities of cortical and hippocampal development that have been documented in this model. This study documents multimodal cognitive deficits associated with CD and can serve as the foundation for future investigations into the mechanisms of and possible therapeutic interventions for this problem. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

DREAM mediates cAMP-dependent, Ca2+-induced stimulation of GFAP gene expression and regulates cortical astrogliogenesis.

PubMed

Cebolla, Beatriz; Fernández-Pérez, Antonio; Perea, Gertrudis; Araque, Alfonso; Vallejo, Mario

2008-06-25

In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to promote astrocyte differentiation of cortical precursors via activation of a cAMP-dependent pathway. Signals acting on progenitor cells of the developing cortex to generate astrocytes activate glial fibrillary acidic protein (GFAP) gene expression, but the transcriptional mechanisms that regulate this activation are unclear. Here, we identify the previously known transcriptional repressor downstream regulatory element antagonist modulator (DREAM) as an activator of GFAP gene expression. We found that DREAM occupies specific sites on the GFAP promoter before and after differentiation is initiated by exposure of cortical progenitor cells to PACAP. PACAP raises intracellular calcium concentration via a mechanism that requires cAMP, and DREAM-mediated transactivation of the GFAP gene requires the integrity of calcium-binding domains. Cortical progenitor cells from dream(-/-) mice fail to express GFAP in response to PACAP. Moreover, the neonatal cortex of dream(-/-) mice exhibits a reduced number of astrocytes and increased number of neurons. These results identify the PACAP-cAMP-Ca(2+)-DREAM cascade as a new pathway to activate GFAP gene expression during astrocyte differentiation.

Coordinated Optimization of Visual Cortical Maps (I) Symmetry-based Analysis

PubMed Central

Reichl, Lars; Heide, Dominik; Löwel, Siegrid; Crowley, Justin C.; Kaschube, Matthias; Wolf, Fred

2012-01-01

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of orientation columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about a hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference. From basic symmetry assumptions we obtain a comprehensive phenomenological classification of possible inter-map coupling energies and examine representative examples. We show that each individual coupling energy leads to a different class of OP solutions with different correlations among the maps such that inferences about the optimization principle from map layout appear viable. We systematically assess whether quantitative laws resembling

Trait- and state-dependent cortical inhibitory deficits in bipolar disorder.

PubMed

Ruiz-Veguilla, Miguel; Martín-Rodríguez, Juan Francisco; Palomar, Francisco J; Porcacchia, Paolo; Álvarez de Toledo, Paloma; Perona-Garcelán, Salvador; Rodríguez-Testal, Juan Francisco; Huertas-Fernández, Ismael; Mir, Pablo

2016-05-01

Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Invasive Cortical Stimulation to Promote Recovery of Function After Stroke

PubMed Central

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

2011-01-01

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

Effects of Alprazolam on Cortical Activity and Tremors in Patients with Essential Tremor

PubMed Central

Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A.; Romero, Juan P.; Saíz-Díaz, Rosana A.; Benito-León, Julián; Rocon, Eduardo

2014-01-01

Background Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4–12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. Methods We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Results Alprazolam significantly attenuated tremors (EMG: 76.2±22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. Conclusions This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor. PMID:24667763

Effects of alprazolam on cortical activity and tremors in patients with essential tremor.

PubMed

Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A; Romero, Juan P; Saíz-Díaz, Rosana A; Benito-León, Julián; Rocon, Eduardo

2014-01-01

Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4-12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Alprazolam significantly attenuated tremors (EMG: 76.2 ± 22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor.

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.

Cortical modulation of the nucleus of the optic tract in the rabbit.

PubMed

Pettorossi, V E; Troiani, D

1983-09-01

We analyzed in rabbits the relationships between the temporooccipital nystagmogenic cortex (NGC)--the region sited at the border between cortical areas 17, 21, and 22--and the nucleus of the optic tract (NOT). Two experimental approaches were used: (a) eye movement analysis before and after electrolytic lesion of the NOT region provided an indication of the importance of the NOT for the interaction between the ocular nystagmus elicited by natural optokinetic stimulation (OKN) and the nystagmus evoked by electrical stimulation of the nystagmogenic area; (b) NOT direction-selective and velocity-sensitive units were tested with single shock or repetitive electrical stimulation of the nystagmogenic region. Single-shock stimulation evoked single or multiple spikes in 50% of NOT units analyzed and repetitive stimuli induced prolonged facilitation and inhibitory rebounds in 70% of the units tested. Comparison of orthodromic activation latencies of the NOT cells (3.2 and 6.1 ms) after cortical stimulation and of antidromic activation latencies of cortical nystagmogenic units (2.6 ms) after NOT shocks, suggested monosynaptic as well as polysynaptic connections between the temporooccipital cortex and the NOT. The existence of such cortical-NOT linkage indicates that the NOT is intercalated between the cortex and the oculomotor centers and represents the most probable site of interaction of the cortical nystagmus pathway with the optokinetic reflex arc.

