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Showing papers in "Cerebral Cortex in 2017"


Journal ArticleDOI
TL;DR: Reliability was lowest for subcortical connections and highest for within‐network cortical connections, and Multivariate reliability was greater than univariate; these findings are among the first to underscore this distinction for functional connectivity.
Abstract: Best practices are currently being developed for the acquisition and processing of resting-state magnetic resonance imaging data used to estimate brain functional organization-or "functional connectivity." Standards have been proposed based on test-retest reliability, but open questions remain. These include how amount of data per subject influences whole-brain reliability, the influence of increasing runs versus sessions, the spatial distribution of reliability, the reliability of multivariate methods, and, crucially, how reliability maps onto prediction of behavior. We collected a dataset of 12 extensively sampled individuals (144 min data each across 2 identically configured scanners) to assess test-retest reliability of whole-brain connectivity within the generalizability theory framework. We used Human Connectome Project data to replicate these analyses and relate reliability to behavioral prediction. Overall, the historical 5-min scan produced poor reliability averaged across connections. Increasing the number of sessions was more beneficial than increasing runs. Reliability was lowest for subcortical connections and highest for within-network cortical connections. Multivariate reliability was greater than univariate. Finally, reliability could not be used to improve prediction; these findings are among the first to underscore this distinction for functional connectivity. A comprehensive understanding of test-retest reliability, including its limitations, supports the development of best practices in the field.

296 citations


Journal ArticleDOI
TL;DR: This work finds that a surprising number of behavioral, demographic, and physiological measures, including fluid intelligence, reading ability, weight, and psychiatric diagnostic scales, correlate with head motion in the Human Connectome Project, and shows that data cleaning strategies reduce the influence of head motion and substantially alter previously reported FC:behavior relationship.
Abstract: A growing field of research explores links between behavioral measures and functional connectivity (FC) assessed using resting-state functional magnetic resonance imaging. Recent studies suggest that measurement of these relationships may be corrupted by head motion artifact. Using data from the Human Connectome Project (HCP), we find that a surprising number of behavioral, demographic, and physiological measures (23 of 122), including fluid intelligence, reading ability, weight, and psychiatric diagnostic scales, correlate with head motion. We demonstrate that "trait" (across-subject) and "state" (across-day, within-subject) effects of motion on FC are remarkably similar in HCP data, suggesting that state effects of motion could potentially mimic trait correlates of behavior. Thus, head motion is a likely source of systematic errors (bias) in the measurement of FC:behavior relationships. Next, we show that data cleaning strategies reduce the influence of head motion and substantially alter previously reported FC:behavior relationship. Our results suggest that spurious relationships mediated by head motion may be widespread in studies linking FC to behavior.

276 citations


Journal ArticleDOI
TL;DR: This work uses ultrahigh‐resolution MRI at 7 T and dedicated image processing tools to demonstrate a systematic relationship between T1‐based intracortical myelin content and functional connectivity, and reveals a consistent spatial pattern throughout different analytic approaches.
Abstract: Research in the macaque monkey suggests that cortical areas with similar microstructure are more likely to be connected. Here, we examine this link in the human cerebral cortex using 2 magnetic resonance imaging (MRI) measures: quantitative T1 maps, which are sensitive to intracortical myelin content and provide an in vivo proxy for cortical microstructure, and resting-state functional connectivity. Using ultrahigh-resolution MRI at 7 T and dedicated image processing tools, we demonstrate a systematic relationship between T1-based intracortical myelin content and functional connectivity. This effect is independent of the proximity of areas. We employ nonlinear dimensionality reduction to characterize connectivity components and identify specific aspects of functional connectivity that are linked to myelin content. Our results reveal a consistent spatial pattern throughout different analytic approaches. While functional connectivity and myelin content are closely linked in unimodal areas, the correspondence is lower in transmodal areas, especially in posteromedial cortex and the angular gyrus. Our findings are in agreement with comprehensive reports linking histologically assessed microstructure and connectivity in different mammalian species and extend them to the human cerebral cortex in vivo.

