Spatial attention improves the quality of population codes in human visual cortex.

PubMed

Saproo, Sameer; Serences, John T

2010-08-01

Selective attention enables sensory input from behaviorally relevant stimuli to be processed in greater detail, so that these stimuli can more accurately influence thoughts, actions, and future goals. Attention has been shown to modulate the spiking activity of single feature-selective neurons that encode basic stimulus properties (color, orientation, etc.). However, the combined output from many such neurons is required to form stable representations of relevant objects and little empirical work has formally investigated the relationship between attentional modulations on population responses and improvements in encoding precision. Here, we used functional MRI and voxel-based feature tuning functions to show that spatial attention induces a multiplicative scaling in orientation-selective population response profiles in early visual cortex. In turn, this multiplicative scaling correlates with an improvement in encoding precision, as evidenced by a concurrent increase in the mutual information between population responses and the orientation of attended stimuli. These data therefore demonstrate how multiplicative scaling of neural responses provides at least one mechanism by which spatial attention may improve the encoding precision of population codes. Increased encoding precision in early visual areas may then enhance the speed and accuracy of perceptual decisions computed by higher-order neural mechanisms.

The medial frontal cortex contributes to but does not organize rat exploratory behavior.

PubMed

Blankenship, Philip A; Stuebing, Sarah L; Winter, Shawn S; Cheatwood, Joseph L; Benson, James D; Whishaw, Ian Q; Wallace, Douglas G

2016-11-12

Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animal's current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Visual Prediction Error Spreads Across Object Features in Human Visual Cortex

PubMed Central

Summerfield, Christopher; Egner, Tobias

2016-01-01

Visual cognition is thought to rely heavily on contextual expectations. Accordingly, previous studies have revealed distinct neural signatures for expected versus unexpected stimuli in visual cortex. However, it is presently unknown how the brain combines multiple concurrent stimulus expectations such as those we have for different features of a familiar object. To understand how an unexpected object feature affects the simultaneous processing of other expected feature(s), we combined human fMRI with a task that independently manipulated expectations for color and motion features of moving-dot stimuli. Behavioral data and neural signals from visual cortex were then interrogated to adjudicate between three possible ways in which prediction error (surprise) in the processing of one feature might affect the concurrent processing of another, expected feature: (1) feature processing may be independent; (2) surprise might “spread” from the unexpected to the expected feature, rendering the entire object unexpected; or (3) pairing a surprising feature with an expected feature might promote the inference that the two features are not in fact part of the same object. To formalize these rival hypotheses, we implemented them in a simple computational model of multifeature expectations. Across a range of analyses, behavior and visual neural signals consistently supported a model that assumes a mixing of prediction error signals across features: surprise in one object feature spreads to its other feature(s), thus rendering the entire object unexpected. These results reveal neurocomputational principles of multifeature expectations and indicate that objects are the unit of selection for predictive vision. SIGNIFICANCE STATEMENT We address a key question in predictive visual cognition: how does the brain combine multiple concurrent expectations for different features of a single object such as its color and motion trajectory? By combining a behavioral protocol that independently varies expectation of (and attention to) multiple object features with computational modeling and fMRI, we demonstrate that behavior and fMRI activity patterns in visual cortex are best accounted for by a model in which prediction error in one object feature spreads to other object features. These results demonstrate how predictive vision forms object-level expectations out of multiple independent features. PMID:27810936

Visual Cortical Representation of Whole Words and Hemifield-split Word Parts.

PubMed

Strother, Lars; Coros, Alexandra M; Vilis, Tutis

2016-02-01

Reading requires the neural integration of visual word form information that is split between our retinal hemifields. We examined multiple visual cortical areas involved in this process by measuring fMRI responses while observers viewed words that changed or repeated in one or both hemifields. We were specifically interested in identifying brain areas that exhibit decreased fMRI responses as a result of repeated versus changing visual word form information in each visual hemifield. Our method yielded highly significant effects of word repetition in a previously reported visual word form area (VWFA) in occipitotemporal cortex, which represents hemifield-split words as whole units. We also identified a more posterior occipital word form area (OWFA), which represents word form information in the right and left hemifields independently and is thus both functionally and anatomically distinct from the VWFA. Both the VWFA and the OWFA were left-lateralized in our study and strikingly symmetric in anatomical location relative to known face-selective visual cortical areas in the right hemisphere. Our findings are consistent with the observation that category-selective visual areas come in pairs and support the view that neural mechanisms in left visual cortex--especially those that evolved to support the visual processing of faces--are developmentally malleable and become incorporated into a left-lateralized visual word form network that supports rapid word recognition and reading.

Distinct encoding of risk and value in economic choice between multiple risky options☆

PubMed Central

Wright, Nicholas D.; Symmonds, Mkael; Dolan, Raymond J.

2013-01-01

Neural encoding of value-based stimuli is suggested to involve representations of summary statistics, including risk and expected value (EV). A more complex, but ecologically more common, context is when multiple risky options are evaluated together. However, it is unknown whether encoding related to option evaluation in these situations involves similar principles. Here we employed fMRI during a task that parametrically manipulated EV and risk in two simultaneously presented lotteries, both of which contained either gains or losses. We found representations of EV in medial prefrontal cortex and anterior insula, an encoding that was dependent on which option was chosen (i.e. chosen and unchosen EV) and whether the choice was over gains or losses. Parietal activity reflected whether the riskier or surer option was selected, whilst activity in a network of regions that also included parietal cortex reflected both combined risk and difference in risk for the two options. Our findings provide support for the idea that summary statistics underpin a representation of value-based stimuli, and further that these summary statistics undergo distinct forms of encoding. PMID:23684860

Changes in corticocortical and corticohippocampal network during absence seizures in WAG/Rij rats revealed with time varying Granger causality.

