Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

ERIC Educational Resources Information Center

Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

2008-01-01

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence

PubMed Central

Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N.; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L.; Liao, Duanping; Bixler, Edward O.

2016-01-01

Study Objectives: To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15–35Hz) range during sleep in an adolescent general population sample. Methods: A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15–25 Hz) and high-beta (25–35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Results: Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Conclusions: Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. Citation: Fernandez-Mendoza J, Li Y, Vgontzas AN, Fang J, Gaines J, Calhoun SL, Liao D, Bixler EO. Insomnia is associated with cortical hyperarousal as early as adolescence. SLEEP 2016;39(5):1029–1036. PMID:26951400

Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials.

PubMed

Trebaul, Lena; Rudrauf, David; Job, Anne-Sophie; Mălîia, Mihai Dragos; Popa, Irina; Barborica, Andrei; Minotti, Lorella; Mîndruţă, Ioana; Kahane, Philippe; David, Olivier

2016-05-01

Effective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. In order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode-tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. Our approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. The model-based template removal was compared to a correction based on the subtraction of the averaged artifact. This new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

Cooper, Emily A.; Norcia, Anthony M.

2015-01-01

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

The Cortically Blind Infant: Educational Guidelines and Suggestions.

ERIC Educational Resources Information Center

Silverrain, Ann

Cortical blindness is defined and its diagnosis is explained. Guidelines and sample activities are presented for use in a cognitive/visual/multi-sensory stimulation program to produce progress in cortically blind infants. The importance of using the eyes from birth through early development in order to form the nerve pathways responsible for…

Detection and mapping of delays in early cortical folding derived from in utero MRI

NASA Astrophysics Data System (ADS)

Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

2011-03-01

Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.

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.

Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices.

PubMed

Zheng, Jing-Jing; Li, Shu-Jing; Zhang, Xiao-Di; Miao, Wan-Ying; Zhang, Dinghong; Yao, Haishan; Yu, Xiang

2014-03-01

Sensory experience is critical to development and plasticity of neural circuits. Here we report a new form of plasticity in neonatal mice, where early sensory experience cross-modally regulates development of all sensory cortices via oxytocin signaling. Unimodal sensory deprivation from birth through whisker deprivation or dark rearing reduced excitatory synaptic transmission in the correspondent sensory cortex and cross-modally in other sensory cortices. Sensory experience regulated synthesis and secretion of the neuropeptide oxytocin as well as its level in the cortex. Both in vivo oxytocin injection and increased sensory experience elevated excitatory synaptic transmission in multiple sensory cortices and significantly rescued the effects of sensory deprivation. Together, these results identify a new function for oxytocin in promoting cross-modal, experience-dependent cortical development. This link between sensory experience and oxytocin is particularly relevant to autism, where hypersensitivity or hyposensitivity to sensory inputs is prevalent and oxytocin is a hotly debated potential therapy.

Relationship between brainstem, cortical and behavioral measures relevant to pitch salience in humans.

PubMed

Krishnan, Ananthanarayan; Bidelman, Gavin M; Smalt, Christopher J; Ananthakrishnan, Saradha; Gandour, Jackson T

2012-10-01

Neural representation of pitch-relevant information at both the brainstem and cortical levels of processing is influenced by language or music experience. However, the functional roles of brainstem and cortical neural mechanisms in the hierarchical network for language processing, and how they drive and maintain experience-dependent reorganization are not known. In an effort to evaluate the possible interplay between these two levels of pitch processing, we introduce a novel electrophysiological approach to evaluate pitch-relevant neural activity at the brainstem and auditory cortex concurrently. Brainstem frequency-following responses and cortical pitch responses were recorded from participants in response to iterated rippled noise stimuli that varied in stimulus periodicity (pitch salience). A control condition using iterated rippled noise devoid of pitch was employed to ensure pitch specificity of the cortical pitch response. Neural data were compared with behavioral pitch discrimination thresholds. Results showed that magnitudes of neural responses increase systematically and that behavioral pitch discrimination improves with increasing stimulus periodicity, indicating more robust encoding for salient pitch. Absence of cortical pitch response in the control condition confirms that the cortical pitch response is specific to pitch. Behavioral pitch discrimination was better predicted by brainstem and cortical responses together as compared to each separately. The close correspondence between neural and behavioral data suggest that neural correlates of pitch salience that emerge in early, preattentive stages of processing in the brainstem may drive and maintain with high fidelity the early cortical representations of pitch. These neural representations together contain adequate information for the development of perceptual pitch salience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.

PubMed

Youssef, Andrew M; Macefield, Vaughan G; Henderson, Luke A

2016-07-01

Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intracranial Cortical Responses during Visual–Tactile Integration in Humans

PubMed Central

Quinn, Brian T.; Carlson, Chad; Doyle, Werner; Cash, Sydney S.; Devinsky, Orrin; Spence, Charles; Halgren, Eric

2014-01-01

Sensory integration of touch and sight is crucial to perceiving and navigating the environment. While recent evidence from other sensory modality combinations suggests that low-level sensory areas integrate multisensory information at early processing stages, little is known about how the brain combines visual and tactile information. We investigated the dynamics of multisensory integration between vision and touch using the high spatial and temporal resolution of intracranial electrocorticography in humans. We present a novel, two-step metric for defining multisensory integration. The first step compares the sum of the unisensory responses to the bimodal response as multisensory responses. The second step eliminates the possibility that double addition of sensory responses could be misinterpreted as interactions. Using these criteria, averaged local field potentials and high-gamma-band power demonstrate a functional processing cascade whereby sensory integration occurs late, both anatomically and temporally, in the temporo–parieto–occipital junction (TPOJ) and dorsolateral prefrontal cortex. Results further suggest two neurophysiologically distinct and temporally separated integration mechanisms in TPOJ, while providing direct evidence for local suppression as a dominant mechanism for synthesizing visual and tactile input. These results tend to support earlier concepts of multisensory integration as relatively late and centered in tertiary multimodal association cortices. PMID:24381279

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis

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.

Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

ERIC Educational Resources Information Center

Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

2008-01-01

Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

Pitch-Responsive Cortical Regions in Congenital Amusia.

PubMed

Norman-Haignere, Sam V; Albouy, Philippe; Caclin, Anne; McDermott, Josh H; Kanwisher, Nancy G; Tillmann, Barbara

2016-03-09

Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work. Copyright © 2016 the authors 0270-6474/16/362986-09$15.00/0.

Nonlinear dynamics of cortical responses to color in the human cVEP.

PubMed

Nunez, Valerie; Shapley, Robert M; Gordon, James

2017-09-01

The main finding of this paper is that the human visual cortex responds in a very nonlinear manner to the color contrast of pure color patterns. We examined human cortical responses to color checkerboard patterns at many color contrasts, measuring the chromatic visual evoked potential (cVEP) with a dense electrode array. Cortical topography of the cVEPs showed that they were localized near the posterior electrode at position Oz, indicating that the primary cortex (V1) was the major source of responses. The choice of fine spatial patterns as stimuli caused the cVEP response to be driven by double-opponent neurons in V1. The cVEP waveform revealed nonlinear color signal processing in the V1 cortex. The cVEP time-to-peak decreased and the waveform's shape was markedly narrower with increasing cone contrast. Comparison of the linear dynamics of retinal and lateral geniculate nucleus responses with the nonlinear dynamics of the cortical cVEP indicated that the nonlinear dynamics originated in the V1 cortex. The nature of the nonlinearity is a kind of automatic gain control that adjusts cortical dynamics to be faster when color contrast is greater.

Development of global cortical networks in early infancy.

PubMed

Homae, Fumitaka; Watanabe, Hama; Otobe, Takayuki; Nakano, Tamami; Go, Tohshin; Konishi, Yukuo; Taga, Gentaro

2010-04-07

Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction.

PubMed

Okabe, Tetsuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Shibasaki, Jun; Osaka, Hitoshi

2014-05-01

Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one.

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

The Serum Response Factor and a Putative Novel Transcription Factor Regulate Expression of the Immediate-Early Gene Arc/Arg3.1 in Cultured Cortical Neurons

PubMed Central

Pintchovski, Sean A.; Peebles, Carol L.; Kim, Hong Joo; Verdin, Eric; Finkbeiner, Steven

2010-01-01

The immediate-early effector gene Arc/Arg3.1 is robustly upregulated by synaptic activity associated with learning and memory. Here we show in primary cortical neuron culture that diverse stimuli induce Arc expression through new transcription. Searching for regulatory regions important for Arc transcription, we found nine DNaseI-sensitive nucleosome-depleted sites at this genomic locus. A reporter gene encompassing these sites responded to synaptic activity in an NMDA receptor–dependent manner, consistent with endogenous Arc mRNA. Responsiveness mapped to two enhancer regions ∼6.5 kb and ∼1.4 kb upstream of Arc. We dissected these regions further and found that the proximal enhancer contains a functional and conserved “Zeste-like” response element that binds a putative novel nuclear protein in neurons. Therefore, activity regulates Arc transcription partly by a novel signaling pathway. We also found that the distal enhancer has a functional and highly conserved serum response element. This element binds serum response factor, which is recruited by synaptic activity to regulate Arc. Thus, Arc is the first target of serum response factor that functions at synapses to mediate plasticity. PMID:19193899

Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis

PubMed Central

Deppe, Michael; Marinell, Jasmin; Krämer, Julia; Duning, Thomas; Ruck, Tobias; Simon, Ole J.; Zipp, Frauke; Wiendl, Heinz; Meuth, Sven G.

2014-01-01

Objective White matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple sclerosis (MS) and in virtually each individual patient. To find a new sensitive and robust marker for WMA we investigated the relationship between cortical surface area, white matter volume (WMV), and whole-brain-surface-averaged rectified cortical extrinsic curvature. Based on geometrical considerations we hypothesized that cortical curvature increases if WMV decreases and the cortical surface area remains constant. Methods In total, 95 participants were enrolled: 30 patients with early and advanced relapsing–remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's disease (AD) and 5 patients with clinically isolated syndrome (CIS). Results 29/30 MS and 5/5 CIS patients showed lower WMV than expected from their intracranial volume (average reduction 13.0%, P < 10− 10), while the cortical surface area showed no significant differences compared with controls. The estimated WMV reductions were correlated with an increase in cortical curvature (R = 0.62, P = 0.000001). Discriminant analysis revealed that the curvature increase was highly specific for the MS and CIS groups (96.7% correct assignments between MS and control groups) and was significantly correlated with reduction of white matter fractional anisotropy, as determined by diffusion tensor imaging and the Expanded Disability Status Scale. As expected by the predominant gray and WM degeneration in AD, no systematic curvature increase was observed in AD. Conclusion Whole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV–cortex disproportionality and allows us to assess “pure” WMA

Sour taste increases swallowing and prolongs hemodynamic responses in the cortical swallowing network

PubMed Central

Kamarunas, Erin; Ludlow, Christy L.

2016-01-01

Sour stimuli have been shown to upregulate swallowing in patients and in healthy volunteers. However, such changes may be dependent on taste-induced increases in salivary flow. Other mechanisms include genetic taster status (Bartoshuk LM, Duffy VB, Green BG, Hoffman HJ, Ko CW, Lucchina LA, Weiffenbach JM. Physiol Behav 82: 109–114, 2004) and differences between sour and other tastes. We investigated the effects of taste on swallowing frequency and cortical activation in the swallowing network and whether taster status affected responses. Three-milliliter boluses of sour, sour with slow infusion, sweet, water, and water with infusion were compared on swallowing frequency and hemodynamic responses. The sour conditions increased swallowing frequency, whereas sweet and water did not. Changes in cortical oxygenated hemoglobin (hemodynamic responses) measured by functional near-infrared spectroscopy were averaged over 30 trials for each condition per participant in the right and left motor cortex, S1 and supplementary motor area for 30 s following bolus onset. Motion artifact in the hemodynamic response occurred 0–2 s after bolus onset, when the majority of swallows occurred. The peak hemodynamic response 2–7 s after bolus onset did not differ by taste, hemisphere, or cortical location. The mean hemodynamic response 17–22 s after bolus onset was highest in the motor regions of both hemispheres, and greater in the sour and infusion condition than in the water condition. Genetic taster status did not alter changes in swallowing frequency or hemodynamic response. As sour taste significantly increased swallowing and cortical activation equally with and without slow infusion, increases in the cortical swallowing were due to sour taste. PMID:27489363

Short-Term Variations in Response Distribution to Cortical Stimulation

ERIC Educational Resources Information Center

Lesser, Ronald P.; Lee, Hyang Woon; Webber, W. R. S.; Prince, Barry; Crone, Nathan E.; Miglioretti, Diana L.

2008-01-01

Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change…

Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia

PubMed Central

Satterthwaite, Theodore D.; Wolf, Daniel H.; Loughead, James; Ruparel, Kosha; Valdez, Jeffrey N.; Siegel, Steven J.; Kohler, Christian G.; Gur, Raquel E.; Gur, Ruben C.

2014-01-01

Objective Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. Here we used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Methods fMRI (3T) BOLD response was examined in 21 controls and 16 patients during a two-choice recognition task using images of human faces. Each target face had previously been displayed with a threatening or non-threatening affect, but here were displayed with neutral affect. Responses to successful recognition and for the effect of previously threatening vs. non-threatening affect were evaluated, and correlations with total BPRS examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Results Patients performed the task more slowly than controls. Controls recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Controls exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed a weakening of that relationship. Conclusions Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between two brain systems often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia. PMID:20194482

Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

PubMed

Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

2010-05-01

Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.

PubMed

Galbraith, G C

2001-06-01

The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.

Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia.

PubMed

Satterthwaite, Theodore D; Wolf, Daniel H; Loughead, James; Ruparel, Kosha; Valdez, Jeffrey N; Siegel, Steven J; Kohler, Christian G; Gur, Raquel E; Gur, Ruben C

2010-04-01

Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship. Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of

Mapping the Speech Code: Cortical Responses Linking the Perception and Production of Vowels

PubMed Central

Schuerman, William L.; Meyer, Antje S.; McQueen, James M.

2017-01-01

The acoustic realization of speech is constrained by the physical mechanisms by which it is produced. Yet for speech perception, the degree to which listeners utilize experience derived from speech production has long been debated. In the present study, we examined how sensorimotor adaptation during production may affect perception, and how this relationship may be reflected in early vs. late electrophysiological responses. Participants first performed a baseline speech production task, followed by a vowel categorization task during which EEG responses were recorded. In a subsequent speech production task, half the participants received shifted auditory feedback, leading most to alter their articulations. This was followed by a second, post-training vowel categorization task. We compared changes in vowel production to both behavioral and electrophysiological changes in vowel perception. No differences in phonetic categorization were observed between groups receiving altered or unaltered feedback. However, exploratory analyses revealed correlations between vocal motor behavior and phonetic categorization. EEG analyses revealed correlations between vocal motor behavior and cortical responses in both early and late time windows. These results suggest that participants' recent production behavior influenced subsequent vowel perception. We suggest that the change in perception can be best characterized as a mapping of acoustics onto articulation. PMID:28439232

Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report.

PubMed

Kurian, Mary; Korff, Christian M; Ranza, Emmanuelle; Bernasconi, Andrea; Lübbig, Anja; Nangia, Srishti; Ramelli, Gian Paolo; Wohlrab, Gabriele; Nordli, Douglas R; Bast, Thomas

2018-01-01

In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions. Focal cortical malformations and monogenic epilepsy syndromes may coexist. Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures. © 2017 Mac Keith Press.

COMMUNICATION: Electrophysiological response dynamics during focal cortical infarction

NASA Astrophysics Data System (ADS)

Chiganos, Terry C., Jr.; Jensen, Winnie; Rousche, Patrick J.

2006-12-01

While the intracellular processes of hypoxia-induced necrosis and the intercellular mechanisms of post-ischemic neurotoxicity associated with stroke are well documented, the dynamic electrophysiological (EP) response of neurons within the core or periinfarct zone remains unclear. The present study validates a method for continuous measurement of the local EP responses during focal cortical infarction induced via photothrombosis. Single microwire electrodes were acutely implanted into the primary auditory cortex of eight rats. Multi-unit neural activity, evoked via a continuous 2 Hz click stimulus, was recorded before, during and after infarction to assess neuronal function in response to local, permanent ischemia. During sham infarction, the average stimulus-evoked peak firing rate over 20 min remained stable at 495.5 ± 14.5 spikes s-1, indicating temporal stability of neural function under normal conditions. Stimulus-evoked peak firing was reliably reduced to background levels (firing frequency in the absence of stimulus) following initiation of photothrombosis over a period of 439 ± 92 s. The post-infarction firing patterns exhibited unique temporal degradation of the peak firing rate, suggesting a variable response to ischemic challenge. Despite the inherent complexity of cerebral ischemia secondary to microvascular occlusion, complete loss of EP function consistently occurred 300-600 s after photothrombosis. The results suggest that microwire recording during photothrombosis provides a simple and highly efficacious strategy for assessing the electrophysiological dynamics of cortical infarction.

Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

PubMed Central

Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

2013-01-01

Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

Discriminating between auditory and motor cortical responses to speech and non-speech mouth sounds

PubMed Central

Agnew, Z.K.; McGettigan, C.; Scott, S.K.

2012-01-01

Several perspectives on speech perception posit a central role for the representation of articulations in speech comprehension, supported by evidence for premotor activation when participants listen to speech. However no experiments have directly tested whether motor responses mirror the profile of selective auditory cortical responses to native speech sounds, or whether motor and auditory areas respond in different ways to sounds. We used fMRI to investigate cortical responses to speech and non-speech mouth (ingressive click) sounds. Speech sounds activated bilateral superior temporal gyri more than other sounds, a profile not seen in motor and premotor cortices. These results suggest that there are qualitative differences in the ways that temporal and motor areas are activated by speech and click sounds: anterior temporal lobe areas are sensitive to the acoustic/phonetic properties while motor responses may show more generalised responses to the acoustic stimuli. PMID:21812557

Binaural sensitivity changes between cortical on and off responses

PubMed Central

Dahmen, Johannes C.; King, Andrew J.; Schnupp, Jan W. H.

2011-01-01

Neurons exhibiting on and off responses with different frequency tuning have previously been described in the primary auditory cortex (A1) of anesthetized and awake animals, but it is unknown whether other tuning properties, including sensitivity to binaural localization cues, also differ between on and off responses. We measured the sensitivity of A1 neurons in anesthetized ferrets to 1) interaural level differences (ILDs), using unmodulated broadband noise with varying ILDs and average binaural levels, and 2) interaural time delays (ITDs), using sinusoidally amplitude-modulated broadband noise with varying envelope ITDs. We also assessed fine-structure ITD sensitivity and frequency tuning, using pure-tone stimuli. Neurons most commonly responded to stimulus onset only, but purely off responses and on-off responses were also recorded. Of the units exhibiting significant binaural sensitivity nearly one-quarter showed binaural sensitivity in both on and off responses, but in almost all (∼97%) of these units the binaural tuning of the on responses differed significantly from that seen in the off responses. Moreover, averaged, normalized ILD and ITD tuning curves calculated from all units showing significant sensitivity to binaural cues indicated that on and off responses displayed different sensitivity patterns across the population. A principal component analysis of ITD response functions suggested a continuous cortical distribution of binaural sensitivity, rather than discrete response classes. Rather than reflecting a release from inhibition without any functional significance, we propose that binaural off responses may be important to cortical encoding of sound-source location. PMID:21562191

Striatal GABA-MRS predicts response inhibition performance and its cortical electrophysiological correlates.

PubMed

Quetscher, Clara; Yildiz, Ali; Dharmadhikari, Shalmali; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Dydak, Ulrike; Beste, Christian

2015-11-01

Response inhibition processes are important for performance monitoring and are mediated via a network constituted by different cortical areas and basal ganglia nuclei. At the basal ganglia level, striatal GABAergic medium spiny neurons are known to be important for response selection, but the importance of the striatal GABAergic system for response inhibition processes remains elusive. Using a novel combination of behavior al, EEG and magnetic resonance spectroscopy (MRS) data, we examine the relevance of the striatal GABAergic system for response inhibition processes. The study shows that striatal GABA levels modulate the efficacy of response inhibition processes. Higher striatal GABA levels were related to better response inhibition performance. We show that striatal GABA modulate specific subprocesses of response inhibition related to pre-motor inhibitory processes through the modulation of neuronal synchronization processes. To our knowledge, this is the first study providing direct evidence for the relevance of the striatal GABAergic system for response inhibition functions and their cortical electrophysiological correlates in humans.

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence.

PubMed

Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L; Liao, Duanping; Bixler, Edward O

2016-05-01

To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15-35Hz) range during sleep in an adolescent general population sample. A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. © 2016 Associated Professional Sleep Societies, LLC.

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

PubMed

McLaughlin, David; Shapley, Robert; Shelley, Michael

2003-01-01

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

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

Human cortical responses to slow and fast binaural beats reveal multiple mechanisms of binaural hearing.

PubMed

Ross, Bernhard; Miyazaki, Takahiro; Thompson, Jessica; Jamali, Shahab; Fujioka, Takako

2014-10-15

When two tones with slightly different frequencies are presented to both ears, they interact in the central auditory system and induce the sensation of a beating sound. At low difference frequencies, we perceive a single sound, which is moving across the head between the left and right ears. The percept changes to loudness fluctuation, roughness, and pitch with increasing beat rate. To examine the neural representations underlying these different perceptions, we recorded neuromagnetic cortical responses while participants listened to binaural beats at a continuously varying rate between 3 Hz and 60 Hz. Binaural beat responses were analyzed as neuromagnetic oscillations following the trajectory of the stimulus rate. Responses were largest in the 40-Hz gamma range and at low frequencies. Binaural beat responses at 3 Hz showed opposite polarity in the left and right auditory cortices. We suggest that this difference in polarity reflects the opponent neural population code for representing sound location. Binaural beats at any rate induced gamma oscillations. However, the responses were largest at 40-Hz stimulation. We propose that the neuromagnetic gamma oscillations reflect postsynaptic modulation that allows for precise timing of cortical neural firing. Systematic phase differences between bilateral responses suggest that separate sound representations of a sound object exist in the left and right auditory cortices. We conclude that binaural processing at the cortical level occurs with the same temporal acuity as monaural processing whereas the identification of sound location requires further interpretation and is limited by the rate of object representations. Copyright © 2014 the American Physiological Society.

Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2014-01-01

Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

Multimodal sensory responses of nucleus reticularis gigantocellularis and the responses' relation to cortical and motor activation.

PubMed

Martin, Eugene M; Pavlides, Constantine; Pfaff, Donald

2010-05-01

The connectivity of large neurons of the nucleus reticularis gigantocellularis (NRGc) in the medullary reticular formation potentially allows both for the integration of stimuli, in several modalities, that would demand immediate action, and for coordinated activation of cortical and motoric activity. We have simultaneously recorded cortical local field potentials, neck muscle electromyograph (EMG), and the neural activity of medullary NRGc neurons in unrestrained, unanesthetized rats to determine whether the activity of the NRGc is consistent with the modulation of general arousal. We observed excitatory responses of individual NRGc neurons to all modalities tested: tactile, visual, auditory, vestibular, and olfactory. Excitation was directly linked to increases in neck muscle EMG amplitude and corresponded with increases in the power of fast oscillations (30 to 80 Hz) of cortical activity and decreases in the power of slow oscillations (2 to 8 Hz). Because these reticular formation neurons can respond to broad ranges of stimuli with increased firing rates associated with the initiation of behavioral responses, we infer that they are part of an elementary "first responder" CNS arousal mechanism.

Multimodal Sensory Responses of Nucleus Reticularis Gigantocellularis and the Responses' Relation to Cortical and Motor Activation

PubMed Central

Pavlides, Constantine; Pfaff, Donald

2010-01-01

The connectivity of large neurons of the nucleus reticularis gigantocellularis (NRGc) in the medullary reticular formation potentially allows both for the integration of stimuli, in several modalities, that would demand immediate action, and for coordinated activation of cortical and motoric activity. We have simultaneously recorded cortical local field potentials, neck muscle electromyograph (EMG), and the neural activity of medullary NRGc neurons in unrestrained, unanesthetized rats to determine whether the activity of the NRGc is consistent with the modulation of general arousal. We observed excitatory responses of individual NRGc neurons to all modalities tested: tactile, visual, auditory, vestibular, and olfactory. Excitation was directly linked to increases in neck muscle EMG amplitude and corresponded with increases in the power of fast oscillations (30 to 80 Hz) of cortical activity and decreases in the power of slow oscillations (2 to 8 Hz). Because these reticular formation neurons can respond to broad ranges of stimuli with increased firing rates associated with the initiation of behavioral responses, we infer that they are part of an elementary “first responder” CNS arousal mechanism. PMID:20181730

Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.

PubMed

Morrell, Martha J

2011-09-27

This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy. A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation. Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function. Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

Auditory cortical responses in patients with cochlear implants

PubMed Central

Burdo, S; Razza, S; Di Berardino, F; Tognola, G

2006-01-01

Summary Currently, the most commonly used electrophysiological tests for cochlear implant evaluation are Averaged Electrical Voltages (AEV), Electrical Advisory Brainstem Responses (EABR) and Neural Response Telemetry (NRT). The present paper focuses on the study of acoustic auditory cortical responses, or slow vertex responses, which are not widely used due to the difficulty in recording, especially in young children. Aims of this study were validation of slow vertex responses and their possible applications in monitoring postimplant results, particularly restoration of hearing and auditory maturation. In practice, the use of tone-bursts, also through hearing aids or cochlear implants, as in slow vertex responses, allows many more frequencies to be investigated and louder intensities to be reached than with other tests based on a click as stimulus. Study design focused on latencies of N1 and P2 slow vertex response peaks in cochlear implants. The study population comprised 45 implant recipients (aged 2 to 70 years), divided into 5 different homogeneous groups according to chronological age, age at onset of deafness, and age at implantation. For each subject, slow vertex responses and free-field auditory responses (PTAS) were recorded for tone-bursts at 500 and 2000 Hz before cochlear implant surgery (using hearing aid amplification) and during scheduled sessions at 3rd and 12th month after implant activation. Results showed that N1 and P2 latencies decreased in all groups starting from 3rd through 12th month after activation. Subjects implanted before school age or at least before age 8 yrs showed the widest latency changes. All subjects showed a reduction in the gap between subjective thresholds (obtained with free field auditory responses) and objective thresholds (obtained with slow vertex responses), obtained in presurgery stage and after cochlear implant. In conclusion, a natural evolution of neurophysiological cortical activities of the auditory pathway

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

PubMed

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

2017-01-01

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

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Aδ or C fibers

PubMed Central

Tran, Tuan D.; Matre, Dagfinn; Casey, Kenneth L.

2008-01-01

Finely myelinated (type Aδ) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. There were two experiments, one with Aδ as CS and C as TS (Aδ-C) and another with these stimuli reversed (C-Aδ). We used intra-epidermal electrical pulses applied to the dorsal left hand at 2 and 1 × pinprick threshold (pp) for the preferential stimulation of Aδ fibers and 37 – 50°C contact heat pulses applied to the left or right thenar and left hypothenar eminences for the preferential stimulation of C fibers. We found that the cortical response to preferential Aδ or C fiber stimulation was attenuated whenever either cortical response preceded the other. Standardized values of peak and integrated amplitudes were < 1 in all paring conditions and in all subjects in both experiments. The suppressive effect varied in magnitude with the intensity of the conditioning stimulus in both Aδ-C and C-Aδ experiments. Furthermore, intra-segmental interaction was differentially effective for Aδ conditioning, (peak amplitude, p < 0.008; ANOVA). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Aδ and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensori-motor functions mediated through the Aδ and C fiber afferent channels. PMID:18308475

Adaptive shaping of cortical response selectivity in the vibrissa pathway

PubMed Central

Zheng, He J. V.; Wang, Qi

2015-01-01

One embodiment of context-dependent sensory processing is bottom-up adaptation, where persistent stimuli decrease neuronal firing rate over hundreds of milliseconds. Adaptation is not, however, simply the fatigue of the sensory pathway, but shapes the information flow and selectivity to stimulus features. Adaptation enhances spatial discriminability (distinguishing stimulus location) while degrading detectability (reporting presence of the stimulus), for both the ideal observer of the cortex and awake, behaving animals. However, how the dynamics of the adaptation shape the cortical response and this detection and discrimination tradeoff is unknown, as is to what degree this phenomenon occurs on a continuum as opposed to a switching of processing modes. Using voltage-sensitive dye imaging in anesthetized rats to capture the temporal and spatial characteristics of the cortical response to tactile inputs, we showed that the suppression of the cortical response, in both magnitude and spatial spread, is continuously modulated by the increasing amount of energy in the adapting stimulus, which is nonuniquely determined by its frequency and velocity. Single-trial ideal observer analysis demonstrated a tradeoff between detectability and spatial discriminability up to a moderate amount of adaptation, which corresponds to the frequency range in natural whisking. This was accompanied by a decrease in both detectability and discriminability with high-energy adaptation, which indicates a more complex coupling between detection and discrimination than a simple switching of modes. Taken together, the results suggest that adaptation operates on a continuum and modulates the tradeoff between detectability and discriminability that has implications for information processing in ethological contexts. PMID:25787959

Evaluating interhemispheric cortical responses to transcranial magnetic stimulation in chronic stroke: A TMS-EEG investigation.

PubMed

Borich, Michael R; Wheaton, Lewis A; Brodie, Sonia M; Lakhani, Bimal; Boyd, Lara A

2016-04-08

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15-30Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Analysis of preplate splitting and early cortical development illuminates the biology of neurological disease.

PubMed

Olson, Eric C

2014-01-01

The development of the layered cerebral cortex starts with a process called preplate splitting. Preplate splitting involves the establishment of prospective cortical layer 6 (L6) neurons within a plexus of pioneer neurons called the preplate. The forming layer 6 splits the preplate into a superficial layer of pioneer neurons called the marginal zone and a deeper layer of pioneer neurons called the subplate. Disruptions of this early developmental event by toxin exposure or mutation are associated with neurological disease including severe intellectual disability. This review explores recent findings that reveal the dynamism of gene expression and morphological differentiation during this early developmental period. Over 1000 genes show expression increases of ≥2-fold during this period in differentiating mouse L6 neurons. Surprisingly, 88% of previously identified non-syndromic intellectual-disability (NS-ID) genes are expressed at this time and show an average expression increase of 1.6-fold in these differentiating L6 neurons. This changing genetic program must, in part, support the dramatic cellular reorganizations that occur during preplate splitting. While different models have been proposed for the formation of a layer of L6 cortical neurons within the preplate, original histological studies and more recent work exploiting transgenic mice suggest that the process is largely driven by the coordinated polarization and coalescence of L6 neurons rather than by cellular translocation or migration. The observation that genes associated with forms of NS-ID are expressed during very early cortical development raises the possibility of studying the relevant biological events at a time point when the cortex is small, contains relatively few cell types, and few functional circuits. This review then outlines how explant models may prove particularly useful in studying the consequence of toxin and mutation on the etiology of some forms of NS-ID.

Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?

PubMed

Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan

2017-11-01

The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.

Reduced short interval cortical inhibition correlates with atomoxetine response in children with attention-deficit hyperactivity disorder (ADHD).

PubMed

Chen, Tina H; Wu, Steve W; Welge, Jeffrey A; Dixon, Stephan G; Shahana, Nasrin; Huddleston, David A; Sarvis, Adam R; Sallee, Floyd R; Gilbert, Donald L

2014-12-01

Clinical trials in children with attention-deficit hyperactivity disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine. The objective of this study was to determine whether transcranial magnetic stimulation-evoked short interval cortical inhibition might be a biomarker predicting, or correlating with, clinical atomoxetine response. At baseline and after 4 weeks of atomoxetine treatment in 7- to 12-year-old children with ADHD, transcranial magnetic stimulation short interval cortical inhibition was measured, blinded to clinical improvement. Primary analysis was by multivariate analysis of covariance. Baseline short interval cortical inhibition did not predict clinical responses. However, paradoxically, after 4 weeks of atomoxetine, mean short interval cortical inhibition was reduced 31.9% in responders and increased 6.1% in nonresponders (analysis of covariance t 41 = 2.88; P = .0063). Percentage reductions in short interval cortical inhibition correlated with reductions in the ADHD Rating Scale (r = 0.50; P = .0005). In children ages 7 to 12 years with ADHD treated with atomoxetine, improvements in clinical symptoms are correlated with reductions in motor cortex short interval cortical inhibition. © The Author(s) 2014.

The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs).

PubMed

Pasman, J W; Rotteveel, J J; de Graaf, R; Stegeman, D F; Visco, Y M

1992-12-01

Recent studies on the maturation of auditory brainstem evoked responses (ABRs) present conflicting results, whereas only sparse reports exist with respect to the maturation of middle latency auditory evoked responses (MLRs) and auditory cortical evoked responses (ACRs). The present study reports the effect of preterm birth on the maturation of auditory evoked responses in low risk preterm infants (27-34 weeks conceptional age). The ABRs indicate a consistent trend towards longer latencies for all individual ABR components and towards longer interpeak latencies in preterm infants. The MLR shows longer latencies for early component P0 in preterm infants. The ACRs show a remarkable difference between preterm and term infants. At 40 weeks CA the latencies of ACR components Na and P2 are significantly longer in term infants, whereas at 52 weeks CA the latencies of the same ACR components are shorter in term infants. The results support the hypothesis that retarded myelination of the central auditory pathway is partially responsible for differences found between preterm infants and term infants with respect to late ABR components and early MLR component P0. Furthermore, mild conductive hearing loss in preterm infants may also play its role. A more complex mechanism is implicated to account for the findings noted with respect to MLR component Na and ACR components Na and P2.