228 citations


Journal ArticleDOI
TL;DR: This work reveals for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions.
Abstract: The insula is a complex structure involved in a wide range of functions. Tracing studies on nonhuman primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state-of-the-art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing an HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro-caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions.

196 citations


Journal ArticleDOI
TL;DR: It is reported, for the first time, that event-specific neural patterns observed in the default mode network are shared across the encoding, recall, and construction of the same real-life episode.
Abstract: Humans are able to mentally construct an episode when listening to another person's recollection, even though they themselves did not experience the events. However, it is unknown how strongly the neural patterns elicited by mental construction resemble those found in the brain of the individual who experienced the original events. Using fMRI and a verbal communication task, we traced how neural patterns associated with viewing specific scenes in a movie are encoded, recalled, and then transferred to a group of naive listeners. By comparing neural patterns across the 3 conditions, we report, for the first time, that event-specific neural patterns observed in the default mode network are shared across the encoding, recall, and construction of the same real-life episode. This study uncovers the intimate correspondences between memory encoding and event construction, and highlights the essential role our common language plays in the process of transmitting one's memories to other brains.

169 citations


Journal ArticleDOI
TL;DR: Widespread increased cortical thickness in ASD is shown, primarily left lateralized, from 6 years onwards, with differences diminishing during adulthood, consistent with the conjecture that developmental patterns of cortical thickness abnormalities reflect delayed cortical maturation and highlight the dynamic nature of morphological abnormalities in ASD.
Abstract: Neuroimaging studies in autism spectrum disorders (ASDs) have provided inconsistent evidence of cortical abnormality. This is probably due to the small sample sizes used in most studies, and important differences in sample characteristics, particularly age, as well as to the heterogeneity of the disorder. To address these issues, we assessed abnormalities in ASD within the Autism Brain Imaging Data Exchange data set, which comprises data from approximately 1100 individuals (~6-55 years). A subset of these data that met stringent quality control and inclusion criteria (560 male subjects; 266 ASD; age = 6-35 years) were used to compute age-specific differences in cortical thickness in ASD and the relationship of any such differences to symptom severity of ASD. Our results show widespread increased cortical thickness in ASD, primarily left lateralized, from 6 years onwards, with differences diminishing during adulthood. The severity of symptoms related to social affect and communication correlated with these cortical abnormalities. These results are consistent with the conjecture that developmental patterns of cortical thickness abnormalities reflect delayed cortical maturation and highlight the dynamic nature of morphological abnormalities in ASD.

149 citations


Journal ArticleDOI
TL;DR: A genome‐wide methylation study on fluorescence‐activated cell sorting‐sorted neuronal nuclei from the frontal cortex of 16 male ASD and 15 male control subjects is reported, providing further evidence that epigenetic alterations in disorder‐relevant tissues may be involved in the biology of ASD.
Abstract: Autism Spectrum Disorder (ASD) is a complex neuropsychiatric syndrome whose etiology includes genetic and environmental components Since epigenetic marks are sensitive to environmental insult, they may be involved in the development of ASD Initial brain studies have suggested a dysregulation of epigenetic marks in ASD However, due to cellular heterogeneity in the brain, these studies have not determined if there is a true change in the neuronal epigenetic signature Here, we report a genome-wide methylation study on fluorescence-activated cell sorting-sorted neuronal nuclei from the frontal cortex of 16 male ASD and 15 male control subjects Using the 450 K BeadArray, we identified 58 differentially methylated regions (DMRs) that included loci associated to GABAergic system genes, particularly ABAT and GABBR1, and brain-specific MicroRNAs Selected DMRs were validated by targeted Next Generation Bisulfite Sequencing Weighted gene correlation network analysis detected 3 co-methylation modules which are significantly correlated to ASD that were enriched for genomic regions underlying neuronal, GABAergic, and immune system genes Finally, we determined an overlap of the 58 ASD-related DMRs with neurodevelopment associated DMRs This investigation identifies alterations in the DNA methylation pattern in ASD cortical neurons, providing further evidence that epigenetic alterations in disorder-relevant tissues may be involved in the biology of ASD