Canonical Organization of Layer 1 Neuron-Led Cortical Inhibitory and Disinhibitory Interneuronal Circuits

PubMed Central

Lee, Alice J.; Wang, Guangfu; Jiang, Xiaolong; Johnson, Seraphina M.; Hoang, Elizabeth T.; Lanté, Fabien; Stornetta, Ruth L.; Beenhakker, Mark P.; Shen, Ying; Julius Zhu, J.

2015-01-01

Interneurons play a key role in cortical function and dysfunction, yet organization of cortical interneuronal circuitry remains poorly understood. Cortical Layer 1 (L1) contains 2 general GABAergic interneuron groups, namely single bouquet cells (SBCs) and elongated neurogliaform cells (ENGCs). SBCs predominantly make unidirectional inhibitory connections (SBC→) with L2/3 interneurons, whereas ENGCs frequently form reciprocal inhibitory and electric connections (ENGC↔) with L2/3 interneurons. Here, we describe a systematic investigation of the pyramidal neuron targets of L1 neuron-led interneuronal circuits in the rat barrel cortex with simultaneous octuple whole-cell recordings and report a simple organizational scheme of the interneuronal circuits. Both SBCs→ and ENGC ↔ L2/3 interneuronal circuits connect to L2/3 and L5, but not L6, pyramidal neurons. SBC → L2/3 interneuronal circuits primarily inhibit the entire dendritic–somato–axonal axis of a few L2/3 and L5 pyramidal neurons located within the same column. In contrast, ENGC ↔ L2/3 interneuronal circuits generally inhibit the distal apical dendrite of many L2/3 and L5 pyramidal neurons across multiple columns. Finally, L1 interneuron-led circuits target distinct subcellular compartments of L2/3 and L5 pyramidal neurons in a L2/3 interneuron type-dependent manner. These results suggest that L1 neurons form canonical interneuronal circuits to control information processes in both supra- and infragranular cortical layers. PMID:24554728

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

PubMed

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

2017-05-01

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

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...

In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

DTIC Science & Technology

2015-09-01

abnormalities in MS associated with changes in cortical myelin and/or iron concentration. The purpose of this project is to evaluate inflammation and...al., 2011). We demonstrated that surface-based mapping of quanti - tative T2* as a function of cortical depth (laminar analysis) from ultra-high...cortical grey matter (NACGM), to better understand their role in determining laminar quanti - tative T2* changes in multiple sclerosis. Materials and

Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy.

PubMed

van Veluw, Susanne J; Biessels, Geert Jan; Klijn, Catharina J M; Rozemuller, Annemieke J M

2016-03-01

To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology. Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury. On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury. This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease. © 2016 American Academy of Neurology.

The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

PubMed

Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

2018-05-16

To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

Somatostatin-Expressing Inhibitory Interneurons in Cortical Circuits

PubMed Central

Yavorska, Iryna; Wehr, Michael

2016-01-01

Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM) inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons. PMID:27746722

High-spatial-resolution mapping of the oxygen concentration in cortical tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jaswal, Rajeshwer S.; Yaseen, Mohammad A.; Fu, Buyin; Boas, David A.; Sakadžic, Sava

2016-03-01

Due to a lack of imaging tools for high-resolution imaging of cortical tissue oxygenation, the detailed maps of the oxygen partial pressure (PO2) around arterioles, venules, and capillaries remain largely unknown. Therefore, we have limited knowledge about the mechanisms that secure sufficient oxygen delivery in microvascular domains during brain activation, and provide some metabolic reserve capacity in diseases that affect either microvascular networks or the regulation of cerebral blood flow (CBF). To address this challenge, we applied a Two-Photon PO2 Microscopy to map PO2 at different depths in mice cortices. Measurements were performed through the cranial window in the anesthetized healthy mice as well as in the mouse models of microvascular dysfunctions. In addition, microvascular morphology was recorded by the two-photon microscopy at the end of each experiment and subsequently segmented. Co-registration of the PO2 measurements and exact microvascular morphology enabled quantification of the tissue PO2 dependence on distance from the arterioles, capillaries, and venules at various depths. Our measurements reveal significant spatial heterogeneity of the cortical tissue PO2 distribution that is dominated by the high oxygenation in periarteriolar spaces. In cases of impaired oxygen delivery due to microvascular dysfunction, significant reduction in tissue oxygenation away from the arterioles was observed. These tissue domains may be the initial sites of cortical injury that can further exacerbate the progression of the disease.

Comparative study on inorganic composition and crystallographic properties of cortical and cancellous bone.