Priming with real motion biases visual cortical response to bistable apparent motion

PubMed Central

Zhang, Qing-fang; Wen, Yunqing; Zhang, Deng; She, Liang; Wu, Jian-young; Dan, Yang; Poo, Mu-ming

2012-01-01

Apparent motion quartet is an ambiguous stimulus that elicits bistable perception, with the perceived motion alternating between two orthogonal paths. In human psychophysical experiments, the probability of perceiving motion in each path is greatly enhanced by a brief exposure to real motion along that path. To examine the neural mechanism underlying this priming effect, we used voltage-sensitive dye (VSD) imaging to measure the spatiotemporal activity in the primary visual cortex (V1) of awake mice. We found that a brief real motion stimulus transiently biased the cortical response to subsequent apparent motion toward the spatiotemporal pattern representing the real motion. Furthermore, intracellular recording from V1 neurons in anesthetized mice showed a similar increase in subthreshold depolarization in the neurons representing the path of real motion. Such short-term plasticity in early visual circuits may contribute to the priming effect in bistable visual perception. PMID:23188797

Different early rearing experiences have long term effects on cortical organization in captive chimpanzees (Pan troglodytes)

PubMed Central

Bogart, Stephanie L.; Bennett, Allyson J.; Schapiro, Steven J.; Reamer, Lisa A.; Hopkins, William D.

2014-01-01

Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition, however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46) with age-group peers. Magnetic resonance brain images were analyzed with a processing program (BrainVISA) that extracts cortical sulci. We obtained various measurements from 11 sulci located throughout the brain, as well as whole brain gyrification and white and grey matter volumes. We found that mother-reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain morphology in chimpanzees and suggests potential differences in the development of white matter expansion and myelination. PMID:24206013

Different early rearing experiences have long-term effects on cortical organization in captive chimpanzees (Pan troglodytes).

PubMed

Bogart, Stephanie L; Bennett, Allyson J; Schapiro, Steven J; Reamer, Lisa A; Hopkins, William D

2014-03-01

Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition; however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46) with age-group peers. Magnetic resonance brain images were analyzed with a processing program (BrainVISA) that extracts cortical sulci. We obtained various measurements from 11 sulci located throughout the brain, as well as whole brain gyrification and white and grey matter volumes. We found that mother-reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain morphology in chimpanzees and suggests potential differences in the development of white matter expansion and myelination. © 2013 John Wiley & Sons Ltd.

Response of Quiescent Cerebral Cortical Astrocytes to Nanofibrillar Scaffold Properties

NASA Astrophysics Data System (ADS)

Ayres, Virginia; Mujdat Tiryaki, Volkan; Xie, Kan; Ahmed, Ijaz; Shreiber, David I.

2013-03-01

We present results of an investigation to examine the hypothesis that the extracellular environment can trigger specific signaling cascades with morphological consequences. Differences in the morphological responses of quiescent cerebral cortical astrocytes cultured on the nanofibrillar matrices versus poly-L-lysine functionalized glass and Aclar, and unfunctionalized Aclar surfaces were demonstrated using atomic force microscopy (AFM) and phalloidin staining of F-actin. The differences and similarities of the morphological responses were consistent with differences and similarities of the surface polarity and surface roughness of the four surfaces investigated in this work, characterized using contact angle and AFM measurements. The three-dimensional capability of AFM was also used to identify differences in cell spreading. An initial quantitative immunolabeling study further identified significant differences in the activation of the Rho GTPases: Cdc42, Rac1, and RhoA, which are upstream regulators of the observed morphological responses: filopodia, lamellipodia, and stress fiber formation. The results support the hypothesis that the extracellular environment can trigger preferential activation of members of the Rho GTPase family with demonstrable morphological consequences for cerebral cortical astrocytes. The support of NSF PHY-095776 is acknowledged.

Spreading Photoparoxysmal EEG Response is Associated with an Abnormal Cortical Excitability Pattern

ERIC Educational Resources Information Center

Siniatchkin, Michael; Groppa, Sergey; Jerosch, Bettina; Muhle, Hiltrud; Kurth, Christoph; Shepherd, Alex J.; Siebner, Hartwig; Stephani, Ulrich

2007-01-01

Photosensitivity or photoparoxysmal response (PPR) is a highly heritable electroencephalographic trait characterized by an abnormal cortical response to intermittent photic stimulation (IPS). In PPR-positive individuals, IPS induces spikes, spike-waves or intermittent slow waves. The PPR may be restricted to posterior visual areas (i.e. local PPR…

Atypical coordination of cortical oscillations in response to speech in autism

PubMed Central

Jochaut, Delphine; Lehongre, Katia; Saitovitch, Ana; Devauchelle, Anne-Dominique; Olasagasti, Itsaso; Chabane, Nadia; Zilbovicius, Monica; Giraud, Anne-Lise

2015-01-01

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations. PMID:25870556

Automated classification of mandibular cortical bone on dental panoramic radiographs for early detection of osteoporosis

NASA Astrophysics Data System (ADS)

Horiba, Kazuki; Muramatsu, Chisako; Hayashi, Tatsuro; Fukui, Tatsumasa; Hara, Takeshi; Katsumata, Akitoshi; Fujita, Hiroshi

2015-03-01

Findings on dental panoramic radiographs (DPRs) have shown that mandibular cortical index (MCI) based on the morphology of mandibular inferior cortex was significantly correlated with osteoporosis. MCI on DPRs can be categorized into one of three groups and has the high potential for identifying patients with osteoporosis. However, most DPRs are used only for diagnosing dental conditions by dentists in their routine clinical work. Moreover, MCI is not generally quantified but assessed subjectively. In this study, we investigated a computer-aided diagnosis (CAD) system that automatically classifies mandibular cortical bone for detection of osteoporotic patients at early stage. First, an inferior border of mandibular bone was detected by use of an active contour method. Second, regions of interest including the cortical bone are extracted and analyzed for its thickness and roughness. Finally, support vector machine (SVM) differentiate cases into three MCI categories by features including the thickness and roughness. Ninety eight DPRs were used to evaluate our proposed scheme. The number of cases classified to Class I, II, and III by a dental radiologist are 56, 25 and 17 cases, respectively. Experimental result based on the leave-one-out cross-validation evaluation showed that the sensitivities for the classes I, II, and III were 94.6%, 57.7% and 94.1%, respectively. Distribution of the groups in the feature space indicates a possibility of MCI quantification by the proposed method. Therefore, our scheme has a potential in identifying osteoporotic patients at an early stage.

Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells

PubMed Central

Martínez-Cañada, Pablo; Halnes, Geir; Fyhn, Marianne

2018-01-01

Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs) and interneurons (INs) not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY). We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed (‘push-pull’) and phase-matched (‘push-push’), as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli when

Cerebral organization of oral and signed language responses: case study evidence from amytal and cortical stimulation studies.

PubMed

Mateer, C A; Rapport, R L; Kettrick, C

1984-01-01

A normally hearing left-handed patient familiar with American Sign Language (ASL) was assessed under sodium amytal conditions and with left cortical stimulation in both oral speech and signed English. Lateralization was mixed but complementary in each language mode: the right hemisphere perfusion severely disrupted motoric aspects of both types of language expression, the left hemisphere perfusion specifically disrupted features of grammatical and semantic usage in each mode of expression. Both semantic and syntactic aspects of oral and signed responses were altered during left posterior temporal-parietal stimulation. Findings are discussed in terms of the neurological organization of ASL and linguistic organization in cases of early left hemisphere damage.

Modeling Early Cortical Serotonergic Deficits in Autism

PubMed Central

Boylan, Carolyn B.; Blue, Mary E.; Hohmann, Christine F.

2007-01-01

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas. PMID:17034875

Modeling early cortical serotonergic deficits in autism.

PubMed

Boylan, Carolyn B; Blue, Mary E; Hohmann, Christine F

2007-01-10

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macro-scopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

PubMed Central

Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

2016-01-01

Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

Different Cortical Dynamics in Face and Body Perception: An MEG study

PubMed Central

Meeren, Hanneke K. M.; de Gelder, Beatrice; Ahlfors, Seppo P.; Hämäläinen, Matti S.; Hadjikhani, Nouchine

2013-01-01

Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120–200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200–700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing. PMID:24039712

The Mechanism for Processing Random-Dot Motion at Various Speeds in Early Visual Cortices

PubMed Central

An, Xu; Gong, Hongliang; McLoughlin, Niall; Yang, Yupeng; Wang, Wei

2014-01-01

All moving objects generate sequential retinotopic activations representing a series of discrete locations in space and time (motion trajectory). How direction-selective neurons in mammalian early visual cortices process motion trajectory remains to be clarified. Using single-cell recording and optical imaging of intrinsic signals along with mathematical simulation, we studied response properties of cat visual areas 17 and 18 to random dots moving at various speeds. We found that, the motion trajectory at low speed was encoded primarily as a direction signal by groups of neurons preferring that motion direction. Above certain transition speeds, the motion trajectory is perceived as a spatial orientation representing the motion axis of the moving dots. In both areas studied, above these speeds, other groups of direction-selective neurons with perpendicular direction preferences were activated to encode the motion trajectory as motion-axis information. This applied to both simple and complex neurons. The average transition speed for switching between encoding motion direction and axis was about 31°/s in area 18 and 15°/s in area 17. A spatio-temporal energy model predicted the transition speeds accurately in both areas, but not the direction-selective indexes to random-dot stimuli in area 18. In addition, above transition speeds, the change of direction preferences of population responses recorded by optical imaging can be revealed using vector maximum but not vector summation method. Together, this combined processing of motion direction and axis by neurons with orthogonal direction preferences associated with speed may serve as a common principle of early visual motion processing. PMID:24682033

Irregular Speech Rate Dissociates Auditory Cortical Entrainment, Evoked Responses, and Frontal Alpha

PubMed Central

Kayser, Stephanie J.; Ince, Robin A.A.; Gross, Joachim

2015-01-01

The entrainment of slow rhythmic auditory cortical activity to the temporal regularities in speech is considered to be a central mechanism underlying auditory perception. Previous work has shown that entrainment is reduced when the quality of the acoustic input is degraded, but has also linked rhythmic activity at similar time scales to the encoding of temporal expectations. To understand these bottom-up and top-down contributions to rhythmic entrainment, we manipulated the temporal predictive structure of speech by parametrically altering the distribution of pauses between syllables or words, thereby rendering the local speech rate irregular while preserving intelligibility and the envelope fluctuations of the acoustic signal. Recording EEG activity in human participants, we found that this manipulation did not alter neural processes reflecting the encoding of individual sound transients, such as evoked potentials. However, the manipulation significantly reduced the fidelity of auditory delta (but not theta) band entrainment to the speech envelope. It also reduced left frontal alpha power and this alpha reduction was predictive of the reduced delta entrainment across participants. Our results show that rhythmic auditory entrainment in delta and theta bands reflect functionally distinct processes. Furthermore, they reveal that delta entrainment is under top-down control and likely reflects prefrontal processes that are sensitive to acoustical regularities rather than the bottom-up encoding of acoustic features. SIGNIFICANCE STATEMENT The entrainment of rhythmic auditory cortical activity to the speech envelope is considered to be critical for hearing. Previous work has proposed divergent views in which entrainment reflects either early evoked responses related to sound encoding or high-level processes related to expectation or cognitive selection. Using a manipulation of speech rate, we dissociated auditory entrainment at different time scales. Specifically, our

In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

PubMed

De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

2014-01-01

Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

In Vivo High-Resolution 7 Tesla MRI Shows Early and Diffuse Cortical Alterations in CADASIL

PubMed Central

De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

2014-01-01

Background and Purpose Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Methods Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. Results MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Conclusions Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined. PMID:25165824

Racial differences in cortical bone and their relationship to biochemical variables in black and white children in the early stages of puberty

PubMed Central

Warden, Stuart J.; Hill, Kathleen M.; Ferira, Ashley J.; Laing, Emma M.; Martin, Berdine R.; Hausman, Dorothy B.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

2014-01-01

Introduction Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of black and white children in the early stages of puberty, and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties. Methods A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n=155 males; n=164 blacks) in the early stages of puberty. Results Blacks had greater cortical volumetric bone mineral density, mass and size compared to whites (all p<0.01), contributing to blacks having 17.0% greater tibial strength (polar strength-strain index [SSIP]) (p<0.001). Turnover markers indicated blacks had higher bone formation (osteocalcin [OC] and bone specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than whites (all p<0.01). Blacks also had lower 25-hydroxyvitamin D [25(OH)D], and higher 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) (all p<0.05). There were no correlations between tibial bone properties, and 25(OH)D and PTH in whites (all p≥0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in blacks, respectively (all p≤0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH and OC. Conclusions Divergence in tibial cortical bone properties between blacks and whites is established by the early stages of puberty with the enhanced cortical bone properties in black children possibly being explained by higher PTH and OC. PMID:23093348

Individual differences in attentional modulation of cortical responses correlate with selective attention performance

PubMed Central

Choi, Inyong; Wang, Le; Bharadwaj, Hari; Shinn-Cunningham, Barbara

2014-01-01

Many studies have shown that attention modulates the cortical representation of an auditory scene, emphasizing an attended source while suppressing competing sources. Yet, individual differences in the strength of this attentional modulation and their relationship with selective attention ability are poorly understood. Here, we ask whether differences in how strongly attention modulates cortical responses reflect differences in normal-hearing listeners’ selective auditory attention ability. We asked listeners to attend to one of three competing melodies and identify its pitch contour while we measured cortical electroencephalographic responses. The three melodies were either from widely separated pitch ranges (“easy trials”), or from a narrow, overlapping pitch range (“hard trials”). The melodies started at slightly different times; listeners attended either the leading or lagging melody. Because of the timing of the onsets, the leading melody drew attention exogenously. In contrast, attending the lagging melody required listeners to direct top-down attention volitionally. We quantified how attention amplified auditory N1 response to the attended melody and found large individual differences in the N1 amplification, even though only correctly answered trials were used to quantify the ERP gain. Importantly, listeners with the strongest amplification of N1 response to the lagging melody in the easy trials were the best performers across other types of trials. Our results raise the possibility that individual differences in the strength of top-down gain control reflect inherent differences in the ability to control top-down attention. PMID:24821552

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

Cortical pitch response components show differential sensitivity to native and nonnative pitch contours

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Suresh, Chandan H.

2015-01-01

The aim of this study is to evaluate how nonspeech pitch contours of varying shape influence latency and amplitude of cortical pitch-specific response (CPR) components differentially as a function of language experience. Stimuli included time-varying, high rising Mandarin Tone 2 (T2) and linear rising ramp (Linear), and steady-state (Flat). Both the latency and magnitude of CPR components were differentially modulated by (i) the overall trajectory of pitch contours (time-varying vs. steady-state), (ii) their pitch acceleration rates (changing vs. constant), and (iii) their linguistic status (lexical vs. non-lexical). T2 elicited larger amplitude than Linear in both language groups, but size of the effect was larger in Chinese than English. The magnitude of CPR components elicited by T2 were larger for Chinese than English at the right temporal electrode site. Using the CPR, we provide evidence in support of experience-dependent modulation of dynamic pitch contours at an early stage of sensory processing. PMID:25306506

The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations

PubMed Central

Quant, Sylvia; Adkin, Allan L; Staines, W Richard; Maki, Brian E; McIlroy, William E

2004-01-01

Background Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation). We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP) centre of pressure (COP) peak displacements and tibialis anterior (TA) muscle activity. Healthy young adults (n = 7) were instructed to continuously track (cognitive task) or not track (control task) a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG) measures were collected. Results Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset) during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. Conclusion Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control. PMID:15147586

The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations.

PubMed

Quant, Sylvia; Adkin, Allan L; Staines, W Richard; Maki, Brian E; McIlroy, William E

2004-05-17

Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation). We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP) centre of pressure (COP) peak displacements and tibialis anterior (TA) muscle activity. Healthy young adults (n = 7) were instructed to continuously track (cognitive task) or not track (control task) a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG) measures were collected. Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset) during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control.

Characterization of Early Cortical Neural Network ...

EPA Pesticide Factsheets

We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentially absent on DIV 2 and developed rapidly between DIV 5 and 12. Spiking activity was primarily sporadic and unorganized at early DIV, and became progressively more organized with time in culture, with bursting parameters, synchrony and network bursting increasing between DIV 5 and 12. We selected 12 features to describe network activity and principal components analysis using these features demonstrated a general segregation of data by age at both the well and plate levels. Using a combination of random forest classifiers and Support Vector Machines, we demonstrated that 4 features (CV of within burst ISI, CV of IBI, network spike rate and burst rate) were sufficient to predict the age (either DIV 5, 7, 9 or 12) of each well recording with >65% accuracy. When restricting the classification problem to a binary decision, we found that classification improved dramatically, e.g. 95% accuracy for discriminating DIV 5 vs DIV 12 wells. Further, we present a novel resampling approach to determine the number of wells that might be needed for conducting comparisons of different treatments using mwMEA plates. Overall, these results demonstrate that network development on mwMEA plates is similar to

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

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

Computational mechanisms underlying cortical responses to the affordance properties of visual scenes

PubMed Central

Epstein, Russell A.

2018-01-01

Biologically inspired deep convolutional neural networks (CNNs), trained for computer vision tasks, have been found to predict cortical responses with remarkable accuracy. However, the internal operations of these models remain poorly understood, and the factors that account for their success are unknown. Here we develop a set of techniques for using CNNs to gain insights into the computational mechanisms underlying cortical responses. We focused on responses in the occipital place area (OPA), a scene-selective region of dorsal occipitoparietal cortex. In a previous study, we showed that fMRI activation patterns in the OPA contain information about the navigational affordances of scenes; that is, information about where one can and cannot move within the immediate environment. We hypothesized that this affordance information could be extracted using a set of purely feedforward computations. To test this idea, we examined a deep CNN with a feedforward architecture that had been previously trained for scene classification. We found that responses in the CNN to scene images were highly predictive of fMRI responses in the OPA. Moreover the CNN accounted for the portion of OPA variance relating to the navigational affordances of scenes. The CNN could thus serve as an image-computable candidate model of affordance-related responses in the OPA. We then ran a series of in silico experiments on this model to gain insights into its internal operations. These analyses showed that the computation of affordance-related features relied heavily on visual information at high-spatial frequencies and cardinal orientations, both of which have previously been identified as low-level stimulus preferences of scene-selective visual cortex. These computations also exhibited a strong preference for information in the lower visual field, which is consistent with known retinotopic biases in the OPA. Visualizations of feature selectivity within the CNN suggested that affordance

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

PubMed

Woodruff, P W; Wright, I C; Bullmore, E T; Brammer, M; Howard, R J; Williams, S C; Shapleske, J; Rossell, S; David, A S; McGuire, P K; Murray, R M

1997-12-01

The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for

Identification of the cortical neurons that mediate antidepressant responses

PubMed Central

Schmidt, Eric F.; Warner-Schmidt, Jennifer; Otopalik, Benjamin G.; Pickett, Sarah B.; Greengard, Paul; Heintz, Nathaniel

2012-01-01

Summary Our understanding of current treatments for depression, and the development of more specific therapies, is limited by the complexity of the circuits controlling mood and the distributed actions of antidepressants. Although the therapeutic efficacy of SSRIs is correlated with increases in cortical activity, the cell types crucial for their action remain unknown. Here we employ bacTRAP translational profiling to show that layer 5 corticostriatal pyramidal cells expressing p11 (S100a10) are strongly and specifically responsive to chronic antidepressant treatment. This response requires p11 and includes the specific induction of Htr4 expression. Cortex-specific deletion of p11 abolishes behavioral responses to SSRI’s, but does not lead to increased depression-like behaviors. Our data identify corticostriatal projection neurons as critical for the response to antidepressants, and suggest that the regulation of serotonergic tone in this single cell type plays a pivotal role in antidepressant therapy. PMID:22632977

Cortical variability in the sensory-evoked response in autism

PubMed Central

Haigh, Sarah M.; Heeger, David J.; Dinstein, Ilan; Minshew, Nancy; Behrmann, Marlene

2016-01-01

Previous findings have shown that individuals with autism spectrum disorder (ASD) evince greater intra-individual variability (IIV) in their sensory-evoked fMRI responses compared to typical control participants. We explore the robustness of this finding with a new sample of high-functioning adults with autism. Participants were presented with visual, somatosensory and auditory stimuli in the scanner whilst they completed a one-back task. While ASD and control participants were statistically indistinguishable with respect to behavioral responses, the new ASD group exhibited greater IIV relative to controls. We also show that the IIV was equivalent across hemispheres and remained stable over the duration of the experiment. This suggests that greater cortical IIV may be a replicable characteristic of sensory systems in autism. PMID:25326820

[Acquired drives. The cortical mechanism responsible to the emergence and development of social existence].

PubMed

József, Knoll

2007-10-01

This paper is a brief interpretation of the theory (J. Knoll: The Brain and Its Self, Springer, 2005) the main message of which is that the appearance of the mammalian brain with the ability to acquire drives ensured the development of social life, and eventually led to the evolution of the human society. In the mammalian brain capable to acquire drives, untrained cortical neurons (Group 1) possess the potentiality to change their functional state in response to practice, training, or experience in three consecutive stages, namely, by getting involved in (a) an extinguishable conditioned reflex (ECR) (Group 2), (b) an inextinguishable conditioned reflex (ICR) (Group 3), or (c)an acquired drive (Group 4). The activity of the cortical neurons belonging to Group 3 and 4 is inseparable from conscious perception. In any moment of life self is the sum of those cortical neurons that have already changed their functional significance and belong to Group 3 or 4. Metaphorically, every human being is born with a telencephalon that resembles a book with over 100 billion empty pages (untrained, naive cortical neurons, Group 1), and with the capacity to inscribe as much as possible in this book throughout life. Whenever a drive is acquired, chains of ICRs are fixed, neurons responsible for emotions are also coupled to the integral whole, thus cognitive/volitional consciousness is necessarily inseparable from an affective state of consciousness. Cortical neurons belonging to Group 3 or 4 continuously synthesize their specific enhancer substance within their capacity. This means that even in the vigilant resting state (leisure), in the absence of a dominant drive, as well as in the non-vigilant resting state (sleeping), the cortical neurons representing the totality of the already fixed ICRs and acquired drives are permanently under the influence of their specific enhancer substance. Although the level of this permanent, undulating activation remains low, it is unpredictable as to

Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation.

PubMed

Geula, C

1998-07-01

Severe pathology in Alzheimer's disease (AD) results in marked disruption of cortical circuitry. Formation of neurofibrillary tangles, neuronal loss, decrease in dendritic extent, and synaptic depletion combine to halt communication among various cortical areas, resulting in anatomic isolation and fragmentation of many cortical zones. The clinical manifestation of this disruption is severe and debilitating cognitive dysfunction, often accompanied by psychiatric and behavioral disturbances and a diminished ability to perform activities of daily living. However, different cortical circuits are not equally vulnerable to AD pathology. In particular, two cortical systems that appear to be involved in the neural processing of memory are selectively vulnerable to degeneration in AD. One consists of connections between the hippocampus and its neighboring cortical structures within the temporal lobe. The second is the cortical cholinergic system that originates in neurons within the basal forebrain and innervates the entire cortical mantle. The circuitry in these systems shows early and severe degenerative changes in the course of AD. The selective vulnerability of these circuits is the probable reason for the early and marked loss of memory observed in these patients. This review presents current knowledge of the general pattern of cortical circuitry, followed by a summary of abnormalities of this circuitry in AD. The cortical circuits that exhibit selective pathology in AD are described in greater detail. Therapeutic implications of the abnormal circuitry in AD are also discussed. For therapies to be effective, early diagnosis of AD is necessary. Future efforts at AD therapy must be combined with an equally intense effort to develop tools capable of early diagnosis of AD, preferably at a preclinical stage before the onset of cognitive symptoms.

Tactile spatial working memory activates the dorsal extrastriate cortical pathway in congenitally blind individuals.

PubMed

Bonino, D; Ricciardi, E; Sani, L; Gentili, C; Vanello, N; Guazzelli, M; Vecchi, T; Pietrini, P

2008-09-01

In sighted individuals, both the visual and tactile version of the same spatial working memory task elicited neural responses in the dorsal "where" cortical pathway (Ricciardi et al., 2006). Whether the neural response during the tactile working memory task is due to visually-based spatial imagery or rather reflects a more abstract, supramodal organization of the dorsal cortical pathway remains to be determined. To understand the role of visual experience on the functional organization of the dorsal cortical stream, using functional magnetic resonance imaging (fMRI) here we examined brain response in four individuals with congenital or early blindness and no visual recollection, while they performed the same tactile spatial working memory task, a one-back recognition of 2D and 3D matrices. The blind subjects showed a significant activation in bilateral posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus, lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas are involved in mental imagery dealing with spatial components in subjects without prior visual experience and in response to a non-visual task. These data indicate that recruitment of the dorsal cortical pathway in response to the tactile spatial working memory task is not mediated by visually-based imagery and that visual experience is not a prerequisite for the development of a more abstract functional organization of the dorsal stream. These findings, along with previous data indicating a similar supramodal functional organization within the ventral cortical pathway and the motion processing brain regions, may contribute to explain how individuals who are born deprived of sight are able to interact effectively with the surrounding world.

O6.5. LINKING CORTICAL AND CONNECTIONAL PATHOLOGY IN SCHIZOPHRENIA

PubMed Central

Di Biase, Maria; Cropley, Vanessa; Cocchi, Luca; Fornito, Alexander; Calamante, Fernando; Ganella, Eleni; Pantelis, Christos; Zalesky, Andrew

2018-01-01

Abstract Background Schizophrenia is associated with cortical thinning and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relation between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration. Methods Structural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy controls to map cortical thickness (CT) and fractional anisotropy (FA) in regionally adjacent infracortical white matter at various cortical depths. Results Between-group differences in CT and infracortical FA were inversely correlated across cortical regions (r=−0.5, p<0.0001), such that the most anisotropic infracortical white matter was found adjacent to regions with extensive cortical thinning. This pattern was evident in early (20 years: r=−0.3, p=0.005) and middle life (30 years: r=−0.4, p=0.004, 40 years: r=−0.3, p=0.04), but not beyond 50 years (p>0.05). Frontal pathology contributed most to this pattern, with extensive cortical thinning in patients compared to controls at all ages (p<0.05); in contrast to initially increased frontal infracortical FA in patients at 30 years, followed by rapid decline in frontal FA with age (rate of annual decline; patients: 0.0012, controls 0.0006, p<0.001). Discussion Cortical thinning and breakdown in white matter anisotropy are inversely related in young schizophrenia patients, with abnormally elevated white matter myelination found adjacent to frontal regions with extensive cortical thinning. We argue that elevated frontal anisotropy reflects regionally-specific, compensatory responses to cortical thinning, which are eventually overwhelmed with increasing illness duration.

Resting lateralized activity predicts the cortical response and appraisal of emotions: an fNIRS study.

PubMed

Balconi, Michela; Grippa, Elisabetta; Vanutelli, Maria Elide

2015-12-01

This study explored the effect of lateralized left-right resting brain activity on prefrontal cortical responsiveness to emotional cues and on the explicit appraisal (stimulus evaluation) of emotions based on their valence. Indeed subjective responses to different emotional stimuli should be predicted by brain resting activity and should be lateralized and valence-related (positive vs negative valence). A hemodynamic measure was considered (functional near-infrared spectroscopy). Indeed hemodynamic resting activity and brain response to emotional cues were registered when subjects (N = 19) viewed emotional positive vs negative stimuli (IAPS). Lateralized index response during resting state, LI (lateralized index) during emotional processing and self-assessment manikin rating were considered. Regression analysis showed the significant predictive effect of resting activity (more left or right lateralized) on both brain response and appraisal of emotional cues based on stimuli valence. Moreover, significant effects were found as a function of valence (more right response to negative stimuli; more left response to positive stimuli) during emotion processing. Therefore, resting state may be considered a predictive marker of the successive cortical responsiveness to emotions. The significance of resting condition for emotional behavior was discussed. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

Maturation of cortical mismatch responses to occasional pitch change in early infancy: effects of presentation rate and magnitude of change.

PubMed

He, Chao; Hotson, Lisa; Trainor, Laurel J

2009-01-01

Previous studies have reported two types of event-related potential (ERP) mismatch responses in infants to infrequent auditory changes: a broad discriminative positivity in younger infants and a negativity resembling adult mismatch negativity (MMN) in older infants. In the present study, we investigated whether the positive discriminative slow wave and the adult-like MMN are functionally distinct by examining how they are affected by presentation rate and magnitude of change. We measured ERPs from adults, 2-month-olds, and 4-month-olds to a repeating piano tone (standard) that occasionally changed in pitch (deviant). The pitch changes between standards and deviants were either small (1/12 octave) or large (1/2 octave) in magnitude, and the stimulus presentation rate was either slow (800 ms SOA) or fast (400 ms SOA). As the presentation rate increased, both adults and 4-month-olds showed an MMN response that decreased in latency, but was unaffected in amplitude. As the magnitude of the pitch change increased, MMN increased in amplitude. On the other hand, only a broad positive mismatch response was seen in 2-month-olds. As the presentation rate increased, 2-month-olds' responses to standard tones decreased in amplitude while their responses to deviant tones were unaffected. The magnitude of the pitch change did not affect 2-month-olds' responses. These results suggest that pitch is processed differently in auditory cortex by 2-month-olds and 4-month-olds, and that a cortical change-detection mechanism for pitch discrimination similar to that of adults emerges between 2 and 4 months of age.

Curtailing effect of awakening on visual responses of cortical neurons by cholinergic activation of inhibitory circuits.

PubMed

Kimura, Rui; Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Kimura, Rie; Ebina, Teppei; Yanagawa, Yuchio; Sohya, Kazuhiro; Tsumoto, Tadaharu

2014-07-23

Visual responsiveness of cortical neurons changes depending on the brain state. Neural circuit mechanism underlying this change is unclear. By applying the method of in vivo two-photon functional calcium imaging to transgenic rats in which GABAergic neurons express fluorescent protein, we analyzed changes in visual response properties of cortical neurons when animals became awakened from anesthesia. In the awake state, the magnitude and reliability of visual responses of GABAergic neurons increased whereas the decay of responses of excitatory neurons became faster. To test whether the basal forebrain (BF) cholinergic projection is involved in these changes, we analyzed effects of electrical and optogenetic activation of BF on visual responses of mouse cortical neurons with in vivo imaging and whole-cell recordings. Electrical BF stimulation in anesthetized animals induced the same direction of changes in visual responses of both groups of neurons as awakening. Optogenetic activation increased the frequency of visually evoked action potentials in GABAergic neurons but induced the delayed hyperpolarization that ceased the late generation of action potentials in excitatory neurons. Pharmacological analysis in slice preparations revealed that photoactivation-induced depolarization of layer 1 GABAergic neurons was blocked by a nicotinic receptor antagonist, whereas non-fast-spiking layer 2/3 GABAergic neurons was blocked only by the application of both nicotinic and muscarinic receptor antagonists. These results suggest that the effect of awakening is mediated mainly through nicotinic activation of layer 1 GABAergic neurons and mixed nicotinic/muscarinic activation of layer 2/3 non-fast-spiking GABAergic neurons, which together curtails the visual responses of excitatory neurons. Copyright © 2014 the authors 0270-6474/14/3410122-12$15.00/0.

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

PubMed Central

Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Cortical evoked responses associated with arousal from sleep.

PubMed

Phillips, Derrick J; Schei, Jennifer L; Meighan, Peter C; Rector, David M

2011-01-01

To determine if low-level intermittent auditory stimuli have the potential to disrupt sleep during 24-h recordings, we assessed arousal occurrence to varying stimulus intensities. Additionally, if stimulus-generated evoked response potential (ERP) components provide a metric of underlying cortical state, then a particular ERP structure may precede an arousal. Physiological electrodes measuring EEG, EKG, and EMG were implanted into 5 adult female Sprague-Dawley rats. We delivered auditory stimuli of varying intensities (50-75 dBa sound pressure level SPL) at random intervals of 6-12 s over a 24-hour period. Recordings were divided into 2-s epochs and scored for sleep/wake state. Following each stimulus, we identified whether the animal stayed asleep or woke. We then sorted the stimuli depending on prior and post-stimulus state, and measured ERP components. Auditory stimuli did not produce a significant increase in the number of arousals compared to silent control periods. Overall, arousal from REM sleep occurred more often compared to quiet sleep. ERPs preceding an arousal had decreased mean area and shorter N1 latency. Low level auditory stimuli did not fragment animal sleep since we observed no significant change in arousal occurrence. Arousals that occurred within 4 s of a stimulus exhibited an ERP mean area and latency had features similar to ERPs generated during wake, indicating that the underlying cortical tissue state may contribute to physiological conditions required for arousal.

Dissociating Cortical Activity during Processing of Native and Non-Native Audiovisual Speech from Early to Late Infancy

PubMed Central

Fava, Eswen; Hull, Rachel; Bortfeld, Heather

2014-01-01

Initially, infants are capable of discriminating phonetic contrasts across the world’s languages. Starting between seven and ten months of age, they gradually lose this ability through a process of perceptual narrowing. Although traditionally investigated with isolated speech sounds, such narrowing occurs in a variety of perceptual domains (e.g., faces, visual speech). Thus far, tracking the developmental trajectory of this tuning process has been focused primarily on auditory speech alone, and generally using isolated sounds. But infants learn from speech produced by people talking to them, meaning they learn from a complex audiovisual signal. Here, we use near-infrared spectroscopy to measure blood concentration changes in the bilateral temporal cortices of infants in three different age groups: 3-to-6 months, 7-to-10 months, and 11-to-14-months. Critically, all three groups of infants were tested with continuous audiovisual speech in both their native and another, unfamiliar language. We found that at each age range, infants showed different patterns of cortical activity in response to the native and non-native stimuli. Infants in the youngest group showed bilateral cortical activity that was greater overall in response to non-native relative to native speech; the oldest group showed left lateralized activity in response to native relative to non-native speech. These results highlight perceptual tuning as a dynamic process that happens across modalities and at different levels of stimulus complexity. PMID:25116572

Close similarity between spatiotemporal frequency tunings of human cortical responses and involuntary manual following responses to visual motion.