118 citations


Journal ArticleDOI
TL;DR: It is reported that a large fraction of myelin in mouse cerebral cortex ensheaths GABAergic interneurons, reaching up to 80% in hippocampal subregions, and it is confirmed that axons of fast-spiking PV interneuron axons are extensively myelinated in the human brain.
Abstract: Myelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite the well-established physiological importance of myelination to neuronal function, relatively little is known about the myelination of GABAergic interneurons in the cerebral cortex. Here, we report that a large fraction of myelin in mouse cerebral cortex ensheaths GABAergic interneurons, reaching up to 80% in hippocampal subregions. Moreover, we find that a very high proportion of neocortical and hippocampal parvalbumin (PV) interneurons exhibit axonal myelination. Using a combination of intracellular recordings and biocytin labeling of ex vivo human neocortex, we also confirm that axons of fast-spiking PV interneurons are extensively myelinated in the human brain. PV interneuron myelination in both mice and humans exhibits a stereotyped topography with a bias towards proximal axonal segments and relatively short internodes (~27 μm) interspersed with branch points. Interestingly, myelin-deficient Shiverer mice exhibit an increased density and more proximal location of en passant boutons, suggesting that myelination might function in part to regulate synapse formation along PV interneuron axons. Taken together, fast-spiking interneuron myelination is likely to have broad implications for cerebral cortex function in health and disease.

114 citations


Journal ArticleDOI
TL;DR: The current experiment demonstrates that the neural alpha response to speech is a surprisingly clear proxy of top-down control, entirely driven by the listening goals of attending versus ignoring degraded speech.
Abstract: Human alpha (~10 Hz) oscillatory power is a prominent neural marker of cognitive effort. When listeners attempt to process and retain acoustically degraded speech, alpha power enhances. It is unclear whether these alpha modulations reflect the degree of acoustic degradation per se or the degradation-driven demand to a listener's attentional control. Using an irrelevant-speech paradigm and measuring the electroencephalogram (EEG), the current experiment demonstrates that the neural alpha response to speech is a surprisingly clear proxy of top-down control, entirely driven by the listening goals of attending versus ignoring degraded speech. While (n = 23) listeners retained the serial order of 9 to-be-recalled digits, one to-be-ignored sentence was presented. Distractibility of the to-be-ignored sentence parametrically varied in acoustic detail (noise-vocoding), with more acoustic detail of distracting speech increasingly disrupting listeners' serial memory recall. Where previous studies had observed decreases in parietal and auditory alpha power with more acoustic detail (of target speech), alpha power here showed the opposite pattern and increased with more acoustic detail in the speech distractor. In sum, the neural alpha response reflects almost exclusively a listener's goal, which is decisive for whether more acoustic detail facilitates comprehension (of attended speech) or enhances distraction (of ignored speech).

106 citations


Journal ArticleDOI
TL;DR: It is emphasized that human parietal cortex does not preferentially represent particular object properties irrespective of task, but together with frontal areas is part of a multiple‐demand and content‐rich cortical network representing task‐relevant object properties.
Abstract: The dorsal, parietal visual stream is activated when seeing objects, but the exact nature of parietal object representations is still under discussion. Here we test 2 specific hypotheses. First, parietal cortex is biased to host some representations more than others, with a different bias compared with ventral areas. A prime example would be object action representations. Second, parietal cortex forms a general multiple-demand network with frontal areas, showing similar task effects and representational content compared with frontal areas. To differentiate between these hypotheses, we implemented a human neuroimaging study with a stimulus set that dissociates associated object action from object category while manipulating task context to be either action- or category-related. Representations in parietal as well as prefrontal areas represented task-relevant object properties (action representations in the action task), with no sign of the irrelevant object property (category representations in the action task). In contrast, irrelevant object properties were represented in ventral areas. These findings emphasize that human parietal cortex does not preferentially represent particular object properties irrespective of task, but together with frontal areas is part of a multiple-demand and content-rich cortical network representing task-relevant object properties.