PubMed

Sysoeva, Marina V; Vinogradova, Lyudmila V; Kuznetsova, Galina D; Sysoev, Ilya V; van Rijn, Clementina M

2016-11-01

Spike-and-wave discharges (SWDs) recorded in the cortical EEGs of WAG/Rij rats are the hallmark for absence epilepsy in this model. Although this type of epilepsy was long regarded as a form of primary generalized epilepsy, it is now recognized that there is an initiation zone - the perioral region of the somatosensory cortex. However, networks involved in spreading the seizure are not yet fully known. Previously, the dynamics of coupling between different layers of the perioral cortical region and between these zones and different thalamic nuclei was studied in time windows around the SWDs, using nonlinear Granger causality. The aim of the present study was to investigate, using the same method, the coupling dynamics between different regions of the cortex and between these regions and the hippocampus. Local field potentials were recorded in the frontal, parietal, and occipital cortices and in the hippocampus of 19 WAG/Rij rats. To detect changes in coupling reliably in a short time window, in order to provide a good temporal resolution, the innovative adapted time varying nonlinear Granger causality method was used. Mutual information function was calculated in addition to validate outcomes. Results of both approaches were tested for significance. The SWD initiation process was revealed as an increase in intracortical interactions starting from 3.5s before the onset of electrographic seizure. The earliest preictal increase in coupling was directed from the frontal cortex to the parietal cortex. Then, the coupling became bidirectional, followed by the involvement of the occipital cortex (1.5s before SWD onset). There was no driving from any cortical region to hippocampus, but a slight increase in coupling from hippocampus to the frontoparietal cortex was observed just before SWD onset. After SWD onset, an abrupt drop in coupling in all studied pairs was observed. In most of the pairs, the decoupling rapidly disappeared, but driving force from hippocampus and occipital cortex to the frontoparietal cortex was reduced until the SWD termination. Involvement of multiple cortical regions in SWD initiation shows the fundamental role of corticocortical feedback loops, forming coupling architecture and triggering the generalized seizure. The results add to the ultimate aim to construct a complete picture of brain interactions preceding and accompanying absence seizures in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

PubMed Central

Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

2009-01-01

‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

Subcortical hematoma caused by cerebral amyloid angiopathy: does the first evidence of hemorrhage occur in the subarachnoid space?

PubMed

Takeda, Shigeki; Yamazaki, Kazunori; Miyakawa, Teruo; Onda, Kiyoshi; Hinokuma, Kaoru; Ikuta, Fusahiro; Arai, Hiroyuki

2003-12-01

Six autopsy cases of subcortical hematoma caused by CAA were examined to elucidate the primary site of hemorrhage. Immunohistochemistry for amyloid beta-protein (A beta) revealed extensive CAA in the intrasulcal meningeal vessels rather than in the cerebral cortical vessels. All of the examined cases had multiple hematomas in the subarachnoid space, mainly in the cerebral sulci, as well as intracerebral hematomas. Each intracerebral hematoma was connected to the subarachnoid hematomas at the depth of cerebral sulci or through the lateral side of the cortex. There was no debris of the cerebral cortical tissue in the subarachnoid hematomas. In case 2, another solitary subarachnoid hematoma, which was not connected to any intracerebral hematoma, was seen. In all of these subarachnoid hematomas, many ruptured A beta-immunopositive arteries were observed. These ruptured arteries did not accompany any debris of the brain tissue, some of them were large in diameter (250-300 microm), and several of them were far from the cerebral cortex. Therefore, it was considered that they were not cortical arteries but meningeal arteries. Within the cerebral cortex, there were only a few ruptured arteries associated with small hemorrhages. There were no ruptured vessels within the intracerebral hematomas. There was a strong suggestion that all of the subarachnoid hematomas, including the solitary one in case 2, originated from the rupture of the meningeal arteries. The present study indicates that in some cases of subcortical hematoma caused by CAA, the primary hemorrhage occurs in the subarachnoid space, in particular the cerebral sulci, because of rupture of multiple meningeal arteries. Infarction occurs subsequently in the cortex around the hematoma, the hematoma penetrates into the brain parenchyma, and finally, a subcortical hematoma is formed.

3-D vision and figure-ground separation by visual cortex.

PubMed

Grossberg, S

1994-01-01

A neural network theory of three-dimensional (3-D) vision, called FACADE theory, is described. The theory proposes a solution of the classical figure-ground problem for biological vision. It does so by suggesting how boundary representations and surface representations are formed within a boundary contour system (BCS) and a feature contour system (FCS). The BCS and FCS interact reciprocally to form 3-D boundary and surface representations that are mutually consistent. Their interactions generate 3-D percepts wherein occluding and occluded object parts are separated, completed, and grouped. The theory clarifies how preattentive processes of 3-D perception and figure-ground separation interact reciprocally with attentive processes of spatial localization, object recognition, and visual search. A new theory of stereopsis is proposed that predicts how cells sensitive to multiple spatial frequencies, disparities, and orientations are combined by context-sensitive filtering, competition, and cooperation to form coherent BCS boundary segmentations. Several factors contribute to figure-ground pop-out, including: boundary contrast between spatially contiguous boundaries, whether due to scenic differences in luminance, color, spatial frequency, or disparity; partially ordered interactions from larger spatial scales and disparities to smaller scales and disparities; and surface filling-in restricted to regions surrounded by a connected boundary. Phenomena such as 3-D pop-out from a 2-D picture, Da Vinci stereopsis, 3-D neon color spreading, completion of partially occluded objects, and figure-ground reversals are analyzed. The BCS and FCS subsystems model aspects of how the two parvocellular cortical processing streams that join the lateral geniculate nucleus to prestriate cortical area V4 interact to generate a multiplexed representation of Form-And-Color-And-DEpth, or FACADE, within area V4. Area V4 is suggested to support figure-ground separation and to interact with cortical mechanisms of spatial attention, attentive object learning, and visual search. Adaptive resonance theory (ART) mechanisms model aspects of how prestriate visual cortex interacts reciprocally with a visual object recognition system in inferotemporal (IT) cortex for purposes of attentive object learning and categorization. Object attention mechanisms of the What cortical processing stream through IT cortex are distinguished from spatial attention mechanisms of the Where cortical processing stream through parietal cortex. Parvocellular BCS and FCS signals interact with the model What stream. Parvocellular FCS and magnocellular motion BCS signals interact with the model Where stream.(ABSTRACT TRUNCATED AT 400 WORDS)