PubMed

Amano, Kaoru; Kimura, Toshitaka; Nishida, Shin'ya; Takeda, Tsunehiro; Gomi, Hiroaki

2009-02-01

Human brain uses visual motion inputs not only for generating subjective sensation of motion but also for directly guiding involuntary actions. For instance, during arm reaching, a large-field visual motion is quickly and involuntarily transformed into a manual response in the direction of visual motion (manual following response, MFR). Previous attempts to correlate motion-evoked cortical activities, revealed by brain imaging techniques, with conscious motion perception have resulted only in partial success. In contrast, here we show a surprising degree of similarity between the MFR and the population neural activity measured by magnetoencephalography (MEG). We measured the MFR and MEG induced by the same motion onset of a large-field sinusoidal drifting grating with changing the spatiotemporal frequency of the grating. The initial transient phase of these two responses had very similar spatiotemporal tunings. Specifically, both the MEG and MFR amplitudes increased as the spatial frequency was decreased to, at most, 0.05 c/deg, or as the temporal frequency was increased to, at least, 10 Hz. We also found in peak latency a quantitative agreement (approximately 100-150 ms) and correlated changes against spatiotemporal frequency changes between MEG and MFR. In comparison with these two responses, conscious visual motion detection is known to be most sensitive (i.e., have the lowest detection threshold) at higher spatial frequencies and have longer and more variable response latencies. Our results suggest a close relationship between the properties of involuntary motor responses and motion-evoked cortical activity as reflected by the MEG.

Linguistic category structure influences early auditory processing: Converging evidence from mismatch responses and cortical oscillations.

PubMed

Scharinger, Mathias; Monahan, Philip J; Idsardi, William J

2016-03-01

While previous research has established that language-specific knowledge influences early auditory processing, it is still controversial as to what aspects of speech sound representations determine early speech perception. Here, we propose that early processing primarily depends on information propagated top-down from abstractly represented speech sound categories. In particular, we assume that mid-vowels (as in 'bet') exert less top-down effects than the high-vowels (as in 'bit') because of their less specific (default) tongue height position as compared to either high- or low-vowels (as in 'bat'). We tested this assumption in a magnetoencephalography (MEG) study where we contrasted mid- and high-vowels, as well as the low- and high-vowels in a passive oddball paradigm. Overall, significant differences between deviants and standards indexed reliable mismatch negativity (MMN) responses between 200 and 300ms post-stimulus onset. MMN amplitudes differed in the mid/high-vowel contrasts and were significantly reduced when a mid-vowel standard was followed by a high-vowel deviant, extending previous findings. Furthermore, mid-vowel standards showed reduced oscillatory power in the pre-stimulus beta-frequency band (18-26Hz), compared to high-vowel standards. We take this as converging evidence for linguistic category structure to exert top-down influences on auditory processing. The findings are interpreted within the linguistic model of underspecification and the neuropsychological predictive coding framework. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction

PubMed Central

Demopoulos, Carly; Yu, Nina; Tripp, Jennifer; Mota, Nayara; Brandes-Aitken, Anne N.; Desai, Shivani S.; Hill, Susanna S.; Antovich, Ashley D.; Harris, Julia; Honma, Susanne; Mizuiri, Danielle; Nagarajan, Srikantan S.; Marco, Elysa J.

2017-01-01

This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8–12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain. PMID:28603492

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

Sample entropy and regularity dimension in complexity analysis of cortical surface structure in early Alzheimer's disease and aging.

PubMed

Chen, Ying; Pham, Tuan D

2013-05-15

We apply for the first time the sample entropy (SampEn) and regularity dimension model for measuring signal complexity to quantify the structural complexity of the brain on MRI. The concept of the regularity dimension is based on the theory of chaos for studying nonlinear dynamical systems, where power laws and entropy measure are adopted to develop the regularity dimension for modeling a mathematical relationship between the frequencies with which information about signal regularity changes in various scales. The sample entropy and regularity dimension of MRI-based brain structural complexity are computed for early Alzheimer's disease (AD) elder adults and age and gender-matched non-demented controls, as well as for a wide range of ages from young people to elder adults. A significantly higher global cortical structure complexity is detected in AD individuals (p<0.001). The increase of SampEn and the regularity dimension are also found to be accompanied with aging which might indicate an age-related exacerbation of cortical structural irregularity. The provided model can be potentially used as an imaging bio-marker for early prediction of AD and age-related cognitive decline. Copyright © 2013 Elsevier B.V. All rights reserved.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

PubMed

Canali, Paola; Sferrazza Papa, Giovanna; Casali, Adenauer G; Schiena, Giandomenico; Fecchio, Matteo; Pigorini, Andrea; Smeraldi, Enrico; Colombo, Cristina; Benedetti, Francesco

2014-12-01

It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

PubMed Central

Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

2014-01-01

Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

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 neurons and networks are dormant but fully responsive during isoelectric brain state.

PubMed

Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane

2017-09-01

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic

The Behavioral Relevance of Cortical Neural Ensemble Responses Emerges Suddenly

PubMed Central

Sadacca, Brian F.; Mukherjee, Narendra; Vladusich, Tony; Li, Jennifer X.

2016-01-01

Whereas many laboratory-studied decisions involve a highly trained animal identifying an ambiguous stimulus, many naturalistic decisions do not. Consumption decisions, for instance, involve determining whether to eject or consume an already identified stimulus in the mouth and are decisions that can be made without training. By standard analyses, rodent cortical single-neuron taste responses come to predict such consumption decisions across the 500 ms preceding the consumption or rejection itself; decision-related firing emerges well after stimulus identification. Analyzing single-trial ensemble activity using hidden Markov models, we show these decision-related cortical responses to be part of a reliable sequence of states (each defined by the firing rates within the ensemble) separated by brief state-to-state transitions, the latencies of which vary widely between trials. When we aligned data to the onset of the (late-appearing) state that dominates during the time period in which single-neuron firing is correlated to taste palatability, the apparent ramp in stimulus-aligned choice-related firing was shown to be a much more precipitous coherent jump. This jump in choice-related firing resembled a step function more than it did the output of a standard (ramping) decision-making model, and provided a robust prediction of decision latency in single trials. Together, these results demonstrate that activity related to naturalistic consumption decisions emerges nearly instantaneously in cortical ensembles. SIGNIFICANCE STATEMENT This paper provides a description of how the brain makes evaluative decisions. The majority of work on the neurobiology of decision making deals with “what is it?” decisions; out of this work has emerged a model whereby neurons accumulate information about the stimulus in the form of slowly increasing firing rates and reach a decision when those firing rates reach a threshold. Here, we study a different kind of more naturalistic decision�

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

PubMed

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

PubMed

Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

2016-08-01

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

Interocular suppression in strabismic amblyopia results in an attenuated and delayed hemodynamic response function in early visual cortex.

PubMed

Farivar, Reza; Thompson, Benjamin; Mansouri, Behzad; Hess, Robert F

2011-12-20

Factors such as strabismus or anisometropia during infancy can disrupt normal visual development and result in amblyopia, characterized by reduced visual function in an otherwise healthy eye and often associated with persistent suppression of inputs from the amblyopic eye by those from the dominant eye. It has become evident from fMRI studies that the cortical response to stimulation of the amblyopic eye is also affected. We were interested to compare the hemodynamic response function (HRF) of early visual cortex to amblyopic vs. dominant eye stimulation. In the first experiment, we found that stimulation of the amblyopic eye resulted in a signal that was both attenuated and delayed in its time to peak. We postulated that this delay may be due to suppressive effects of the dominant eye and, in our second experiment, measured the cortical response of amblyopic eye stimulation under two conditions--where the dominant eye was open and seeing a static pattern (high suppression) or where the dominant eye was patched and closed (low suppression). We found that the HRF in response to amblyopic eye stimulation depended on whether the dominant eye was open. This effect was manifested as both a delayed HRF under the suppressed condition and an amplitude reduction.

Attention Influences Single Unit and Local Field Potential Response Latencies in Visual Cortical Area V4

PubMed Central

Sundberg, Kristy A.; Mitchell, Jude F.; Gawne, Timothy J.

2012-01-01

Many previous studies have demonstrated that changes in selective attention can alter the response magnitude of visual cortical neurons, but there has been little evidence for attention affecting response latency. Small latency differences, though hard to detect, can potentially be of functional importance, and may also give insight into the mechanisms of neuronal computation. We therefore reexamined the effect of attention on the response latency of both single units and the local field potential (LFP) in primate visual cortical area V4. We find that attention does produce small (1–2 ms) but significant reductions in the latency of both the spiking and LFP responses. Though attention, like contrast elevation, reduces response latencies, we find that the two have different effects on the magnitude of the LFP. Contrast elevations increase and attention decreases the magnitude of the initial deflection of the stimulus-evoked LFP. Both contrast elevation and attention increase the magnitude of the spiking response. We speculate that latencies may be reduced at higher contrast because stronger stimulus inputs drive neurons more rapidly to spiking threshold, while attention may reduce latencies by placing neurons in a more depolarized state closer to threshold before stimulus onset. PMID:23136440

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors.

PubMed

Sivarao, Digavalli V; Chen, Ping; Senapati, Arun; Yang, Yili; Fernandes, Alda; Benitex, Yulia; Whiterock, Valerie; Li, Yu-Wen; Ahlijanian, Michael K

2016-08-01

Schizophrenia patients exhibit dysfunctional gamma oscillations in response to simple auditory stimuli or more complex cognitive tasks, a phenomenon explained by reduced NMDA transmission within inhibitory/excitatory cortical networks. Indeed, a simple steady-state auditory click stimulation paradigm at gamma frequency (~40 Hz) has been reproducibly shown to reduce entrainment as measured by electroencephalography (EEG) in patients. However, some investigators have reported increased phase locking factor (PLF) and power in response to 40 Hz auditory stimulus in patients. Interestingly, preclinical literature also reflects this contradiction. We investigated whether a graded deficiency in NMDA transmission can account for such disparate findings by administering subanesthetic ketamine (1-30 mg/kg, i.v.) or vehicle to conscious rats (n=12) and testing their EEG entrainment to 40 Hz click stimuli at various time points (~7-62 min after treatment). In separate cohorts, we examined in vivo NMDA channel occupancy and tissue exposure to contextualize ketamine effects. We report a robust inverse relationship between PLF and NMDA occupancy 7 min after dosing. Moreover, ketamine could produce inhibition or disinhibition of the 40 Hz response in a temporally dynamic manner. These results provide for the first time empirical data to understand how cortical NMDA transmission deficit may lead to opposite modulation of the auditory steady-state response (ASSR). Importantly, our findings posit that 40 Hz ASSR is a pharmacodynamic biomarker for cortical NMDA function that is also robustly translatable. Besides schizophrenia, such a functional biomarker may be of value to neuropsychiatric disorders like bipolar and autism spectrum where 40 Hz ASSR deficits have been documented.

Locating the cortical bottleneck for slow reading in peripheral vision

PubMed Central

Yu, Deyue; Jiang, Yi; Legge, Gordon E.; He, Sheng

2015-01-01

Yu, Legge, Park, Gage, and Chung (2010) suggested that the neural bottleneck for slow peripheral reading is located in nonretinotopic areas. We investigated the potential rate-limiting neural site for peripheral reading using fMRI, and contrasted peripheral reading with recognition of peripherally presented line drawings of common objects. We measured the BOLD responses to both text (three-letter words/nonwords) and line-drawing objects presented either in foveal or peripheral vision (10° lower right visual field) at three presentation rates (2, 4, and 8/second). The statistically significant interaction effect of visual field × presentation rate on the BOLD response for text but not for line drawings provides evidence for distinctive processing of peripheral text. This pattern of results was obtained in all five regions of interest (ROIs). At the early retinotopic cortical areas, the BOLD signal slightly increased with increasing presentation rate for foveal text, and remained fairly constant for peripheral text. In the Occipital Word-Responsive Area (OWRA), Visual Word Form Area (VWFA), and object sensitive areas (LO and PHA), the BOLD responses to text decreased with increasing presentation rate for peripheral but not foveal presentation. In contrast, there was no rate-dependent reduction in BOLD response for line-drawing objects in all the ROIs for either foveal or peripheral presentation. Only peripherally presented text showed a distinctive rate-dependence pattern. Although it is possible that the differentiation starts to emerge at the early retinotopic cortical representation, the neural bottleneck for slower reading of peripherally presented text may be a special property of peripheral text processing in object category selective cortex. PMID:26237299

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions

PubMed Central

Wagatsuma, Nobuhiko; Sakai, Ko

2017-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions.

PubMed

Wagatsuma, Nobuhiko; Sakai, Ko

2016-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional

Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

PubMed Central

Ramanathan, Dhakshin S.; Conner, James M.; Anilkumar, Arjun A.

2014-01-01

Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

PubMed Central

Desgent, Sébastien; Duss, Sandra; Sanon, Nathalie T.; Lema, Pablo; Lévesque, Maxime; Hébert, David; Rébillard, Rose-Marie; Bibeau, Karine; Brochu, Michèle; Carmant, Lionel

2012-01-01

During development, the risk of developing mesial temporal lobe epilepsy (MTLE) increases when the developing brain is exposed to more than one insult in early life. Early life insults include abnormalities of cortical development, hypoxic-ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have developed a two-hit model of MTLE characterized by two early-life insults: a freeze lesion-induced cortical malformation at post-natal day 1 (P1), and a prolonged hyperthermic seizure (HS) at P10. As early life stressors lead to sexual dimorphism in both acute response and long-term outcome, we hypothesized that our model could lead to gender-based differences in acute stress response and long-term risk of developing MTLE. Male and female pups underwent a freeze-lesion induced cortical microgyrus at P1 and were exposed to HS at P10. Animals were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma corticosterone levels were used to measure stress response at P1 and P10. To confirm the role of sex steroids, androgenized female pups received daily testosterone injections to the mother pre-natally and post-natally for nine days while undergoing both insults. We demonstrated that after both insults females did not develop MTLE while all males did. This correlated with a rise in corticosterone levels at P1 following the lesion in males only. Interestingly, all androgenized females showed a similar rise in corticosterone at P1, and also developed MTLE. Moreover, we found that the cortical lesion significantly decreased the latency to generalized convulsion during hyperthermia at P10 in both genders. The cortical dysplasia volumes at adulthood were also similar between male and female individuals. Our data demonstrate sexual dimorphism in long-term vulnerability to develop epilepsy in the lesion + hyperthermia animal model of MTLE and suggest that the response to early-life stress at P1 contributes significantly to epileptogenesis in a

Characteristics of AMPA receptor-mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1-4

PubMed Central

Dai, Wei-Min; Egebjerg, Jan; Lambert, John D C

2001-01-01

Electrophysiological recordings have been used to characterize responses mediated by AMPA receptors expressed by cultured rat cortical and spinal cord neurones. The EC50 values for AMPA were 17 and 11 μM, respectively.Responses of cortical neurones to AMPA were inhibited competitively by NBQX (pKi=6.6). Lower concentrations of NBQX (⩽1 μM) also potentiated the plateau responses of spinal cord neurones to AMPA, which could be attributed to a depression of desensitization to AMPA.GYKI 52466 inhibited responses of spinal cord neurones to AMPA to about twice the extent of responses of cortical neurones.Blockade of AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of spinal cord neurones (6.8 fold) significantly more than responses of cortical neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5 fold by CTZ, while responses of spinal cord neurones were unaffected.Ultra-fast applications of AMPA to outside-out patches showed responses of spinal cord neurones desensitized by 97.5% and exhibit marked inward rectification, whereas cortical neurones desensitized by 91% and exhibited slight outward rectification. The time constants of deactivation and desensitization were about twice as fast in spinal cord than cortical neurones.In cortical neurones, single-cell RT – PCR showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed together in 67% of neurones, predominantly as the flip variants (78%). GluR2 was detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and 29% of neurones, respectively. For spinal cord neurones, GluR4o was detected in 81% of neurones, whereas predominantly flop versions of GluR1, 2 and 3 were detected in 38, 13 and 13% of neurones, respectively. These expression patterns are related to the respective pharmacological and mechanistic properties. PMID:11309259

The development of cortical connections.

PubMed

Price, David J; Kennedy, Henry; Dehay, Colette; Zhou, Libing; Mercier, Marjorie; Jossin, Yves; Goffinet, André M; Tissir, Fadel; Blakey, Daniel; Molnár, Zoltán

2006-02-01

The cortex receives its major sensory input from the thalamus via thalamocortical axons, and cortical neurons are interconnected in complex networks by corticocortical and callosal axons. Our understanding of the mechanisms generating the circuitry that confers functional properties on cortical neurons and networks, although poor, has been advanced significantly by recent research on the molecular mechanisms of thalamocortical axonal guidance and ordering. Here we review recent advances in knowledge of how thalamocortical axons are guided and how they maintain order during that process. Several studies have shown the importance in this process of guidance molecules including Eph receptors and ephrins, members of the Wnt signalling pathway and members of a novel planar cell polarity pathway. Signalling molecules and transcription factors expressed with graded concentrations across the cortex are important in establishing cortical maps of the topography of sensory surfaces. Neural activity, both spontaneous and evoked, plays a role in refining thalamocortical connections but recent work has indicated that neural activity is less important than was previously thought for the development of some early maps. A strategy used widely in the development of corticocortical and callosal connections is the early overproduction of projections followed by selection after contact with the target structure. Here we discuss recent work in primates indicating that elimination of juvenile projections is not a major mechanism in the development of pathways feeding information forward to higher levels of cortical processing, although its use is common to developing feedback pathways.

Cortical maturation and myelination in healthy toddlers and young children.

PubMed

Deoni, Sean C L; Dean, Douglas C; Remer, Justin; Dirks, Holly; O'Muircheartaigh, Jonathan

2015-07-15

The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6 years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1 year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development. Copyright © 2015. Published by Elsevier Inc.

Cortical visual dysfunction in children: a clinical study.

PubMed

Dutton, G; Ballantyne, J; Boyd, G; Bradnam, M; Day, R; McCulloch, D; Mackie, R; Phillips, S; Saunders, K

1996-01-01

Damage to the cerebral cortex was responsible for impairment in vision in 90 of 130 consecutive children referred to the Vision Assessment Clinic in Glasgow. Cortical blindness was seen in 16 children. Only 2 were mobile, but both showed evidence of navigational blind-sight. Cortical visual impairment, in which it was possible to estimate visual acuity but generalised severe brain damage precluded estimation of cognitive visual function, was observed in 9 children. Complex disorders of cognitive vision were seen in 20 children. These could be divided into five categories and involved impairment of: (1) recognition, (2) orientation, (3) depth perception, (4) perception of movement and (5) simultaneous perception. These disorders were observed in a variety of combinations. The remaining children showed evidence of reduced visual acuity and/ or visual field loss, but without detectable disorders of congnitive visual function. Early recognition of disorders of cognitive vision is required if active training and remediation are to be implemented.

Pain Catastrophising Affects Cortical Responses to Viewing Pain in Others

PubMed Central

Fallon, Nicholas

2015-01-01

Pain catastrophising is an exaggerated cognitive attitude implemented during pain or when thinking about pain. Catastrophising was previously associated with increased pain severity, emotional distress and disability in chronic pain patients, and is also a contributing factor in the development of neuropathic pain. To investigate the neural basis of how pain catastrophising affects pain observed in others, we acquired EEG data in groups of participants with high (High-Cat) or low (Low-Cat) pain catastrophising scores during viewing of pain scenes and graphically matched pictures not depicting imminent pain. The High-Cat group attributed greater pain to both pain and non-pain pictures. Source dipole analysis of event-related potentials during picture viewing revealed activations in the left (PHGL) and right (PHGR) paraphippocampal gyri, rostral anterior (rACC) and posterior cingulate (PCC) cortices. The late source activity (600–1100 ms) in PHGL and PCC was augmented in High-Cat, relative to Low-Cat, participants. Conversely, greater source activity was observed in the Low-Cat group during the mid-latency window (280–450 ms) in the rACC and PCC. Low-Cat subjects demonstrated a significantly stronger correlation between source activity in PCC and pain and arousal ratings in the long latency window, relative to high pain catastrophisers. Results suggest augmented activation of limbic cortex and higher order pain processing cortical regions during the late processing period in high pain catastrophisers viewing both types of pictures. This pattern of cortical activations is consistent with the distorted and magnified cognitive appraisal of pain threats in high pain catastrophisers. In contrast, high pain catastrophising individuals exhibit a diminished response during the mid-latency period when attentional and top-down resources are ascribed to observed pain. PMID:26186545

The association between later cortical potentials and later phases of postural reactions evoked by perturbations to upright stance.

PubMed

Quant, Sylvia; Maki, Brian E; McIlroy, William E

2005-06-24

Previous studies have suggested that early cortical potentials (e.g. N1) that are evoked by perturbations to upright stance are associated with sensory processing of the initial perturbation and that later potentials may represent cognitive processing of this perturbation. However, it has also been suggested that later cortical potentials could reflect sensory and motor processing of later phases of the postural reaction. The current study set out to provide additional insight into the association between perturbation-evoked cortical potentials and postural reactions evoked by whole-body perturbations. By altering the deceleration onset of the perturbation, which altered the timing of later postural responses, we determined whether changes in later postural responses were associated with changes in later potentials. Based on previous work, we hypothesized that later potentials would not be associated with changes in later postural responses. During stance, seven healthy young adults were instructed to maintain their balance following two types of perturbations: (1) acceleration phase immediately followed by a deceleration phase (TASK 1), and (2) acceleration phase followed by a delayed deceleration phase (TASK 2). In spite of profound task differences in later postural responses, results revealed no significant differences in later potentials. This work provides additional support for the idea that latter elements of perturbation-evoked cortical responses are likely independent of evoked motor reactions required to maintain stability.

Cortical columns and the tendency of neighboring neurons to act similarly.

PubMed

Legéndy, C R

1978-12-08

A tendency by neighboring cortical neurons to act similarly (spatial assimilation) is derived analytically from an assumed facilitatory interaction between the involved neurons at an early age, possibly before the critical period in the cat, an assumed plastic modifiability of the thalamo-cortical contacts at the same earlier time, and exposure of the network at the same time to a largely arbitrary sequence of inputs coming from outside the cortex. The calculational result is that during the assumed period of thalamo-cortical plasticity neuron responses tend toward greater similarity within the approximate range where cortico-cortical excitation dominates over inhibition and toward greater dissimilarity where inhibition dominates over excitation. Through the result, the calculation correctly predicts the horizontal extent of certain cortical columns. In the visual cortex of certain animals the horizontal distance of most dissimilar preferred orientation (90 degrees difference) is about the same as the distance of most dissimilar eye preference (from center of left-eye to center of right-eye region), and both are roughly the same as the range of strongest intracortical inhibition. The sequence of inputs coming from outside the cortex is mathematically allowed to be random, which suggests that signals originating inside the nervous system, as exist in a sensorially deprived animal, without help from genetic specifications, are adequate to give rise to spatial assimilation.

Dual response of BDNF to sublethal concentrations of beta-amyloid peptides in cultured cortical neurons.

PubMed

Aliaga, E; Silhol, M; Bonneau, N; Maurice, T; Arancibia, S; Tapia-Arancibia, L

2010-01-01

Beta-amyloid (Abeta) deposition is one important pathological hallmark in Alzheimer's disease (AD). However, low levels of Abeta may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of Abeta on total BDNF (panBDNF), BDNF transcripts (I, II, IV and VI), trkB.FL, trkB.T1 and p75(NGFR) mRNA expression in cultured cortical neurons. We have shown that Abeta exhibited a dual response on BDNF mRNA, i.e. an increase at short times (3-5 h) and a dramatic decrease at longer times (24 or 48 h). The early increase in BDNF expression seems to be driven by increased expression of transcripts I and IV. The BDNF drop was specific since did not occur for other mRNAs examined. The BDNF protein content showed a similar profile but did not follow the dramatic reduction as its encoding mRNA. These observations may help to explain cognitive deficits observed at initial stages of AD.

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

Subcortical functional reorganization due to early blindness

PubMed Central

Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly

2015-01-01

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746

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

Cortical activity during cued picture naming predicts individual differences in stuttering frequency

PubMed Central

Mock, Jeffrey R.; Foundas, Anne L.; Golob, Edward J.

2016-01-01

Objective Developmental stuttering is characterized by fluent speech punctuated by stuttering events, the frequency of which varies among individuals and contexts. Most stuttering events occur at the beginning of an utterance, suggesting neural dynamics associated with stuttering may be evident during speech preparation. Methods This study used EEG to measure cortical activity during speech preparation in men who stutter, and compared the EEG measures to individual differences in stuttering rate as well as to a fluent control group. Each trial contained a cue followed by an acoustic probe at one of two onset times (early or late), and then a picture. There were two conditions: a speech condition where cues induced speech preparation of the picture’s name and a control condition that minimized speech preparation. Results Across conditions stuttering frequency correlated to cue-related EEG beta power and auditory ERP slow waves from early onset acoustic probes. Conclusions The findings reveal two new cortical markers of stuttering frequency that were present in both conditions, manifest at different times, are elicited by different stimuli (visual cue, auditory probe), and have different EEG responses (beta power, ERP slow wave). Significance The cue-target paradigm evoked brain responses that correlated to pre-experimental stuttering rate. PMID:27472545

Cortical activity during cued picture naming predicts individual differences in stuttering frequency.

PubMed

Mock, Jeffrey R; Foundas, Anne L; Golob, Edward J

2016-09-01

Developmental stuttering is characterized by fluent speech punctuated by stuttering events, the frequency of which varies among individuals and contexts. Most stuttering events occur at the beginning of an utterance, suggesting neural dynamics associated with stuttering may be evident during speech preparation. This study used EEG to measure cortical activity during speech preparation in men who stutter, and compared the EEG measures to individual differences in stuttering rate as well as to a fluent control group. Each trial contained a cue followed by an acoustic probe at one of two onset times (early or late), and then a picture. There were two conditions: a speech condition where cues induced speech preparation of the picture's name and a control condition that minimized speech preparation. Across conditions stuttering frequency correlated to cue-related EEG beta power and auditory ERP slow waves from early onset acoustic probes. The findings reveal two new cortical markers of stuttering frequency that were present in both conditions, manifest at different times, are elicited by different stimuli (visual cue, auditory probe), and have different EEG responses (beta power, ERP slow wave). The cue-target paradigm evoked brain responses that correlated to pre-experimental stuttering rate. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Early indices of deviance detection in humans and animal models.

PubMed

Grimm, Sabine; Escera, Carles; Nelken, Israel

2016-04-01

Detecting unexpected stimuli in the environment is a critical function of the auditory system. Responses to unexpected "deviant" sounds are enhanced compared to responses to expected stimuli. At the human scalp, deviance detection is reflected in the mismatch negativity (MMN) and in an enhancement of the middle-latency response (MLR). Single neurons often respond more strongly to a stimulus when rare than when common, a phenomenon termed stimulus-specific adaptation (SSA). Here we compare stimulus-specific adaptation with scalp-recorded deviance-related responses. We conclude that early markers of deviance detection in the time range of the MLR could be a direct correlate of cortical SSA. Both occur at an early level of cortical activation, both are robust findings with low-probability stimuli, and both show properties of genuine deviance detection. Their causal relation with the later scalp-recorded MMN is a key question in this field. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Flexible timing by temporal scaling of cortical responses

PubMed Central

Wang, Jing; Narain, Devika; Hosseini, Eghbal A.; Jazayeri, Mehrdad

2017-01-01

Musicians can perform at different tempos, speakers can control the cadence of their speech, and children can flexibly vary their temporal expectations of events. To understand the neural basis of such flexibility, we recorded from the medial frontal cortex of nonhuman primates trained to produce different time intervals with different effectors. Neural responses were heterogeneous, nonlinear and complex, and exhibited a remarkable form of temporal invariance: firing rate profiles were temporally scaled to match the produced intervals. Recording from downstream neurons in the caudate and thalamic neurons projecting to the medial frontal cortex indicated that this phenomenon originates within cortical networks. Recurrent neural network models trained to perform the task revealed that temporal scaling emerges from nonlinearities in the network and degree of scaling is controlled by the strength of external input. These findings demonstrate a simple and general mechanism for conferring temporal flexibility upon sensorimotor and cognitive functions. PMID:29203897

Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

PubMed Central

Saproo, Sameer

2010-01-01

Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population

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

Early caregiving and physiological stress responses.

PubMed

Luecken, Linda J; Lemery, Kathryn S

2004-05-01

Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

Subcortical functional reorganization due to early blindness.

PubMed

Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

2015-04-01

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.

Functional signature of recovering cortex: dissociation of local field potentials and spiking activity in somatosensory cortices of spinal cord injured monkeys.

PubMed

Wang, Zheng; Qi, Hui-Xin; Kaas, Jon H; Roe, Anna W; Chen, Li Min

2013-11-01

After disruption of dorsal column afferents at high cervical spinal levels in adult monkeys, somatosensory cortical neurons recover responsiveness to tactile stimulation of the hand; this reactivation correlates with a recovery of hand use. However, it is not known if all neuronal response properties recover, and whether different cortical areas recover in a similar manner. To address this, we recorded neuronal activity in cortical area 3b and S2 in adult squirrel monkeys weeks after unilateral lesion of the dorsal columns. We found that in response to vibrotactile stimulation, local field potentials remained robust at all frequency ranges. However, neuronal spiking activity failed to follow at high frequencies (≥15 Hz). We suggest that the failure to generate spiking activity at high stimulus frequency reflects a changed balance of inhibition and excitation in both area 3b and S2, and that this mismatch in spiking and local field potential is a signature of an early phase of recovering cortex (

Adult Astrogenesis and the Etiology of Cortical Neurodegeneration

PubMed Central

Mohn, Tal C.; Koob, Andrew O.

2015-01-01

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

Sleep/wake dependent changes in cortical glucose concentrations.

PubMed

Dash, Michael B; Bellesi, Michele; Tononi, Giulio; Cirelli, Chiara

2013-01-01

Most of the energy in the brain comes from glucose and supports glutamatergic activity. The firing rate of cortical glutamatergic neurons, as well as cortical extracellular glutamate levels, increase with time spent awake and decline throughout non rapid eye movement sleep, raising the question whether glucose levels reflect behavioral state and sleep/wake history. Here chronic (2-3 days) electroencephalographic recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of glucose ([gluc]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to 3 h of sleep deprivation. [Gluc] progressively increased during non rapid eye movement sleep and declined during rapid eye movement sleep, while during wake an early decline in [gluc] was followed by an increase 8-15 min after awakening. There was a significant time of day effect during the dark phase, when rats are mostly awake, with [gluc] being significantly lower during the last 3-4 h of the night relative to the first 3-4 h. Moreover, the duration of the early phase of [gluc] decline during wake was longer after prolonged wake than after consolidated sleep. Thus, the sleep/wake history may affect the levels of glucose available to the brain upon awakening. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Emergent categorical representation of natural, complex sounds resulting from the early post-natal sound environment

PubMed Central

Bao, Shaowen; Chang, Edward F.; Teng, Ching-Ling; Heiser, Marc A.; Merzenich, Michael M.

2013-01-01

Cortical sensory representations can be reorganized by sensory exposure in an epoch of early development. The adaptive role of this type of plasticity for natural sounds in sensory development is, however, unclear. We have reared rats in a naturalistic, complex acoustic environment and examined their auditory representations. We found that cortical neurons became more selective to spectrotemporal features in the experienced sounds. At the neuronal population level, more neurons were involved in representing the whole set of complex sounds, but fewer neurons actually responded to each individual sound, but with greater magnitudes. A comparison of population-temporal responses to the experienced complex sounds revealed that cortical responses to different renderings of the same song motif were more similar, indicating that the cortical neurons became less sensitive to natural acoustic variations associated with stimulus context and sound renderings. By contrast, cortical responses to sounds of different motifs became more distinctive, suggesting that cortical neurons were tuned to the defining features of the experienced sounds. These effects lead to emergent “categorical” representations of the experienced sounds, which presumably facilitate their recognition. PMID:23747304

Thalamo-cortical activation and connectivity during response preparation in adults with persistent and remitted ADHD.

PubMed

Clerkin, Suzanne M; Schulz, Kurt P; Berwid, Olga G; Fan, Jin; Newcorn, Jeffrey H; Tang, Cheuk Y; Halperin, Jeffrey M

2013-09-01

The neural correlates of stimulus-driven processes, such as response preparation, have been posited to be associated with the onset of attention deficit hyperactivity disorder (ADHD) while being distinct from the neural mechanisms associated with recovery. The authors tested this hypothesis in adults with remitted and persistent ADHD. Thirty-eight young adults who were diagnosed with combined-type ADHD in childhood (probands) and 32 carefully matched comparison subjects were followed longitudinally and scanned with functional MRI while performing an event-related cued reaction time task. Probands were characterized as individuals with persistent or remitted ADHD. Differences in thalamo-cortical activation and functional connectivity during response preparation between comparison subjects and probands and between individuals with persistent ADHD and those with remitted ADHD were assessed by contrasting neural activation and functional connectivity during cue or noncue events. Probands exhibited less cue-related activation than comparison subjects in the thalamus, anterior cingulate cortex, supplementary motor area, inferior parietal lobe, and dorsolateral prefrontal cortex despite similar overall patterns of activation. There were no differences in activation between individuals in the remitted ADHD group and those in the persistent ADHD group in any hypothesized regions. However, cue-related functional connectivity between the right thalamus and brainstem was greater in comparison subjects relative to probands, and cue-related connectivity was greater between the right thalamus and prefrontal regions in individuals with remitted ADHD relative to those with persistent ADHD. Decreased thalamo-cortical activation during response preparation was present in adults diagnosed with ADHD in childhood regardless of symptom remission in adulthood, and may be partly driven by less functional coordination between the brainstem and thalamus. Greater functional integration of the

Horizontal integration and cortical dynamics.

PubMed

Gilbert, C D

1992-07-01

We have discussed several results that lead to a view that cells in the visual system are endowed with dynamic properties, influenced by context, expectation, and long-term modifications of the cortical network. These observations will be important for understanding how neuronal ensembles produce a system that perceives, remembers, and adapts to injury. The advantage to being able to observe changes at early stages in a sensory pathway is that one may be able to understand the way in which neuronal ensembles encode and represent images at the level of their receptive field properties, of cortical topographies, and of the patterns of connections between cells participating in a network.