101 citations


Journal ArticleDOI
TL;DR: Computational principles to correlated axes of functional and cytoarchitectonic segregation in human VTC are linked, in which parallel processing across domains occurs along a lateral‐medial axis while transformations of information within domain occur along an anterior‐posterior axis.
Abstract: A fundamental hypothesis in neuroscience proposes that underlying cellular architecture (cytoarchitecture) contributes to the functionality of a brain area. However, this hypothesis has not been tested in human ventral temporal cortex (VTC) that contains domain-specific regions causally involved in perception. To fill this gap in knowledge, we used cortex-based alignment to register functional regions from living participants to cytoarchitectonic areas in ex vivo brains. This novel approach reveals 3 findings. First, there is a consistent relationship between domain-specific regions and cytoarchitectonic areas: each functional region is largely restricted to 1 cytoarchitectonic area. Second, extracting cytoarchitectonic profiles from face- and place-selective regions after back-projecting each region to 20-μm thick histological sections indicates that cytoarchitectonic properties distinguish these regions from each other. Third, some cytoarchitectonic areas contain more than 1 domain-specific region. For example, face-, body-, and character-selective regions are located within the same cytoarchitectonic area. We summarize these findings with a parsimonious hypothesis incorporating how cellular properties may contribute to functional specialization in human VTC. Specifically, we link computational principles to correlated axes of functional and cytoarchitectonic segregation in human VTC, in which parallel processing across domains occurs along a lateral-medial axis while transformations of information within domain occur along an anterior-posterior axis.

Journal ArticleDOI
TL;DR: These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.
Abstract: Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.

Journal ArticleDOI
TL;DR: It is suggested that behavioral goals alter how the brain extracts semantic features from the visual world by effectively disentangles population responses for downstream read-out by sculpting representational geometry in late-stage perceptual areas.
Abstract: Humans prioritize different semantic qualities of a complex stimulus depending on their behavioral goals. These semantic features are encoded in distributed neural populations, yet it is unclear how attention might operate across these distributed representations. To address this, we presented participants with naturalistic video clips of animals behaving in their natural environments while the participants attended to either behavior or taxonomy. We used models of representational geometry to investigate how attentional allocation affects the distributed neural representation of animal behavior and taxonomy. Attending to animal behavior transiently increased the discriminability of distributed population codes for observed actions in anterior intraparietal, pericentral, and ventral temporal cortices. Attending to animal taxonomy while viewing the same stimuli increased the discriminability of distributed animal category representations in ventral temporal cortex. For both tasks, attention selectively enhanced the discriminability of response patterns along behaviorally relevant dimensions. These findings suggest that behavioral goals alter how the brain extracts semantic features from the visual world. Attention effectively disentangles population responses for downstream read-out by sculpting representational geometry in late-stage perceptual areas.

Journal ArticleDOI
TL;DR: Findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection‐related retrieval deficits in this population.
Abstract: Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.

Journal ArticleDOI
TL;DR: In this article, the authors examined whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socioeconomic status, SES) and fetal neurodevelopment, and identified candidate biological processes underlying such association.
Abstract: This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.

Journal ArticleDOI
TL;DR: While both areas appear to be implicated in the processing of translational motion, only the anterior region (MST/TO‐2) makes a causal contribution to the perception of radial motion.
Abstract: Two subdivisions of human V5/MT+: one located posteriorly (MT/TO-1) and the other more anteriorly (MST/TO-2) were identified in human participants using functional magnetic resonance imaging on the basis of their representations of the ipsilateral versus contralateral visual field. These subdivisions were then targeted for disruption by the application of repetitive transcranial magnetic stimulation (rTMS). The rTMS was delivered to cortical areas while participants performed direction discrimination tasks involving 3 different types of moving stimuli defined by the translational, radial, or rotational motion of dot patterns. For translational motion, performance was significantly reduced relative to baseline when rTMS was applied to both MT/TO-1 and MST/TO-2. For radial motion, there was a differential effect between MT/TO-1 and MST/TO-2, with only disruption of the latter area affecting performance. The rTMS failed to reveal a complete dissociation between MT/TO-1 and MST/TO-2 in terms of their contribution to the perception of rotational motion. On the basis of these results, MT/TO-1 and MST/TO-2 appear to be functionally distinct subdivisions of hV5/MT+. While both areas appear to be implicated in the processing of translational motion, only the anterior region (MST/TO-2) makes a causal contribution to the perception of radial motion.