PubMed

Wang, Xiao-Yan; Zuo, Yi; Huang, Di; Hou, Xian-Deng; Li, Yu-Bao

2010-12-01

To comparatively investigate the inorganic composition and crystallographic properties of cortical and cancellous bone via thermal treatment under 700 °C. Thermogravimetric measurement, infrared spectrometer, X-ray diffraction, chemical analysis and X-ray photo-electron spectrometer were used to test the physical and chemical properties of cortical and cancellous bone at room temperature 250 °C, 450 °C, and 650 °C, respectively. The process of heat treatment induced an extension in the a-lattice parameter and changes of the c-lattice parameter, and an increase in the crystallinity reflecting lattice rearrangement after release of lattice carbonate and possible lattice water. The mineral content in cortical and cancellous bone was 73.2wt% and 71.5wt%, respectively. For cortical bone, the weight loss was 6.7% at the temperature from 60 °C to 250 °C, 17.4% from 250 °C to 450 °C, and 2.7% from 450 °C to 700 °C. While the weight loss for the cancellous bone was 5.8%, 19.9%, and 2.8 % at each temperature range, the Ca/P ratio of cortical bone was 1.69 which is higher than the 1.67 of stoichiometric HA due to the B-type CO₃²⁻ substitution in apatite lattice. The Ca/P ratio of cancellous bone was lower than 1.67, suggesting the presence of more calcium deficient apatite. The collagen fibers of cortical bone were arrayed more orderly than those of cancellous bone, while their mineralized fibers ollkded similar. The minerals in both cortical and cancellous bone are composed of poorly crystallized nano-size apatite crystals with lattice carbonate and possible lattice water. The process of heat treatment induces a change of the lattice parameter, resulting in lattice rearrangement after the release of lattice carbonate and lattice water and causing an increase in crystal size and crystallinity. This finding is helpful for future biomaterial design, preparation and application. Copyright © 2010 The Editorial Board of Biomedical and Environmental Sciences

Longitudinal changes in cortical thickness in autism and typical development.

PubMed

Zielinski, Brandon A; Prigge, Molly B D; Nielsen, Jared A; Froehlich, Alyson L; Abildskov, Tracy J; Anderson, Jeffrey S; Fletcher, P Thomas; Zygmunt, Kristen M; Travers, Brittany G; Lange, Nicholas; Alexander, Andrew L; Bigler, Erin D; Lainhart, Janet E

2014-06-01

The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and

Longitudinal changes in cortical thickness in autism and typical development

PubMed Central

Prigge, Molly B. D.; Nielsen, Jared A.; Froehlich, Alyson L.; Abildskov, Tracy J.; Anderson, Jeffrey S.; Fletcher, P. Thomas; Zygmunt, Kristen M.; Travers, Brittany G.; Lange, Nicholas; Alexander, Andrew L.; Bigler, Erin D.; Lainhart, Janet E.

2014-01-01

The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3–36 years) and 60 males with typical development (mean age = 18 years; range 4–39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and

Retinoic acid from the meninges regulates cortical neuron generation.

PubMed

Siegenthaler, Julie A; Ashique, Amir M; Zarbalis, Konstantinos; Patterson, Katelin P; Hecht, Jonathan H; Kane, Maureen A; Folias, Alexandra E; Choe, Youngshik; May, Scott R; Kume, Tsutomu; Napoli, Joseph L; Peterson, Andrew S; Pleasure, Samuel J

2009-10-30

Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

Retinoic acid from the meninges regulates cortical neuron generation

PubMed Central

Siegenthaler, Julie A.; Ashique, Amir M.; Zarbalis, Konstantinos; Patterson, Katelin P.; Hecht, Jonathan H.; Kane, Maureen A.; Folias, Alexandra E.; Choe, Youngshik; May, Scott R.; Kume, Tsutomu; Napoli, Joseph L.; Peterson, Andrew S.; Pleasure, Samuel J.

2009-01-01

Summary Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10 and Raldh2 expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants and Rdh10 mutants had a cortical phenotype similar to the Foxc1-null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis. PMID:19879845

Cortical regions associated with orthostatic stress in conscious humans

NASA Astrophysics Data System (ADS)

Kimmerly, Derek S.; O'Leary, Debbie D.; Cechetto, Angela; Shoemaker, Kevin J.

2005-08-01

The purpose of this study was to determine the cortical structures associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging (fMRI). Heart rate (HR) and LBNP were simultaneously monitored during scanning. Central venous pressure (CVP), muscle sympathetic nerve activity (MSNA) and arterial blood pressure (ABP) were measured on a separate day. Random effects analyses (SPM2) were used to evaluate fMRI signal changes that correlated separately with both LBNP and HR (15 and 35-mmHg versus 5-mmHg LBNP). LBNP at 15- and 35-mmHg decreased CVP and increased MSNA, both P < 0.05 versus baseline) but only LBNP at 35- mmHg elevated HR. ABP was similar at all levels of LBNP . Cortical regions demonstrating increased activity at higher HR and greater LBNP included the right superior posterior insula and the cerebellum. Conversely, bilateral anterior insular cortices, the right anterior cingulate, amygdala, and mediodorsal nucleus of the thalamus showed decreased neural activation.

[Effect of anti-osteoporotic agents on cortical microstructure].

PubMed

Ito, Masako

2013-07-01

The incidence of non-vertebral fracture increases in old age, and the deterioration of cortical micro-structure is considered to be one of important reason to cause non-vertebral fracture. In this chapter, the age-related change of cortical microstructure, relationship with bone strength are discussed as well as the effect of anti-osteoporotic drugs on cortical bone ; bisphosphonate, teriparatide, active vitamin D3, and denosumab.