Common oscillatory mechanisms across multiple memory systems

NASA Astrophysics Data System (ADS)

Headley, Drew B.; Paré, Denis

2017-01-01

The cortex, hippocampus, and striatum support dissociable forms of memory. While each of these regions contains specialized circuitry supporting their respective functions, all structure their activities across time with delta, theta, and gamma rhythms. We review how these oscillations are generated and how they coordinate distinct memory systems during encoding, consolidation, and retrieval. First, gamma oscillations occur in all regions and coordinate local spiking, compressing it into short population bursts. Second, gamma oscillations are modulated by delta and theta oscillations. Third, oscillatory dynamics in these memory systems can operate in either a "slow" or "fast" mode. The slow mode happens during slow-wave sleep and is characterized by large irregular activity in the hippocampus and delta oscillations in cortical and striatal circuits. The fast mode occurs during active waking and rapid eye movement (REM) sleep and is characterized by theta oscillations in the hippocampus and its targets, along with gamma oscillations in the rest of cortex. In waking, the fast mode is associated with the efficacious encoding and retrieval of declarative and procedural memories. Theta and gamma oscillations have similar relationships with encoding and retrieval across multiple forms of memory and brain regions, despite regional differences in microcircuitry and information content. Differences in the oscillatory coordination of memory systems during sleep might explain why the consolidation of some forms of memory is sensitive to slow-wave sleep, while others depend on REM. In particular, theta oscillations appear to support the consolidation of certain types of procedural memories during REM, while delta oscillations during slow-wave sleep seem to promote declarative and procedural memories.

Estimates of segregation and overlap of functional connectivity networks in the human cerebral cortex.

PubMed

Yeo, B T Thomas; Krienen, Fenna M; Chee, Michael W L; Buckner, Randy L

2014-03-01

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. © 2013.

Estimates of Segregation and Overlap of Functional Connectivity Networks in the Human Cerebral Cortex

PubMed Central

Yeo, BT Thomas; Krienen, Fenna M; Chee, Michael WL; Buckner, Randy L

2014-01-01

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1,000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. PMID:24185018

Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.

PubMed

Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

2012-06-07

In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. Copyright © 2012 Elsevier Inc. All rights reserved.

Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque

PubMed Central

Fukushima, Makoto; Saunders, Richard C.; Leopold, David A.; Mishkin, Mortimer; Averbeck, Bruno B.

2012-01-01

Summary In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here we used chronic micro-electrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. PMID:22681693

Evidence for a Functional Hierarchy of Association Networks.

PubMed

Choi, Eun Young; Drayna, Garrett K; Badre, David

2018-05-01

Patient lesion and neuroimaging studies have identified a rostral-to-caudal functional gradient in the lateral frontal cortex (LFC) corresponding to higher-order (complex or abstract) to lower-order (simple or concrete) cognitive control. At the same time, monkey anatomical and human functional connectivity studies show that frontal regions are reciprocally connected with parietal and temporal regions, forming parallel and distributed association networks. Here, we investigated the link between the functional gradient of LFC regions observed during control tasks and the parallel, distributed organization of association networks. Whole-brain fMRI task activity corresponding to four orders of hierarchical control [Badre, D., & D'Esposito, M. Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex. Journal of Cognitive Neuroscience, 19, 2082-2099, 2007] was compared with a resting-state functional connectivity MRI estimate of cortical networks [Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 1125-1165, 2011]. Critically, at each order of control, activity in the LFC and parietal cortex overlapped onto a common association network that differed between orders. These results are consistent with a functional organization based on separable association networks that are recruited during hierarchical control. Furthermore, corticostriatal functional connectivity MRI showed that, consistent with their participation in functional networks, rostral-to-caudal LFC and caudal-to-rostral parietal regions had similar, order-specific corticostriatal connectivity that agreed with a striatal gating model of hierarchical rule use. Our results indicate that hierarchical cognitive control is subserved by parallel and distributed association networks, together forming multiple localized functional gradients in different parts of association cortex. As such, association networks, while connectionally organized in parallel, may be functionally organized in a hierarchy via dynamic interaction with the striatum.

Direct observation of organic contaminant uptake, storage, and metabolism within plant roots.

PubMed

Wild, Edward; Dent, John; Thomas, Gareth O; Jones, Kevin C

2005-05-15

Two-photon excitation microscopy (TPEM) is used to visualize and track the uptake and movement of anthracene and phenanthrene from a contaminated growth medium into living unmodified roots of maize and wheat over a 56-day period. The degradation of anthracene was also directly observed within the cortex cells of both species. The power of this technique is that neither the plant nor the compound require altering (staining or sectioning) to visualize them, meaning they are in their natural form throughout the experiment. Initially both compounds bound to the epidermis along the zone of elongation, passing through the epidermal cells to reach the cortex within the root hair, and branching zones of the root. The PAHs entered the epidermis radially; however, once within the cortex cells this movement was dominated by slow lateral movement of both compounds toward the shoot. Highly focused "streams" of compound were observed to form over time; zones where phenanthrene concentrated extended up to 1500 microm in length over a 56-day period, for example, passing through several adjoining cells, and were detectable in cell walls and cell vacuoles. Radial movement was not observed to extend beyond the cortex cells to reach the vascular tissues of the plant. The longitudinal movement of both compounds was not observed to extend beyond the root base into the stem or vegetative parts of the plant. The lateral movement of both compounds within the cortex cells was dominated by movement within the cell walls, suggesting apoplastic flow through multiple cell walls, but with a low level of symplastic movement to transport compound into the cellular vacuoles. Degradation of anthracene to the partial breakdown products anthrone, anthraquinone, and hydroxyanthraquinone was observed directly in the zones of root elongation and branching. The technique and observations have important applications to the fields of agrochemistry and phytoremediation.

Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex.