Construction of 4D high-definition cortical surface atlases of infants: Methods and applications.

PubMed

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

2015-10-01

In neuroimaging, cortical surface atlases play a fundamental role for spatial normalization, analysis, visualization, and comparison of results across individuals and different studies. However, existing cortical surface atlases created for adults are not suitable for infant brains during the first two postnatal years, which is the most dynamic period of postnatal structural and functional development of the highly-folded cerebral cortex. Therefore, spatiotemporal cortical surface atlases for infant brains are highly desired yet still lacking for accurate mapping of early dynamic brain development. To bridge this significant gap, leveraging our infant-dedicated computational pipeline for cortical surface-based analysis and the unique longitudinal infant MRI dataset acquired in our research center, in this paper, we construct the first spatiotemporal (4D) high-definition cortical surface atlases for the dynamic developing infant cortical structures at seven time points, including 1, 3, 6, 9, 12, 18, and 24 months of age, based on 202 serial MRI scans from 35 healthy infants. For this purpose, we develop a novel method to ensure the longitudinal consistency and unbiasedness to any specific subject and age in our 4D infant cortical surface atlases. Specifically, we first compute the within-subject mean cortical folding by unbiased groupwise registration of longitudinal cortical surfaces of each infant. Then we establish longitudinally-consistent and unbiased inter-subject cortical correspondences by groupwise registration of the geometric features of within-subject mean cortical folding across all infants. Our 4D surface atlases capture both longitudinally-consistent dynamic mean shape changes and the individual variability of cortical folding during early brain development. Experimental results on two independent infant MRI datasets show that using our 4D infant cortical surface atlases as templates leads to significantly improved accuracy for spatial normalization

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central

Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

2017-01-01

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

PubMed

Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

2017-01-01

Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

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.

Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

PubMed

Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

2010-07-01

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

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

The cortical response to the oral perception of fat emulsions and the effect of taster status

PubMed Central

Eldeghaidy, Sally; Marciani, Luca; McGlone, Francis; Hollowood, Tracey; Hort, Joanne; Head, Kay; Taylor, Andrew J.; Busch, Johanneke; Spiller, Robin C.; Gowland, Penny A.

2011-01-01

The rewarding attributes of foods containing fat are associated with the increase in fat consumption, but little is known of how the complex physical and chemical properties of orally ingested fats are represented and decoded in the brain nor how this impacts feeding behavior within the population. Here, functional MRI (fMRI) is used to assess the brain response to isoviscous, isosweet fat emulsions of increasing fat concentration and to investigate the correlation of behavioral and neuroimaging responses with taster status (TS). Cortical areas activated in response to fat, and those areas positively correlated with fat concentration, were identified. Significant responses that positively correlated with increasing fat concentration were found in the anterior insula, frontal operculum and secondary somatosensory cortex (SII), anterior cingulate cortex, and amygdala. Assessing the effect of TS revealed a strong correlation with self-reported preference of the samples and with cortical response in somatosensory areas [primary somatosensory cortex (SI), SII, and midinsula] and the primary taste area (anterior insula) and a trend in reward areas (amygdala and orbitofrontal cortex). This finding of a strong correlation with TS in somatosensory areas supports the theory of increased mechanosensory trigeminal innervation in high 6-n-propyl-2-thiouracil (PROP) tasters and has been linked to a higher risk of obesity. The interindividual differences in blood oxygenation level-dependent (BOLD) amplitude with TS indicates that segmenting populations by TS will reduce the heterogeneity of BOLD responses, improving signal detection power. PMID:21389303

Context matters: Anterior and posterior cortical midline responses to sad movie scenes.

PubMed

Schlochtermeier, L H; Pehrs, C; Bakels, J-H; Jacobs, A M; Kappelhoff, H; Kuchinke, L

2017-04-15

Narrative movies can create powerful emotional responses. While recent research has advanced the understanding of neural networks involved in immersive movie viewing, their modulation within a movie's dynamic context remains inconclusive. In this study, 24 healthy participants passively watched sad scene climaxes taken from 24 romantic comedies, while brain activity was measured using functional magnetic resonance (fMRI). To study effects of context, the sad scene climaxes were presented with either coherent scene context, replaced non-coherent context or without context. In a second viewing, the same clips were rated continuously for sadness. The ratings varied over time with peaks of experienced sadness within the assumed climax intervals. Activations in anterior and posterior cortical midline regions increased if presented with both coherent and replaced context, while activation in the temporal gyri decreased. This difference was more pronounced for the coherent context condition. Psycho-Physiological interactions (PPI) analyses showed a context-dependent coupling of midline regions with occipital visual and sub-cortical reward regions. Our results demonstrate the pivotal role of midline structures and their interaction with perceptual and reward areas in processing contextually embedded socio-emotional information in movies. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortical Representations of Symbols, Objects, and Faces Are Pruned Back during Early Childhood

PubMed Central

Pinel, Philippe; Dehaene, Stanislas; Pelphrey, Kevin A.

2011-01-01

Regions of human ventral extrastriate visual cortex develop specializations for natural categories (e.g., faces) and cultural artifacts (e.g., words). In adults, category-based specializations manifest as greater neural responses in visual regions of the brain (e.g., fusiform gyrus) to some categories over others. However, few studies have examined how these specializations originate in the brains of children. Moreover, it is as yet unknown whether the development of visual specializations hinges on “increases” in the response to the preferred categories, “decreases” in the responses to nonpreferred categories, or “both.” This question is relevant to a long-standing debate concerning whether neural development is driven by building up or pruning back representations. To explore these questions, we measured patterns of visual activity in 4-year-old children for 4 categories (faces, letters, numbers, and shoes) using functional magnetic resonance imaging. We report 2 key findings regarding the development of visual categories in the brain: 1) the categories “faces” and “symbols” doubly dissociate in the fusiform gyrus before children can read and 2) the development of category-specific responses in young children depends on cortical responses to nonpreferred categories that decrease as preferred category knowledge is acquired. PMID:20457691

Cortical Activity during Manual Response Inhibition Guided by Color and Orientation Cues

PubMed Central

Cai, Weidong; Leung, Hoi-Chung

2009-01-01

It has been suggested that the right inferior frontal gyrus (IFG) plays a critical role in manual response inhibition, although neuroimaging studies of healthy adults have also reported widespread activations in other cortical regions during a variety of response inhibition tasks. We conducted a functional magnetic resonance imaging (fMRI) experiment to examine whether the activation of the IFG is dependent on the type of visuo-motor associations during response inhibition by varying the feature of the stop signal (color vs. orientation) in the stop-signal task. Results from 12 subjects showed that the bilateral ventral posterior IFG, anterior insula, inferior frontal junction (IFJ), middle temporal gyrus (MTG) and fusiform gyrus (FG) are active during response inhibition cued by both color and orientation stop signals. While only the MTG showed differential activity to the two stop signals, both MTG and FG showed significantly stronger activity during successful than unsuccessful stopping of unwanted responses cued by orientation and color, respectively. Our findings suggest that the right ventral posterior IFG may play a more general role in response inhibition regardless of the feature of the visual signal, while successful inhibition may depend on efficient processing of the signal. PMID:19401178

The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies

PubMed Central

2013-01-01

Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral

Input-Specific Gain Modulation by Local Sensory Context Shapes Cortical and Thalamic Responses to Complex Sounds.

PubMed

Williamson, Ross S; Ahrens, Misha B; Linden, Jennifer F; Sahani, Maneesh

2016-07-20

Sensory neurons are customarily characterized by one or more linearly weighted receptive fields describing sensitivity in sensory space and time. We show that in auditory cortical and thalamic neurons, the weight of each receptive field element depends on the pattern of sound falling within a local neighborhood surrounding it in time and frequency. Accounting for this change in effective receptive field with spectrotemporal context improves predictions of both cortical and thalamic responses to stationary complex sounds. Although context dependence varies among neurons and across brain areas, there are strong shared qualitative characteristics. In a spectrotemporally rich soundscape, sound elements modulate neuronal responsiveness more effectively when they coincide with sounds at other frequencies, and less effectively when they are preceded by sounds at similar frequencies. This local-context-driven lability in the representation of complex sounds-a modulation of "input-specific gain" rather than "output gain"-may be a widespread motif in sensory processing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Neural responses of rat cortical layers due to infrared neural modulation and photoablation of thalamocortical brain slices

NASA Astrophysics Data System (ADS)

Jenkins, J. Logan; Kao, Chris C.; Cayce, Jonathan M.; Mahadevan-Jansen, Anita; Jansen, E. Duco

2017-02-01

Infrared neural modulation (INM) is a label-free method for eliciting neural activity with high spatial selectivity in mammalian models. While there has been an emphasis on INM research towards applications in the peripheral nervous system and the central nervous system (CNS), the biophysical mechanisms by which INM occurs remains largely unresolved. In the rat CNS, INM has been shown to elicit and inhibit neural activity, evoke calcium signals that are dependent on glutamate transients and astrocytes, and modulate inhibitory GABA currents. So far, in vivo experiments have been restricted to layers I and II of the rat cortex which consists mainly of astrocytes, inhibitory neurons, and dendrites from deeper excitatory neurons owing to strong absorption of light in these layers. Deeper cortical layers (III-VI) have vastly different cell type composition, consisting predominantly of excitatory neurons which can be targeted for therapies such as deep brain stimulation. The neural responses to infrared light of deeper cortical cells have not been well defined. Acute thalamocortical brain slices will allow us to analyze the effects of INS on various components of the cortex, including different cortical layers and cell populations. In this study, we present the use of photoablation with an erbium:YAG laser to reduce the thickness of the dead cell zone near the cutting surface of brain slices. This technique will allow for more optical energy to reach living cells, which should contribute the successful transduction of pulsed infrared light to neural activity. In the future, INM-induced neural responses will lead to a finer characterization of the parameter space for the neuromodulation of different cortical cell types and may contribute to understanding the cell populations that are important for allowing optical stimulation of neurons in the CNS.

Determinants of motion response anisotropies in human early visual cortex: the role of configuration and eccentricity.

PubMed

Maloney, Ryan T; Watson, Tamara L; Clifford, Colin W G

2014-10-15

Anisotropies in the cortical representation of various stimulus parameters can reveal the fundamental mechanisms by which sensory properties are analysed and coded by the brain. One example is the preference for motion radial to the point of fixation (i.e. centripetal or centrifugal) exhibited in mammalian visual cortex. In two experiments, this study used functional magnetic resonance imaging (fMRI) to explore the determinants of these radial biases for motion in functionally-defined areas of human early visual cortex, and in particular their dependence upon eccentricity which has been indicated in recent reports. In one experiment, the cortical response to wide-field random dot kinematograms forming 16 different complex motion patterns (including centrifugal, centripetal, rotational and spiral motion) was measured. The response was analysed according to preferred eccentricity within four different eccentricity ranges. Response anisotropies were characterised by enhanced activity for centripetal or centrifugal patterns that changed systematically with eccentricity in visual areas V1-V3 and hV4 (but not V3A/B or V5/MT+). Responses evolved from a preference for centrifugal over centripetal patterns close to the fovea, to a preference for centripetal over centrifugal at the most peripheral region stimulated, in agreement with previous work. These effects were strongest in V2 and V3. In a second experiment, the stimuli were restricted to within narrow annuli either close to the fovea (0.75-1.88°) or further in the periphery (4.82-6.28°), in a way that preserved the local motion information available in the first experiment. In this configuration a preference for radial motion (centripetal or centrifugal) persisted but the dependence upon eccentricity disappeared. Again this was clearest in V2 and V3. A novel interpretation of the dependence upon eccentricity of motion anisotropies in early visual cortex is offered that takes into account the spatiotemporal

The participation of cortical amygdala in innate, odor-driven behavior

PubMed Central

Root, Cory M.; Denny, Christine A.; Hen, René; Axel, Richard

2014-01-01

Innate behaviors are observed in naïve animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviors are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centers have been anatomically defined1-3 but the specific pathways responsible for innate responses to volatile odors have not been identified. We have devised genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviors. Moreover, we have employed the promoter of the activity-dependent gene, arc, to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odors that elicit innate behaviors. Optical activation of these neurons leads to appropriate behaviors that recapitulate the responses to innate odors. These data indicate that the cortical amygdala plays a critical role in the generation of innate odor-driven behaviors but do not preclude the participation of cortical amygdala in learned olfactory behaviors. PMID:25383519

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

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

Predictive information processing is a fundamental learning mechanism present in early development: evidence from infants.

PubMed

Trainor, Laurel J

2012-02-01

Evidence is presented that predictive coding is fundamental to brain function and present in early infancy. Indeed, mismatch responses to unexpected auditory stimuli are among the earliest robust cortical event-related potential responses, and have been measured in young infants in response to many types of deviation, including in pitch, timing, and melodic pattern. Furthermore, mismatch responses change quickly with specific experience, suggesting that predictive coding reflects a powerful, early-developing learning mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum.

PubMed

Alahmadi, Adnan A S; Samson, Rebecca S; Gasston, David; Pardini, Matteo; Friston, Karl J; D'Angelo, Egidio; Toosy, Ahmed T; Wheeler-Kingshott, Claudia A M

2016-06-01

Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

Left cortical specialization for visual letter strings predicts rudimentary knowledge of letter-sound association in preschoolers

PubMed Central

Lochy, Aliette; Van Reybroeck, Marie; Rossion, Bruno

2016-01-01

Reading, one of the most important cultural inventions of human society, critically depends on posterior brain areas of the left hemisphere in proficient adult readers. In children, this left hemispheric cortical specialization for letter strings is typically detected only after approximately 1 y of formal schooling and reading acquisition. Here, we recorded scalp electrophysiological (EEG) brain responses in 5-y-old (n = 40) prereaders presented with letter strings appearing every five items in rapid streams of pseudofonts (6 items per second). Within 2 min of recording only, letter strings evoked a robust specific response over the left occipito-temporal cortex at the predefined frequency of 1.2 Hz (i.e., 6 Hz/5). Interindividual differences in the amplitude of this electrophysiological response are significantly related to letter knowledge, a preschool predictor of later reading ability. These results point to the high potential of this rapidly collected behavior-free measure to assess reading ability in developmental populations. These findings were replicated in a second experiment (n = 26 preschool children), where familiar symbols and line drawings of objects evoked right-lateralized and bilaterally specific responses, respectively, showing the specificity of the early left hemispheric dominance for letter strings. Collectively, these findings indicate that limited knowledge of print in young children, before formal education, is sufficient to develop specialized left lateralized neuronal circuits, thereby pointing to an early onset and rapid impact of left hemispheric reentrant sound mapping on posterior cortical development. PMID:27402739

Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.

PubMed

Nguyen, Tuong-Vi; McCracken, James T; Ducharme, Simon; Cropp, Brett F; Botteron, Kelly N; Evans, Alan C; Karama, Sherif

2013-06-26

Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

Family history of psychosis moderates early auditory cortical response abnormalities in non-psychotic bipolar disorder

PubMed Central

Hamm, Jordan P; Ethridge, Lauren E; Shapiro, John R; Pearlson, Godfrey D; Tamminga, Carol A; Sweeney, John A; Keshavan, Matcheri S; Thaker, Gunvant K; Clementz, Brett A

2017-01-01

Objectives Bipolar I disorder is a disabling illness affecting 1% of people worldwide. Family and twin studies suggest that psychotic bipolar disorder (BDP) represents a homogenous subgroup with an etiology distinct from non-psychotic bipolar disorder (BDNP) and partially shared with schizophrenia. Studies of auditory electrophysiology [e.g., paired-stimulus and oddball measured with electroencephalography (EEG)] consistently report deviations in psychotic groups (schizophrenia, BDP), yet such studies comparing BDP and BDNP are sparse and, in some cases, conflicting. Auditory EEG responses are significantly reduced in unaffected relatives of psychosis patients, suggesting that they may relate to both psychosis liability and expression. Methods While 64-sensor EEGs were recorded, age- and gender-matched samples of 70 BDP, 35 BDNP {20 with a family history of psychosis [BDNP(+)]}, and 70 psychiatrically healthy subjects were presented typical auditory paired-stimuli and auditory oddball paradigms. Results Oddball P3b reductions were present and indistinguishable across all patient groups. P2s to paired-stimuli were abnormal only in BDP and BDNP(+). Conversely, N1 reductions to stimuli in both paradigms and P3a reductions were present in both BDP and BDNP(−) groups but were absent in BDNP(+). Conclusions While nearly all auditory neural response components studied were abnormal in BDP, BDNP abnormalities at early- and mid-latencies were moderated by family psychosis history. The relationship between psychosis expression, heritable psychosis risk, and neurophysiology within bipolar disorder, therefore, may be complex. Consideration of such clinical disease heterogeneity may be important for future investigations of the pathophysiology of major psychiatric disturbance. PMID:23941660

Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

PubMed

Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

2017-11-01

The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortical Photostimulation Technology for Vision Prosthesis

DTIC Science & Technology

2017-05-01

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...SUPPLEMENTARY NOTES 14. ABSTRACT The overall goal of the project is to evaluate the feasibility of using photochemical stimulation of cortical neurons as the...glutamate, which can directly stimulate cortical neurons. The new caged molecule has an absorption peak in the visible wavelength range, at 458 nm

Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses

PubMed Central

Matre, Dagfinn; Hu, Li; Viken, Leif A.; Hjelle, Ingri B.; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

2015-01-01

Study Objectives: Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. Design: A paired crossover study. Intervention: Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Setting: Laboratory experiment at research center. Participants: Self-reported healthy volunteers (n = 21, age range: 18–31 y). Measurements and Results: Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Conclusion: Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. Citation: Matre D, Hu L, Viken LA, Hjelle IB, Wigemyr M, Knardahl S, Sand T, Nilsen KB. Experimental sleep restriction facilitates pain and electrically induced cortical responses. SLEEP 2015;38(10):1607–1617. PMID:26194577

Parallel processing of general and specific threat during early stages of perception

PubMed Central

2016-01-01

Differential processing of threat can consummate as early as 100 ms post-stimulus. Moreover, early perception not only differentiates threat from non-threat stimuli but also distinguishes among discrete threat subtypes (e.g. fear, disgust and anger). Combining spatial-frequency-filtered images of fear, disgust and neutral scenes with high-density event-related potentials and intracranial source estimation, we investigated the neural underpinnings of general and specific threat processing in early stages of perception. Conveyed in low spatial frequencies, fear and disgust images evoked convergent visual responses with similarly enhanced N1 potentials and dorsal visual (middle temporal gyrus) cortical activity (relative to neutral cues; peaking at 156 ms). Nevertheless, conveyed in high spatial frequencies, fear and disgust elicited divergent visual responses, with fear enhancing and disgust suppressing P1 potentials and ventral visual (occipital fusiform) cortical activity (peaking at 121 ms). Therefore, general and specific threat processing operates in parallel in early perception, with the ventral visual pathway engaged in specific processing of discrete threats and the dorsal visual pathway in general threat processing. Furthermore, selectively tuned to distinctive spatial-frequency channels and visual pathways, these parallel processes underpin dimensional and categorical threat characterization, promoting efficient threat response. These findings thus lend support to hybrid models of emotion. PMID:26412811

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.

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.

Transcranial fluorescence imaging of auditory cortical plasticity regulated by acoustic environments in mice.

PubMed

Takahashi, Kuniyuki; Hishida, Ryuichi; Kubota, Yamato; Kudoh, Masaharu; Takahashi, Sugata; Shibuki, Katsuei

2006-03-01

Functional brain imaging using endogenous fluorescence of mitochondrial flavoprotein is useful for investigating mouse cortical activities via the intact skull, which is thin and sufficiently transparent in mice. We applied this method to investigate auditory cortical plasticity regulated by acoustic environments. Normal mice of the C57BL/6 strain, reared in various acoustic environments for at least 4 weeks after birth, were anaesthetized with urethane (1.7 g/kg, i.p.). Auditory cortical images of endogenous green fluorescence in blue light were recorded by a cooled CCD camera via the intact skull. Cortical responses elicited by tonal stimuli (5, 10 and 20 kHz) exhibited mirror-symmetrical tonotopic maps in the primary auditory cortex (AI) and anterior auditory field (AAF). Depression of auditory cortical responses regarding response duration was observed in sound-deprived mice compared with naïve mice reared in a normal acoustic environment. When mice were exposed to an environmental tonal stimulus at 10 kHz for more than 4 weeks after birth, the cortical responses were potentiated in a frequency-specific manner in respect to peak amplitude of the responses in AI, but not for the size of the responsive areas. Changes in AAF were less clear than those in AI. To determine the modified synapses by acoustic environments, neural responses in cortical slices were investigated with endogenous fluorescence imaging. The vertical thickness of responsive areas after supragranular electrical stimulation was significantly reduced in the slices obtained from sound-deprived mice. These results suggest that acoustic environments regulate the development of vertical intracortical circuits in the mouse auditory cortex.

The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

PubMed

Ramcharan, M A; Faillace, M E; Guengerich, Z; Williams, V A; Jepsen, K J

2017-03-01

How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains. Age-related changes in cortical and trabecular traits have been well studied; however, very little is known about how these bone tissues co-develop from day 1 of postnatal growth to establish functional structures by adulthood. In this study, we aimed to establish how cortical and trabecular tissues within the lumbar vertebral body change during growth for three inbred mouse strains that express wide variation in adult bone structure and function. Bone traits were quantified for lumbar vertebral bodies of female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse strains from 1 to 105 days of age (n = 6-10 mice/age/strain). Inter-strain differences in external bone size were observed as early as 1 day of age. Reciprocal and rapid changes in the trabecular bone volume fraction and alignment in the direction of axial compression were observed by 7 days of age. Importantly, the inter-strain difference in adult trabecular bone volume fraction was established by 7 days of age. Early variation in external bone size and trabecular architecture was followed by progressive increases in cortical area between 28 and 105 days of age, with the greatest increases in cortical area seen in the mouse strain with the lowest trabecular mass. Establishing the temporal changes in bone morphology for three inbred mouse strains revealed that genetic variation in adult trabecular traits were established early in postnatal development. Early variation in trabecular architecture preceded strain-specific increases in cortical area and changes in cortical thickness. This study

The participation of cortical amygdala in innate, odour-driven behaviour.

PubMed

Root, Cory M; Denny, Christine A; Hen, René; Axel, Richard

2014-11-13

Innate behaviours are observed in naive animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centres have been anatomically defined, but the specific pathways responsible for innate responses to volatile odours have not been identified. Here we devise genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviours. Moreover, we use the promoter of the activity-dependent gene arc to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odours that elicit innate behaviours. Optical activation of these neurons leads to appropriate behaviours that recapitulate the responses to innate odours. These data indicate that the cortical amygdala plays a critical role in generating innate odour-driven behaviours but do not preclude its participation in learned olfactory behaviours.

Brainstem origins for cortical 'what' and 'where' pathways in the auditory system.

PubMed

Kraus, Nina; Nicol, Trent

2005-04-01

We have developed a data-driven conceptual framework that links two areas of science: the source-filter model of acoustics and cortical sensory processing streams. The source-filter model describes the mechanics behind speech production: the identity of the speaker is carried largely in the vocal cord source and the message is shaped by the ever-changing filters of the vocal tract. Sensory processing streams, popularly called 'what' and 'where' pathways, are well established in the visual system as a neural scheme for separately carrying different facets of visual objects, namely their identity and their position/motion, to the cortex. A similar functional organization has been postulated in the auditory system. Both speaker identity and the spoken message, which are simultaneously conveyed in the acoustic structure of speech, can be disentangled into discrete brainstem response components. We argue that these two response classes are early manifestations of auditory 'what' and 'where' streams in the cortex. This brainstem link forges a new understanding of the relationship between the acoustics of speech and cortical processing streams, unites two hitherto separate areas in science, and provides a model for future investigations of auditory function.

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.

Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

PubMed Central

Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

2012-01-01

Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

Cortical connective field estimates from resting state fMRI activity.

PubMed

Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V; Dumoulin, Serge O; Renken, Remco; Curčić-Blake, Branislava; Cornelissen, Frans W

2014-01-01

One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that-despite some variability in CF estimates between RS scans-neural properties such as CF maps and CF size can be derived from resting state data.

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.

Reduced Short Interval Cortical Inhibition Correlates with Atomoxetine Response in Children with ADHD

PubMed Central

Chen, Tina H.; Wu, Steve W.; Welge, Jeffrey A.; Dixon, Stephan; Shahana, Nasrin; Huddleston, David A.; Sarvis, Adam R.; Sallee, Floyd R.; Gilbert, Donald L.

2014-01-01

Clinical trials in children with Attention Deficit Hyperactivity Disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine (ATX). The objective of this study was to determine whether Transcranial Magnetic Stimulation (TMS)-evoked Short Interval Cortical Inhibition (SICI) might be a biomarker predicting, or correlating with, clinical ATX response. At baseline and after 4 weeks of ATX treatment in 7–12 year old children with ADHD, TMS-SICI was measured, blinded to clinical improvement. Primary analysis was by multivariate ANCOVA. Baseline SICI did not predict clinical responses. However, paradoxically, after 4 weeks of ATX, mean SICI was reduced 31.9% in responders and increased 6.1% in non-responders (ANCOVA t41=2.88; p = .0063). Percent reductions in SICI correlated with reductions in ADHD-Rating Scale (ADHDRS) (r = .50; p = .0005). In children ages 7–12 years with ADHD treated with ATX, improvements in clinical symptoms are correlated with reductions in motor cortex SICI. PMID:24413361

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

PubMed

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

2015-08-01

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

Relating normalization to neuronal populations across cortical areas

PubMed Central

Alberts, Joshua J.; Cohen, Marlene R.

2016-01-01

Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. PMID:27358313

Cry presence and amplitude do not reflect cortical processing of painful stimuli in newborns with distinct responses to touch or cold.

PubMed

Maitre, Nathalie L; Stark, Ann R; McCoy Menser, Carrie C; Chorna, Olena D; France, Daniel J; Key, Alexandra F; Wilkens, Ken; Moore-Clingenpeel, Melissa; Wilkes, Don M; Bruehl, Stephen

2017-09-01

Newborns requiring hospitalisation frequently undergo painful procedures. Prevention of pain in infants is of prime concern because of adverse associations with physiological and neurological development. However, pain mitigation is currently guided by behavioural observation assessments that have not been validated against direct evidence of pain processing in the brain. The aim of this study was to determine whether cry presence or amplitude is a valid indicator of pain processing in newborns. Prospective observational cohort. Newborn nursery. Healthy infants born at >37 weeks and <42 weeks gestation. We prospectively studied newborn cortical responses to light touch, cold and heel stick, and the amplitude of associated infant vocalisations using our previously published paradigms of time-locked electroencephalogram (EEG) with simultaneous audio recordings. Latencies of cortical peak responses to each of the three stimuli type were significantly different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had cries in response to light touch, cold and heel stick, respectively. Cry in response to non-painful stimuli did not predict cry in response to heel stick. All infants with EEG data had measurable pain responses to heel stick, whether they cried or not. There was no association between presence or amplitude of cries and cortical nociceptive amplitudes. In newborns with distinct brain responses to light touch, cold and pain, cry presence or amplitude characteristics do not provide adequate behavioural markers of pain signalling in the brain. New bedside assessments of newborn pain may need to be developed using brain-based methodologies as benchmarks in order to provide optimal pain mitigation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Outcome of epilepsy surgery in focal cortical dysplasia

PubMed Central

Kral, T; Clusmann, H; Blumcke, I; Fimmers, R; Ostertun, B; Kurthen, M; Schramm, J

2003-01-01

Objective: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. Methods and subjects: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). Results: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. Conclusions: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies. PMID:12531945

Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

PubMed Central

Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

2015-01-01

Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

Left-Lateralized Contributions of Saccades to Cortical Activity During a One-Back Word Recognition Task.

PubMed

Chang, Yu-Cherng C; Khan, Sheraz; Taulu, Samu; Kuperberg, Gina; Brown, Emery N; Hämäläinen, Matti S; Temereanca, Simona

2018-01-01

Saccadic eye movements are an inherent component of natural reading, yet their contribution to information processing at subsequent fixation remains elusive. Here we use anatomically-constrained magnetoencephalography (MEG) to examine cortical activity following saccades as healthy human subjects engaged in a one-back word recognition task. This activity was compared with activity following external visual stimulation that mimicked saccades. A combination of procedures was employed to eliminate saccadic ocular artifacts from the MEG signal. Both saccades and saccade-like external visual stimulation produced early-latency responses beginning ~70 ms after onset in occipital cortex and spreading through the ventral and dorsal visual streams to temporal, parietal and frontal cortices. Robust differential activity following the onset of saccades vs. similar external visual stimulation emerged during 150-350 ms in a left-lateralized cortical network. This network included: (i) left lateral occipitotemporal (LOT) and nearby inferotemporal (IT) cortex; (ii) left posterior Sylvian fissure (PSF) and nearby multimodal cortex; and (iii) medial parietooccipital (PO), posterior cingulate and retrosplenial cortices. Moreover, this left-lateralized network colocalized with word repetition priming effects. Together, results suggest that central saccadic mechanisms influence a left-lateralized language network in occipitotemporal and temporal cortex above and beyond saccadic influences at preceding stages of information processing during visual word recognition.

Left-Lateralized Contributions of Saccades to Cortical Activity During a One-Back Word Recognition Task

PubMed Central

Chang, Yu-Cherng C.; Khan, Sheraz; Taulu, Samu; Kuperberg, Gina; Brown, Emery N.; Hämäläinen, Matti S.; Temereanca, Simona

2018-01-01

Saccadic eye movements are an inherent component of natural reading, yet their contribution to information processing at subsequent fixation remains elusive. Here we use anatomically-constrained magnetoencephalography (MEG) to examine cortical activity following saccades as healthy human subjects engaged in a one-back word recognition task. This activity was compared with activity following external visual stimulation that mimicked saccades. A combination of procedures was employed to eliminate saccadic ocular artifacts from the MEG signal. Both saccades and saccade-like external visual stimulation produced early-latency responses beginning ~70 ms after onset in occipital cortex and spreading through the ventral and dorsal visual streams to temporal, parietal and frontal cortices. Robust differential activity following the onset of saccades vs. similar external visual stimulation emerged during 150–350 ms in a left-lateralized cortical network. This network included: (i) left lateral occipitotemporal (LOT) and nearby inferotemporal (IT) cortex; (ii) left posterior Sylvian fissure (PSF) and nearby multimodal cortex; and (iii) medial parietooccipital (PO), posterior cingulate and retrosplenial cortices. Moreover, this left-lateralized network colocalized with word repetition priming effects. Together, results suggest that central saccadic mechanisms influence a left-lateralized language network in occipitotemporal and temporal cortex above and beyond saccadic influences at preceding stages of information processing during visual word recognition. PMID:29867372

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

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

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.

Origin and Properties of Striatal Local Field Potential Responses to Cortical Stimulation: Temporal Regulation by Fast Inhibitory Connections

PubMed Central

Galiñanes, Gregorio L.; Braz, Barbara Y.; Murer, Mario Gustavo

2011-01-01

Evoked striatal field potentials are seldom used to study corticostriatal communication in vivo because little is known about their origin and significance. Here we show that striatal field responses evoked by stimulating the prelimbic cortex in mice are reduced by more than 90% after infusing the AMPA receptor antagonist CNQX close to the recording electrode. Moreover, the amplitude of local field responses and dPSPs recorded in striatal medium spiny neurons increase in parallel with increasing stimulating current intensity. Finally, the evoked striatal fields show several of the basic known properties of corticostriatal transmission, including paired pulse facilitation and topographical organization. As a case study, we characterized the effect of local GABAA receptor blockade on striatal field and multiunitary action potential responses to prelimbic cortex stimulation. Striatal activity was recorded through a 24 channel silicon probe at about 600 µm from a microdialysis probe. Intrastriatal administration of the GABAA receptor antagonist bicuculline increased by 65±7% the duration of the evoked field responses. Moreover, the associated action potential responses were markedly enhanced during bicuculline infusion. Bicuculline enhancement took place at all the striatal sites that showed a response to cortical stimulation before drug infusion, but sites showing no field response before bicuculline remained unresponsive during GABAA receptor blockade. Thus, the data demonstrate that fast inhibitory connections exert a marked temporal regulation of input-output transformations within spatially delimited striatal networks responding to a cortical input. Overall, we propose that evoked striatal fields may be a useful tool to study corticostriatal synaptic connectivity in relation to behavior. PMID:22163020

Modulation of early cortical processing during divided attention to non-contiguous locations

PubMed Central

Frey, Hans-Peter; Schmid, Anita M.; Murphy, Jeremy W.; Molholm, Sophie; Lalor, Edmund C.; Foxe, John J.

2015-01-01

We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. While for several years the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed using high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classical pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing timeframes in hierarchically early visual regions and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention. PMID:24606564

[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

Emotions in word and face processing: early and late cortical responses.

PubMed

Schacht, Annekathrin; Sommer, Werner

2009-04-01

Recent research suggests that emotion effects in word processing resemble those in other stimulus domains such as pictures or faces. The present study aims to provide more direct evidence for this notion by comparing emotion effects in word and face processing in a within-subject design. Event-related brain potentials (ERPs) were recorded as participants made decisions on the lexicality of emotionally positive, negative, and neutral German verbs or pseudowords, and on the integrity of intact happy, angry, and neutral faces or slightly distorted faces. Relative to neutral and negative stimuli both positive verbs and happy faces elicited posterior ERP negativities that were indistinguishable in scalp distribution and resembled the early posterior negativities reported by others. Importantly, these ERP modulations appeared at very different latencies. Therefore, it appears that similar brain systems reflect the decoding of both biological and symbolic emotional signals of positive valence, differing mainly in the speed of meaning access, which is more direct and faster for facial expressions than for words.

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

PubMed

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

1996-01-01

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

The effect of binaural beats on verbal working memory and cortical connectivity.