Journal ArticleDOI
TL;DR: A fMRI neural decoding study in humans shows that this pathway culminates in the right inferior frontal cortex face area (rIFFA) with a representation of individual identities that has been disentangled from variable visual features in different images of the same person.
Abstract: Neural models of a distributed system for face perception implicate a network of regions in the ventral visual stream for recognition of identity. Here, we report a functional magnetic resonance imaging (fMRI) neural decoding study in humans that shows that this pathway culminates in the right inferior frontal cortex face area (rIFFA) with a representation of individual identities that has been disentangled from variable visual features in different images of the same person. At earlier stages in the pathway, processing begins in early visual cortex and the occipital face area with representations of head view that are invariant across identities, and proceeds to an intermediate level of representation in the fusiform face area in which identity is emerging but still entangled with head view. Three-dimensional, view-invariant representation of identities in the rIFFA may be the critical link to the extended system for face perception, affording activation of person knowledge and emotional responses to familiar faces.

Journal ArticleDOI
TL;DR: The morpho‐electrotonic analysis shows 2 distinct classes of pyramidal neurons from L2 and L3 in the human temporal cortex removed after brain surgery; the basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites.
Abstract: There have been few quantitative characterizations of the morphological, biophysical, and cable properties of neurons in the human neocortex. We employed feature-based statistical methods on a rare data set of 60 3D reconstructed pyramidal neurons from L2 and L3 in the human temporal cortex (HL2/L3 PCs) removed after brain surgery. Of these cells, 25 neurons were also characterized physiologically. Thirty-two morphological features were analyzed (e.g., dendritic surface area, 36 333 ± 18 157 μm2; number of basal trees, 5.55 ± 1.47; dendritic diameter, 0.76 ± 0.28 μm). Eighteen features showed a significant gradual increase with depth from the pia (e.g., dendritic length and soma radius). The other features showed weak or no correlation with depth (e.g., dendritic diameter). The basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites. Unlike the morphological features, the active biophysical features (e.g., spike shapes and rates) and passive/cable features (e.g., somatic input resistance, 47.68 ± 15.26 MΩ, membrane time constant, 12.03 ± 1.79 ms, average dendritic cable length, 0.99 ± 0.24) were depth-independent. A novel descriptor for apical dendritic topology yielded 2 distinct classes, termed hereby as "slim-tufted" and "profuse-tufted" HL2/L3 PCs; the latter class tends to fire at higher rates. Thus, our morpho-electrotonic analysis shows 2 distinct classes of HL2/L3 PCs.

Journal ArticleDOI
TL;DR: The results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance between centroids compared with a NT population.
Abstract: Background While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, clinically they share some phenotypic features and have high comorbidity. Regardless, most studies have focused on only one condition, with considerable heterogeneity in their results. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics. Method Graph theory was used to analyse topological properties of structural covariance networks across both conditions and relative to a neurotypical (NT; n = 87) group using data from the ABIDE (autism; n = 62) and ADHD-200 datasets (ADHD; n = 69). Regional cortical thickness was used to construct the structural covariance networks. This was analysed in a theoretical framework examining potential differences in long and short-range connectivity, with a specific focus on relation between central graph measures and cortical thickness. Results We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance between centroids compared with a NT population. The 2 conditions also show divergence. Namely, there is less modular overlap between the 2 conditions than there is between each condition and the NT group. The ADHD group also showed reduced cortical thickness and lower degree in hub regions than the autism group. Lastly, the ADHD group also showed reduced wiring costs compared with the autism groups. Conclusions Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Furthermore, autism and ADHD both showed alterations in the relation between inter-regional covariance and centroid distance, where both groups show a steeper decline in covariance as a function of distance. The 2 groups also diverge on modular organization, cortical thickness of hub regions and wiring cost of the covariance network. Thus, on some network features the groups are distinct, yet on others there is convergence.