PubMed

Kirsch, V; Keeser, D; Hergenroeder, T; Erat, O; Ertl-Wagner, B; Brandt, T; Dieterich, M

2016-04-01

Structural and functional interconnections of the bilateral central vestibular network have not yet been completely delineated. This includes both ipsilateral and contralateral pathways and crossing sites on the way from the vestibular nuclei via the thalamic relay stations to multiple "vestibular cortex" areas. This study investigated "vestibular" connectivity in the living human brain in between the vestibular nuclei and the parieto-insular vestibular cortex (PIVC) by combined structural and functional connectivity mapping using diffusion tensor imaging and functional connectivity magnetic resonance imaging in 24 healthy right-handed volunteers. We observed a congruent functional and structural link between the vestibular nuclei and the ipsilateral and contralateral PIVC. Five separate and distinct vestibular pathways were identified: three run ipsilaterally, while the two others cross either in the pons or the midbrain. Two of the ipsilateral projections run through the posterolateral or paramedian thalamic subnuclei, while the third bypasses the thalamus to reach the inferior part of the insular cortex directly. Both contralateral pathways travel through the posterolateral thalamus. At the cortical level, the PIVC regions of both hemispheres with a right hemispherical dominance are interconnected transcallosally through the antero-caudal splenium. The above-described bilateral vestibular circuitry in its entirety takes the form of a structure of a rope ladder extending from the brainstem to the cortex with three crossings in the brainstem (vestibular nuclei, pons, midbrain), none at thalamic level and a fourth cortical crossing through the splenium of the corpus callosum.

Multisensory connections of monkey auditory cerebral cortex

PubMed Central

Smiley, John F.; Falchier, Arnaud

2009-01-01

Functional studies have demonstrated multisensory responses in auditory cortex, even in the primary and early auditory association areas. The features of somatosensory and visual responses in auditory cortex suggest that they are involved in multiple processes including spatial, temporal and object-related perception. Tract tracing studies in monkeys have demonstrated several potential sources of somatosensory and visual inputs to auditory cortex. These include potential somatosensory inputs from the retroinsular (RI) and granular insula (Ig) cortical areas, and from the thalamic posterior (PO) nucleus. Potential sources of visual responses include peripheral field representations of areas V2 and prostriata, as well as the superior temporal polysensory area (STP) in the superior temporal sulcus, and the magnocellular medial geniculate thalamic nucleus (MGm). Besides these sources, there are several other thalamic, limbic and cortical association structures that have multisensory responses and may contribute cross-modal inputs to auditory cortex. These connections demonstrated by tract tracing provide a list of potential inputs, but in most cases their significance has not been confirmed by functional experiments. It is possible that the somatosensory and visual modulation of auditory cortex are each mediated by multiple extrinsic sources. PMID:19619628

Fluctuation scaling in the visual cortex at threshold

NASA Astrophysics Data System (ADS)

Medina, José M.; Díaz, José A.

2016-05-01

Fluctuation scaling relates trial-to-trial variability to the average response by a power function in many physical processes. Here we address whether fluctuation scaling holds in sensory psychophysics and its functional role in visual processing. We report experimental evidence of fluctuation scaling in human color vision and form perception at threshold. Subjects detected thresholds in a psychophysical masking experiment that is considered a standard reference for studying suppression between neurons in the visual cortex. For all subjects, the analysis of threshold variability that results from the masking task indicates that fluctuation scaling is a global property that modulates detection thresholds with a scaling exponent that departs from 2, β =2.48 ±0.07 . We also examine a generalized version of fluctuation scaling between the sample kurtosis K and the sample skewness S of threshold distributions. We find that K and S are related and follow a unique quadratic form K =(1.19 ±0.04 ) S2+(2.68 ±0.06 ) that departs from the expected 4/3 power function regime. A random multiplicative process with weak additive noise is proposed based on a Langevin-type equation. The multiplicative process provides a unifying description of fluctuation scaling and the quadratic S -K relation and is related to on-off intermittency in sensory perception. Our findings provide an insight into how the human visual system interacts with the external environment. The theoretical methods open perspectives for investigating fluctuation scaling and intermittency effects in a wide variety of natural, economic, and cognitive phenomena.

Pre-orthographic character string processing and parietal cortex: a role for visual attention in reading?

PubMed

Lobier, Muriel; Peyrin, Carole; Le Bas, Jean-François; Valdois, Sylviane

2012-07-01

The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of character type. While the superior parietal lobule has been shown to be involved in multiple letter processing, further data is necessary to extend these results to non-letter characters. The purpose of this study is to identify the neural correlates of pre-orthographic character string processing independently of character type. Fourteen skilled adult readers carried out multiple and single element visual categorization tasks with alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of parietal cortex in multiple element processing was further probed with a priori defined anatomical regions of interest (ROIs). Participants activated posterior parietal cortex more strongly for multiple than single element processing. ROI analyses showed that bilateral SPL/BA7 was more strongly activated for multiple than single element processing, regardless of character type. In contrast, no multiple element specific activity was found in inferior parietal lobules. These results suggests that parietal mechanisms are involved in pre-orthographic character string processing. We argue that in general, attentional mechanisms are involved in visual word recognition, as an early step of word visual analysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Grid cell hexagonal patterns formed by fast self-organized learning within entorhinal cortex.

PubMed

Mhatre, Himanshu; Gorchetchnikov, Anatoli; Grossberg, Stephen

2012-02-01

Grid cells in the dorsal segment of the medial entorhinal cortex (dMEC) show remarkable hexagonal activity patterns, at multiple spatial scales, during spatial navigation. It has previously been shown how a self-organizing map can convert firing patterns across entorhinal grid cells into hippocampal place cells that are capable of representing much larger spatial scales. Can grid cell firing fields also arise during navigation through learning within a self-organizing map? This article describes a simple and general mathematical property of the trigonometry of spatial navigation which favors hexagonal patterns. The article also develops a neural model that can learn to exploit this trigonometric relationship. This GRIDSmap self-organizing map model converts path integration signals into hexagonal grid cell patterns of multiple scales. GRIDSmap creates only grid cell firing patterns with the observed hexagonal structure, predicts how these hexagonal patterns can be learned from experience, and can process biologically plausible neural input and output signals during navigation. These results support an emerging unified computational framework based on a hierarchy of self-organizing maps for explaining how entorhinal-hippocampal interactions support spatial navigation. Copyright © 2010 Wiley Periodicals, Inc.