Sensorimotor rhythm-based brain-computer interface training: the impact on motor cortical responsiveness

NASA Astrophysics Data System (ADS)

Pichiorri, F.; De Vico Fallani, F.; Cincotti, F.; Babiloni, F.; Molinari, M.; Kleih, S. C.; Neuper, C.; Kübler, A.; Mattia, D.

2011-04-01

The main purpose of electroencephalography (EEG)-based brain-computer interface (BCI) technology is to provide an alternative channel to support communication and control when motor pathways are interrupted. Despite the considerable amount of research focused on the improvement of EEG signal detection and translation into output commands, little is known about how learning to operate a BCI device may affect brain plasticity. This study investigated if and how sensorimotor rhythm-based BCI training would induce persistent functional changes in motor cortex, as assessed with transcranial magnetic stimulation (TMS) and high-density EEG. Motor imagery (MI)-based BCI training in naïve participants led to a significant increase in motor cortical excitability, as revealed by post-training TMS mapping of the hand muscle's cortical representation; peak amplitude and volume of the motor evoked potentials recorded from the opponens pollicis muscle were significantly higher only in those subjects who develop a MI strategy based on imagination of hand grasping to successfully control a computer cursor. Furthermore, analysis of the functional brain networks constructed using a connectivity matrix between scalp electrodes revealed a significant decrease in the global efficiency index for the higher-beta frequency range (22-29 Hz), indicating that the brain network changes its topology with practice of hand grasping MI. Our findings build the neurophysiological basis for the use of non-invasive BCI technology for monitoring and guidance of motor imagery-dependent brain plasticity and thus may render BCI a viable tool for post-stroke rehabilitation.

Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia.

PubMed

Battistella, G; Fuertinger, S; Fleysher, L; Ozelius, L J; Simonyan, K

2016-10-01

Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. We used a combination of independent component analysis and linear discriminant analysis of resting-state functional magnetic resonance imaging data to investigate brain organization in different SD phenotypes (abductor versus adductor type) and putative genotypes (familial versus sporadic cases) and to characterize neural markers for genotype/phenotype categorization. We found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with SD compared with healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortices. When categorizing between different forms of SD, the combination of measures from the left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder. © 2016 EAN.

Altered cortical excitability in anorexia nervosa.

PubMed

Khedr, E M; El Fetoh, N A; El Bieh, E; Ali, A M; Karim, A A

2014-09-01

Recent EEG and positron emission tomography (PET) studies have reported hyperactivation of the right hemisphere in anorexia nervosa (AN). The aim of the present study was to test this notion by examining cortical excitability in subjects with AN using transcranial magnetic stimulation (TMS). We investigated thirteen patients meeting the DSM IV diagnostic criteria for AN and 14 controls age and sex matched. Each subject was assessed clinically using the Eating Disorder Inventory (EDI), the Eating Attitude Test (EAT) and Beck's Depression Inventory (BDI-II). TMS measures involved resting and active motor thresholds (RMT, AMT) as well as motor evoked potentials (MEP), cortical silent period duration (CSP), transcallosal inhibition (TCI), and short latency intracortical inhibition (SICI) of the first dorsal interosseous muscle (FDI) were assessed. Cortical esophageal MEP latencies (CL) were also recorded. The RMT and MEP onset latency of the FDI and the esophagus as well as duration of the TCI were significantly reduced in anorexic patients compared to the control group. There were no significant differences neither in AMT nor CSP between patients and controls. Moreover, we found significant negative correlations between the EAT scores and RMT, and TCI duration. Although anorexic patients had significantly higher BDI score, there was no correlation between it and cortical excitability. Anorexic individuals are characterized by pathologically increased motor and esophageal cortical excitability that significantly correlates with clinical symptoms of anorexia nervosa. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Differential effect of visual motion adaption upon visual cortical excitability.

PubMed

Lubeck, Astrid J A; Van Ombergen, Angelique; Ahmad, Hena; Bos, Jelte E; Wuyts, Floris L; Bronstein, Adolfo M; Arshad, Qadeer

2017-03-01

The objectives of this study were 1 ) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2 ) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing. NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual

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

Degraded attentional modulation of cortical neural populations in strabismic amblyopia

PubMed Central

Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

2016-01-01

Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI–informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye. PMID:26885628

Degraded attentional modulation of cortical neural populations in strabismic amblyopia.

PubMed

Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

2016-01-01

Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI-informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye.

Cortical thickness abnormalities in late adolescence with online gaming addiction.

PubMed

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

A Role for Prefrontal Cortical NMDA Receptors in Murine Alcohol-Heightened Aggression.

PubMed

Newman, Emily L; Terunuma, Miho; Wang, Tiffany L; Hewage, Nishani; Bicakci, Matthew B; Moss, Stephen J; DeBold, Joseph F; Miczek, Klaus A

2018-05-01

-heightened aggression. GluN2D-containing NMDARs are highly expressed on cortical parvalbumin-containing interneurons, suggesting that, in a subset of individuals, alcohol may functionally alter signal integration within cortical microcircuits to dysregulate threat reactivity and promote aggression. This work suggests that targeting GluN2D-NMDARs may be of use in reducing the impact of alcohol-related violence in the human population.