Journal ArticleDOI
TL;DR: The findings observed here in the mPFC are consistent with those previously reported in the hippocampus and striatum, suggesting that the sequentially activated time cells are not specific to these areas, but are part of a common representational motif across regions.
Abstract: A subset of hippocampal neurons, known as "time cells" fire sequentially for circumscribed periods of time within a delay interval. We investigated whether medial prefrontal cortex (mPFC) also contains time cells and whether their qualitative properties differ from those in the hippocampus and striatum. We studied the firing correlates of neurons in the rodent mPFC during a temporal discrimination task. On each trial, the animals waited for a few seconds in the stem of a T-maze. A subpopulation of units fired in a sequence consistently across trials for a circumscribed period during the delay interval. These sequentially activated time cells showed temporal accuracy that decreased as time passed as measured by both the width of their firing fields and the number of cells that fired at a particular part of the interval. The firing dynamics of the time cells was significantly better explained with the elapse of time than with the animals' position and velocity. The findings observed here in the mPFC are consistent with those previously reported in the hippocampus and striatum, suggesting that the sequentially activated time cells are not specific to these areas, but are part of a common representational motif across regions.

Journal ArticleDOI
TL;DR: Comparisons and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex.
Abstract: We compare several major white-matter tracts in human and macaque occipital lobe using diffusion magnetic resonance imaging. The comparison suggests similarities but also significant differences in the tracts. There are several apparently homologous tracts in the 2 species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. We could identify the macaque VOF (mVOF), which has been little studied. Its position is consistent with classical invasive anatomical studies by Wernicke. VOF homology is supported by similarity of the endpoints in V3A and ventral V4 across species. The mVOF fibers intertwine with the dorsal segment of the ILF, but the human VOF appears to be lateral to the ILF. These similarities and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex.

Journal ArticleDOI
TL;DR: It is proposed that subregions of DPC (anterior IPS) and VPC (AG) exhibit counterpointed functions sensitive to task/item-difficulty irrespective of cognitive domain that serve as top-down executively penetrated and automatic bottom-up domain-general buffers of active information, respectively.
Abstract: Numerous cognitive domains have been associated with the lateral parietal cortex, yet how these disparate functions are packed into this region remains unclear. Whilst areas within the dorsal and the ventral parietal cortex (DPC and VPC) show differential function, there is considerable disagreement as to what these functions might be. Studies focussed on individual domains have plotted out variations of function across the region. Direct cross-domain comparisons are rare yet, when they have been undertaken, at least some regions (particularly the intraparietal sulcus [IPS] and core angular gyrus [AG]) appear to have contrastive domain-general qualities. In order to pursue this parietal puzzle, this study utilized both functional and resting-state magnetic resonance imaging to investigate a potential unifying neurocomputational framework-in which both domain general as well as domain-selective regions arise from differential patterns of connectivity into subregions of the lateral parietal cortex. Specifically we found that, consistent with their contrastive patterns of functional connectivity, subregions of DPC (anterior IPS) and VPC (AG) exhibit counterpointed functions sensitive to task/item-difficulty irrespective of cognitive domain. We propose that these regions serve as top-down executively penetrated and automatic bottom-up domain-general buffers of active information, respectively. In contrast, other parietal and nonparietal regions are tuned toward specific domains.

Journal ArticleDOI
TL;DR: The findings illustrate how multivariate network analyses can be used to investigate the roles of specific regions within the large‐scale network, while also accounting for global network changes.
Abstract: A common approach in memory research is to isolate the function(s) of individual brain regions, such as the hippocampus, without addressing how those regions interact with the larger network. To investigate the properties of the hippocampus embedded within large-scale networks, we used functional magnetic resonance imaging and graph theory to characterize complex hippocampal interactions during the active retrieval of vivid versus dim visual memories. The study yielded 4 main findings. First, the right hippocampus displayed greater communication efficiency with the network (shorter path length) and became a more convergent structure for information integration (higher centrality measures) for vivid than dim memories. Second, vivid minus dim differences in our graph theory measures of interest were greater in magnitude for the right hippocampus than for any other region in the 90-region network. Moreover, the right hippocampus significantly reorganized its set of direct connections from dim to vivid memory retrieval. Finally, beyond the hippocampus, communication throughout the whole-brain network was more efficient (shorter global path length) for vivid than dim memories. In sum, our findings illustrate how multivariate network analyses can be used to investigate the roles of specific regions within the large-scale network, while also accounting for global network changes.