Resolving response, decision, and strategic control: evidence for a functional topography in dorsomedial prefrontal cortex.

PubMed

Venkatraman, Vinod; Rosati, Alexandra G; Taren, Adrienne A; Huettel, Scott A

2009-10-21

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands--response, decision, and strategic--each of which could be mapped onto independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled.

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex.

PubMed

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-07-06

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.

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.

Resolving Response, Decision, and Strategic Control: Evidence for a Functional Topography in Dorsomedial Prefrontal Cortex

PubMed Central

Venkatraman, Vinod; Rosati, Alexandra G.; Taren, Adrienne A.; Huettel, Scott A.

2009-01-01

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands – response, decision, and strategic – each of which could be mapped on to independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC, and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled. PMID:19846703

Combining tractography and cortical measures to test system-specific hypotheses in multiple sclerosis

PubMed Central

Gorgoraptis, Nikos; Wheeler-Kingshott, Claudia AM; Jenkins, Thomas M; Altmann, Daniel R; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2010-01-01

The objective was to test three motor system-specific hypotheses in multiple sclerosis patients: (i) corticospinal tract and primary motor cortex imaging measures differ between multiple sclerosis patients and controls; (ii) in patients, these measures correlate with disability; (iii) in patients, corticospinal tract measures correlate with measures of the ipsilateral primary motor cortex. Eleven multiple sclerosis patients with a history of hemiparesis attributable to a lesion within the contralateral corticospinal tract, and 12 controls were studied. We used two advanced imaging techniques: (i) diffusion-based probabilistic tractography, to obtain connectivity and fractional anisotropy of the corticospinal tract; and (ii) FreeSurfer, to measure volume, thickness, surface area, and curvature of precentral and paracentral cortices. Differences in these measures between patients and controls, and relationships between each other and to clinical scores, were investigated. Patients showed lower corticospinal tract fractional anisotropy and smaller volume and surface area of the precentral gyrus than controls. In patients, corticospinal tract connectivity and paracentral cortical volume, surface area, and curvature were lower with increasing disability; lower connectivity of the affected corticospinal tract was associated with greater surface area of the ipsilateral paracentral cortex. Corticospinal tract connectivity and new measures of the primary motor cortex, such as surface area and curvature, reflect the underlying white and grey matter damage that contributes to disability. The correlation between lower connectivity of the affected corticospinal tract and greater surface area of the ipsilateral paracentral cortex suggests the possibility of cortical adaptation. Combining tractography and cortical measures is a useful approach in testing hypotheses which are specific to clinically relevant functional systems in multiple sclerosis, and can be applied to other neurological diseases. PMID:20215478

Dissociation of Subtraction and Multiplication in the Right Parietal Cortex: Evidence from Intraoperative Cortical Electrostimulation

ERIC Educational Resources Information Center

Yu, Xiaodan; Chen, Chuansheng; Pu, Song; Wu, Chenxing; Li, Yongnian; Jiang, Tao; Zhou, Xinlin

2011-01-01

Previous research has consistently shown that the left parietal cortex is critical for numerical processing, but the role of the right parietal lobe has been much less clear. This study used the intraoperative cortical electrical stimulation approach to investigate neural dissociation in the right parietal cortex for subtraction and…

Topography and collateralization of dopaminergic projections to primary motor cortex in rats.

PubMed

Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R

2015-05-01

Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables

PubMed Central

Kennerley, Steven W.; Wallis, Jonathan D.

2009-01-01

Damage to the frontal lobe can cause severe decision-making impairments. A mechanism that may underlie this is that neurons in the frontal cortex encode many variables that contribute to the valuation of a choice, such as its costs, benefits and probability of success. However, optimal decision-making requires that one considers these variables, not only when faced with the choice, but also when evaluating the outcome of the choice, in order to adapt future behaviour appropriately. To examine the role of the frontal cortex in encoding the value of different choice outcomes, we simultaneously recorded the activity of multiple single neurons in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) while subjects evaluated the outcome of choices involving manipulations of probability, payoff and cost. Frontal neurons encoded many of the parameters that enabled the calculation of the value of these variables, including the onset and offset of reward and the amount of work performed, and often encoded the value of outcomes across multiple decision variables. In addition, many neurons encoded both the predicted outcome during the choice phase of the task as well as the experienced outcome in the outcome phase of the task. These patterns of selectivity were more prevalent in ACC relative to OFC and LPFC. These results support a role for the frontal cortex, principally ACC, in selecting between choice alternatives and evaluating the outcome of that selection thereby ensuring that choices are optimal and adaptive. PMID:19453638

The parietal cortex in sensemaking: the dissociation of multiple types of spatial information.

PubMed

Sun, Yanlong; Wang, Hongbin

2013-01-01

According to the data-frame theory, sensemaking is a macrocognitive process in which people try to make sense of or explain their observations by processing a number of explanatory structures called frames until the observations and frames become congruent. During the sensemaking process, the parietal cortex has been implicated in various cognitive tasks for the functions related to spatial and temporal information processing, mathematical thinking, and spatial attention. In particular, the parietal cortex plays important roles by extracting multiple representations of magnitudes at the early stages of perceptual analysis. By a series of neural network simulations, we demonstrate that the dissociation of different types of spatial information can start early with a rather similar structure (i.e., sensitivity on a common metric), but accurate representations require specific goal-directed top-down controls due to the interference in selective attention. Our results suggest that the roles of the parietal cortex rely on the hierarchical organization of multiple spatial representations and their interactions. The dissociation and interference between different types of spatial information are essentially the result of the competition at different levels of abstraction.