PubMed

Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A; Leonessa, Alexander

2017-04-01

Synchronization in activated regions of cortical networks affect the brain's frequency response, which has been associated with a wide range of states and abilities, including memory. A non-invasive method for manipulating cortical synchronization is binaural beats. Binaural beats take advantage of the brain's response to two pure tones, delivered independently to each ear, when those tones have a small frequency mismatch. The mismatch between the tones is interpreted as a beat frequency, which may act to synchronize cortical oscillations. Neural synchrony is particularly important for working memory processes, the system controlling online organization and retention of information for successful goal-directed behavior. Therefore, manipulation of synchrony via binaural beats provides a unique window into working memory and associated connectivity of cortical networks. In this study, we examined the effects of different acoustic stimulation conditions during an N-back working memory task, and we measured participant response accuracy and cortical network topology via EEG recordings. Six acoustic stimulation conditions were used: None, Pure Tone, Classical Music, 5 Hz binaural beats, 10 Hz binaural beats, and 15 Hz binaural beats. We determined that listening to 15 Hz binaural beats during an N-Back working memory task increased the individual participant's accuracy, modulated the cortical frequency response, and changed the cortical network connection strengths during the task. Only the 15 Hz binaural beats produced significant change in relative accuracy compared to the None condition. Listening to 15 Hz binaural beats during the N-back task activated salient frequency bands and produced networks characterized by higher information transfer as compared to other auditory stimulation conditions.

Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

PubMed

Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

2017-09-01

The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

PubMed Central

Guo, Bing-bing; Zheng, Xiao-lin; Lu, Zhen-gang; Wang, Xing; Yin, Zheng-qin; Hou, Wen-sheng; Meng, Ming

2015-01-01

Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only “see” pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern. PMID:26692860

Background noise exerts diverse effects on the cortical encoding of foreground sounds.

PubMed

Malone, B J; Heiser, Marc A; Beitel, Ralph E; Schreiner, Christoph E

2017-08-01

In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions. NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may

Early sensory encoding of affective prosody: neuromagnetic tomography of emotional category changes.

PubMed

Thönnessen, Heike; Boers, Frank; Dammers, Jürgen; Chen, Yu-Han; Norra, Christine; Mathiak, Klaus

2010-03-01

In verbal communication, prosodic codes may be phylogenetically older than lexical ones. Little is known, however, about early, automatic encoding of emotional prosody. This study investigated the neuromagnetic analogue of mismatch negativity (MMN) as an index of early stimulus processing of emotional prosody using whole-head magnetoencephalography (MEG). We applied two different paradigms to study MMN; in addition to the traditional oddball paradigm, the so-called optimum design was adapted to emotion detection. In a sequence of randomly changing disyllabic pseudo-words produced by one male speaker in neutral intonation, a traditional oddball design with emotional deviants (10% happy and angry each) and an optimum design with emotional (17% happy and sad each) and nonemotional gender deviants (17% female) elicited the mismatch responses. The emotional category changes demonstrated early responses (<200 ms) at both auditory cortices with larger amplitudes at the right hemisphere. Responses to the nonemotional change from male to female voices emerged later ( approximately 300 ms). Source analysis pointed at bilateral auditory cortex sources without robust contribution from other such as frontal sources. Conceivably, both auditory cortices encode categorical representations of emotional prosodic. Processing of cognitive feature extraction and automatic emotion appraisal may overlap at this level enabling rapid attentional shifts to important social cues. Copyright (c) 2009 Elsevier Inc. All rights reserved.

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

Relating normalization to neuronal populations across cortical areas.

PubMed

Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

2016-09-01

Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

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

Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study.

PubMed

Di Lorenzo, Cherubino; Coppola, Gianluca; Bracaglia, Martina; Di Lenola, Davide; Evangelista, Maurizio; Sirianni, Giulio; Rossi, Paolo; Di Lorenzo, Giorgio; Serrao, Mariano; Parisi, Vincenzo; Pierelli, Francesco

2016-01-01

Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine. Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs. After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks. KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

Modeling a space-variant cortical representation for apparent motion.

PubMed

Wurbs, Jeremy; Mingolla, Ennio; Yazdanbakhsh, Arash

2013-08-06

Receptive field sizes of neurons in early primate visual areas increase with eccentricity, as does temporal processing speed. The fovea is evidently specialized for slow, fine movements while the periphery is suited for fast, coarse movements. In either the fovea or periphery discrete flashes can produce motion percepts. Grossberg and Rudd (1989) used traveling Gaussian activity profiles to model long-range apparent motion percepts. We propose a neural model constrained by physiological data to explain how signals from retinal ganglion cells to V1 affect the perception of motion as a function of eccentricity. Our model incorporates cortical magnification, receptive field overlap and scatter, and spatial and temporal response characteristics of retinal ganglion cells for cortical processing of motion. Consistent with the finding of Baker and Braddick (1985), in our model the maximum flash distance that is perceived as an apparent motion (Dmax) increases linearly as a function of eccentricity. Baker and Braddick (1985) made qualitative predictions about the functional significance of both stimulus and visual system parameters that constrain motion perception, such as an increase in the range of detectable motions as a function of eccentricity and the likely role of higher visual processes in determining Dmax. We generate corresponding quantitative predictions for those functional dependencies for individual aspects of motion processing. Simulation results indicate that the early visual pathway can explain the qualitative linear increase of Dmax data without reliance on extrastriate areas, but that those higher visual areas may serve as a modulatory influence on the exact Dmax increase.

Contribution of different classes of glutamate receptors in the corticostriatal polysynaptic responses from striatal direct and indirect projection neurons

PubMed Central

2013-01-01

Background Previous work showed differences in the polysynaptic activation of GABAergic synapses during corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (dSPNs and iSPNs). Here, we now show differences and similarities in the polysynaptic activation of cortical glutamatergic synapses on the same responses. Corticostriatal contacts have been extensively studied. However, several questions remain unanswered, e.g.: what are the differences and similarities in the responses to glutamate in dSPNs and iSPNs? Does glutamatergic synaptic activation exhibits a distribution of latencies over time in vitro? That would be a strong suggestion of polysynaptic cortical convergence. What is the role of kainate receptors in corticostriatal transmission? Current-clamp recordings were used to answer these questions. One hypothesis was: if prolonged synaptic activation distributed along time was present, then it would be mainly generated from the cortex, and not from the striatum. Results By isolating responses from AMPA-receptors out of the complex suprathreshold response of SPNs, it is shown that a single cortical stimulus induces early and late synaptic activation lasting hundreds of milliseconds. Prolonged responses depended on cortical stimulation because they could not be elicited using intrastriatal stimulation, even if GABAergic transmission was blocked. Thus, the results are not explained by differences in evoked inhibition. Moreover, inhibitory participation was larger after cortical than after intrastriatal stimulation. A strong activation of interneurons was obtained from the cortex, demonstrating that polysynaptic activation includes the striatum. Prolonged kainate (KA) receptor responses were also elicited from the cortex. Responses of dSPNs and iSPNs did not depend on the cortical area stimulated. In contrast to AMPA-receptors, responses from NMDA- and KA-receptors do not exhibit early and late responses, but generate slow

Modulation of early cortical processing during divided attention to non-contiguous locations.

PubMed

Frey, Hans-Peter; Schmid, Anita M; Murphy, Jeremy W; Molholm, Sophie; Lalor, Edmund C; Foxe, John J

2014-05-01

We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. Whereas, for several years, the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed by the use of high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classic pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced, and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing time-frames in hierarchically early visual regions, and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood. PMID:24755274

Mapping callosal morphology in early- and late-onset elderly depression: an index of distinct changes in cortical connectivity.

PubMed

Ballmaier, Martina; Kumar, Anand; Elderkin-Thompson, Virginia; Narr, Katherine L; Luders, Eileen; Thompson, Paul M; Hojatkashani, Cornelius; Pham, Daniel; Heinz, Andreas; Toga, Arthur W

2008-06-01

There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age = 68.00, SD+/-5.83), 22 patients with late-onset depression (mean age = 74.50, SD+/-8.09) and 34 elderly control subjects (mean age = 72.38; SD+/-6.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late- vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late- from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late- and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than early-onset depression, with potentially important implications for research and therapy.

The effect of binaural beats on verbal working memory and cortical connectivity

NASA Astrophysics Data System (ADS)

Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A.; Leonessa, Alexander

2017-04-01

Objective. Synchronization in activated regions of cortical networks affect the brain’s frequency response, which has been associated with a wide range of states and abilities, including memory. A non-invasive method for manipulating cortical synchronization is binaural beats. Binaural beats take advantage of the brain’s response to two pure tones, delivered independently to each ear, when those tones have a small frequency mismatch. The mismatch between the tones is interpreted as a beat frequency, which may act to synchronize cortical oscillations. Neural synchrony is particularly important for working memory processes, the system controlling online organization and retention of information for successful goal-directed behavior. Therefore, manipulation of synchrony via binaural beats provides a unique window into working memory and associated connectivity of cortical networks. Approach. In this study, we examined the effects of different acoustic stimulation conditions during an N-back working memory task, and we measured participant response accuracy and cortical network topology via EEG recordings. Six acoustic stimulation conditions were used: None, Pure Tone, Classical Music, 5 Hz binaural beats, 10 Hz binaural beats, and 15 Hz binaural beats. Main results. We determined that listening to 15 Hz binaural beats during an N-Back working memory task increased the individual participant’s accuracy, modulated the cortical frequency response, and changed the cortical network connection strengths during the task. Only the 15 Hz binaural beats produced significant change in relative accuracy compared to the None condition. Significance. Listening to 15 Hz binaural beats during the N-back task activated salient frequency bands and produced networks characterized by higher information transfer as compared to other auditory stimulation conditions.

Cortical Responses to Chinese Phonemes in Preschoolers Predict Their Literacy Skills at School Age.

PubMed

Hong, Tian; Shuai, Lan; Frost, Stephen J; Landi, Nicole; Pugh, Kenneth R; Shu, Hua

2018-01-01

We investigated whether preschoolers with poor phonological awareness (PA) skills had impaired cortical basis for detecting speech feature, and whether speech perception influences future literacy outcomes in preschoolers. We recorded ERP responses to speech in 52 Chinese preschoolers. The results showed that the poor PA group processed speech changes differentially compared to control group in mismatch negativity (MMN) and late discriminative negativity (LDN). Furthermore, speech perception in kindergarten could predict literacy outcomes after literacy acquisition. These suggest that impairment in detecting speech features occurs before formal reading instruction, and that speech perception plays an important role in reading development.

Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology

PubMed Central

McNamara, Robert K; Vannest, Jennifer J; Valentine, Christina J

2015-01-01

Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies. PMID:25815252

The response of cortical neurons to in vivo-like input current: theory and experiment: II. Time-varying and spatially distributed inputs.

PubMed

Giugliano, Michele; La Camera, Giancarlo; Fusi, Stefano; Senn, Walter

2008-11-01

The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane's inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite-soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons.

Axono-cortical evoked potentials: A proof-of-concept study.

PubMed

Mandonnet, E; Dadoun, Y; Poisson, I; Madadaki, C; Froelich, S; Lozeron, P

2016-04-01

Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients with Childhood-Onset Schizophrenia

ERIC Educational Resources Information Center

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2011-01-01

Objective: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to…

Nanoscale laminin coating modulates cortical scarring response around implanted silicon microelectrode arrays

NASA Astrophysics Data System (ADS)

He, Wei; McConnell, George C.; Bellamkonda, Ravi V.

2006-12-01

Neural electrodes could significantly enhance the quality of life for patients with sensory and/or motor deficits as well as improve our understanding of brain functions. However, long-term electrical connectivity between neural tissue and recording sites is compromised by the development of astroglial scar around the recording probes. In this study we investigate the effect of a nanoscale laminin (LN) coating on Si-based neural probes on chronic cortical tissue reaction in a rat model. Tissue reaction was evaluated after 1 day, 1 week, and 4 weeks post-implant for coated and uncoated probes using immunohistochemical techniques to evaluate activated microglia/macrophages (ED-1), astrocytes (GFAP) and neurons (NeuN). The coating did not have an observable effect on neuronal density or proximity to the electrode surface. However, the response of microglia/macrophages and astrocytes was altered by the coating. One day post-implant, we observed an ~60% increase in ED-1 expression near LN-coated probe sites compared with control uncoated probe sites. Four weeks post-implant, we observed an ~20% reduction in ED-1 expression along with an ~50% reduction in GFAP expression at coated relative to uncoated probe sites. These results suggest that LN has a stimulatory effect on early microglia activation, accelerating the phagocytic function of these cells. This hypothesis is further supported by the increased mRNA expression of several pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) in cultured microglia on LN-bound Si substrates. LN immunostaining of coated probes immediately after insertion and retrieval demonstrates that the coating integrity is not compromised by the shear force during insertion. We speculate, based on these encouraging results, that LN coating of Si neural probes could potentially improve chronic neural recordings through dispersion of the astroglial scar.

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

In Vivo Voltage-Sensitive Dye Study of Lateral Spreading of Cortical Activity in Mouse Primary Visual Cortex Induced by a Current Impulse

PubMed Central

Fehérvári, Tamás Dávid; Sawai, Hajime; Yagi, Tetsuya

2015-01-01

In the mammalian primary visual cortex (V1), lateral spreading of excitatory potentials is believed to be involved in spatial integrative functions, but the underlying cortical mechanism is not well understood. Visually-evoked population-level responses have been shown to propagate beyond the V1 initial activation site in mouse, similar to higher mammals. Visually-evoked responses are, however, affected by neuronal circuits prior to V1 (retina, LGN), making the separate analysis of V1 difficult. Intracortical stimulation eliminates these initial processing steps. We used in vivo RH1691 voltage-sensitive dye (VSD) imaging and intracortical microstimulation in adult C57BL/6 mice to elucidate the spatiotemporal properties of population-level signal spreading in V1 cortical circuits. The evoked response was qualitatively similar to that measured in single-cell electrophysiological experiments in rodents: a fast transient fluorescence peak followed by a fast and a slow decrease or hyperpolarization, similar to EPSP and fast and slow IPSPs in single cells. The early cortical response expanded at speeds commensurate with long horizontal projections (at 5% of the peak maximum, 0.08–0.15 m/s) however, the bulk of the VSD signal propagated slowly (at half-peak maximum, 0.05–0.08 m/s) suggesting an important role of regenerative multisynaptic transmission through short horizontal connections in V1 spatial integrative functions. We also found a tendency for a widespread and fast cortical response suppression in V1, which was eliminated by GABAA-antagonists gabazine and bicuculline methiodide. Our results help understand the neuronal circuitry involved in lateral spreading in V1. PMID:26230520

Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

PubMed

Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

2014-09-10

Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia.

PubMed

Chiappelli, Joshua; Rowland, Laura M; Notarangelo, Francesca M; Wijtenburg, S Andrea; Thomas, Marian A R; Pocivavsek, Ana; Jones, Aaron; Wisner, Krista; Kochunov, Peter; Schwarcz, Robert; Hong, L Elliot

2018-04-18

Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia. In 56 patients with schizophrenia and 58 healthy controls, our results confirm that levels of KYNA in saliva increase following psychological stress. The magnitude of the effect correlated negatively with proton magnetic resonance spectroscopy (MRS) glutamate + glutamine (r = -.31, p = .017) and glutamate (r = -0.27, p = .047) levels in the ACC in patients but not in the controls (all p ≥ .45). Although, a causal relationship cannot be ascertained in this cross-sectional study, these findings suggest a potentially meaningful link between central glutamate levels and kynurenine pathway response to stress in individuals with schizophrenia.

Heightened amygdala responsiveness in s-carriers of 5-HTTLPR genetic polymorphism reflects enhanced cortical rather than subcortical inputs: An MEG study.

PubMed

Luo, Qian; Holroyd, Tom; Mitchell, Derek; Yu, Henry; Cheng, Xi; Hodgkinson, Colin; Chen, Gang; McCaffrey, Daniel; Goldman, David; Blair, R James

2017-09-01

Short allele carriers (S-carriers) of the serotonin transporter gene (5-HTTLPR) show an elevated amygdala response to emotional stimuli relative to long allele carriers (LL-homozygous). However, whether this reflects increased responsiveness of the amygdala generally or interactions between the amygdala and the specific input systems remains unknown. It is argued that the amygdala receives input via a quick subcortical and a slower cortical pathway. If the elevated amygdala response in S-carriers reflects generally increased amygdala responding, then group differences in amygdala should be seen across the amygdala response time course. However, if the difference is a secondary consequence of enhanced amygdala-cortical interactions, then group differences might only be present later in the amygdala response. Using magnetoencephalography (MEG), we found an enhanced amygdala response to fearful expressions starting 40-50 ms poststimulus. However, group differences in the amygdala were only seen 190-200 ms poststimulus, preceded by increased superior temporal sulcus (STS) responses in S-carriers from 130 to 140 ms poststimulus. An enhanced amygdala response to angry expressions started 260-270 ms poststimulus with group differences in the amygdala starting at 160-170 ms poststimulus onset, preceded by increased STS responses in S-carriers from 150 to 160 ms poststimulus. These suggest that enhanced amygdala responses in S-carriers might reflect enhanced STS-amygdala connectivity in S-carriers. Hum Brain Mapp 38:4313-4321, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cortical Responses to Speech Sounds in 3- and 6-Month-Old Infants Fed Breast Milk, Milk Formula, or Soy Formula

USDA-ARS?s Scientific Manuscript database

The influence of the three most common infant diets (breast milk, milk-based and soy-based formulas) on growth, behavioral development, and cortical responses (ERPs) to the consonant-vowel syllable /pa/, was examined in 130 healthy infants from an ongoing longitudinal study of 600 from birth through...

Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas

PubMed Central

Sellers, Kristin K.; Bennett, Davis V.; Hutt, Axel; Williams, James H.

2015-01-01

During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

Non-linear Membrane Properties in Entorhinal Cortical Stellate Cells Reduce Modulation of Input-Output Responses by Voltage Fluctuations

PubMed Central

Fernandez, Fernando R.; Malerba, Paola; White, John A.

2015-01-01

The presence of voltage fluctuations arising from synaptic activity is a critical component in models of gain control, neuronal output gating, and spike rate coding. The degree to which individual neuronal input-output functions are modulated by voltage fluctuations, however, is not well established across different cortical areas. Additionally, the extent and mechanisms of input-output modulation through fluctuations have been explored largely in simplified models of spike generation, and with limited consideration for the role of non-linear and voltage-dependent membrane properties. To address these issues, we studied fluctuation-based modulation of input-output responses in medial entorhinal cortical (MEC) stellate cells of rats, which express strong sub-threshold non-linear membrane properties. Using in vitro recordings, dynamic clamp and modeling, we show that the modulation of input-output responses by random voltage fluctuations in stellate cells is significantly limited. In stellate cells, a voltage-dependent increase in membrane resistance at sub-threshold voltages mediated by Na+ conductance activation limits the ability of fluctuations to elicit spikes. Similarly, in exponential leaky integrate-and-fire models using a shallow voltage-dependence for the exponential term that matches stellate cell membrane properties, a low degree of fluctuation-based modulation of input-output responses can be attained. These results demonstrate that fluctuation-based modulation of input-output responses is not a universal feature of neurons and can be significantly limited by subthreshold voltage-gated conductances. PMID:25909971

Non-linear Membrane Properties in Entorhinal Cortical Stellate Cells Reduce Modulation of Input-Output Responses by Voltage Fluctuations.

PubMed

Fernandez, Fernando R; Malerba, Paola; White, John A

2015-04-01

The presence of voltage fluctuations arising from synaptic activity is a critical component in models of gain control, neuronal output gating, and spike rate coding. The degree to which individual neuronal input-output functions are modulated by voltage fluctuations, however, is not well established across different cortical areas. Additionally, the extent and mechanisms of input-output modulation through fluctuations have been explored largely in simplified models of spike generation, and with limited consideration for the role of non-linear and voltage-dependent membrane properties. To address these issues, we studied fluctuation-based modulation of input-output responses in medial entorhinal cortical (MEC) stellate cells of rats, which express strong sub-threshold non-linear membrane properties. Using in vitro recordings, dynamic clamp and modeling, we show that the modulation of input-output responses by random voltage fluctuations in stellate cells is significantly limited. In stellate cells, a voltage-dependent increase in membrane resistance at sub-threshold voltages mediated by Na+ conductance activation limits the ability of fluctuations to elicit spikes. Similarly, in exponential leaky integrate-and-fire models using a shallow voltage-dependence for the exponential term that matches stellate cell membrane properties, a low degree of fluctuation-based modulation of input-output responses can be attained. These results demonstrate that fluctuation-based modulation of input-output responses is not a universal feature of neurons and can be significantly limited by subthreshold voltage-gated conductances.

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.

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.

Simultaneous imaging of intrinsic optical signals and cerebral vessel responses during cortical spreading depression in rats

NASA Astrophysics Data System (ADS)

Li, Pengcheng; Chen, Shangbin; Luo, Weihua; Luo, Qingming

2003-12-01

Cortical spreading depression (CSD) is an important disease model for migraine and cerebral ischemia. We investigated the spatio-temporal characteristics of the intrinsic optical signals (IOS) at 570 nm and the cerebral blood vessel responses during CSD simultaneously by optical reflectance imaging in vivo. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. A four-phasic IOS response was observed at pial arteries and parenchymal sites in all experimental animals and an initial slight pial arteries dilation (21.5%+/-13.6%) and constriction (-4.2%+/-3.5%) precedes the dramatic dilation (69.2%+/-26.1%) of pial arterioles was recorded. Our experimental results show a high correlation (r = 0.89+/-0.025) between the IOS response and the diameter changes of the cerebral blood vessels during CSD in rats.

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

PubMed Central

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2012-01-01

Objective Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to “normalize” by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. Method Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval–matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. Results As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. Conclusions Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings. PMID:21703497

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

APC sets the Wnt tone necessary for cerebral cortical progenitor development.

PubMed

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S

2017-08-15

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.

APC sets the Wnt tone necessary for cerebral cortical progenitor development

PubMed Central

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E.S.

2017-01-01

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC–β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC–β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. PMID:28916710

Quantitative analysis of neuronal response properties in primary and higher-order auditory cortical fields of awake house mice (Mus musculus)

PubMed Central

Joachimsthaler, Bettina; Uhlmann, Michaela; Miller, Frank; Ehret, Günter; Kurt, Simone

2014-01-01

Because of its great genetic potential, the mouse (Mus musculus) has become a popular model species for studies on hearing and sound processing along the auditory pathways. Here, we present the first comparative study on the representation of neuronal response parameters to tones in primary and higher-order auditory cortical fields of awake mice. We quantified 12 neuronal properties of tone processing in order to estimate similarities and differences of function between the fields, and to discuss how far auditory cortex (AC) function in the mouse is comparable to that in awake monkeys and cats. Extracellular recordings were made from 1400 small clusters of neurons from cortical layers III/IV in the primary fields AI (primary auditory field) and AAF (anterior auditory field), and the higher-order fields AII (second auditory field) and DP (dorsoposterior field). Field specificity was shown with regard to spontaneous activity, correlation between spontaneous and evoked activity, tone response latency, sharpness of frequency tuning, temporal response patterns (occurrence of phasic responses, phasic-tonic responses, tonic responses, and off-responses), and degree of variation between the characteristic frequency (CF) and the best frequency (BF) (CF–BF relationship). Field similarities were noted as significant correlations between CFs and BFs, V-shaped frequency tuning curves, similar minimum response thresholds and non-monotonic rate-level functions in approximately two-thirds of the neurons. Comparative and quantitative analyses showed that the measured response characteristics were, to various degrees, susceptible to influences of anesthetics. Therefore, studies of neuronal responses in the awake AC are important in order to establish adequate relationships between neuronal data and auditory perception and acoustic response behavior. PMID:24506843

Jealousy increased by induced relative left frontal cortical activity.

PubMed

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

2015-10-01

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

Economic Value Biases Uncertain Perceptual Choices in the Parietal and Prefrontal Cortices

PubMed Central

Summerfield, Christopher; Koechlin, Etienne

2010-01-01

An observer detecting a noisy sensory signal is biased by the costs and benefits associated with its presence or absence. When these costs and benefits are asymmetric, sensory, and economic information must be integrated to inform the final choice. However, it remains unknown how this information is combined at the neural or computational levels. To address this question, we asked healthy human observers to judge the presence or absence of a noisy sensory signal under economic conditions that favored yes responses (liberal blocks), no responses (conservative blocks), or neither response (neutral blocks). Economic information biased fast choices more than slow choices, suggesting that value and sensory information are integrated early in the decision epoch. More formal simulation analyses using an Ornstein–Uhlenbeck process demonstrated that the influence of economic information was best captured by shifting the origin of evidence accumulation toward the more valuable bound. We then used the computational model to generate trial-by-trial estimates of decision-related evidence that were based on combined sensory and economic information (the decision variable or DV), and regressed these against fMRI activity recorded whilst participants performed the task. Extrastriate visual regions responded to the level of sensory input (momentary evidence), but fMRI signals in the parietal and prefrontal cortices responded to the decision variable. These findings support recent single-neuron data suggesting that economic information biases decision-related signals in higher cortical regions. PMID:21267421

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

PubMed

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

2018-05-01

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

Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations.

PubMed

Barriga-Rivera, Alejandro; Morley, John W; Lovell, Nigel H; Suaning, Gregg J

2016-08-01

Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.

Astrocytes refine cortical connectivity at dendritic spines

PubMed Central

Risher, W Christopher; Patel, Sagar; Kim, Il Hwan; Uezu, Akiyoshi; Bhagat, Srishti; Wilton, Daniel K; Pilaz, Louis-Jan; Singh Alvarado, Jonnathan; Calhan, Osman Y; Silver, Debra L; Stevens, Beth; Calakos, Nicole; Soderling, Scott H; Eroglu, Cagla

2014-01-01

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.04047.001 PMID:25517933

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

Objective Assessment of Spectral Ripple Discrimination in Cochlear Implant Listeners Using Cortical Evoked Responses to an Oddball Paradigm

PubMed Central

Lopez Valdes, Alejandro; Mc Laughlin, Myles; Viani, Laura; Walshe, Peter; Smith, Jaclyn; Zeng, Fan-Gang; Reilly, Richard B.

2014-01-01

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R2 = 0.60, p<0.01). This method can objectively assess CI spectral resolution performance, providing a potential tool for the evaluation and follow-up of CI listeners who have difficulty performing psychoacoustic tests, such as pediatric or new users. PMID:24599314

Objective assessment of spectral ripple discrimination in cochlear implant listeners using cortical evoked responses to an oddball paradigm.

PubMed

Lopez Valdes, Alejandro; Mc Laughlin, Myles; Viani, Laura; Walshe, Peter; Smith, Jaclyn; Zeng, Fan-Gang; Reilly, Richard B

2014-01-01

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R2=0.60, p<0.01). This method can objectively assess CI spectral resolution performance, providing a potential tool for the evaluation and follow-up of CI listeners who have difficulty performing psychoacoustic tests, such as pediatric or new users.

Deficient cortical face-sensitive N170 responses and basic visual processing in schizophrenia.

PubMed

Maher, S; Mashhoon, Y; Ekstrom, T; Lukas, S; Chen, Y

2016-01-01

Face detection, an ability to identify a visual stimulus as a face, is impaired in patients with schizophrenia. It is unclear whether impaired face processing in this psychiatric disorder results from face-specific domains or stems from more basic visual domains. In this study, we examined cortical face-sensitive N170 response in schizophrenia, taking into account deficient basic visual contrast processing. We equalized visual contrast signals among patients (n=20) and controls (n=20) and between face and tree images, based on their individual perceptual capacities (determined using psychophysical methods). We measured N170, a putative temporal marker of face processing, during face detection and tree detection. In controls, N170 amplitudes were significantly greater for faces than trees across all three visual contrast levels tested (perceptual threshold, two times perceptual threshold and 100%). In patients, however, N170 amplitudes did not differ between faces and trees, indicating diminished face selectivity (indexed by the differential responses to face vs. tree). These results indicate a lack of face-selectivity in temporal responses of brain machinery putatively responsible for face processing in schizophrenia. This neuroimaging finding suggests that face-specific processing is compromised in this psychiatric disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

Relational Associative Learning Induces Cross-Modal Plasticity in Early Visual Cortex

PubMed Central

Headley, Drew B.; Weinberger, Norman M.

2015-01-01

Neurobiological theories of memory posit that the neocortex is a storage site of declarative memories, a hallmark of which is the association of two arbitrary neutral stimuli. Early sensory cortices, once assumed uninvolved in memory storage, recently have been implicated in associations between neutral stimuli and reward or punishment. We asked whether links between neutral stimuli also could be formed in early visual or auditory cortices. Rats were presented with a tone paired with a light using a sensory preconditioning paradigm that enabled later evaluation of successful association. Subjects that acquired this association developed enhanced sound evoked potentials in their primary and secondary visual cortices. Laminar recordings localized this potential to cortical Layers 5 and 6. A similar pattern of activation was elicited by microstimulation of primary auditory cortex in the same subjects, consistent with a cortico-cortical substrate of association. Thus, early sensory cortex has the capability to form neutral stimulus associations. This plasticity may constitute a declarative memory trace between sensory cortices. PMID:24275832

Cortical firing and sleep homeostasis.

PubMed

Vyazovskiy, Vladyslav V; Olcese, Umberto; Lazimy, Yaniv M; Faraguna, Ugo; Esser, Steve K; Williams, Justin C; Cirelli, Chiara; Tononi, Giulio

2009-09-24

The need to sleep grows with the duration of wakefulness and dissipates with time spent asleep, a process called sleep homeostasis. What are the consequences of staying awake on brain cells, and why is sleep needed? Surprisingly, we do not know whether the firing of cortical neurons is affected by how long an animal has been awake or asleep. Here, we found that after sustained wakefulness cortical neurons fire at higher frequencies in all behavioral states. During early NREM sleep after sustained wakefulness, periods of population activity (ON) are short, frequent, and associated with synchronous firing, while periods of neuronal silence are long and frequent. After sustained sleep, firing rates and synchrony decrease, while the duration of ON periods increases. Changes in firing patterns in NREM sleep correlate with changes in slow-wave activity, a marker of sleep homeostasis. Thus, the systematic increase of firing during wakefulness is counterbalanced by staying asleep.

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.

Inactivation of basolateral amygdala specifically eliminates palatability-related information in cortical sensory responses.

PubMed

Piette, Caitlin E; Baez-Santiago, Madelyn A; Reid, Emily E; Katz, Donald B; Moran, Anan

2012-07-18

Evidence indirectly implicates the amygdala as the primary processor of emotional information used by cortex to drive appropriate behavioral responses to stimuli. Taste provides an ideal system with which to test this hypothesis directly, as neurons in both basolateral amygdala (BLA) and gustatory cortex (GC)-anatomically interconnected nodes of the gustatory system-code the emotional valence of taste stimuli (i.e., palatability), in firing rate responses that progress similarly through "epochs." The fact that palatability-related firing appears one epoch earlier in BLA than GC is broadly consistent with the hypothesis that such information may propagate from the former to the latter. Here, we provide evidence supporting this hypothesis, assaying taste responses in small GC single-neuron ensembles before, during, and after temporarily inactivating BLA in awake rats. BLA inactivation (BLAx) changed responses in 98% of taste-responsive GC neurons, altering the entirety of every taste response in many neurons. Most changes involved reductions in firing rate, but regardless of the direction of change, the effect of BLAx was epoch-specific: while firing rates were changed, the taste specificity of responses remained stable; information about taste palatability, however, which normally resides in the "Late" epoch, was reduced in magnitude across the entire GC sample and outright eliminated in most neurons. Only in the specific minority of neurons for which BLAx enhanced responses did palatability specificity survive undiminished. Our data therefore provide direct evidence that BLA is a necessary component of GC gustatory processing, and that cortical palatability processing in particular is, in part, a function of BLA activity.

Inactivation of basolateral amygdala specifically eliminates palatability-related information in cortical sensory responses

PubMed Central

Piette, Caitlin E.; Baez-Santiago, Madelyn A.; Reid, Emily E.; Katz, Donald B.; Moran, Anan

2012-01-01

Evidence indirectly implicates the amygdala as the primary processor of emotional information used by cortex to drive appropriate behavioral responses to stimuli. Taste provides an ideal system with which to test this hypothesis directly, as neurons in both basolateral amygdala (BLA) and gustatory cortex (GC)—anatomically interconnected nodes of the gustatory system—code the emotional valence of taste stimuli (i.e., palatability), in firing rate responses that progress similarly through “epochs.” The fact that palatability-related firing appears one epoch earlier in BLA than GC is broadly consistent with the hypothesis that such information may propagate from the former to the latter. Here, we provide evidence supporting this hypothesis, assaying taste responses in small GC single-neuron ensembles before, during and after temporarily inactivating BLA (BLAx) in awake rats. BLAx changed responses in 98% of taste-responsive GC neurons, altering the entirety of every taste response in many neurons. Most changes involved reductions in firing rate, but regardless of the direction of change, the effect of BLAx was epoch-specific: while firing rates were changed, the taste-specificity of responses remained stable; information about taste palatability, however, which normally resides in the “Late” epoch, was reduced in magnitude across the entire GC sample and outright eliminated in most neurons. Only in the specific minority of neurons for which BLAx enhanced responses did palatability-specificity survive undiminished. Our data therefore provide direct evidence that BLA is a necessary component of GC gustatory processing, and that cortical palatability processing in particular is, in part, a function of BLA activity. PMID:22815512

Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway.

PubMed

Saengjaroentham, Chonlawan; Supornsilpchai, Weera; Ji-Au, Wilawan; Srikiatkhachorn, Anan; Maneesri-le Grand, Supang

2015-02-01

Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.