Early visual cortical structural changes in diabetic patients without diabetic retinopathy.

PubMed

Ferreira, Fábio S; Pereira, João M S; Reis, Aldina; Sanches, Mafalda; Duarte, João V; Gomes, Leonor; Moreno, Carolina; Castelo-Branco, Miguel

2017-11-01

It is known that diabetic patients have changes in cortical morphometry as compared to controls, but it remains to be clarified whether the visual cortex is a disease target, even when diabetes complications such as retinopathy are absent. Therefore, we compared type 2 diabetes patients without diabetic retinopathy with control subjects using magnetic resonance imaging to assess visual cortical changes when retinal damage is not yet present. We performed T1-weighted imaging in 24 type 2 diabetes patients without diabetic retinopathy and 27 age- and gender-matched controls to compare gray matter changes in the occipital cortex between groups using voxel based morphometry. Patients without diabetic retinopathy showed reduced gray matter volume in the occipital lobe when compared with controls. Reduced gray matter volume in the occipital cortex was found in diabetic patients without retinal damage. We conclude that cortical early visual processing regions may be affected in diabetic patients even before retinal damage occurs.

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

A Patient with Posterior Cortical Atrophy Possesses a Novel Mutation in the Presenilin 1 Gene

PubMed Central

Sitek, Emilia J.; Narożańska, Ewa; Pepłońska, Beata; Filipek, Sławomir; Barczak, Anna; Styczyńska, Maria; Mlynarczyk, Krzysztof; Brockhuis, Bogna; Portelius, Erik; Religa, Dorota; Barcikowska, Maria

2013-01-01

Posterior cortical atrophy is a dementia syndrome with symptoms of cortical visual dysfunction, associated with amyloid plaques and neurofibrillary tangles predominantly affecting visual association cortex. Most patients diagnosed with posterior cortical atrophy will finally develop a typical Alzheimer's disease. However, there are a variety of neuropathological processes, which could lead towards a clinical presentation of posterior cortical atrophy. Mutations in the presenilin 1 gene, affecting the function of γ-secretase, are the most common genetic cause of familial, early-onset Alzheimer's disease. Here we present a patient with a clinical diagnosis of posterior cortical atrophy who harbors a novel Presenilin 1 mutation (I211M). In silico analysis predicts that the mutation could influence the interaction between presenilin 1 and presenilin1 enhancer-2 protein, a protein partner within the γ-secretase complex. These findings along with published literature support the inclusion of posterior cortical atrophy on the Alzheimer's disease spectrum. PMID:23593396

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

A time-course analysis of changes in cerebral metal levels following a controlled cortical impact.

PubMed

Portbury, Stuart D; Hare, Dominic J; Sgambelloni, Charlotte; Finkelstein, David I; Adlard, Paul A

2016-02-01

Traumatic brain injury (TBI) is complicated by a sudden and dramatic change in brain metal levels, including iron (Fe), copper (Cu) and zinc (Zn). Specific 'metallo-pathological' features of TBI include increased non-heme bound Fe and the liberation of free Zn ions, both of which may contribute to the pathogenesis of TBI. To further characterise the metal dyshomeostasis that occurs following brain trauma, we performed a quantitative time-course survey of spatial Fe, Cu and Zn distribution in mice receiving a controlled cortical impact TBI. Images of brain metal levels produced using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) in the upper quadrant of the ipsilateral hemisphere were compared to the corresponding contralateral hemisphere, together with regional areas radiating toward the center of the brain from the site of lesion. Significant regional and time point specific elevations in Fe, Zn and Cu were detected immediately and up to 28 days after TBI. The magnitude and timeframe of many of these changes suggest that TBI results in a pronounced and sustained alteration in normal metal levels within the brain. Such alterations are likely to play a role in both the short- and long-term consequences of head trauma and suggest that pharmacological modulation to normalize these metal levels may be efficacious in improving functional outcome.

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.

The stability of mandibular prognathism corrected by bilateral sagittal split osteotomies: a comparison of bi-cortical osteosynthesis and mono-cortical osteosynthesis.

PubMed

Hsu, S S-P; Huang, C-S; Chen, P K-T; Ko, E W-C; Chen, Y-R

2012-02-01

This study evaluated the differences in surgical changes and post-surgical changes between bi-cortical and mono-cortical osteosynthesis (MCO) in the correction of skeletal Class III malocclusion with bilateral sagittal split osteotomies (BSSOs). Twenty-five patients had bi-cortical osteosynthesis (BCO), 32 patients had mono-cortical fixation. Lateral and postero-anterior cephalometric radiographs, taken at the time of surgery, before surgery, 1 month after surgery, and on completion of orthodontic treatment (mean 9.9 months after surgery), were obtained for evaluation. Cephalometric analysis and superimposition were used to investigate the surgical and post-surgical changes. Independent t-test was performed to compare the difference between the two groups. Pearson's correlations were tested to evaluate the factors related to the relapse of the mandible. The sagittal relapse rate was 20% in the bi-cortical and 25% in the mono-cortical group. The forward-upward rotation of the mandible in the post-surgical period contributed most of the sagittal relapse. There were no statistically significant differences in sagittal and vertical changes between the two groups during surgery and in the post-surgical period. No factors were found to correlate with post-surgical relapse, but the intergonial width increased more in the bi-cortical group. The study suggested that both methods of skeletal fixation had similar postoperative stability. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Diagnostic Significance of Cortical Superficial Siderosis for Alzheimer Disease in Patients with Cognitive Impairment.