The Parietal Cortex in Sensemaking: The Dissociation of Multiple Types of Spatial Information

PubMed Central

Sun, Yanlong; Wang, Hongbin

2013-01-01

According to the data-frame theory, sensemaking is a macrocognitive process in which people try to make sense of or explain their observations by processing a number of explanatory structures called frames until the observations and frames become congruent. During the sensemaking process, the parietal cortex has been implicated in various cognitive tasks for the functions related to spatial and temporal information processing, mathematical thinking, and spatial attention. In particular, the parietal cortex plays important roles by extracting multiple representations of magnitudes at the early stages of perceptual analysis. By a series of neural network simulations, we demonstrate that the dissociation of different types of spatial information can start early with a rather similar structure (i.e., sensitivity on a common metric), but accurate representations require specific goal-directed top-down controls due to the interference in selective attention. Our results suggest that the roles of the parietal cortex rely on the hierarchical organization of multiple spatial representations and their interactions. The dissociation and interference between different types of spatial information are essentially the result of the competition at different levels of abstraction. PMID:23710165

Functional Specialization and Flexibility in Human Association Cortex

PubMed Central

Yeo, B. T. Thomas; Krienen, Fenna M.; Eickhoff, Simon B.; Yaakub, Siti N.; Fox, Peter T.; Buckner, Randy L.; Asplund, Christopher L.; Chee, Michael W.L.

2015-01-01

The association cortex supports cognitive functions enabling flexible behavior. Here, we explored the organization of human association cortex by mathematically formalizing the notion that a behavioral task engages multiple cognitive components, which are in turn supported by multiple overlapping brain regions. Application of the model to a large data set of neuroimaging experiments (N = 10 449) identified complex zones of frontal and parietal regions that ranged from being highly specialized to highly flexible. The network organization of the specialized and flexible regions was explored with an independent resting-state fMRI data set (N = 1000). Cortical regions specialized for the same components were strongly coupled, suggesting that components function as partially isolated networks. Functionally flexible regions participated in multiple components to different degrees. This heterogeneous selectivity was predicted by the connectivity between flexible and specialized regions. Functionally flexible regions might support binding or integrating specialized brain networks that, in turn, contribute to the ability to execute multiple and varied tasks. PMID:25249407

Experience-Dependent Synaptic Plasticity in V1 Occurs without Microglial CX3CR1

PubMed Central

Stevens, Beth

2017-01-01

Brief monocular deprivation (MD) shifts ocular dominance and reduces the density of thalamic synapses in layer 4 of the mouse primary visual cortex (V1). We found that microglial lysosome content is also increased as a result of MD. Previous studies have shown that the microglial fractalkine receptor CX3CR1 is involved in synaptic development and hippocampal plasticity. We therefore tested the hypothesis that neuron-to-microglial communication via CX3CR1 is an essential component of visual cortical development and plasticity in male mice. Our data show that CX3CR1 is not required for normal development of V1 responses to visual stimulation, multiple forms of experience-dependent plasticity, or the synapse loss that accompanies MD in layer 4. By ruling out an essential role for fractalkine signaling, our study narrows the search for understanding how microglia respond to active synapse modification in the visual cortex. SIGNIFICANCE STATEMENT Microglia in the visual cortex respond to monocular deprivation with increased lysosome content, but signaling through the fractalkine receptor CX3CR1 is not an essential component in the mechanisms of visual cortical development or experience-dependent synaptic plasticity. PMID:28951447

Intraoperative Mapping of Expressive Language Cortex Using Passive Real-Time Electrocorticography

DTIC Science & Technology

2016-08-26

lsev ie r .com/ locate /ebcrCase ReportIntraoperative mapping of expressive language cortex using passive real-time electrocorticographyAmiLyn M...case report, we investigated the utility and practicality of passive intraoperative functional mapping of expressive language cortex using high...expressive lan- guage regions. In preparation of tumor resection, the patient underwent multiple functional language mapping procedures. We examined

Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1

PubMed Central

Ryu, Stephen I.; Shenoy, Krishna V.; Cunningham, John P.; Churchland, Mark M.

2016-01-01

Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure—a basic example is the frequency spectrum—and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were ‘simplest’ (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models. PMID:27814353

Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

PubMed

Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

2017-01-01

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Form and motion make independent contributions to the response to biological motion in occipitotemporal cortex.

PubMed

Thompson, James C; Baccus, Wendy

2012-01-02

Psychophysical and computational studies have provided evidence that both form and motion cues are used in the perception of biological motion. However, neuroimaging and neurophysiological studies have suggested that the neural processing of actions in temporal cortex might rely on form cues alone. Here we examined the contribution of form and motion to the spatial pattern of response to biological motion in ventral and lateral occipitotemporal cortex, using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). We found that selectivity to intact versus scrambled biological motion in lateral occipitotemporal cortex was correlated with selectivity for bodies and not for motion. However, this appeared to be due to the fact that subtracting scrambled from intact biological motion removes any contribution of local motion cues. Instead, we found that form and motion made independent contributions to the spatial pattern of responses to biological motion in lateral occipitotemporal regions MT, MST, and the extrastriate body area. The motion contribution was position-dependent, and consistent with the representation of contra- and ipsilateral visual fields in MT and MST. In contrast, only form contributed to the response to biological motion in the fusiform body area, with a bias towards central versus peripheral presentation. These results indicate that the pattern of response to biological motion in ventral and lateral occipitotemporal cortex reflects the linear combination of responses to form and motion. Copyright © 2011 Elsevier Inc. All rights reserved.

The effects of anterior arcuate and dorsomedial frontal cortex lesions on visually guided eye movements: 2. Paired and multiple targets.