PET-Based Confirmation of Orientation Sensitivity of TMS-Induced Cortical Activation in Humans

PubMed Central

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2017-01-01

Background Currently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks. Objective/hypothesis To more thoroughly investigate this inconsistency, we sought to determine whether neocortical surface orientation was a critical determinant of regional activation. Methods MR images were used to construct cortical and scalp surfaces for 18 subjects. The angle (θ) between the cortical surface normal and its nearest scalp normal for ~50,000 cortical points per subject was used to quantify cortical location (i.e., gyral vs. sulcal). TMS-induced activations of primary motor cortex (M1) were compared to brain activations recorded during a finger-tapping task using concurrent positron emission tomographic (PET) imaging. Results Brain activations were primarily sulcal for both the TMS and task activations (P < 0.001 for both) compared to the overall cortical surface orientation. Also, the location of maximal blood flow in response to either TMS or finger-tapping correlated well using the cortical surface orientation angle or distance to scalp (P < 0.001 for both) as criteria for comparison between different neocortical activation modalities. Conclusion This study provides further evidence that a major factor in cortical activation using TMS is the orientation of the cortical surface with respect to the induced electric field. The results show that, despite the gyral crown of the cortex being subjected to a larger magnetic field magnitude, the sulcal bank of M1 had larger cerebral blood flow (CBF) responses during TMS. PMID:23827648

A method for vibrational assessment of cortical bone

NASA Astrophysics Data System (ADS)

Song, Yan; Gunaratne, Gemunu H.

2006-09-01

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

BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons.

PubMed

David, Alexandre; Tiveron, Marie-Catherine; Defays, Axel; Beclin, Christophe; Camosseto, Voahirana; Gatti, Evelina; Cremer, Harold; Pierre, Philippe

2007-01-15

The brain-associated LAMP-like molecule (BAD-LAMP) is a new member of the family of lysosome associated membrane proteins (LAMPs). In contrast to other LAMPs, which show a widespread expression, BAD-LAMP expression in mice is confined to the postnatal brain and therein to neuronal subpopulations in layers II/III and V of the neocortex. Onset of expression strictly parallels cortical synaptogenesis. In cortical neurons, the protein is found in defined clustered vesicles, which accumulate along neurites where it localizes with phosphorylated epitopes of neurofilament H. In primary neurons, BAD-LAMP is endocytosed, but is not found in classical lysosomal/endosomal compartments. Modification of BAD-LAMP by addition of GFP revealed a cryptic lysosomal retention motif, suggesting that the cytoplasmic tail of BAD-LAMP is actively interacting with, or modified by, molecules that promote its sorting away from lysosomes. Analysis of BAD-LAMP endocytosis in transfected HeLa cells provided evidence that the protein recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. Thus, BAD-LAMP is an unconventional LAMP-like molecule and defines a new endocytic compartment in specific subtypes of cortical projection neurons. The striking correlation between the appearance of BAD-LAMP and cortical synatogenesis points towards a physiological role of this vesicular determinant for neuronal function.

Oxytocin Enables Maternal Behavior by Balancing Cortical Inhibition

PubMed Central

Marlin, Bianca J.; Mitre, Mariela; D’amour, James A.; Chao, Moses V.; Froemke, Robert C.

2015-01-01

Oxytocin is important for social interactions and maternal behavior. However, little is known about when, where, and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behavior in female mice by enhancing auditory cortical pup call responses. Retrieval behavior required left but not right auditory cortex, was accelerated by oxytocin in left auditory cortex, and oxytocin receptors were preferentially expressed in left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally-precise excitatory and inhibitory responses in left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing. PMID:25874674

Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players.

PubMed

Chieffo, Raffaella; Straffi, Laura; Inuggi, Alberto; Gonzalez-Rosa, Javier J; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

2016-01-01

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.

Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players

PubMed Central

Inuggi, Alberto; Gonzalez-Rosa, Javier J.; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

2016-01-01

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere. PMID:27336584

Amygdala lesions do not compromise the cortical network for false-belief reasoning.

PubMed

Spunt, Robert P; Elison, Jed T; Dufour, Nicholas; Hurlemann, René; Saxe, Rebecca; Adolphs, Ralph

2015-04-14

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM--false-belief reasoning--suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.

Amygdala lesions do not compromise the cortical network for false-belief reasoning

PubMed Central

Elison, Jed T.; Dufour, Nicholas; Hurlemann, René; Saxe, Rebecca; Adolphs, Ralph

2015-01-01

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM—false-belief reasoning—suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition. PMID:25825732

Long-Lasting Crossmodal Cortical Reorganization Triggered by Brief Postnatal Visual Deprivation.

PubMed

Collignon, Olivier; Dormal, Giulia; de Heering, Adelaide; Lepore, Franco; Lewis, Terri L; Maurer, Daphne

2015-09-21

Animal and human studies have demonstrated that transient visual deprivation early in life, even for a very short period, permanently alters the response properties of neurons in the visual cortex and leads to corresponding behavioral visual deficits. While it is acknowledged that early-onset and longstanding blindness leads the occipital cortex to respond to non-visual stimulation, it remains unknown whether a short and transient period of postnatal visual deprivation is sufficient to trigger crossmodal reorganization that persists after years of visual experience. In the present study, we characterized brain responses to auditory stimuli in 11 adults who had been deprived of all patterned vision at birth by congenital cataracts in both eyes until they were treated at 9 to 238 days of age. When compared to controls with typical visual experience, the cataract-reversal group showed enhanced auditory-driven activity in focal visual regions. A combination of dynamic causal modeling with Bayesian model selection indicated that this auditory-driven activity in the occipital cortex was better explained by direct cortico-cortical connections with the primary auditory cortex than by subcortical connections. Thus, a short and transient period of visual deprivation early in life leads to enduring large-scale crossmodal reorganization of the brain circuitry typically dedicated to vision. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visual Attention Model Based on Statistical Properties of Neuron Responses

PubMed Central

Duan, Haibin; Wang, Xiaohua

2015-01-01

Visual attention is a mechanism of the visual system that can select relevant objects from a specific scene. Interactions among neurons in multiple cortical areas are considered to be involved in attentional allocation. However, the characteristics of the encoded features and neuron responses in those attention related cortices are indefinite. Therefore, further investigations carried out in this study aim at demonstrating that unusual regions arousing more attention generally cause particular neuron responses. We suppose that visual saliency is obtained on the basis of neuron responses to contexts in natural scenes. A bottom-up visual attention model is proposed based on the self-information of neuron responses to test and verify the hypothesis. Four different color spaces are adopted and a novel entropy-based combination scheme is designed to make full use of color information. Valuable regions are highlighted while redundant backgrounds are suppressed in the saliency maps obtained by the proposed model. Comparative results reveal that the proposed model outperforms several state-of-the-art models. This study provides insights into the neuron responses based saliency detection and may underlie the neural mechanism of early visual cortices for bottom-up visual attention. PMID:25747859

Characterization of Early Cortical Neural Network Development in Multiwell Microelectrode Array Plates

EPA Science Inventory

We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentiall...

Decreased occipital cortical glutamate levels in response to successful cognitive-behavioral therapy and pharmacotherapy for major depressive disorder.

PubMed

Abdallah, Chadi G; Niciu, Mark J; Fenton, Lisa R; Fasula, Madonna K; Jiang, Lihong; Black, Anne; Rothman, Douglas L; Mason, Graeme F; Sanacora, Gerard

2014-01-01

Previous studies have demonstrated that antidepressant medication and electroconvulsive therapy increase occipital cortical γ-aminobutyric acid (GABA) in major depressive disorder (MDD), but a small pilot study failed to show a similar effect of cognitive-behavioral therapy (CBT) on occipital GABA. In light of these findings we sought to determine if baseline GABA levels predict treatment response and to broaden the analysis to other metabolites and neurotransmitters in this larger study. A total of 40 MDD outpatients received baseline proton magnetic resonance spectroscopy (1H-MRS), and 30 subjects completed both pre- and post-CBT 1H-MRS; 9 CBT nonresponders completed an open-label medication phase followed by an additional/3rd 1H-MRS. The magnitude of treatment response was correlated with occipital amino acid neurotransmitter levels. Baseline GABA did not predict treatment outcome. Furthermore, there was no significant effect of CBT on GABA levels. However, we found a significant group × time interaction (F1, 28 = 6.30, p = 0.02), demonstrating reduced glutamate in CBT responders, with no significant glutamate change in CBT nonresponders. These findings corroborate the lack of effect of successful CBT on occipital cortical GABA levels in a larger sample. A reduction in glutamate levels following treatment, on the other hand, correlated with successful CBT and antidepressant medication response. Based on this finding and other reports, decreased occipital glutamate may be an antidepressant response biomarker. Healthy control comparator and nonintervention groups may shed light on the sensitivity and specificity of these results.

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

PubMed Central

Ries, Michele L.; Jabbar, Britta M.; Schmitz, Taylor W.; Trivedi, Mehul A.; Gleason, Carey E.; Carlsson, Cynthia M.; Rowley, Howard A.; Asthana, Sanjay; Johnson, Sterling C.

2009-01-01

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. PMID:17445294

The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome.

PubMed

Diker, Sevda; Has, Arzu Ceylan; Kurne, Aslı; Göçmen, Rahşan; Oğuz, Kader Karlı; Karabudak, Rana

2016-11-01

Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques.

PubMed

Gias, Carlos; Jones, Myles; Keegan, David; Adamson, Peter; Greenwood, John; Lund, Ray; Martindale, John; Johnston, David; Berwick, Jason; Mayhew, John; Coffey, Peter

2007-04-01

The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested. In contrast, a cortical response was elicited in most of the transplanted rats to luminance changes and in many of those a response was also evoked to pattern stimulation. Although the transplanted rats did not respond to high spatial frequency information we found evidence of preservation in the cortical processing of luminance changes and low spatial frequency stimulation. Anatomical sections of transplanted rat retinas confirmed the capacity of RPE transplantation to rescue photoreceptors. Good correlation was found between photoreceptor survival and the extent of cortical function preservation determined with optical imaging techniques. This study determined the efficacy of RPE transplantation to preserve visual cortical processing and established optical imaging as a powerful technique for its assessment.

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.

PubMed

Thimm, Andreas; Funke, Klaus

2015-02-15

Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks. Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20�

Cortical Feedback Regulates Feedforward Retinogeniculate Refinement

PubMed Central

Thompson, Andrew D; Picard, Nathalie; Min, Lia; Fagiolini, Michela; Chen, Chinfei

2016-01-01

SUMMARY According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection. PMID:27545712

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

PubMed Central

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Control of cortical neuronal migration by glutamate and GABA

PubMed Central

Luhmann, Heiko J.; Fukuda, A.; Kilb, W.

2015-01-01

Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

Longitudinal MRI Study of Cortical Development through Early Childhood in Autism

PubMed Central

Schumann, C.M.; Bloss, C.S.; Barnes, C. Carter; Wideman, G.M.; Carper, R.A.; Akshoomoff, N.; Pierce, K.; Hagler, D.; Schork, N.; Lord, C.; Courchesne, E.

2010-01-01

Cross-sectional MRI studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however this has never been confirmed by a longitudinal study. We carried out the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent utilizing structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of Autistic Disorder at ~48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter was significantly enlarged in toddlers with Autistic Disorder, with the most severe enlargement occurring in frontal, temporal and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with Autistic Disorder that was mainly characterized by a quadratic age effect. Females with Autistic Disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers in order to determine the underlying neuropathological processes causing the onset of autistic symptoms. PMID:20335478

Reduced response cluster size in early visual areas explains the acuity deficit in amblyopia.

PubMed

Huang, Yufeng; Feng, Lixia; Zhou, Yifeng

2017-05-03

Focal visual stimulation typically results in the activation of a large portion of the early visual cortex. This spread of activity is attributed to long-range lateral interactions. Such long-range interactions may serve to stabilize a visual representation or to simply modulate incoming signals, and any associated dysfunction in long-range activation may reduce sensitivity to visual information in conditions such as amblyopia. We sought to measure the dispersion of cortical activity following local visual stimulation in a group of patients with amblyopia and matched normal. Twenty adult anisometropic amblyopes and 10 normal controls participated in this study. Using a multifocal stimulation, we simultaneously measured cluster sizes to multiple stimulation points in the visual field. We found that the functional MRI (fMRI) response cluster size that corresponded to the fellow eye was significantly larger as opposed to that corresponding to the amblyopic eye and that the fMRI response cluster size at the two more central retinotopic locations correlated with amblyopia acuity deficit. Our results suggest that the amblyopic visual cortex has a diminished long-range communication as evidenced by significantly smaller cluster of activity as measured with fMRI. These results have important implications for models of amblyopia and approaches to treatment.

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

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

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

PubMed Central

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

2015-01-01

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

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.

Effects of GABAA receptor inhibition on response properties of barrel cortical neurons in C-fiber-depleted rats.

PubMed

Farazifard, Rasoul; Kiani, Roozbeh; Esteky, Hossein

2005-07-19

C-fiber depletion results in expansion of low threshold somatosensory mechanoreceptive fields. In this study, we investigated the role of intact C-fibers in GABAA-mediated inhibition in barrel cortical neurons. We used electronically controlled mechanical stimulation of whiskers to quantitatively examine the responses of barrel cells to whisker displacements. After systemic injection of picrotoxin neuronal responses were recorded at 5 min intervals for 20 min and then at 10 min intervals for 100 min. Picrotoxin injection caused a 3-fold increase in response magnitude of adjacent whisker stimulation and 1.4-fold increase in response magnitude of principal whisker stimulation with a maximum enhancement 50 min after the injection. There was no significant change in spontaneous activity following picrotoxin injection. The response enhancement and receptive field expansion observed in normal rats were completely absent in the C-fiber-depleted rats. These results suggest that the GABAA-mediated inhibition that modulates the receptive field functional organization of the barrel cortex depends on intact C-fibers.

Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice.

PubMed

Fonseca, Raquel; Carvalho, Rui A; Lemos, Cristina; Sequeira, Ana C; Pita, Inês R; Carvalho, Fábio; Silva, Carlos D; Prediger, Rui D S; Jarak, Ivana; Cunha, Rodrigo A; Fontes Ribeiro, Carlos A; Köfalvi, Attila; Pereira, Frederico C

2017-02-01

We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown. Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i.p.), and their frontal cortical metabolic status was characterized after probing their mood and anxiety-related phenotypes 3 days postinjection. Methamphetamine induced depressive-like behavior, as indicated by the decreased grooming time in the splash test and by a transient decrease in sucrose preference. At this time, METH did not alter anxiety-like behavior or motor functions. Depolarization-induced glucose uptake was reduced in frontocortical slices from METH-treated mice compared to controls. Consistently, astrocytic glucose transporter (GluT1) density was lower in the METH group. A proton high rotation magic angle spinning (HRMAS) spectroscopic approach revealed that METH induced a significant decrease in N-acetyl aspartate (NAA) and glutamate levels, suggesting that METH decreased neuronal glutamatergic function in frontal cortex. We report, for the first time, that a single METH injection triggers early self-care and hedonic deficits and impairs frontal cortical energetics in mice. © 2016 John Wiley & Sons Ltd.

Delayed and Temporally Imprecise Neurotransmission in Reorganizing Cortical Microcircuits

PubMed Central

Barnes, Samuel J.; Cheetham, Claire E.; Liu, Yan; Bennett, Sophie H.; Albieri, Giorgia; Jorstad, Anne A.; Knott, Graham W.

2015-01-01

Synaptic neurotransmission is modified at cortical connections throughout life. Varying the amplitude of the postsynaptic response is one mechanism that generates flexible signaling in neural circuits. The timing of the synaptic response may also play a role. Here, we investigated whether weakening and loss of an entire connection between excitatory cortical neurons was foreshadowed in the timing of the postsynaptic response. We made electrophysiological recordings in rat primary somatosensory cortex that was undergoing experience-dependent loss of complete local excitatory connections. The synaptic latency of pyramid–pyramid connections, which typically comprise multiple synapses, was longer and more variable. Connection strength and latency were not correlated. Instead, prolonged latency was more closely related to progression of connection loss. The action potential waveform and axonal conduction velocity were unaffected, suggesting that the altered timing of neurotransmission was attributable to a synaptic mechanism. Modeling studies indicated that increasing the latency and jitter at a subset of synapses reduced the number of action potentials fired by a postsynaptic neuron. We propose that prolonged synaptic latency and diminished temporal precision of neurotransmission are hallmarks of impending loss of a cortical connection. PMID:26085628

Developmental Exposure to Cocaine Dynamically Dysregulates Cortical Arc/Arg3.1 Modulation in Response to a Challenge.

PubMed

Caffino, Lucia; Giannotti, Giuseppe; Mottarlini, Francesca; Racagni, Giorgio; Fumagalli, Fabio

2017-02-01

During adolescence, the medial prefrontal cortex (mPFC) is still developing. We have previously shown that developmental cocaine exposure alters mPFC's ability to cope with challenging events. In this manuscript, we exposed rats developmentally treated with cocaine to a novelty task and analyzed the molecular changes of mPFC. Rats were exposed to cocaine from post-natal day (PND) 28 to PND 42 and sacrificed at PND 43, immediately after the novel object recognition (NOR) test. Cocaine-treated rats spent more time exploring the novel object than saline-treated counterparts, suggesting an increased response to novelty. The messenger RNA (mRNA) and protein levels of the immediate early gene Arc/Arg3.1 were reduced in both infralimbic (IL) and prelimbic (PL) cortices highlighting a baseline reduction of mPFC neuronal activity as a consequence of developmental exposure to cocaine. Intriguingly, significant molecular changes were observed in the IL, but not PL, cortex in response to the combination of cocaine exposure and test such as a marked upregulation of both Arc/Arg3.1 mRNA and protein levels only in cocaine-treated rats. As for proteins, such increase was observed only in the post-synaptic density and not in the whole homogenate, suggesting psychostimulant-induced changes in trafficking of Arc/Arg3.1 or an increased local translation. Notably, the same profile of Arc/Arg3.1 was observed for post-synaptic density (PSD)-95 leading to the possibility that Arc/Arg3.1 and PSD-95 bridge together to promote aberrant synaptic connectivity in IL cortex following repeated exposure to cocaine during brain development.

Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence.

PubMed

Cunningham, Miles Gregory; Bhattacharyya, Sujoy; Benes, Francine Mary

2002-11-11

Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood. Copyright 2002 Wiley-Liss, Inc.

Sequencing the Cortical Processing of Pitch-Evoking Stimuli using EEG Analysis and Source Estimation

PubMed Central

Butler, Blake E.; Trainor, Laurel J.

2012-01-01

Cues to pitch include spectral cues that arise from tonotopic organization and temporal cues that arise from firing patterns of auditory neurons. fMRI studies suggest a common pitch center is located just beyond primary auditory cortex along the lateral aspect of Heschl’s gyrus, but little work has examined the stages of processing for the integration of pitch cues. Using electroencephalography, we recorded cortical responses to high-pass filtered iterated rippled noise (IRN) and high-pass filtered complex harmonic stimuli, which differ in temporal and spectral content. The two stimulus types were matched for pitch saliency, and a mismatch negativity (MMN) response was elicited by infrequent pitch changes. The P1 and N1 components of event-related potentials (ERPs) are thought to arise from primary and secondary auditory areas, respectively, and to result from simple feature extraction. MMN is generated in secondary auditory cortex and is thought to act on feature-integrated auditory objects. We found that peak latencies of both P1 and N1 occur later in response to IRN stimuli than to complex harmonic stimuli, but found no latency differences between stimulus types for MMN. The location of each ERP component was estimated based on iterative fitting of regional sources in the auditory cortices. The sources of both the P1 and N1 components elicited by IRN stimuli were located dorsal to those elicited by complex harmonic stimuli, whereas no differences were observed for MMN sources across stimuli. Furthermore, the MMN component was located between the P1 and N1 components, consistent with fMRI studies indicating a common pitch region in lateral Heschl’s gyrus. These results suggest that while the spectral and temporal processing of different pitch-evoking stimuli involves different cortical areas during early processing, by the time the object-related MMN response is formed, these cues have been integrated into a common representation of pitch. PMID:22740836

Feedforward Inhibition Allows Input Summation to Vary in Recurrent Cortical Networks

PubMed Central

2018-01-01

Abstract Brain computations depend on how neurons transform inputs to spike outputs. Here, to understand input-output transformations in cortical networks, we recorded spiking responses from visual cortex (V1) of awake mice of either sex while pairing sensory stimuli with optogenetic perturbation of excitatory and parvalbumin-positive inhibitory neurons. We found that V1 neurons’ average responses were primarily additive (linear). We used a recurrent cortical network model to determine whether these data, as well as past observations of nonlinearity, could be described by a common circuit architecture. Simulations showed that cortical input-output transformations can be changed from linear to sublinear with moderate (∼20%) strengthening of connections between inhibitory neurons, but this change away from linear scaling depends on the presence of feedforward inhibition. Simulating a variety of recurrent connection strengths showed that, compared with when input arrives only to excitatory neurons, networks produce a wider range of output spiking responses in the presence of feedforward inhibition. PMID:29682603

Response-dependent dynamics of cell-specific inhibition in cortical networks in vivo

PubMed Central

El-Boustani, Sami; Sur, Mriganka

2014-01-01

In the visual cortex, inhibitory neurons alter the computations performed by target cells via combination of two fundamental operations, division and subtraction. The origins of these operations have been variously ascribed to differences in neuron classes, synapse location or receptor conductances. Here, by utilizing specific visual stimuli and single optogenetic probe pulses, we show that the function of parvalbumin-expressing and somatostatin-expressing neurons in mice in vivo is governed by the overlap of response timing between these neurons and their targets. In particular, somatostatin-expressing neurons respond at longer latencies to small visual stimuli compared with their target neurons and provide subtractive inhibition. With large visual stimuli, however, they respond at short latencies coincident with their target cells and switch to provide divisive inhibition. These results indicate that inhibition mediated by these neurons is a dynamic property of cortical circuits rather than an immutable property of neuronal classes. PMID:25504329

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

PubMed

Mouthaan, B E; van 't Klooster, M A; Keizer, D; Hebbink, G J; Leijten, F S S; Ferrier, C H; van Putten, M J A M; Zijlmans, M; Huiskamp, G J M

2016-02-01

Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cortical blindness and posterior reversible encephalopathy syndrome in an older patient

PubMed Central

Ait, Sabrina; Gilbert, Thomas; Cotton, Francois; Bonnefoy, Marc

2012-01-01

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity. It associates, to varying extents, neurological symptoms such as headaches, confusion, seizures and visual alterations from haemianopsia to cortical blindness. The diagnosis relies on brain MRI, showing signs of subcortical and cortical oedema in the posterior regions of the brain, with hypersignals in T2/fluid attenuated inversion recovery (FLAIR) or diffusion sequences. With early diagnosis and control of the causal factors, the symptoms and radiological signs can be – as the name implies – totally regressive. PRES can be caused by various heterogeneous factors, such as hypertension, side effect of drug therapies, eclampsia, sepsis or autoimmune diseases. The authors report here the case of an 86-year-old woman, presenting totally regressive cortical blindness and seizures, with compatible imaging. PMID:22669215

Sensory Cortical Population Dynamics Uniquely Track Behavior across Learning and Extinction

PubMed Central

Katz, Donald B.

2014-01-01

Neural responses in many cortical regions encode information relevant to behavior: information that necessarily changes as that behavior changes with learning. Although such responses are reasonably theorized to be related to behavior causation, the true nature of that relationship cannot be clarified by simple learning studies, which show primarily that responses change with experience. Neural activity that truly tracks behavior (as opposed to simply changing with experience) will not only change with learning but also change back when that learning is extinguished. Here, we directly probed for this pattern, recording the activity of ensembles of gustatory cortical single neurons as rats that normally consumed sucrose avidly were trained first to reject it (i.e., conditioned taste aversion learning) and then to enjoy it again (i.e., extinction), all within 49 h. Both learning and extinction altered cortical responses, consistent with the suggestion (based on indirect evidence) that extinction is a novel form of learning. But despite the fact that, as expected, postextinction single-neuron responses did not resemble “naive responses,” ensemble response dynamics changed with learning and reverted with extinction: both the speed of stimulus processing and the relationships among ensemble responses to the different stimuli tracked behavioral relevance. These data suggest that population coding is linked to behavior with a fidelity that single-neuron coding is not. PMID:24453316

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

A Near-Infrared Spectroscopy Study on Cortical Hemodynamic Responses to Normal and Whispered Speech in 3- to 7-Year-Old Children

ERIC Educational Resources Information Center

Remijn, Gerard B.; Kikuchi, Mitsuru; Yoshimura, Yuko; Shitamichi, Kiyomi; Ueno, Sanae; Tsubokawa, Tsunehisa; Kojima, Haruyuki; Higashida, Haruhiro; Minabe, Yoshio

2017-01-01

Purpose: The purpose of this study was to assess cortical hemodynamic response patterns in 3- to 7-year-old children listening to two speech modes: normally vocalized and whispered speech. Understanding whispered speech requires processing of the relatively weak, noisy signal, as well as the cognitive ability to understand the speaker's reason for…

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

Prefrontal cortical minicolumn: from executive control to disrupted cognitive processing

PubMed Central

Casanova, Manuel F.

2014-01-01

The prefrontal cortex of the primate brain has a modular architecture based on the aggregation of neurons in minicolumnar arrangements having afferent and efferent connections distributed across many brain regions to represent, select and/or maintain behavioural goals and executive commands. Prefrontal cortical microcircuits are assumed to play a key role in the perception to action cycle that integrates relevant information about environment, and then selects and enacts behavioural responses. Thus, neurons within the interlaminar microcircuits participate in various functional states requiring the integration of signals across cortical layers and the selection of executive variables. Recent research suggests that executive abilities emerge from cortico-cortical interactions between interlaminar prefrontal cortical microcircuits, whereas their disruption is involved in a broad spectrum of neurologic and psychiatric disorders such as autism, schizophrenia, Alzheimer’s and drug addiction. The focus of this review is on the structural, functional and pathological approaches involving cortical minicolumns. Based on recent technological progress it has been demonstrated that microstimulation of infragranular cortical layers with patterns of microcurrents derived from supragranular layers led to an increase in cognitive performance. This suggests that interlaminar prefrontal cortical microcircuits are playing a causal role in improving cognitive performance. An important reason for the new interest in cortical modularity comes from both the impressive progress in understanding anatomical, physiological and pathological facets of cortical microcircuits and the promise of neural prosthetics for patients with neurological and psychiatric disorders. PMID:24531625

Shining a light on posterior cortical atrophy.

PubMed

Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Boeve, Bradley F; Cappa, Stefano F; Dickerson, Bradford C; Dubois, Bruno; Graff-Radford, Neill R; Krolak-Salmon, Pierre; Lehmann, Manja; Mendez, Mario F; Pijnenburg, Yolande; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Tim; Tang-Wai, David F; van der Flier, Wiesje M; Bain, Lisa; Carrillo, Maria C; Fox, Nick C

2013-07-01

Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Auditory cortical function during verbal episodic memory encoding in Alzheimer's disease.

PubMed

Dhanjal, Novraj S; Warren, Jane E; Patel, Maneesh C; Wise, Richard J S

2013-02-01

Episodic memory encoding of a verbal message depends upon initial registration, which requires sustained auditory attention followed by deep semantic processing of the message. Motivated by previous data demonstrating modulation of auditory cortical activity during sustained attention to auditory stimuli, we investigated the response of the human auditory cortex during encoding of sentences to episodic memory. Subsequently, we investigated this response in patients with mild cognitive impairment (MCI) and probable Alzheimer's disease (pAD). Using functional magnetic resonance imaging, 31 healthy participants were studied. The response in 18 MCI and 18 pAD patients was then determined, and compared to 18 matched healthy controls. Subjects heard factual sentences, and subsequent retrieval performance indicated successful registration and episodic encoding. The healthy subjects demonstrated that suppression of auditory cortical responses was related to greater success in encoding heard sentences; and that this was also associated with greater activity in the semantic system. In contrast, there was reduced auditory cortical suppression in patients with MCI, and absence of suppression in pAD. Administration of a central cholinesterase inhibitor (ChI) partially restored the suppression in patients with pAD, and this was associated with an improvement in verbal memory. Verbal episodic memory impairment in AD is associated with altered auditory cortical function, reversible with a ChI. Although these results may indicate the direct influence of pathology in auditory cortex, they are also likely to indicate a partially reversible impairment of feedback from neocortical systems responsible for sustained attention and semantic processing. Copyright © 2012 American Neurological Association.

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain.

PubMed

Pacheco-Costa, Rafael; Davis, Hannah M; Sorenson, Chad; Hon, Mary C; Hassan, Iraj; Reginato, Rejane D; Allen, Matthew R; Bellido, Teresita; Plotkin, Lilian I

2015-12-01

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. Copyright © 2015 Elsevier Inc. All rights reserved.

Network Supervision of Adult Experience and Learning Dependent Sensory Cortical Plasticity.

PubMed

Blake, David T

2017-06-18

The brain is capable of remodeling throughout life. The sensory cortices provide a useful preparation for studying neuroplasticity both during development and thereafter. In adulthood, sensory cortices change in the cortical area activated by behaviorally relevant stimuli, by the strength of response within that activated area, and by the temporal profiles of those responses. Evidence supports forms of unsupervised, reinforcement, and fully supervised network learning rules. Studies on experience-dependent plasticity have mostly not controlled for learning, and they find support for unsupervised learning mechanisms. Changes occur with greatest ease in neurons containing α-CamKII, which are pyramidal neurons in layers II/III and layers V/VI. These changes use synaptic mechanisms including long term depression. Synaptic strengthening at NMDA-containing synapses does occur, but its weak association with activity suggests other factors also initiate changes. Studies that control learning find support of reinforcement learning rules and limited evidence of other forms of supervised learning. Behaviorally associating a stimulus with reinforcement leads to a strengthening of cortical response strength and enlarging of response area with poor selectivity. Associating a stimulus with omission of reinforcement leads to a selective weakening of responses. In some preparations in which these associations are not as clearly made, neurons with the most informative discharges are relatively stronger after training. Studies analyzing the temporal profile of responses associated with omission of reward, or of plasticity in studies with different discriminanda but statistically matched stimuli, support the existence of limited supervised network learning. © 2017 American Physiological Society. Compr Physiol 7:977-1008, 2017. Copyright © 2017 John Wiley & Sons, Inc.

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.

Sp8 and COUP-TF1 reciprocally regulate patterning and Fgf signaling in cortical progenitors.

PubMed

Borello, Ugo; Madhavan, Mayur; Vilinsky, Ilya; Faedo, Andrea; Pierani, Alessandra; Rubenstein, John; Campbell, Kenneth

2014-06-01

To gain new insights into the transcriptional regulation of cortical development, we examined the role of the transcription factor Sp8, which is downstream of Fgf8 signaling and known to promote rostral cortical development. We have used a binary transgenic system to express Sp8 throughout the mouse telencephalon in a temporally restricted manner. Our results show that misexpression of Sp8 throughout the telencephalon, at early but not late embryonic stages, results in cortical hypoplasia, which is accompanied by increased cell death, reduced proliferation, and precocious neuronal differentiation. Misexpression of Sp8 at early developmental stages represses COUP-TF1 expression, a negative effector of Fgf signaling and a key promoter of posterior cortical identity, while ablation of Sp8 has the opposite effect. In addition, transgenic misexpression of COUP-TF1 resulted in downregulation of Sp8, indicating a reciprocal cross-regulation between these 2 transcription factors. Although Sp8 has been suggested to induce and/or maintain Fgf8 expression in the embryonic telencephalon, neither Fgf8 nor Fgf15 was upregulated using our gain-of-function approach. However, misexpression of Sp8 greatly increased the expression of Fgf target molecules, suggesting enhanced Fgf signaling. Thus, we propose that Sp8 promotes rostral and dorsomedial cortical development by repressing COUP-TF1 and promoting Fgf signaling in pallial progenitors.

Sp8 and COUP-TF1 Reciprocally Regulate Patterning and Fgf Signaling in Cortical Progenitors

PubMed Central

Borello, Ugo; Madhavan, Mayur; Vilinsky, Ilya; Faedo, Andrea; Pierani, Alessandra; Rubenstein, John; Campbell, Kenneth

2014-01-01

To gain new insights into the transcriptional regulation of cortical development, we examined the role of the transcription factor Sp8, which is downstream of Fgf8 signaling and known to promote rostral cortical development. We have used a binary transgenic system to express Sp8 throughout the mouse telencephalon in a temporally restricted manner. Our results show that misexpression of Sp8 throughout the telencephalon, at early but not late embryonic stages, results in cortical hypoplasia, which is accompanied by increased cell death, reduced proliferation, and precocious neuronal differentiation. Misexpression of Sp8 at early developmental stages represses COUP-TF1 expression, a negative effector of Fgf signaling and a key promoter of posterior cortical identity, while ablation of Sp8 has the opposite effect. In addition, transgenic misexpression of COUP-TF1 resulted in downregulation of Sp8, indicating a reciprocal cross-regulation between these 2 transcription factors. Although Sp8 has been suggested to induce and/or maintain Fgf8 expression in the embryonic telencephalon, neither Fgf8 nor Fgf15 was upregulated using our gain-of-function approach. However, misexpression of Sp8 greatly increased the expression of Fgf target molecules, suggesting enhanced Fgf signaling. Thus, we propose that Sp8 promotes rostral and dorsomedial cortical development by repressing COUP-TF1 and promoting Fgf signaling in pallial progenitors. PMID:23307639

Modification of response functions of cat visual cortical cells by spatially congruent perturbing stimuli.

PubMed

Kabara, J F; Bonds, A B

2001-12-01

Responses of cat striate cortical cells to a drifting sinusoidal grating were modified by the superimposition of a second, perturbing grating (PG) that did not excite the cell when presented alone. One consequence of the presence of a PG was a shift in the tuning curves. The orientation tuning of all 41 cells exposed to a PG and the spatial frequency tuning of 83% of the 23 cells exposed to a PG showed statistically significant dislocations of both the response function peak and center of mass from their single grating values. As found in earlier reports, the presence of PGs suppressed responsiveness. However, reductions measured at the single grating optimum orientation or spatial frequency were on average 1.3 times greater than the suppression found at the peak of the response function modified by the presence of the PG. Much of the loss in response seen at the single grating optimum is thus a result of a shift in the tuning function rather than outright suppression. On average orientation shifts were repulsive and proportional (approximately 0.10 deg/deg) to the angle between the perturbing stimulus and the optimum single grating orientation. Shifts in the spatial frequency response function were both attractive and repulsive, resulting in an overall average of zero. For both simple and complex cells, PGs generally broadened orientation response function bandwidths. Similarly, complex cell spatial frequency response function bandwidths broadened. Simple cell spatial frequency response functions usually did not change, and those that did broadened only 4% on average. These data support the hypothesis that additional sinusoidal components in compound stimuli retune cells' response functions for orientation and spatial frequency.