PubMed

Inoue, Y; Nakajima, M; Uetani, H; Hirai, T; Ueda, M; Kitajima, M; Utsunomiya, D; Watanabe, M; Hashimoto, M; Ikeda, M; Yamashita, Y; Ando, Y

2016-02-01

Because the diagnostic significance of cortical superficial siderosis for Alzheimer disease and the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds have been unclear, we investigated the association between cortical superficial siderosis and clinicoradiologic characteristics of patients with cognitive impairment. We studied 347 patients (217 women, 130 men; mean age, 74 ± 9 years) who visited our memory clinic and underwent MR imaging (3T SWI). We analyzed the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds plus clinical characteristics including types of dementia. We used multivariate logistic regression analysis to determine the diagnostic significance of cortical superficial siderosis for Alzheimer disease. Twelve patients (3.5%) manifested cortical superficial siderosis. They were older (P = .026) and had strictly lobar cerebral microbleeds significantly more often than did patients without cortical superficial siderosis (50.0% versus 19.4%, P = .02); the occurrence of strictly deep and mixed cerebral microbleeds, however, did not differ in the 2 groups. Alzheimer disease was diagnosed in 162 (46.7%) patients. Of these, 8 patients (4.9%) had cortical superficial siderosis. In the multivariate logistic regression analysis for the diagnosis of Alzheimer disease, lacunar infarcts were negatively and independently associated with Alzheimer disease (P = .007). Although cortical superficial siderosis was associated with a strictly lobar cerebral microbleed location, it was not independently associated with Alzheimer disease in a memory clinic setting. Additional studies are required to investigate the temporal changes of these cerebral amyloid angiopathy-related MR imaging findings. © 2016 by American Journal of Neuroradiology.

Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.

PubMed

Chandana, Sreenivasa R; Behen, Michael E; Juhász, Csaba; Muzik, Otto; Rothermel, Robert D; Mangner, Thomas J; Chakraborty, Pulak K; Chugani, Harry T; Chugani, Diane C

2005-01-01

The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

Autosomal dominant cortical tremor, myoclonus and epilepsy.

PubMed

Striano, Pasquale; Zara, Federico

2016-09-01

The term 'cortical tremor' was first introduced by Ikeda and colleagues to indicate a postural and action-induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug-resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well-delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.

Language Mapping in Multilingual Patients: Electrocorticography and Cortical Stimulation During Naming

PubMed Central

Cervenka, Mackenzie C.; Boatman-Reich, Dana F.; Ward, Julianna; Franaszczuk, Piotr J.; Crone, Nathan E.

2011-01-01

Multilingual patients pose a unique challenge when planning epilepsy surgery near language cortex because the cortical representations of each language may be distinct. These distinctions may not be evident with routine electrocortical stimulation mapping (ESM). Electrocorticography (ECoG) has recently been used to detect task-related spectral perturbations associated with functional brain activation. We hypothesized that using broadband high gamma augmentation (HGA, 60–150 Hz) as an index of cortical activation, ECoG would complement ESM in discriminating the cortical representations of first (L1) and second (L2) languages. We studied four adult patients for whom English was a second language, in whom subdural electrodes (a total of 358) were implanted to guide epilepsy surgery. Patients underwent ECoG recordings and ESM while performing the same visual object naming task in L1 and L2. In three of four patients, ECoG found sites activated during naming in one language but not the other. These language-specific sites were not identified using ESM. In addition, ECoG HGA was observed at more sites during L2 versus L1 naming in two patients, suggesting that L2 processing required additional cortical resources compared to L1 processing in these individuals. Post-operative language deficits were identified in three patients (one in L2 only). These deficits were predicted by ECoG spectral mapping but not by ESM. These results suggest that pre-surgical mapping should include evaluation of all utilized languages to avoid post-operative functional deficits. Finally, this study suggests that ECoG spectral mapping may potentially complement the results of ESM of language. PMID:21373361

Partial volume correction using cortical surfaces

NASA Astrophysics Data System (ADS)

Blaasvær, Kamille R.; Haubro, Camilla D.; Eskildsen, Simon F.; Borghammer, Per; Otzen, Daniel; Ostergaard, Lasse R.