PubMed

Schiller, P H; Chou, I

2000-01-01

This study examined the effects of anterior arcuate and dorsomedial frontal cortex lesions on the execution of saccadic eye movements made to paired and multiple targets in rhesus monkeys. Identical paired targets were presented with various temporal asynchronies to determine the temporal offset required to yield equal probability choices to either target. In the intact animal equal probability choices were typically obtained when the targets appeared simultaneously. After unilateral anterior arcuate lesions a major shift arose in the temporal offset required to obtain equal probability choices for paired targets that necessitated presenting the target in the hemifield contralateral to the lesion more than 100 ms prior to the target in the ipsilateral hemifield. This deficit was still pronounced 1 year after the lesion. Dorsomedial frontal cortex lesions produced much smaller but significant shifts in target selection that recovered more rapidly. Paired lesions produced deficits similar to those observed with anterior arcuate lesions alone. Major deficits were also observed on a multiple target temporal discrimination task after anterior arcuate but not after dorsomedial frontal cortex lesions. These results suggest that the frontal eye fields that reside in anterior bank of the arcuate sulcus play an important role in temporal processing and in target selection. Dorsomedial frontal cortex, that contains the medial eye fields, plays a much less important role in the execution of these tasks.

Using a Large-scale Neural Model of Cortical Object Processing to Investigate the Neural Substrate for Managing Multiple Items in Short-term Memory.

PubMed

Liu, Qin; Ulloa, Antonio; Horwitz, Barry

2017-11-01

Many cognitive and computational models have been proposed to help understand working memory. In this article, we present a simulation study of cortical processing of visual objects during several working memory tasks using an extended version of a previously constructed large-scale neural model [Tagamets, M. A., & Horwitz, B. Integrating electrophysiological and anatomical experimental data to create a large-scale model that simulates a delayed match-to-sample human brain imaging study. Cerebral Cortex, 8, 310-320, 1998]. The original model consisted of arrays of Wilson-Cowan type of neuronal populations representing primary and secondary visual cortices, inferotemporal (IT) cortex, and pFC. We added a module representing entorhinal cortex, which functions as a gating module. We successfully implemented multiple working memory tasks using the same model and produced neuronal patterns in visual cortex, IT cortex, and pFC that match experimental findings. These working memory tasks can include distractor stimuli or can require that multiple items be retained in mind during a delay period (Sternberg's task). Besides electrophysiology data and behavioral data, we also generated fMRI BOLD time series from our simulation. Our results support the involvement of IT cortex in working memory maintenance and suggest the cortical architecture underlying the neural mechanisms mediating particular working memory tasks. Furthermore, we noticed that, during simulations of memorizing a list of objects, the first and last items in the sequence were recalled best, which may implicate the neural mechanism behind this important psychological effect (i.e., the primacy and recency effect).

The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks

PubMed Central

Vanneste, Sven; De Ridder, Dirk

2012-01-01

Tinnitus is the perception of a sound in the absence of an external sound source. It is characterized by sensory components such as the perceived loudness, the lateralization, the tinnitus type (pure tone, noise-like) and associated emotional components, such as distress and mood changes. Source localization of quantitative electroencephalography (qEEG) data demonstrate the involvement of auditory brain areas as well as several non-auditory brain areas such as the anterior cingulate cortex (dorsal and subgenual), auditory cortex (primary and secondary), dorsal lateral prefrontal cortex, insula, supplementary motor area, orbitofrontal cortex (including the inferior frontal gyrus), parahippocampus, posterior cingulate cortex and the precuneus, in different aspects of tinnitus. Explaining these non-auditory brain areas as constituents of separable subnetworks, each reflecting a specific aspect of the tinnitus percept increases the explanatory power of the non-auditory brain areas involvement in tinnitus. Thus, the unified percept of tinnitus can be considered an emergent property of multiple parallel dynamically changing and partially overlapping subnetworks, each with a specific spontaneous oscillatory pattern and functional connectivity signature. PMID:22586375

Neurons in the Frontal Lobe Encode the Value of Multiple Decision Variables

PubMed Central

Kennerley, Steven W.; Dahmubed, Aspandiar F.; Lara, Antonio H.; Wallis, Jonathan D.

2009-01-01

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making. PMID:18752411

From sensation to cognition.

PubMed

Mesulam, M M

1998-06-01

Sensory information undergoes extensive associative elaboration and attentional modulation as it becomes incorporated into the texture of cognition. This process occurs along a core synaptic hierarchy which includes the primary sensory, upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones of the cerebral cortex. Connections from one zone to another are reciprocal and allow higher synaptic levels to exert a feedback (top-down) influence upon earlier levels of processing. Each cortical area provides a nexus for the convergence of afferents and divergence of efferents. The resultant synaptic organization supports parallel as well as serial processing, and allows each sensory event to initiate multiple cognitive and behavioural outcomes. Upstream sectors of unimodal association areas encode basic features of sensation such as colour, motion, form and pitch. More complex contents of sensory experience such as objects, faces, word-forms, spatial locations and sound sequences become encoded within downstream sectors of unimodal areas by groups of coarsely tuned neurons. The highest synaptic levels of sensory-fugal processing are occupied by heteromodal, paralimbic and limbic cortices, collectively known as transmodal areas. The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampal-entorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration. All cognitive processes arise from analogous associative transformations of similar sets of sensory inputs. The differences in the resultant cognitive operation are determined by the anatomical and physiological properties of the transmodal node that acts as the critical gateway for the dominant transformation. Interconnected sets of transmodal nodes provide anatomical and computational epicentres for large-scale neurocognitive networks. In keeping with the principles of selectively distributed processing, each epicentre of a large-scale network displays a relative specialization for a specific behavioural component of its principal neurospychological domain. The destruction of transmodal epicentres causes global impairments such as multimodal anomia, neglect and amnesia, whereas their selective disconnection from relevant unimodal areas elicits modality-specific impairments such as prosopagnosia, pure word blindness and category-specific anomias. The human brain contains at least five anatomically distinct networks. The network for spatial awareness is based on transmodal epicentres in the posterior parietal cortex and the frontal eye fields; the language network on epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network on epicentres in the hippocampal-entorhinal complex and the amygdala; the face-object recognition network on epicentres in the midtemporal and temporopolar cortices; and the working memory-executive function network on epicentres in the lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual sensory modalities give rise to streams of processing directed to transmodal nodes belonging to each of these networks. The fidelity of sensory channels is actively protected through approximately four synaptic levels of sensory-fugal processing. The modality-specific cortices at these four synaptic levels encode the most veridical representations of experience. Attentional, motivational and emotional modulations, including those related to working memory, novelty-seeking and mental imagery, become increasingly more pronounced within downstream components of unimodal areas, where they help to create a highly edited subjective version of the world. (ABSTRACT TRUNCATED)

The neural basis of stereotypic impact on multiple social categorization.