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

Prediction in the service of comprehension: modulated early brain responses to omitted speech segments.

PubMed

Bendixen, Alexandra; Scharinger, Mathias; Strauß, Antje; Obleser, Jonas

2014-04-01

Speech signals are often compromised by disruptions originating from external (e.g., masking noise) or internal (e.g., inaccurate articulation) sources. Speech comprehension thus entails detecting and replacing missing information based on predictive and restorative neural mechanisms. The present study targets predictive mechanisms by investigating the influence of a speech segment's predictability on early, modality-specific electrophysiological responses to this segment's omission. Predictability was manipulated in simple physical terms in a single-word framework (Experiment 1) or in more complex semantic terms in a sentence framework (Experiment 2). In both experiments, final consonants of the German words Lachs ([laks], salmon) or Latz ([lats], bib) were occasionally omitted, resulting in the syllable La ([la], no semantic meaning), while brain responses were measured with multi-channel electroencephalography (EEG). In both experiments, the occasional presentation of the fragment La elicited a larger omission response when the final speech segment had been predictable. The omission response occurred ∼125-165 msec after the expected onset of the final segment and showed characteristics of the omission mismatch negativity (MMN), with generators in auditory cortical areas. Suggestive of a general auditory predictive mechanism at work, this main observation was robust against varying source of predictive information or attentional allocation, differing between the two experiments. Source localization further suggested the omission response enhancement by predictability to emerge from left superior temporal gyrus and left angular gyrus in both experiments, with additional experiment-specific contributions. These results are consistent with the existence of predictive coding mechanisms in the central auditory system, and suggestive of the general predictive properties of the auditory system to support spoken word recognition. Copyright © 2014 Elsevier Ltd. All

Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone.

PubMed

O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A; Lawless, Sean M; Williams, Rebecca M; Zipfel, Warren R; Olson, Eric C

2012-07-07

The secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction. The total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite "exclusion zone" which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs. These findings indicate Reelin promotes directional dendritic growth into

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

Effects of Long-term Diving Training on Cortical Gyrification.

PubMed

Zhang, Yuanchao; Zhao, Lu; Bi, Wenwei; Wang, Yue; Wei, Gaoxia; Evans, Alan; Jiang, Tianzi

2016-06-20

During human brain development, cortical gyrification, which is believed to facilitate compact wiring of neural circuits, has been shown to follow an inverted U-shaped curve, coinciding with the two-stage neurodevelopmental process of initial synaptic overproduction with subsequent pruning. This trajectory allows postnatal experiences to refine the wiring, which may manifest as endophenotypic changes in cortical gyrification. Diving experts, typical elite athletes who commence intensive motor training at a very young age in their early childhood, serve ideal models for examining the gyrification changes related to long-term intensive diving training. Using local gyrification index (LGI), we compared the cortical gyrification between 12 diving experts and 12 controls. Compared with controls, diving experts showed widespread LGI reductions in regions relevant to diving performance. Negative correlations between LGIs and years of diving training were also observed in diving experts. Further exploratory network efficiency analysis of structural cortical networks, inferred from interregional correlation of LGIs, revealed comparable global and local efficiency in diving experts relative to controls. These findings suggest that gyrification reductions in diving experts may be the result of long-term diving training which could refine the neural circuitry (via synaptic pruning) and might be the anatomical substrate underlying their extraordinary diving performance.

Numerosity processing in early visual cortex.

PubMed

Fornaciai, Michele; Brannon, Elizabeth M; Woldorff, Marty G; Park, Joonkoo

2017-08-15

While parietal cortex is thought to be critical for representing numerical magnitudes, we recently reported an event-related potential (ERP) study demonstrating selective neural sensitivity to numerosity over midline occipital sites very early in the time course, suggesting the involvement of early visual cortex in numerosity processing. However, which specific brain area underlies such early activation is not known. Here, we tested whether numerosity-sensitive neural signatures arise specifically from the initial stages of visual cortex, aiming to localize the generator of these signals by taking advantage of the distinctive folding pattern of early occipital cortices around the calcarine sulcus, which predicts an inversion of polarity of ERPs arising from these areas when stimuli are presented in the upper versus lower visual field. Dot arrays, including 8-32dots constructed systematically across various numerical and non-numerical visual attributes, were presented randomly in either the upper or lower visual hemifields. Our results show that neural responses at about 90ms post-stimulus were robustly sensitive to numerosity. Moreover, the peculiar pattern of polarity inversion of numerosity-sensitive activity at this stage suggested its generation primarily in V2 and V3. In contrast, numerosity-sensitive ERP activity at occipito-parietal channels later in the time course (210-230ms) did not show polarity inversion, indicating a subsequent processing stage in the dorsal stream. Overall, these results demonstrate that numerosity processing begins in one of the earliest stages of the cortical visual stream. Copyright © 2017 Elsevier Inc. All rights reserved.

[Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

PubMed

Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

2014-05-20

Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Differentiation of neuropsychological features between posterior cortical atrophy and early onset Alzheimer's disease.

PubMed

Li, Jieying; Wu, Liyong; Tang, Yi; Zhou, Aihong; Wang, Fen; Xing, Yi; Jia, Jianping

2018-05-10

Posterior cortical atrophy (PCA) is a group of clinical syndromes characterized by visuospatial and visuoperceptual impairment, with memory relatively preserved. Although PCA is pathologically almost identical to Alzheimer's disease (AD), they have different cognitive features. Those differences have only rarely been reported in any Chinese population. The purpose of the study is to establish neuropsychological tests that distinguish the clinical features of PCA from early onset AD (EOAD). Twenty-one PCA patients, 20 EOAD patients, and 20 healthy controls participated in this study. Patients had disease duration of ≤4 years. All participants completed a series of neuropsychological tests to evaluate their visuospatial, visuoperceptual, visuo-constructive, language, executive function, memory, calculation, writing, and reading abilities. The cognitive features of PCA and EOAD were compared. All the neuropsychological test scores showed that both the PCA and EOAD patients were significantly more impaired than people in the control group. However, PCA patients were significantly more impaired than EOAD patients in visuospatial, visuoperceptual, and visuo-constructive function, as well as in handwriting, and reading Chinese characters. The profile of neuropsychological test results highlights cognitive features that differ between PCA and EOAD. One surprising result is that the two syndromes could be distinguished by patients' ability to read and write Chinese characters. Tests based on these characteristics could therefore form a brief PCA neuropsychological examination that would improve the diagnosis of PCA.

Syllabic discrimination in premature human infants prior to complete formation of cortical layers

PubMed Central

Mahmoudzadeh, Mahdi; Dehaene-Lambertz, Ghislaine; Fournier, Marc; Kongolo, Guy; Goudjil, Sabrina; Dubois, Jessica; Grebe, Reinhard; Wallois, Fabrice

2013-01-01

The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. Many neurons are still located in the subplate and in the process of migrating to their final location. Nevertheless, we observed several points of similarity with the adult linguistic network. First, whereas syllables elicited larger right than left responses, the posterior temporal region escaped this general pattern, showing faster and more sustained responses over the left than over the right hemisphere. Second, discrimination responses to a change of phoneme (ba vs. ga) and a change of human voice (male vs. female) were already present and involved inferior frontal areas, even in the youngest infants (29-wk gestational age). Third, whereas both types of changes elicited responses in the right frontal region, the left frontal region only reacted to a change of phoneme. These results demonstrate a sophisticated organization of perisylvian areas at the very onset of cortical circuitry, 3 mo before term. They emphasize the influence of innate factors on regions involved in linguistic processing and social communication in humans. PMID:23440196

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

PubMed

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

2018-03-07

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

Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report.

PubMed

Stephen, Joshi; Nampoothiri, Sheela; Vinayan, K P; Yesodharan, Dhanya; Remesh, Preetha; Gahl, William A; Malicdan, May Christine V

2018-05-16

Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes: a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy. Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype.

Inverted-U Function Relating Cortical Plasticity and Task Difficulty

PubMed Central

Engineer, Navzer D.; Engineer, Crystal T.; Reed, Amanda C.; Pandya, Pritesh K.; Jakkamsetti, Vikram; Moucha, Raluca; Kilgard, Michael P.

2012-01-01

Many psychological and physiological studies with simple stimuli have suggested that perceptual learning specifically enhances the response of primary sensory cortex to task-relevant stimuli. The aim of this study was to determine whether auditory discrimination training on complex tasks enhances primary auditory cortex responses to a target sequence relative to non-target and novel sequences. We collected responses from more than 2,000 sites in 31 rats trained on one of six discrimination tasks that differed primarily in the similarity of the target and distractor sequences. Unlike training with simple stimuli, long-term training with complex stimuli did not generate target specific enhancement in any of the groups. Instead, cortical receptive field size decreased, latency decreased, and paired pulse depression decreased in rats trained on the tasks of intermediate difficulty while tasks that were too easy or too difficult either did not alter or degraded cortical responses. These results suggest an inverted-U function relating neural plasticity and task difficulty. PMID:22249158

Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls.

PubMed

Ortiz Alonso, Tomás; Santos, Juan Matías; Ortiz Terán, Laura; Borrego Hernández, Mayelin; Poch Broto, Joaquín; de Erausquin, Gabriel Alejandro

2015-01-01

Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision.

Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls

PubMed Central

Ortiz Alonso, Tomás; Santos, Juan Matías; Ortiz Terán, Laura; Borrego Hernández, Mayelin; Poch Broto, Joaquín; de Erausquin, Gabriel Alejandro

2015-01-01

Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision. PMID:26225827

Contribution of Innate Cortical Mechanisms to the Maturation of Orientation Selectivity in Parvalbumin Interneurons

PubMed Central

Figueroa Velez, Dario X.; Ellefsen, Kyle L.; Hathaway, Ethan R.; Carathedathu, Mathew C.

2017-01-01

The maturation of cortical parvalbumin-positive (PV) interneurons depends on the interaction of innate and experience-dependent factors. Dark-rearing experiments suggest that visual experience determines when broad orientation selectivity emerges in visual cortical PV interneurons. Here, using neural transplantation and in vivo calcium imaging of mouse visual cortex, we investigated whether innate mechanisms contribute to the maturation of orientation selectivity in PV interneurons. First, we confirmed earlier findings showing that broad orientation selectivity emerges in PV interneurons by 2 weeks after vision onset, ∼35 d after these cells are born. Next, we assessed the functional development of transplanted PV (tPV) interneurons. Surprisingly, 25 d after transplantation (DAT) and >2 weeks after vision onset, we found that tPV interneurons have not developed broad orientation selectivity. By 35 DAT, however, broad orientation selectivity emerges in tPV interneurons. Transplantation does not alter orientation selectivity in host interneurons, suggesting that the maturation of tPV interneurons occurs independently from their endogenous counterparts. Together, these results challenge the notion that the onset of vision solely determines when PV interneurons become broadly tuned. Our results reveal that an innate cortical mechanism contributes to the emergence of broad orientation selectivity in PV interneurons. SIGNIFICANCE STATEMENT Early visual experience and innate developmental programs interact to shape cortical circuits. Visual-deprivation experiments have suggested that the onset of visual experience determines when interneurons mature in the visual cortex. Here we used neuronal transplantation and cellular imaging of visual responses to investigate the maturation of parvalbumin-positive (PV) interneurons. Our results suggest that the emergence of broad orientation selectivity in PV interneurons is innately timed. PMID:28123018

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.

Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

PubMed

Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

2017-11-17

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence.

PubMed

Luby, Joan L; Belden, Andy C; Jackson, Joshua J; Lessov-Schlaggar, Christina N; Harms, Michael P; Tillman, Rebecca; Botteron, Kelly; Whalen, Diana; Barch, Deanna M

2016-01-01

The trajectory of cortical gray matter development in childhood has been characterized by early neurogenesis and volume increase, peaking at puberty followed by selective elimination and myelination, resulting in volume loss and thinning. This inverted U-shaped trajectory, as well as cortical thickness, has been associated with cognitive and emotional function. Synaptic pruning-based volume decline has been related to experience-dependent plasticity in animals. To date, there have been no data to inform whether and how childhood depression might be associated with this trajectory. To examine the effects of early childhood depression, from the preschool age to the school age period, on cortical gray matter development measured across 3 waves of neuroimaging from late school age to early adolescence. Data were collected in an academic research setting from September 22, 2003, to December 13, 2014, on 193 children aged 3 to 6 years from the St Louis, Missouri, metropolitan area who were observed for up to 11 years in a longitudinal behavioral and neuroimaging study of childhood depression. Multilevel modeling was applied to explore the association between the number of childhood depression symptoms and prior diagnosis of major depressive disorder and the trajectory of gray matter change across 3 scan waves. Data analysis was conducted from October 29, 2014, to September 28, 2015. Volume, thickness, and surface area of cortical gray matter measured using structural magnetic resonance imaging at 3 scan waves. Of the 193 children, 90 had a diagnosis of major depressive disorder; 116 children had 3 full waves of neuroimaging scans. Findings demonstrated marked alterations in cortical gray matter volume loss (slope estimate, -0.93 cm³; 95% CI, -1.75 to -0.10 cm³ per scan wave) and thinning (slope estimate, -0.0044 mm; 95% CI, -0.0077 to -0.0012 mm per scan wave) associated with experiencing an episode of major depressive disorder before the first magnetic resonance

Piracetam in the treatment of cortical myoclonus.

PubMed

Genton, P; Guerrini, R; Remy, C

1999-03-01

This paper reviews existing publications on the use of piracetam for the treatment of cortical myoclonus of various etiologies and includes the personal experience of the authors in progressive myoclonus epilepsy. Two double-blind comparisons with placebo provided results which allow recommendations for the dosage and usage of piracetam in cortical myoclonus. Wide individual variation (7-24g daily) exists in dosage requirements but responses are dose-related so that dosage should be increased until an optimum effect is obtained. Tolerability after long-term use of piracetam in high dosage has been very good and without toxicity or serious adverse effects. Side effects have been occasional, mild and transient. The authors present their experience of 12 patients with progressive myoclonus epilepsy in whom the administration of up to 45 g piracetam daily, when added to existing anti-epileptic treatment, caused marked and sometimes spectacular improvement and was without significant adverse effects. Improvement was maintained for up to 7 years. The use of piracetam for disabling cortical myoclonus of any etiology, either as an addition to existing antimyoclonic drugs or as monotherapy, may bring about profound improvement in disability and quality of life. Piracetam should be considered a first-line drug for the treatment of cortical myoclonus.

Exercise induces cortical plasticity after neonatal spinal cord injury in the rat

PubMed Central

Kao, T; Shumsky, JS; Murray, M; Moxon, KA

2009-01-01

Exercise-induced cortical plasticity is associated with improved functional outcome after brain or nerve injury. Exercise also improves functional outcomes after spinal cord injury, but its effects on cortical plasticity are not known. The goal of this investigation was to study the effect of moderate exercise (treadmill locomotion, 3 min/day, 5days/week) on the somatotopic organization of forelimb and hindlimb somatosensory cortex (SI) after neonatal thoracic transection. We used adult rats spinalized as neonates because some of these animals develop weight-supported stepping and, therefore, the relationship between cortical plasticity and stepping could also be examined. Acute, single-neuron mapping was used to determine the percentage of cortical cells responding to cutaneous forelimb stimulation in normal, spinalized, and exercised spinalized rats. Multiple single neuron recording from arrays of chronically implanted microwires examined the magnitude of response of these cells in normal and exercised spinalized rats. Our results show that exercise not only increased the percentage of responding cells in the hindlimb SI, but also increased the magnitude of the response of these cells. This increase in response magnitude was correlated with behavioral outcome measures. In the forelimb SI, neonatal transection reduced the percentage of responding cells to forelimb stimulation but exercise reversed this loss. This restoration in the percentage of responding cells after exercise was accompanied by an increase in their response magnitude. Therefore, the increase in responsiveness of hindlimb SI to forelimb stimulation after neonatal transection and exercise may be due, in part, to the effect of exercise on the forelimb SI. PMID:19515923

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.

Cortical thickness and surface area in neonates at high risk for schizophrenia.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H; Shen, Dinggang

2016-01-01

smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.

Plasticity in neuromagnetic cortical responses suggests enhanced auditory object representation

PubMed Central

2013-01-01

Background Auditory perceptual learning persistently modifies neural networks in the central nervous system. Central auditory processing comprises a hierarchy of sound analysis and integration, which transforms an acoustical signal into a meaningful object for perception. Based on latencies and source locations of auditory evoked responses, we investigated which stage of central processing undergoes neuroplastic changes when gaining auditory experience during passive listening and active perceptual training. Young healthy volunteers participated in a five-day training program to identify two pre-voiced versions of the stop-consonant syllable ‘ba’, which is an unusual speech sound to English listeners. Magnetoencephalographic (MEG) brain responses were recorded during two pre-training and one post-training sessions. Underlying cortical sources were localized, and the temporal dynamics of auditory evoked responses were analyzed. Results After both passive listening and active training, the amplitude of the P2m wave with latency of 200 ms increased considerably. By this latency, the integration of stimulus features into an auditory object for further conscious perception is considered to be complete. Therefore the P2m changes were discussed in the light of auditory object representation. Moreover, P2m sources were localized in anterior auditory association cortex, which is part of the antero-ventral pathway for object identification. The amplitude of the earlier N1m wave, which is related to processing of sensory information, did not change over the time course of the study. Conclusion The P2m amplitude increase and its persistence over time constitute a neuroplastic change. The P2m gain likely reflects enhanced object representation after stimulus experience and training, which enables listeners to improve their ability for scrutinizing fine differences in pre-voicing time. Different trajectories of brain and behaviour changes suggest that the preceding effect

Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions.

PubMed

Goard, Michael J; Pho, Gerald N; Woodson, Jonathan; Sur, Mriganka

2016-08-04

Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution.

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

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

PubMed

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

2017-09-01

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

Mapping the cortical representation of speech sounds in a syllable repetition task.

PubMed

Markiewicz, Christopher J; Bohland, Jason W

2016-11-01

Speech repetition relies on a series of distributed cortical representations and functional pathways. A speaker must map auditory representations of incoming sounds onto learned speech items, maintain an accurate representation of those items in short-term memory, interface that representation with the motor output system, and fluently articulate the target sequence. A "dorsal stream" consisting of posterior temporal, inferior parietal and premotor regions is thought to mediate auditory-motor representations and transformations, but the nature and activation of these representations for different portions of speech repetition tasks remains unclear. Here we mapped the correlates of phonetic and/or phonological information related to the specific phonemes and syllables that were heard, remembered, and produced using a series of cortical searchlight multi-voxel pattern analyses trained on estimates of BOLD responses from individual trials. Based on responses linked to input events (auditory syllable presentation), predictive vowel-level information was found in the left inferior frontal sulcus, while syllable prediction revealed significant clusters in the left ventral premotor cortex and central sulcus and the left mid superior temporal sulcus. Responses linked to output events (the GO signal cueing overt production) revealed strong clusters of vowel-related information bilaterally in the mid to posterior superior temporal sulcus. For the prediction of onset and coda consonants, input-linked responses yielded distributed clusters in the superior temporal cortices, which were further informative for classifiers trained on output-linked responses. Output-linked responses in the Rolandic cortex made strong predictions for the syllables and consonants produced, but their predictive power was reduced for vowels. The results of this study provide a systematic survey of how cortical response patterns covary with the identity of speech sounds, which will help to constrain

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

PubMed

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

2010-07-01

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

Distribution of Response Time, Cortical, and Cardiac Correlates during Emotional Interference in Persons with Subclinical Psychotic Symptoms

PubMed Central

Holper, Lisa K. B.; Aleksandrowicz, Alekandra; Müller, Mario; Ajdacic-Gross, Vladeta; Haker, Helene; Fallgatter, Andreas J.; Hagenmuller, Florence; Kawohl, Wolfram; Rössler, Wulf

2016-01-01

A psychosis phenotype can be observed below the threshold of clinical detection. The study aimed to investigate whether subclinical psychotic symptoms are associated with deficits in controlling emotional interference, and whether cortical brain and cardiac correlates of these deficits can be detected using functional near-infrared spectroscopy (fNIRS). A data set derived from a community sample was obtained from the Zurich Program for Sustainable Development of Mental Health Services. 174 subjects (mean age 29.67 ± 6.41, 91 females) were assigned to four groups ranging from low to high levels of subclinical psychotic symptoms (derived from the Symptom Checklist-90-R). Emotional interference was assessed using the emotional Stroop task comprising neutral, positive, and negative conditions. Statistical distributional methods based on delta plots [behavioral response time (RT) data] and quantile analysis (fNIRS data) were applied to evaluate the emotional interference effects. Results showed that both interference effects and disorder-specific (i.e., group-specific) effects could be detected, based on behavioral RTs, cortical hemodynamic signals (brain correlates), and heart rate variability (cardiac correlates). Subjects with high compared to low subclinical psychotic symptoms revealed significantly reduced amplitudes in dorsolateral prefrontal cortices (interference effect, p < 0.001) and middle temporal gyrus (disorder-specific group effect, p < 0.001), supported by behavioral and heart rate results. The present findings indicate that distributional analyses methods can support the detection of emotional interference effects in the emotional Stroop. The results suggested that subjects with high subclinical psychosis exhibit enhanced emotional interference effects. Based on these observations, subclinical psychosis may therefore prove to represent a valid extension of the clinical psychosis phenotype. PMID:27660608

Distribution of Response Time, Cortical, and Cardiac Correlates during Emotional Interference in Persons with Subclinical Psychotic Symptoms.

PubMed

Holper, Lisa K B; Aleksandrowicz, Alekandra; Müller, Mario; Ajdacic-Gross, Vladeta; Haker, Helene; Fallgatter, Andreas J; Hagenmuller, Florence; Kawohl, Wolfram; Rössler, Wulf

2016-01-01

A psychosis phenotype can be observed below the threshold of clinical detection. The study aimed to investigate whether subclinical psychotic symptoms are associated with deficits in controlling emotional interference, and whether cortical brain and cardiac correlates of these deficits can be detected using functional near-infrared spectroscopy (fNIRS). A data set derived from a community sample was obtained from the Zurich Program for Sustainable Development of Mental Health Services. 174 subjects (mean age 29.67 ± 6.41, 91 females) were assigned to four groups ranging from low to high levels of subclinical psychotic symptoms (derived from the Symptom Checklist-90-R). Emotional interference was assessed using the emotional Stroop task comprising neutral, positive, and negative conditions. Statistical distributional methods based on delta plots [behavioral response time (RT) data] and quantile analysis (fNIRS data) were applied to evaluate the emotional interference effects. Results showed that both interference effects and disorder-specific (i.e., group-specific) effects could be detected, based on behavioral RTs, cortical hemodynamic signals (brain correlates), and heart rate variability (cardiac correlates). Subjects with high compared to low subclinical psychotic symptoms revealed significantly reduced amplitudes in dorsolateral prefrontal cortices (interference effect, p < 0.001) and middle temporal gyrus (disorder-specific group effect, p < 0.001), supported by behavioral and heart rate results. The present findings indicate that distributional analyses methods can support the detection of emotional interference effects in the emotional Stroop. The results suggested that subjects with high subclinical psychosis exhibit enhanced emotional interference effects. Based on these observations, subclinical psychosis may therefore prove to represent a valid extension of the clinical psychosis phenotype.

Long-Term Citalopram Treatment Alters the Stress Responses of the Cortical Dopamine and Noradrenaline Systems: the Role of Cortical 5-HT1A Receptors

PubMed Central

Kaneko, Fumi; Kishikawa, Yuki; Hanada, Yuuki; Yamada, Makiko; Kakuma, Tatsuyuki; Kawahara, Hiroshi; Nishi, Akinori

2016-01-01

Background: Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants. Methods: The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in the rat prefrontal cortex to acute handling stress were evaluated using in vivo microdialysis. Results: Acute handling stress increased dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into the prefrontal cortex. The dopamine response was abolished by long-term treatment with citalopram, and the abolished dopamine response was reversed by local infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the prefrontal cortex. On the other hand, long-term treatment with citalopram reduced the basal noradrenaline levels (approximately 40% of the controls), but not the basal dopamine levels. The noradrenaline response was maintained despite the low basal noradrenaline levels. Signaling from the 5-HT1A receptors and α2-adrenoceptors was not involved in the decrease in the basal noradrenaline levels but partially affected the noradrenaline response. Conclusions: Chronic citalopram treatment differentially suppresses the dopamine and noradrenaline systems in the prefrontal cortex, and the dopamine stress response was preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings provide insight into how antidepressants modulate the dopamine and noradrenaline systems to overcome acute stress. PMID

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.

Changes of motor-cortical oscillations associated with motor learning.

PubMed

Pollok, B; Latz, D; Krause, V; Butz, M; Schnitzler, A

2014-09-05

Motor learning results from practice but also between practice sessions. After skill acquisition early consolidation results in less interference with other motor tasks and even improved performance of the newly learned skill. A specific significance of the primary motor cortex (M1) for early consolidation has been suggested. Since synchronized oscillatory activity is assumed to facilitate neuronal plasticity, we here investigate alterations of motor-cortical oscillations by means of event-related desynchronization (ERD) at alpha (8-12 Hz) and beta (13-30 Hz) frequencies in healthy humans. Neuromagnetic activity was recorded using a 306-channel whole-head magnetoencephalography (MEG) system. ERD was investigated in 15 subjects during training on a serial reaction time task and 10 min after initial training. The data were compared with performance during a randomly varying sequence serving as control condition. The data reveal a stepwise decline of alpha-band ERD associated with faster reaction times replicating previous findings. The amount of beta-band suppression was significantly correlated with reduction of reaction times. While changes of alpha power have been related to lower cognitive control after initial skill acquisition, the present data suggest that the amount of beta suppression represents a neurophysiological marker of early cortical reorganization associated with motor learning. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

ERIC Educational Resources Information Center

Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

2014-01-01

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

Transcranial magnetic stimulation reveals cortical hyperexcitability in episodic cluster headache.

PubMed

Cosentino, Guiseppe; Brighina, Filippo; Brancato, Sara; Valentino, Francesca; Indovino, Serena; Fierro, Brigida

2015-01-01

Evidence shows involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation. In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (ie, motor threshold, input-output curves, cortical silent period) and paired-pulse (ie, intracortical facilitation, short intracortical inhibition) transcranial magnetic stimulation in both hemispheres. Thirteen patients were evaluated outside bout and the remaining 12 patients inside bout. Our results showed increased slope of the input-output curves after stimulation of both hemispheres in patients outside bout and in the hemisphere contralateral to the headache side in patients inside bout. Increased intracortical facilitation was observed in the hemisphere ipsilateral to the headache side in patients evaluated both outside and inside bout; reduced short intracortical inhibition was observed in patients inside bout ipsilateral to the side of pain. In conclusion, we provide evidence of increased cortical excitability in episodic CH both outside and inside bout, especially in the hemisphere ipsilateral to the side of headache attacks. Our results suggest that an abnormal regulation of cortical excitability could be involved in the pathophysiology of CH. We investigated cortical excitability in episodic cluster headache by using transcranial magnetic stimulation, providing evidence of cortical hyperexcitability in patients both inside and outside bout. We suggest that an abnormal state of cortical excitability could be involved in the pathophysiology of the disease. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-02-01

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

Recognition memory for Braille or spoken words: an fMRI study in early blind.

PubMed

Burton, Harold; Sinclair, Robert J; Agato, Alvin

2012-02-15

We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5years. In an event-related design, we studied blood oxygen level-dependent responses to studied ("old") compared to novel ("new") words. Presentation mode was in Braille or spoken. Responses were larger for identified "new" words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken "new" words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with "old"/"new" recognition. Left dorsolateral prefrontal cortex had larger responses to "old" words only with Braille. Larger occipital cortex responses to "new" Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for "new" words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering "old" words. A larger response when identifying "new" words possibly resulted from exhaustive recollecting the sensory properties of "old" words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a "sensory echo" that aids recollection. Copyright © 2011 Elsevier B.V. All rights reserved.

Influence of callosal transfer on visual cortical evoked response and the implication in the development of a visual prosthesis.

PubMed

Siu, Timothy L; Morley, John W

2007-12-01

The development of a visual prosthesis has been limited by an incomplete understanding of functional changes of the visual cortex accompanying deafferentation. In particular, the role of the corpus callosum in modulating these changes has not been fully evaluated. Recent experimental evidence suggests that through synaptic modulation, short-term (4-5 days) visual deafferentation can induce plastic changes in the visual cortex, leading to adaptive enhancement of residual visual input. We therefore investigated whether a compensatory rerouting of visual information can occur via the indirect transcallosal linkage after deafferentation and the influence of this interhemispheric communication on the visual evoked response of each hemisphere. In albino rabbits, misrouting of uncrossed optic fibres reduces ipsilateral input to a negligible degree. We thus took advantage of this congenital anomaly to model unilateral cortical and ocular deafferentation by eliminating visual input from one eye and recorded the visual evoked potential (VEP) from the intact eye. In keeping with the chiasmal anomaly, no VEP was elicited from the hemisphere ipsilateral to the intact eye. This remained unchanged following unilateral visual deafferentation. The amplitude and latency of the VEP in the fellow hemisphere, however, were significantly decreased in the deafferented animals. Our data suggest that callosal linkage does not contribute to visual evoked responses and this is not changed after short-term deafferentation. The decrease in amplitude and latency of evoked responses in the hemisphere ipsilateral to the treated eye, however, confirms the facilitatory role of callosal transfer. This observation highlights the importance of bicortical stimulation in the future design of a cortical visual prosthesis.

GABAergic Inhibition in Visual Cortical Plasticity

PubMed Central

Sale, Alessandro; Berardi, Nicoletta; Spolidoro, Maria; Baroncelli, Laura; Maffei, Lamberto

2010-01-01

Experience is required for the shaping and refinement of developing neural circuits during well defined periods of early postnatal development called critical periods. Many studies in the visual cortex have shown that intracortical GABAergic circuitry plays a crucial role in defining the time course of the critical period for ocular dominance plasticity. With the end of the critical period, neural plasticity wanes and recovery from the effects of visual defects on visual acuity (amblyopia) or binocularity is much reduced or absent. Recent results pointed out that intracortical inhibition is a fundamental limiting factor for adult cortical plasticity and that its reduction by means of different pharmacological and environmental strategies makes it possible to greatly enhance plasticity in the adult visual cortex, promoting ocular dominance plasticity and recovery from amblyopia. Here we focus on the role of intracortical GABAergic circuitry in controlling both developmental and adult cortical plasticity. We shall also discuss the potential clinical application of these findings to neurological disorders in which synaptic plasticity is compromised because of excessive intracortical inhibition. PMID:20407586

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

Cortical oscillations modulated by congruent and incongruent audiovisual stimuli.

PubMed

Herdman, A T; Fujioka, T; Chau, W; Ross, B; Pantev, C; Picton, T W

2004-11-30

Congruent or incongruent grapheme-phoneme stimuli are easily perceived as one or two linguistic objects. The main objective of this study was to investigate the changes in cortical oscillations that reflect the processing of congruent and incongruent audiovisual stimuli. Graphemes were Japanese Hiragana characters for four different vowels (/a/, /o/, /u/, and /i/). They were presented simultaneously with their corresponding phonemes (congruent) or non-corresponding phonemes (incongruent) to native-speaking Japanese participants. Participants' reaction times to the congruent audiovisual stimuli were significantly faster by 57 ms as compared to reaction times to incongruent stimuli. We recorded the brain responses for each condition using a whole-head magnetoencephalograph (MEG). A novel approach to analysing MEG data, called synthetic aperture magnetometry (SAM), was used to identify event-related changes in cortical oscillations involved in audiovisual processing. The SAM contrast between congruent and incongruent responses revealed greater event-related desynchonization (8-16 Hz) bilaterally in the occipital lobes and greater event-related synchronization (4-8 Hz) in the left transverse temporal gyrus. Results from this study further support the concept of interactions between the auditory and visual sensory cortices in multi-sensory processing of audiovisual objects.

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.

Anatomical segregation of representations of personally familiar and famous people in the temporal and parietal cortices.

PubMed

Sugiura, Motoaki; Sassa, Yuko; Watanabe, Jobu; Akitsuki, Yuko; Maeda, Yasuhiro; Matsue, Yoshihiko; Kawashima, Ryuta

2009-10-01

Person recognition has been assumed to entail many types of person-specific cognitive responses, including retrieval of knowledge, episodic recollection, and emotional responses. To demonstrate the cortical correlates of this modular structure of multimodal person representation, we investigated neural responses preferential to personally familiar people and responses dependent on familiarity with famous people in the temporal and parietal cortices. During functional magnetic resonance imaging (fMRI) measurements, normal subjects recognized personally familiar names (personal) or famous names with high or low degrees of familiarity (high or low, respectively). Effects of familiarity with famous people (i.e., high-low) were identified in the bilateral angular gyri, the left supramarginal gyrus, the middle part of the bilateral posterior cingulate cortices, and the left precuneus. Activation preferentially relevant to personally familiar people (i.e., personal-high) was identified in the bilateral temporo-parietal junctions, the right anterolateral temporal cortices, posterior middle temporal gyrus, posterior cingulate cortex (with a peak in the posterodorsal part), and the left precuneus; these activation foci exhibited varying degrees of activation for high and low names. An equivalent extent of activation was observed for all familiar names in the bilateral temporal poles, the left orbito-insular junction, the middle temporal gyrus, and the anterior part of the posterior cingulate cortex. The results demonstrated that distinct cortical areas supported different types of cognitive responses, induced to different degrees during recognition of famous and personally familiar people, providing neuroscientific evidence for the modularity of multimodal person representation.