2010-03-01

Partial volume effect (PVE) in positron emission tomography (PET) leads to inaccurate estimation of regional metabolic activities among neighbouring tissues with different tracer concentration. This may be one of the main limiting factors in the utilization of PET in clinical practice. Partial volume correction (PVC) methods have been widely studied to address this issue. MRI based PVC methods are well-established.1 Their performance depend on the quality of the co-registration of the MR and PET dataset, on the correctness of the estimated point-spread function (PSF) of the PET scanner and largely on the performance of the segmentation method that divide the brain into brain tissue compartments.1, 2 In the present study a method for PVC is suggested, that utilizes cortical surfaces, to obtain detailed anatomical information. The objectives are to improve the performance of PVC, facilitate a study of the relationship between metabolic activity in the cerebral cortex and cortical thicknesses, and to obtain an improved visualization of PET data. The gray matter metabolic activity after performing PVC was recovered by 99.7 - 99.8 % , in relation to the true activity when testing on simple simulated data with different PSFs and by 97.9 - 100 % when testing on simulated brain PET data at different cortical thicknesses. When studying the relationship between metabolic activities and anatomical structures it was shown on simulated brain PET data, that it is important to correct for PVE in order to get the true relationship.

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. �

Influence of basis images and skull position on evaluation of cortical bone thickness in cone beam computed tomography.

PubMed

Nascimento, Monikelly do Carmo Chagas; Boscolo, Solange Maria de Almeida; Haiter-Neto, Francisco; Santos, Emanuela Carla Dos; Lambrichts, Ivo; Pauwels, Ruben; Jacobs, Reinhilde

2017-06-01

The aim of this study was to assess the influence of the number of basis images and the orientation of the skull on the evaluation of cortical alveolar bone in cone beam computed tomography (CBCT). Eleven skulls with a total of 59 anterior teeth were selected. CBCT images were acquired by using 4 protocols, by varying the rotation of the tube-detector arm and the orientation of the skull (protocol 1: 360°/0°; protocol 2: 180°/0°; protocol 3: 180°/90°; protocol 4: 180°/180°). Observers evaluated cortical bone as absent, thin, or thick. Direct observation of the skulls was used as the gold standard. Intra- and interobserver agreement, as well as agreement of scoring between the 3 bone thickness classifications, were calculated by using the κ statistic. The Wilcoxon signed-rank test was used to compare the 4 protocols. For lingual cortical bone, protocol 1 showed no statistical difference from the gold standard. Higher reliability was found in protocol 3 for absent (κ = 0.80) and thin (κ = 0.47) cortices, whereas for thick cortical bone, protocol 2 was more consistent (κ = 0.60). In buccal cortical bone, protocol 1 obtained the highest agreement for absent cortices (κ = 0.61), whereas protocol 4 was better for thin cortical plates (κ = 0.38) and protocol 2 for thick cortical plates (κ = 0.40). No consistent effect of the number of basis images or head orientation for visual detection of alveolar bone was detected, except for lingual cortical bone, for which full rotation scanning showed improved visualization. Copyright © 2017 Elsevier Inc. All rights reserved.

Exacerbated Glial Response in the Aged Mouse Hippocampus Following Controlled Cortical Impact Injury

PubMed Central

Sandhir, Rajat; Onyszchuk, Gregory; Berman, Nancy E. J.

2008-01-01

Old age is associated with enhanced susceptibility to and poor recovery from brain injury. An exacerbated microglial and astrocyte response to brain injury might be involved in poor outcomes observed in the elderly. The present study was therefore designed to quantitate the expression of markers of microglia and astrocyte activation using real-time RT-PCR, immunoblot and immunohistochemical analysis in aging brain in response to brain injury. We examined the hippocampus, a region that undergoes secondary neuron death, in aged (21–24 month) and adult (5–6 month) mice following controlled cortical impact (CCI) injury to the sensorimotor cortex. Basal mRNA expression of CD11b and Iba1, markers of activated microglia, was higher in aged hippocampus as compared to the adult. The mRNA expression of microglial markers increased and reached maximum 3 days post injury in both adult and aged mice, but was higher in the aged mice at all time points studied, and in the aged mice the return to baseline levels was delayed. Basal mRNA expression of GFAP and S100B, markers of activated astrocytes, was higher in aged mice. Both markers increased and reached maximum 7 days post injury. The mRNA expression of astrocyte markers returned to near basal levels rapidly after injury in the adult mice, whereas again in the aged mice return to baseline was delayed. Immunochemical analysis using Iba1 and GFAP antibodies indicate accentuated glial responses in the aged hippocampus after injury. The pronounced and prolonged activation of microglia and astrocytes in hippocampus may contribute to worse cognitive outcomes in the elderly following TBI. PMID:18692046

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.

Automated cortical auditory evoked potentials threshold estimation in neonates.