Journal ArticleDOI
TL;DR: Results show that semantic similarity is encoded by a range of cortical areas, including multimodal association (e.g., anterior inferior frontal, posterior middle temporal) and modality‐preferential (premotor) cortex and that the representational geometries in these regions are partly dependent on semantic type, with semantic similarity among action‐related words crossing lexical‐semantic category boundaries.
Abstract: Language comprehension engages a distributed network of frontotemporal, parietal, and sensorimotor regions, but it is still unclear how meaning of words and their semantic relationships are represented and processed within these regions and to which degrees lexico-semantic representations differ between regions and semantic types. We used fMRI and representational similarity analysis to relate word-elicited multivoxel patterns to semantic similarity between action and object words. In left inferior frontal (BA 44-45-47), left posterior middle temporal and left precentral cortex, the similarity of brain response patterns reflected semantic similarity among action-related verbs, as well as across lexical classes-between action verbs and tool-related nouns and, to a degree, between action verbs and food nouns, but not between action verbs and animal nouns. Instead, posterior inferior temporal cortex exhibited a reverse response pattern, which reflected the semantic similarity among object-related nouns, but not action-related words. These results show that semantic similarity is encoded by a range of cortical areas, including multimodal association (e.g., anterior inferior frontal, posterior middle temporal) and modality-preferential (premotor) cortex and that the representational geometries in these regions are partly dependent on semantic type, with semantic similarity among action-related words crossing lexical-semantic category boundaries.

Journal ArticleDOI
TL;DR: It is shown that layer 5 cortico-superior-collicular pyramidal neuron act as bandpass filters, resonating with a broad peak at ∼3 Hz, whereas layer 6 neurons act as low-pass filters.
Abstract: In the auditory cortex (AC), corticofugal projections arise from each level of the auditory system and are considered to provide feedback "loops" important to modulate the flow of ascending information. It is well established that the cortex can influence the response of neurons in the superior colliculus (SC) via descending corticofugal projections. However, little is known about the relative contribution of different pyramidal neurons to these projections in the SC. We addressed this question by taking advantage of anterograde and retrograde neuronal tracing to directly examine the laminar distribution, long-range projections, and electrophysiological properties of pyramidal neurons projecting from the AC to the SC of the mouse brain. Here we show that layer 5 cortico-superior-collicular pyramidal neurons act as bandpass filters, resonating with a broad peak at ∼3 Hz, whereas layer 6 neurons act as low-pass filters. The dissimilar subthreshold properties of layer 5 and layer 6 cortico-superior-collicular pyramidal neurons can be described by differences in the hyperpolarization-activated cyclic nucleotide-gated cation h-current (Ih). Ih also reduced the summation of short trains of artificial excitatory postsynaptic potentials injected at the soma of layer 5, but not layer 6, cortico-superior-collicular pyramidal neurons, indicating a differential dampening effect of Ih on these neurons.

Journal ArticleDOI
TL;DR: The use of paired‐pulse transcranial magnetic stimulation as a biomarker to track the course of cortical inhibitory dysfunction post‐TBI is highlighted and the neuroprotective role of PNNs on PV+ cell function suggests antioxidant treatment or Otx2 enhancement as a promising prophylaxis for post-TBI symptoms.
Abstract: Many neuropsychiatric symptoms that follow traumatic brain injury (TBI), including mood disorders, sleep disturbance, chronic pain, and posttraumatic epilepsy (PTE) are attributable to compromised cortical inhibition. However, the temporal trajectory of cortical inhibition loss and its underlying mechanisms are not known. Using paired-pulse transcranial magnetic stimulation (ppTMS) and immunohistochemistry, we tracked functional and cellular changes of cortical inhibitory network elements after fluid-percussion injury (FPI) in rats. ppTMS revealed a progressive loss of cortical inhibition as early as 2 weeks after FPI. This profile paralleled the increasing levels of cortical oxidative stress, which was accompanied by a gradual loss of parvalbumin (PV) immunoreactivity in perilesional cortex. Preceding the PV loss, we identified a degradation of the perineuronal net (PNN)-a specialized extracellular structure enwrapping cortical PV-positive (PV+) inhibitory interneurons which binds the PV+ cell maintenance factor, Otx2. The trajectory of these impairments underlies the reduced inhibitory tone, which can contribute to posttraumatic neurological conditions, such as PTE. Taken together, our results highlight the use of ppTMS as a biomarker to track the course of cortical inhibitory dysfunction post-TBI. Moreover, the neuroprotective role of PNNs on PV+ cell function suggests antioxidant treatment or Otx2 enhancement as a promising prophylaxis for post-TBI symptoms.