Cortical membrane potential signature of optimal states for sensory signal detection

PubMed Central

McGinley, Matthew J.; David, Stephen V.; McCormick, David A.

2015-01-01

The neural correlates of optimal states for signal detection task performance are largely unknown. One hypothesis holds that optimal states exhibit tonically depolarized cortical neurons with enhanced spiking activity, such as occur during movement. We recorded membrane potentials of auditory cortical neurons in mice trained on a challenging tone-in-noise detection task while assessing arousal with simultaneous pupillometry and hippocampal recordings. Arousal measures accurately predicted multiple modes of membrane potential activity, including: rhythmic slow oscillations at low arousal, stable hyperpolarization at intermediate arousal, and depolarization during phasic or tonic periods of hyper-arousal. Walking always occurred during hyper-arousal. Optimal signal detection behavior and sound-evoked responses, at both sub-threshold and spiking levels, occurred at intermediate arousal when pre-decision membrane potentials were stably hyperpolarized. These results reveal a cortical physiological signature of the classically-observed inverted-U relationship between task performance and arousal, and that optimal detection exhibits enhanced sensory-evoked responses and reduced background synaptic activity. PMID:26074005

Visual Cortical Function in Very Low Birth Weight Infants without Retinal or Cerebral Pathology

PubMed Central

Hou, Chuan; Norcia, Anthony M.; Madan, Ashima; Tith, Solina; Agarwal, Rashi

2011-01-01

Purpose. Preterm infants are at high risk of visual and neural developmental deficits. However, the development of visual cortical function in preterm infants with no retinal or neurologic morbidity has not been well defined. To determine whether premature birth itself alters visual cortical function, swept parameter visual evoked potential (sVEP) responses of healthy preterm infants were compared with those of term infants. Methods. Fifty-two term infants and 58 very low birth weight (VLBW) infants without significant retinopathy of prematurity or neurologic morbidities were enrolled. Recruited VLBW infants were between 26 and 33 weeks of gestational age, with birth weights of less than 1500 g. Spatial frequency, contrast, and vernier offset sweep VEP tuning functions were measured at 5 to 7 months' corrected age. Acuity and contrast thresholds were derived by extrapolating the tuning functions to 0 amplitude. These thresholds and suprathreshold response amplitudes were compared between groups. Results. Preterm infants showed increased thresholds (indicating decreased sensitivity to visual stimuli) and reductions in amplitudes for all three measures. These changes in cortical responsiveness were larger in the <30 weeks ' gestational age subgroup than in the ≥30 weeks' gestational age subgroup. Conclusions. Preterm infants with VLBW had measurable and significant changes in cortical responsiveness that were correlated with gestational age. These results suggest that premature birth in the absence of identifiable retinal or neurologic abnormalities has a significant effect on visual cortical sensitivity at 5 to 7 months' of corrected age and that gestational age is an important factor in visual development. PMID:22025567

Cortical entrainment to music and its modulation by expertise

PubMed Central

Doelling, Keith B.; Poeppel, David

2015-01-01

Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta–theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15–30 Hz)—often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition. PMID:26504238

Cortical entrainment to music and its modulation by expertise.

PubMed

Doelling, Keith B; Poeppel, David

2015-11-10

Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta-theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.

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

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

PubMed Central

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

2014-01-01

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

Distributed Bandpass Filtering and Signal Demodulation in Cortical Network Models

NASA Astrophysics Data System (ADS)

McDonnell, Mark D.

Experimental recordings of cortical activity often exhibit narrowband oscillations, at various center frequencies ranging in the order of 1-200 Hz. Many neuronal mechanisms are known to give rise to oscillations, but here we focus on a population effect known as sparsely synchronised oscillations. In this effect, individual neurons in a cortical network fire irregularly at slow average spike rates (1-10 Hz), but the population spike rate oscillates at gamma frequencies (greater than 40 Hz) in response to spike bombardment from the thalamus. These cortical networks form recurrent (feedback) synapses. Here we describe a model of sparsely synchronized population oscillations using the language of feedback control engineering, where we treat spiking as noisy feedback. We show, using a biologically realistic model of synaptic current that includes a delayed response to inputs, that the collective behavior of the neurons in the network is like a distributed bandpass filter acting on the network inputs. Consequently, the population response has the character of narrowband random noise, and therefore has an envelope and instantaneous frequency with lowpass characteristics. Given that there exist biologically plausible neuronal mechanisms for demodulating the envelope and instantaneous frequency, we suggest there is potential for similar effects to be exploited in nanoscale electronics implementations of engineered communications receivers.

Cortical Response Variability as a Developmental Index of Selective Auditory Attention

ERIC Educational Resources Information Center

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…

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex

PubMed Central

Thimm, Andreas; Funke, Klaus

2015-01-01

Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW–PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4–5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events. PMID:25504571

Speech acquisition predicts regions of enhanced cortical response to auditory stimulation in autism spectrum individuals.

PubMed

Samson, F; Zeffiro, T A; Doyon, J; Benali, H; Mottron, L

2015-09-01

A continuum of phenotypes makes up the autism spectrum (AS). In particular, individuals show large differences in language acquisition, ranging from precocious speech to severe speech onset delay. However, the neurological origin of this heterogeneity remains unknown. Here, we sought to determine whether AS individuals differing in speech acquisition show different cortical responses to auditory stimulation and morphometric brain differences. Whole-brain activity following exposure to non-social sounds was investigated. Individuals in the AS were classified according to the presence or absence of Speech Onset Delay (AS-SOD and AS-NoSOD, respectively) and were compared with IQ-matched typically developing individuals (TYP). AS-NoSOD participants displayed greater task-related activity than TYP in the inferior frontal gyrus and peri-auditory middle and superior temporal gyri, which are associated with language processing. Conversely, the AS-SOD group only showed enhanced activity in the vicinity of the auditory cortex. We detected no differences in brain structure between groups. This is the first study to demonstrate the existence of differences in functional brain activity between AS individuals divided according to their pattern of speech development. These findings support the Trigger-threshold-target model and indicate that the occurrence of speech onset delay in AS individuals depends on the location of cortical functional reallocation, which favors perception in AS-SOD and language in AS-NoSOD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cortical modulation of auditory processing in the midbrain

PubMed Central

Bajo, Victoria M.; King, Andrew J.

2013-01-01

In addition to their ascending pathways that originate at the receptor cells, all sensory systems are characterized by extensive descending projections. Although the size of these connections often outweighs those that carry information in the ascending auditory pathway, we still have a relatively poor understanding of the role they play in sensory processing. In the auditory system one of the main corticofugal projections links layer V pyramidal neurons with the inferior colliculus (IC) in the midbrain. All auditory cortical fields contribute to this projection, with the primary areas providing the largest outputs to the IC. In addition to medium and large pyramidal cells in layer V, a variety of cell types in layer VI make a small contribution to the ipsilateral corticocollicular projection. Cortical neurons innervate the three IC subdivisions bilaterally, although the contralateral projection is relatively small. The dorsal and lateral cortices of the IC are the principal targets of corticocollicular axons, but input to the central nucleus has also been described in some studies and is distinctive in its laminar topographic organization. Focal electrical stimulation and inactivation studies have shown that the auditory cortex can modify almost every aspect of the response properties of IC neurons, including their sensitivity to sound frequency, intensity, and location. Along with other descending pathways in the auditory system, the corticocollicular projection appears to continually modulate the processing of acoustical signals at subcortical levels. In particular, there is growing evidence that these circuits play a critical role in the plasticity of neural processing that underlies the effects of learning and experience on auditory perception by enabling changes in cortical response properties to spread to subcortical nuclei. PMID:23316140

Self-Referential Processing, Rumination, and Cortical Midline Structures in Major Depression

PubMed Central

Nejad, Ayna Baladi; Fossati, Philippe; Lemogne, Cédric

2013-01-01

Major depression is associated with a bias toward negative emotional processing and increased self-focus, i.e., the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature, and is conceptualized as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasized in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course, and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. Self-referential processing in major depression seems associated with abnormally increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralized task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment. PMID:24124416

Distinct Spatiotemporal Activation Patterns of the Perirhinal-Entorhinal Network in Response to Cortical and Amygdala Input

PubMed Central

Willems, Janske G. P.; Wadman, Wytse J.; Cappaert, Natalie L. M.

2016-01-01

The perirhinal (PER) and entorhinal cortex (EC) receive input from the agranular insular cortex (AiP) and the subcortical lateral amygdala (LA) and the main output area is the hippocampus. Information transfer through the PER/EC network however, is not always guaranteed. It is hypothesized that this network actively regulates the (sub)cortical activity transfer to the hippocampal network and that the inhibitory system is involved in this function. This study determined the recruitment by the AiP and LA afferents in PER/EC network with the use of voltage sensitive dye (VSD) imaging in horizontal mouse brain slices. Electrical stimulation (500 μA) of the AiP induced activity that gradually propagated predominantly in the rostro-caudal direction: from the PER to the lateral EC (LEC). In the presence of 1 μM of the competitive γ-aminobutyric acid (GABAA) receptor antagonist bicuculline, AiP stimulation recruited the medial EC (MEC) as well. In contrast, LA stimulation (500 μA) only induced activity in the deep layers of the PER. In the presence of bicuculline, the initial population activity in the PER propagated further towards the superficial layers and the EC after a delay. The latency of evoked responses decreased with increasing stimulus intensities (50–500 μA) for both the AiP and LA stimuli. The stimulation threshold for evoking responses in the PER/EC network was higher for the LA than for the AiP. This study showed that the extent of the PER/EC network activation depends on release of inhibition. When GABAA dependent inhibition is reduced, both the AiP and the LA activate spatially overlapping regions, although in a distinct spatiotemporal fashion. It is therefore hypothesized that the inhibitory network regulates excitatory activity from both cortical and subcortical areas that has to be transmitted through the PER/EC network. PMID:27378860

Cortical brain development in nonpsychotic siblings of patients with childhood-onset schizophrenia.

PubMed

Gogtay, Nitin; Greenstein, Deanna; Lenane, Marge; Clasen, Liv; Sharp, Wendy; Gochman, Pete; Butler, Philip; Evans, Alan; Rapoport, Judith

2007-07-01

Cortical gray matter (GM) loss is marked and progressive in childhood-onset schizophrenia (COS) during adolescence but becomes more circumscribed by early adulthood. Nonpsychotic siblings of COS probands could help evaluate whether the cortical GM abnormalities are familial/trait markers. To map cortical development in nonpsychotic siblings of COS probands. Using an automated measurement and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in healthy full siblings (n = 52, 113 scans; age 8 through 28 years) of patients with COS, contrasting them with age-, sex-, and scan interval-matched healthy controls (n = 52, 108 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. An ongoing COS study at the National Institute of Mental Health. Fifty-two healthy full siblings of patients with COS, aged 8 through 28 years, and 52 healthy controls. Longitudinal trajectories of cortical GM development in healthy siblings of patients with COS compared with matched healthy controls and exploratory measure of the relationship between developmental GM trajectories and the overall functioning as defined by the Global Assessment Scale (GAS) score. Younger, healthy siblings of patients with COS showed significant GM deficits in the left prefrontal and bilateral temporal cortices and smaller deficits in the right prefrontal and inferior parietal cortices compared with the controls. These cortical deficits in siblings disappeared by age 20 years and the process of deficit reduction correlated with overall functioning (GAS scores) at the last scan. Prefrontal and temporal GM loss in COS appears to be a familial/trait marker. Amelioration of regional GM deficits in healthy siblings was associated with higher global functioning (GAS scores), suggesting a relationship between brain plasticity and functional outcome for these nonpsychotic, nonspectrum siblings.

Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals.

PubMed

Klein, Denise; Mok, Kelvin; Chen, Jen-Kai; Watkins, Kate E

2014-04-01

We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development. Copyright © 2013 Elsevier Inc. All rights reserved.

Cortical activation patterns correlate with speech understanding after cochlear implantation

PubMed Central

Olds, Cristen; Pollonini, Luca; Abaya, Homer; Larky, Jannine; Loy, Megan; Bortfeld, Heather; Beauchamp, Michael S.; Oghalai, John S.

2015-01-01

Objectives Cochlear implants are a standard therapy for deafness, yet the ability of implanted patients to understand speech varies widely. To better understand this variability in outcomes, we used functional near-infrared spectroscopy (fNIRS) to image activity within regions of the auditory cortex and compare the results to behavioral measures of speech perception. Design We studied 32 deaf adults hearing through cochlear implants and 35 normal-hearing controls. We used fNIRS to measure responses within the lateral temporal lobe and the superior temporal gyrus to speech stimuli of varying intelligibility. The speech stimuli included normal speech, channelized speech (vocoded into 20 frequency bands), and scrambled speech (the 20 frequency bands were shuffled in random order). We also used environmental sounds as a control stimulus. Behavioral measures consisted of the Speech Reception Threshold, CNC words, and AzBio Sentence tests measured in quiet. Results Both control and implanted participants with good speech perception exhibited greater cortical activations to natural speech than to unintelligible speech. In contrast, implanted participants with poor speech perception had large, indistinguishable cortical activations to all stimuli. The ratio of cortical activation to normal speech to that of scrambled speech directly correlated with the CNC Words and AzBio Sentences scores. This pattern of cortical activation was not correlated with auditory threshold, age, side of implantation, or time after implantation. Turning off the implant reduced cortical activations in all implanted participants. Conclusions Together, these data indicate that the responses we measured within the lateral temporal lobe and the superior temporal gyrus correlate with behavioral measures of speech perception, demonstrating a neural basis for the variability in speech understanding outcomes after cochlear implantation. PMID:26709749

Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

PubMed

Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

2012-03-01

The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

Cortical complexity in bipolar disorder applying a spherical harmonics approach.

PubMed

Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

2017-05-30

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis.

PubMed

Cosottini, Mirco; Pesaresi, Ilaria; Piazza, Selina; Diciotti, Stefano; Cecchi, Paolo; Fabbri, Serena; Carlesi, Cecilia; Mascalchi, Mario; Siciliano, Gabriele

2012-03-01

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended

Brain signatures of moral sensitivity in adolescents with early social deprivation.

PubMed

Escobar, María Josefina; Huepe, David; Decety, Jean; Sedeño, Lucas; Messow, Marie Kristin; Baez, Sandra; Rivera-Rei, Álvaro; Canales-Johnson, Andrés; Morales, Juan Pablo; Gómez, David Maximiliano; Schröeder, Johannes; Manes, Facundo; López, Vladimir; Ibánez, Agustín

2014-06-19

The present study examined neural responses associated with moral sensitivity in adolescents with a background of early social deprivation. Using high-density electroencephalography (hdEEG), brain activity was measured during an intentional inference task, which assesses rapid moral decision-making regarding intentional or unintentional harm to people and objects. We compared the responses to this task in a socially deprived group (DG) with that of a control group (CG). The event-related potentials (ERPs) results showed atypical early and late frontal cortical markers associated with attribution of intentionality during moral decision-making in DG (especially regarding intentional harm to people). The source space of the hdEEG showed reduced activity for DG compared with CG in the right prefrontal cortex, bilaterally in the ventromedial prefrontal cortex (vmPFC), and right insula. Moreover, the reduced response in vmPFC for DG was predicted by higher rates of externalizing problems. These findings demonstrate the importance of the social environment in early moral development, supporting a prefrontal maturation model of social deprivation.

Assessment of hearing threshold in adults with hearing loss using an automated system of cortical auditory evoked potential detection.

PubMed

Durante, Alessandra Spada; Wieselberg, Margarita Bernal; Roque, Nayara; Carvalho, Sheila; Pucci, Beatriz; Gudayol, Nicolly; de Almeida, Kátia

The use of hearing aids by individuals with hearing loss brings a better quality of life. Access to and benefit from these devices may be compromised in patients who present difficulties or limitations in traditional behavioral audiological evaluation, such as newborns and small children, individuals with auditory neuropathy spectrum, autism, and intellectual deficits, and in adults and the elderly with dementia. These populations (or individuals) are unable to undergo a behavioral assessment, and generate a growing demand for objective methods to assess hearing. Cortical auditory evoked potentials have been used for decades to estimate hearing thresholds. Current technological advances have lead to the development of equipment that allows their clinical use, with features that enable greater accuracy, sensitivity, and specificity, and the possibility of automated detection, analysis, and recording of cortical responses. To determine and correlate behavioral auditory thresholds with cortical auditory thresholds obtained from an automated response analysis technique. The study included 52 adults, divided into two groups: 21 adults with moderate to severe hearing loss (study group); and 31 adults with normal hearing (control group). An automated system of detection, analysis, and recording of cortical responses (HEARLab ® ) was used to record the behavioral and cortical thresholds. The subjects remained awake in an acoustically treated environment. Altogether, 150 tone bursts at 500, 1000, 2000, and 4000Hz were presented through insert earphones in descending-ascending intensity. The lowest level at which the subject detected the sound stimulus was defined as the behavioral (hearing) threshold (BT). The lowest level at which a cortical response was observed was defined as the cortical electrophysiological threshold. These two responses were correlated using linear regression. The cortical electrophysiological threshold was, on average, 7.8dB higher than the

Early attempts to visualize cortical monoamine nerve terminals.

PubMed

Hökfelt, Tomas

2016-08-15

The Falck-Hillarp, formaldehyde fluorescence method for the demonstration of monoamine neurons in a microscope was established in Lund, Sweden and published in 1962. In the same year Hillarp moved to Karolinska Institutet in Stockholm. Two years later Dahlström and Fuxe published the famous supplement in Acta Physiologica Scandinavica, describing the distribution of the dopamine, noradrenaline and serotonin cell groups in the rat brain. This landmark paper also represented an important contribution to an emerging discipline in neuroscience - chemical neuroanatomy. During the following years several modifications of the original method were developed, attempting to solve some shortcomings, one being the reproducible demonstration of noradrenaline nerve terminals in cortical regions. One result was the paper focused on in the present article, which also describes other efforts in the same direction going on in parallel, primarily, in Lund and Stockholm. As a result there was, in the mid 1970s, a fairly complete knowledge of the catecholamine systems in the rat brain. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

Task-dependent response conflict monitoring and cognitive control in anterior cingulate and dorsolateral prefrontal cortices.

PubMed

Kim, Chobok; Chung, Chongwook; Kim, Jeounghoon

2013-11-06

Previous experience affects our behavior in terms of adjustments. It has been suggested that the conflict monitor-controller system implemented in the prefrontal cortex plays a critical role in such adjustments. Previous studies suggested that there exists multiple conflict monitor-controller systems associated with the level of information (i.e., stimulus and response levels). In this study, we sought to test whether different types of conflicts occur at the same information processing level (i.e., response level) are independently processed. For this purpose, we designed a task paradigm to measure two different types of response conflicts using color-based and location-based conflict stimuli and measured the conflict adaptation effects associated with the two types of conflicts either independently (i.e., single conflict conditions) or simultaneously (i.e., a double-conflict condition). The behavioral results demonstrated that performance on current incongruent trials was faster only when the preceding trial was the same type of response conflict regardless of whether they included a single- or double-conflict. Imaging data also showed that anterior cingulate and dorsolateral prefrontal cortices operate in a task-specific manner. These findings suggest that there may be multiple monitor-controller loops for color-based and location-based conflicts even at the same response level. Importantly, our results suggest that double-conflict processing is qualitatively different from single-conflict processing although double-conflict shares the same sources of conflict with two single-conflict conditions. © 2013 Published by Elsevier B.V.

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

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.

Neural network models for spatial data mining, map production, and cortical direction selectivity

NASA Astrophysics Data System (ADS)

Parsons, Olga

A family of ARTMAP neural networks for incremental supervised learning has been developed over the last decade. The Sensor Exploitation Group of MIT Lincoln Laboratory (LL) has incorporated an early version of this network as the recognition engine of a hierarchical system for fusion and data mining of multiple registered geospatial images. The LL system has been successfully fielded, but it is limited to target vs. non-target identifications and does not produce whole maps. This dissertation expands the capabilities of the LL system so that it learns to identify arbitrarily many target classes at once and can thus produce a whole map. This new spatial data mining system is designed particularly to cope with the highly skewed class distributions of typical mapping problems. Specification of a consistent procedure and a benchmark testbed has permitted the evaluation of candidate recognition networks as well as pre- and post-processing and feature extraction options. The resulting default ARTMAP network and mapping methodology set a standard for a variety of related mapping problems and application domains. The second part of the dissertation investigates the development of cortical direction selectivity. The possible role of visual experience and oculomotor behavior in the maturation of cells in the primary visual cortex is studied. The responses of neurons in the thalamus and cortex of the cat are modeled when natural scenes are scanned by several types of eye movements. Inspired by the Hebbian-like synaptic plasticity, which is based upon correlations between cell activations, the second-order statistical structure of thalamo-cortical activity is examined. In the simulations, patterns of neural activity that lead to a correct refinement of cell responses are observed during visual fixation, when small ocular movements occur, but are not observed in the presence of large saccades. Simulations also replicate experiments in which kittens are reared under stroboscopic

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

Early response to psychological trauma--what GPs can do.

PubMed

Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

2013-09-01

There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.

PubMed

Le Moëllic, Cathy; Ouvrard-Pascaud, Antoine; Capurro, Claudia; Cluzeaud, Francoise; Fay, Michel; Jaisser, Frederic; Farman, Nicolette; Blot-Chabaud, Marcel

2004-05-01

Effects of aldosterone on its target cells have long been considered to be mediated exclusively through the genomic pathway; however, evidence has been provided for rapid effects of the hormone that may involve nongenomic mechanisms. Whether an interaction exists between these two signaling pathways is not yet established. In this study, the authors show that aldosterone triggers both early nongenomic and late genomic increase in sodium transport in the RCCD(2) rat cortical collecting duct cell line. In these cells, the early (up to 2.5 h) aldosterone-induced increase in short-circuit current (Isc) is not blocked by the mineralocorticoid receptor (MR) antagonist RU26752, it does not require mRNA or protein synthesis, and it involves the PKCalpha signaling pathway. In addition, this early response is reproduced by aldosterone-BSA, which acts at the cell surface and presumably does not enter the cells (aldo-BSA is unable to trigger the late response). The authors also show that MR is rapidly phosphorylated on serine and threonine residues by aldosterone or aldosterone-BSA. In contrast, the late (4 to 24 h) aldosterone-induced increase in ion transport occurs through activation of the MR and requires mRNA and protein synthesis. Interestingly, nongenomic and genomic aldosterone actions appear to be interdependent. Blocking the PKCalpha pathway results in the inhibition of the late genomic response to aldosterone, as demonstrated by the suppression of aldosterone-induced increase in MR transactivation activity, alpha1 Na(+)/K(+)/ATPase mRNA, and Isc. These data suggest cross-talk between the nongenomic and genomic responses to aldosterone in renal cells and suggest that the aldosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation. E-mail: marcel.blot-chabaud@pharmacie.univ-mrs.fr

Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner

PubMed Central

Bressler, David W.; Fortenbaugh, Francesca C.; Robertson, Lynn C.; Silver, Michael A.

2013-01-01

Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. PMID:23562388

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.

Attention enhances multi-voxel representation of novel objects in frontal, parietal and visual cortices.

PubMed

Woolgar, Alexandra; Williams, Mark A; Rich, Anina N

2015-04-01

Selective attention is fundamental for human activity, but the details of its neural implementation remain elusive. One influential theory, the adaptive coding hypothesis (Duncan, 2001, An adaptive coding model of neural function in prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single neurons in certain frontal and parietal regions dynamically adjust their responses to selectively encode relevant information. This selective representation may in turn support selective processing in more specialized brain regions such as the visual cortices. Here, we use multi-voxel decoding of functional magnetic resonance images to demonstrate selective representation of attended--and not distractor--objects in frontal, parietal, and visual cortices. In addition, we highlight a critical role for task demands in determining which brain regions exhibit selective coding. Strikingly, representation of attended objects in frontoparietal cortex was highest under conditions of high perceptual demand, when stimuli were hard to perceive and coding in early visual cortex was weak. Coding in early visual cortex varied as a function of attention and perceptual demand, while coding in higher visual areas was sensitive to the allocation of attention but robust to changes in perceptual difficulty. Consistent with high-profile reports, peripherally presented objects could also be decoded from activity at the occipital pole, a region which corresponds to the fovea. Our results emphasize the flexibility of frontoparietal and visual systems. They support the hypothesis that attention enhances the multi-voxel representation of information in the brain, and suggest that the engagement of this attentional mechanism depends critically on current task demands. Copyright © 2015 Elsevier Inc. All rights reserved.

Using modern human cortical bone distribution to test the systemic robusticity hypothesis.

PubMed

Baab, Karen L; Copes, Lynn E; Ward, Devin L; Wells, Nora; Grine, Frederick E

2018-06-01

The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial

Recognition Memory for Braille or Spoken Words: An fMRI study in Early Blind

PubMed Central

Burton, Harold; Sinclair, Robert J.; Agato, Alvin

2012-01-01

We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5 yrs. In an event-related design, we studied blood oxygen level-dependent responses to studied (“old”) compared to novel (“new”) words. Presentation mode was in Braille or spoken. Responses were larger for identified “new” words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken “new” words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with “old”/“new” recognition. Left dorsolateral prefrontal cortex had larger responses to “old” words only with Braille. Larger occipital cortex responses to “new” Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for “new” words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering “old” words. A larger response when identifying “new” words possibly resulted from exhaustive recollecting the sensory properties of “old” words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a “sensory echo” that aids recollection. PMID:22251836

Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study.

PubMed

Parisi, V; Colacino, G; Milazzo, G; Scuderi, A C; Manni, G

1999-09-01

The retinal dysfunction and the delayed visual cortex responses shown by patients affected by glaucoma can be objectively assessed by Pattern Electroretinogram (PERG) and Visual Evoked Potentials (VEP) recordings. The present study aims to evaluate the effects of nicergoline on the retinal function and on the visual cortical responses in glaucoma patients. Sixty patients (mean age 44.6+/-3.7) with open angle glaucoma were enrolled. The patients were divided into two groups: NG Group, where 30 patients were treated with nicergoline (Cebran((R)), 2 cps day) for 30 days; and CG Group, where 30 patients were not treated. Simultaneous recordings of PERG and VEP were performed in NG patients at the baseline, at 30 days after treatment with nicergoline (day 30), and at 45 days from the end of the treatment (day 75). PERG and VEP were recorded in CG patients at the baseline and after 30 and 75 days. The visual stimulus for recording PERGs and VEPs was a checkerboard whose elements subtended a visual arc of 60' and 15' with a 70% contrast, and alternated at a frequency of 2 Hz. At the baseline none of the electrophysiological parameters observed in NG Group patients differed (P>0.05) from those of CG Group patients. At days 30 and 75, in CG Group patients the values of the PERG and VEP parameters were unmodified (P>0.05) with respect to the baseline. In NG Group patients, the 30-day treatment period with nicergoline induced a significant (P<0.01) improvement of the PERG and VEP parameters. At day 75 all the electrophysiological parameters of NG Group did not differ significantly (P>0.05) from those at the baseline. Treatment with nicergoline induces an improvement of the retinal function and of the visual cortical responses in patients affected by glaucoma. This effect disappears within 45 days after the suspension of the treatment. Copyright 1999 Academic Press.

Do Gravity-Related Sensory Information Enable the Enhancement of Cortical Proprioceptive Inputs When Planning a Step in Microgravity?

PubMed Central

Saradjian, Anahid H.; Paleressompoulle, Dany; Louber, Didier; Coyle, Thelma; Blouin, Jean; Mouchnino, Laurence

2014-01-01

We recently found that the cortical response to proprioceptive stimulation was greater when participants were planning a step than when they stood still, and that this sensory facilitation was suppressed in microgravity. The aim of the present study was to test whether the absence of gravity-related sensory afferents during movement planning in microgravity prevented the proprioceptive cortical processing to be enhanced. We reestablished a reference frame in microgravity by providing and translating a horizontal support on which the participants were standing and verified whether this procedure restored the proprioceptive facilitation. The slight translation of the base of support (lateral direction), which occurred prior to step initiation, stimulated at least cutaneous and vestibular receptors. The sensitivity to proprioceptive stimulation was assessed by measuring the amplitude of the cortical somatosensory-evoked potential (SEP, over the Cz electrode) following the vibration of the leg muscle. The vibration lasted 1 s and the participants were asked to either initiate a step at the vibration offset or to remain still. We found that the early SEP (90–160 ms) was smaller when the platform was translated than when it remained stationary, revealing the existence of an interference phenomenon (i.e., when proprioceptive stimulation is preceded by the stimulation of different sensory modalities evoked by the platform translation). By contrast, the late SEP (550 ms post proprioceptive stimulation onset) was greater when the translation preceded the vibration compared to a condition without pre-stimulation (i.e., no translation). This suggests that restoring a body reference system which is impaired in microgravity allowed a greater proprioceptive cortical processing. Importantly, however, the late SEP was similarly increased when participants either produced a step or remained still. We propose that the absence of step-induced facilitation of proprioceptive cortical

Model Cortical Association Fields Account for the Time Course and Dependence on Target Complexity of Human Contour Perception

PubMed Central

Gintautas, Vadas; Ham, Michael I.; Kunsberg, Benjamin; Barr, Shawn; Brumby, Steven P.; Rasmussen, Craig; George, John S.; Nemenman, Ilya; Bettencourt, Luís M. A.; Kenyon, Garret T.

2011-01-01

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas. PMID:21998562

Functional networks in parallel with cortical development associate with executive functions in children.

PubMed

Zhong, Jidan; Rifkin-Graboi, Anne; Ta, Anh Tuan; Yap, Kar Lai; Chuang, Kai-Hsiang; Meaney, Michael J; Qiu, Anqi

2014-07-01

Children begin performing similarly to adults on tasks requiring executive functions in late childhood, a transition that is probably due to neuroanatomical fine-tuning processes, including myelination and synaptic pruning. In parallel to such structural changes in neuroanatomical organization, development of functional organization may also be associated with cognitive behaviors in children. We examined 6- to 10-year-old children's cortical thickness, functional organization, and cognitive performance. We used structural magnetic resonance imaging (MRI) to identify areas with cortical thinning, resting-state fMRI to identify functional organization in parallel to cortical development, and working memory/response inhibition tasks to assess executive functioning. We found that neuroanatomical changes in the form of cortical thinning spread over bilateral frontal, parietal, and occipital regions. These regions were engaged in 3 functional networks: sensorimotor and auditory, executive control, and default mode network. Furthermore, we found that working memory and response inhibition only associated with regional functional connectivity, but not topological organization (i.e., local and global efficiency of information transfer) of these functional networks. Interestingly, functional connections associated with "bottom-up" as opposed to "top-down" processing were more clearly related to children's performance on working memory and response inhibition, implying an important role for brain systems involved in late childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

PubMed Central

Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

2015-01-01

SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

Age of language acquisition and cortical language organization in multilingual patients undergoing awake brain mapping.

PubMed

Fernández-Coello, Alejandro; Havas, Viktória; Juncadella, Montserrat; Sierpowska, Joanna; Rodríguez-Fornells, Antoni; Gabarrós, Andreu

2017-06-01

OBJECTIVE Most knowledge regarding the anatomical organization of multilingualism is based on aphasiology and functional imaging studies. However, the results have still to be validated by the gold standard approach, namely electrical stimulation mapping (ESM) during awake neurosurgical procedures. In this ESM study the authors describe language representation in a highly specific group of 13 multilingual individuals, focusing on how age of acquisition may influence the cortical organization of language. METHODS Thirteen patients who had a high degree of proficiency in multiple languages and were harboring lesions within the dominant, left hemisphere underwent ESM while being operated on under awake conditions. Demographic and language data were recorded in relation to age of language acquisition (for native languages and early- and late-acquired languages), neuropsychological pre- and postoperative language testing, the number and location of language sites, and overlapping distribution in terms of language acquisition time. Lesion growth patterns and histopathological characteristics, location, and size were also recorded. The distribution of language sites was analyzed with respect to age of acquisition and overlap. RESULTS The functional language-related sites were distributed in the frontal (55%), temporal (29%), and parietal lobes (16%). The total number of native language sites was 47. Early-acquired languages (including native languages) were represented in 97 sites (55 overlapped) and late-acquired languages in 70 sites (45 overlapped). The overlapping distribution was 20% for early-early, 71% for early-late, and 9% for late-late. The average lesion size (maximum diameter) was 3.3 cm. There were 5 fast-growing and 7 slow-growing lesions. CONCLUSIONS Cortical language distribution in multilingual patients is not homogeneous, and it is influenced by age of acquisition. Early-acquired languages have a greater cortical representation than languages acquired

Recording human cortical population spikes non-invasively--An EEG tutorial.

PubMed

Waterstraat, Gunnar; Fedele, Tommaso; Burghoff, Martin; Scheer, Hans-Jürgen; Curio, Gabriel

2015-07-30

Non-invasively recorded somatosensory high-frequency oscillations (sHFOs) evoked by electric nerve stimulation are markers of human cortical population spikes. Previously, their analysis was based on massive averaging of EEG responses. Advanced neurotechnology and optimized off-line analysis can enhance the signal-to-noise ratio of sHFOs, eventually enabling single-trial analysis. The rationale for developing dedicated low-noise EEG technology for sHFOs is unfolded. Detailed recording procedures and tailored analysis principles are explained step-by-step. Source codes in Matlab and Python are provided as supplementary material online. Combining synergistic hardware and analysis improvements, evoked sHFOs at around 600 Hz ('σ-bursts') can be studied in single-trials. Additionally, optimized spatial filters increase the signal-to-noise ratio of components at about 1 kHz ('κ-bursts') enabling their detection in non-invasive surface EEG. sHFOs offer a unique possibility to record evoked human cortical population spikes non-invasively. The experimental approaches and algorithms presented here enable also non-specialized EEG laboratories to combine measurements of conventional low-frequency EEG with the analysis of concomitant cortical population spike responses. Copyright © 2014 Elsevier B.V. All rights reserved.