PubMed

Oliveira, Lilian Sanches; Didoné, Dayane Domeneghini; Durante, Alessandra Spada

2018-02-02

The evaluation of Cortical Auditory Evoked Potential has been the focus of scientific studies in infants. Some authors have reported that automated response detection is effective in exploring these potentials in infants, but few have reported their efficacy in the search for thresholds. To analyze the latency, amplitude and thresholds of Cortical Auditory Evoked Potential using an automatic response detection device in a neonatal population. This is a cross-sectional, observational study. Cortical Auditory Evoked Potentials were recorded in response to pure-tone stimuli of the frequencies 500, 1000, 2000 and 4000Hz presented in an intensity range between 0 and 80dB HL using a single channel recording. P1 was performed in an exclusively automated fashion, using Hotelling's T 2 statistical test. The latency and amplitude were obtained manually by three examiners. The study comprised 39 neonates up to 28 days old of both sexes with presence of otoacoustic emissions and no risk factors for hearing loss. With the protocol used, Cortical Auditory Evoked Potential responses were detected in all subjects at high intensity and thresholds. The mean thresholds were 24.8±10.4dB NA, 25±9.0dB NA, 28±7.8dB NA and 29.4±6.6dB HL for 500, 1000, 2000 and 4000Hz, respectively. Reliable responses were obtained in the assessment of cortical auditory potentials in the neonates assessed with a device for automatic response detection. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Cortical gyrification is abnormal in children with prenatal alcohol exposure.

PubMed

Hendrickson, Timothy J; Mueller, Bryon A; Sowell, Elizabeth R; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Wozniak, Jeffrey R

2017-01-01

Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined. Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure. Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ). Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.

Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

PubMed Central

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M.; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction. PMID:23326379

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

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

DICCCOL: Dense Individualized and Common Connectivity-Based Cortical Landmarks

PubMed Central

Zhu, Dajiang; Guo, Lei; Jiang, Xi; Zhang, Tuo; Zhang, Degang; Chen, Hanbo; Deng, Fan; Faraco, Carlos; Jin, Changfeng; Wee, Chong-Yaw; Yuan, Yixuan; Lv, Peili; Yin, Yan; Hu, Xiaolei; Duan, Lian; Hu, Xintao; Han, Junwei; Wang, Lihong; Shen, Dinggang; Miller, L Stephen

2013-01-01

Is there a common structural and functional cortical architecture that can be quantitatively encoded and precisely reproduced across individuals and populations? This question is still largely unanswered due to the vast complexity, variability, and nonlinearity of the cerebral cortex. Here, we hypothesize that the common cortical architecture can be effectively represented by group-wise consistent structural fiber connections and take a novel data-driven approach to explore the cortical architecture. We report a dense and consistent map of 358 cortical landmarks, named Dense Individualized and Common Connectivity–based Cortical Landmarks (DICCCOLs). Each DICCCOL is defined by group-wise consistent white-matter fiber connection patterns derived from diffusion tensor imaging (DTI) data. Our results have shown that these 358 landmarks are remarkably reproducible over more than one hundred human brains and possess accurate intrinsically established structural and functional cross-subject correspondences validated by large-scale functional magnetic resonance imaging data. In particular, these 358 cortical landmarks can be accurately and efficiently predicted in a new single brain with DTI data. Thus, this set of 358 DICCCOL landmarks comprehensively encodes the common structural and functional cortical architectures, providing opportunities for many applications in brain science including mapping human brain connectomes, as demonstrated in this work. PMID:22490548

Biological and cognitive correlates of cortical curvature in schizophrenia.

PubMed

Lubeiro, Alba; de Luis-García, Rodrigo; Rodríguez, Margarita; Álvarez, Aldara; de la Red, Henar; Molina, Vicente

2017-10-27

Mean cortical curvature may relate to cortico-cortical connections integrity. We explored the association between prefrontal (PFC) cortical curvature and fractional anisotropy (FA) values for tracts connecting PFC and relevant cortical regions. In schizophrenia Anatomical and diffusion magnetic resonance images were obtained from 34 patients (16 of them first-episodes) and 32 healthy controls. We calculated curvature at rostral lateral prefrontal (RLPF) and superior medial prefrontal (SMPF) areas and mean FA for the tracts respectively connecting RLPF and SMPF areas with anterior caudal cingulate (ACC), superior temporal gyrus (STG) and superior parietal SP regions. Cognitive and clinical data were collected, including baseline symptoms, Clinical Global Impression change scores from baseline to follow-up, illness duration and treatment dosage. Patients showed significantly lower FA values in the tracts linking right RLPF-ACC, right SMPF-SPG and bilaterally PFC-STG. FA values in short-range cortico-cortical connections (linking PFC and ACC) were inversely associated with PFC curvature. In patients, cognitive performance was negatively associated with PFC curvature. Larger curvature values were associated to lack of clinical improvement at follow-up. We conclude that cortical curvature is influenced by integrity in short-range cortico-cortical connections and relates to cognition and clinical outcome in schizophrenia patients. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Automated cortical bone segmentation for multirow-detector CT imaging with validation and application to human studies

PubMed Central

Li, Cheng; Jin, Dakai; Chen, Cheng; Letuchy, Elena M.; Janz, Kathleen F.; Burns, Trudy L.; Torner, James C; Levy, Steven M.; Saha, Punam K

2015-01-01

Purpose: Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined. Methods: The algorithm is completed in two major steps—(1) bone filling, alignment, and region-of-interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation—(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation. Results: An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD-CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro-CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19–20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height