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

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TL;DR: CCS cells can make activities of frontal areas in concert with those of nonfrontal area using corticocortical loops, whereas CPn cells are more involved in closed corticostriatal loops than CCS cells.
Abstract: The frontal cortical areas make a coordinated response that generates appropriate behavior commands, using individual local circuits with corticostriatal and corticocortical connections in longer time scales than sensory areas. In secondary motor cortex (M2), situated between the prefrontal and primary motor areas, major subtypes of layer 5 corticostriatal cells are crossed-corticostriatal (CCS) cells innervating both sides of striatum, and corticopontine (CPn) cells projecting to the ipsilateral striatum and pontine nuclei. CCS cells innervate CPn cells unidirectionally: the former are therefore hierarchically higher than the latter among L5 corticostriatal cells. CCS cells project directly to both frontal and nonfrontal areas. On the other hand, CPn cells innervate the thalamus and layer 1a of frontal areas, where thalamic fibers relaying basal ganglia outputs are distributed. Thus, CCS cells can make activities of frontal areas in concert with those of nonfrontal area using corticocortical loops, whereas CPn cells are more involved in closed corticostriatal loops than CCS cells. Since reciprocal connections between CPn cells with facilitatory synapses may be related to persistent activity, CPn cells play a key role of longer time constant processes in corticostriatal as well as in corticocortical loops between the frontal areas.

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TL;DR: Findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance.
Abstract: Advances in functional magnetic resonance imaging have made it possible to provide real-time feedback on brain activity. Neurofeedback has been applied to therapeutic interventions for psychiatric disorders. Since many studies have shown that most psychiatric disorders exhibit abnormal brain networks, a novel experimental paradigm named connectivity neurofeedback, which can directly modulate a brain network, has emerged as a promising approach to treat psychiatric disorders. Here, we investigated the hypothesis that connectivity neurofeedback can induce the aimed direction of change in functional connectivity, and the differential change in cognitive performance according to the direction of change in connectivity. We selected the connectivity between the left primary motor cortex and the left lateral parietal cortex as the target. Subjects were divided into 2 groups, in which only the direction of change (an increase or a decrease in correlation) in the experimentally manipulated connectivity differed between the groups. As a result, subjects successfully induced the expected connectivity changes in either of the 2 directions. Furthermore, cognitive performance significantly and differentially changed from preneurofeedback to postneurofeedback training between the 2 groups. These findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance.

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TL;DR: It is suggested that, although in the intact system there is considerable crosstalk between dorsal and ventral cortices, object representations in dorsal cortex can be computed independently from those in ventral cortex.
Abstract: An established conceptualization of visual cortical function is one in which ventral regions mediate object perception while dorsal regions support spatial information processing and visually guided action. This division has been contested by evidence showing that dorsal regions are also engaged in the representation of object shape, even when actions are not required. The critical question is whether these dorsal, object-based representations are dissociable from ventral representations, and whether they play a functional role in object recognition. We examined the neural and behavioral profile of patients with impairments in object recognition following ventral cortex damage. In a functional magnetic resonanace imaging experiment, the blood oxygen level-dependent response in the ventral, but not dorsal, cortex of the patients evinced less sensitivity to object 3D structure compared with that of healthy controls. Consistently, in psychophysics experiments, the patients exhibited significant impairments in object perception, but still revealed residual sensitivity to object-based structural information. Together, these findings suggest that, although in the intact system there is considerable crosstalk between dorsal and ventral cortices, object representations in dorsal cortex can be computed independently from those in ventral cortex. While dorsal representations alone are unable to support normal object perception, they can, nevertheless, support a coarse description of object structural information.