PubMed

Hehman, Eric; Ingbretsen, Zachary A; Freeman, Jonathan B

2014-11-01

Perceivers extract multiple social dimensions from another's face (e.g., race, emotion), and these dimensions can become linked due to stereotypes (e.g., Black individuals → angry). The current research examined the neural basis of detecting and resolving conflicts between top-down stereotypes and bottom-up visual information in person perception. Participants viewed faces congruent and incongruent with stereotypes, via variations in race and emotion, while neural activity was measured using fMRI. Hand movements en route to race/emotion responses were recorded using mouse-tracking to behaviorally index individual differences in stereotypical associations during categorization. The medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) showed stronger activation to faces that violated stereotypical expectancies at the intersection of multiple social categories (i.e., race and emotion). These regions were highly sensitive to the degree of incongruency, exhibiting linearly increasing responses as race and emotion became stereotypically more incongruent. Further, the ACC exhibited greater functional connectivity with the lateral fusiform cortex, a region implicated in face processing, when viewing stereotypically incongruent (relative to congruent) targets. Finally, participants with stronger behavioral tendencies to link race and emotion stereotypically during categorization showed greater dorsolateral prefrontal cortex activation to stereotypically incongruent targets. Together, the findings provide insight into how conflicting stereotypes at the nexus of multiple social dimensions are resolved at the neural level to accurately perceive other people. Copyright © 2014 Elsevier Inc. All rights reserved.

Cholinergic neurons and fibres in the rat visual cortex.

PubMed

Parnavelas, J G; Kelly, W; Franke, E; Eckenstein, F

1986-06-01

Choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was localized immunocytochemically in neurons and fibres in the rat visual cortex using a monoclonal antibody. ChAT-labelled cells were non-pyramidal neurons, primarily of the bipolar form, distributed in layers II through VI but concentrated in layers II & III. Their perikarya contained a large nucleus and a small amount of perinuclear cytoplasm. The somata and dendrites of all labelled cells received Gray's type I and type II synapses. ChAT-stained axons formed a dense and diffuse network throughout the visual cortex and particularly in layer V. Electron microscopy revealed that the great majority formed type II synaptic contacts with dendrites of various sizes, unlabelled non-pyramidal somata and, on a few occasions, with ChAT-labelled cells. However, a very small number of terminals appeared to form type I synaptic contacts. This study describes the morphological organization of the cholinergic system in the visual cortex, the function of which has been under extensive investigation.

Content Representation in the Human Medial Temporal Lobe

PubMed Central

Liang, Jackson C.; Wagner, Anthony D.

2013-01-01

Current theories of medial temporal lobe (MTL) function focus on event content as an important organizational principle that differentiates MTL subregions. Perirhinal and parahippocampal cortices may play content-specific roles in memory, whereas hippocampal processing is alternately hypothesized to be content specific or content general. Despite anatomical evidence for content-specific MTL pathways, empirical data for content-based MTL subregional dissociations are mixed. Here, we combined functional magnetic resonance imaging with multiple statistical approaches to characterize MTL subregional responses to different classes of novel event content (faces, scenes, spoken words, sounds, visual words). Univariate analyses revealed that responses to novel faces and scenes were distributed across the anterior–posterior axis of MTL cortex, with face responses distributed more anteriorly than scene responses. Moreover, multivariate pattern analyses of perirhinal and parahippocampal data revealed spatially organized representational codes for multiple content classes, including nonpreferred visual and auditory stimuli. In contrast, anterior hippocampal responses were content general, with less accurate overall pattern classification relative to MTL cortex. Finally, posterior hippocampal activation patterns consistently discriminated scenes more accurately than other forms of content. Collectively, our findings indicate differential contributions of MTL subregions to event representation via a distributed code along the anterior–posterior axis of MTL that depends on the nature of event content. PMID:22275474

Renal cortex segmentation using optimal surface search with novel graph construction.

PubMed

Li, Xiuli; Chen, Xinjian; Yao, Jianhua; Zhang, Xing; Tian, Jie

2011-01-01

In this paper, we propose a novel approach to solve the renal cortex segmentation problem, which has rarely been studied. In this study, the renal cortex segmentation problem is handled as a multiple-surfaces extraction problem, which is solved using the optimal surface search method. We propose a novel graph construction scheme in the optimal surface search to better accommodate multiple surfaces. Different surface sub-graphs are constructed according to their properties, and inter-surface relationships are also modeled in the graph. The proposed method was tested on 17 clinical CT datasets. The true positive volume fraction (TPVF) and false positive volume fraction (FPVF) are 74.10% and 0.08%, respectively. The experimental results demonstrate the effectiveness of the proposed method.

Deficits in visual search for conjunctions of motion and form after parietal damage but with spared hMT+/V5.

PubMed

Dent, Kevin; Lestou, Vaia; Humphreys, Glyn W

2010-02-01

It has been argued that area hMT+/V5 in humans acts as a motion filter, enabling targets defined by a conjunction of motion and form to be efficiently selected. We present data indicating that (a) damage to parietal cortex leads to a selective problem in processing motion-form conjunctions, and (b) that the presence of a structurally and functional intact hMT+/V5 is not sufficient for efficient search for motion-form conjunctions. We suggest that, in addition to motion-processing areas (e.g., hMT+/V5), the posterior parietal cortex is necessary for efficient search with motion-form conjunctions, so that damage to either brain region may bring about deficits in search. We discuss the results in terms of the involvement of the posterior parietal cortex in the top-down guidance of search or in the binding of motion and form information.

Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

PubMed Central

Allen, William E.; Kauvar, Isaac V.; Chen, Michael Z.; Richman, Ethan B.; Yang, Samuel J.; Chan, Ken; Gradinaru, Viviana; Deverman, Benjamin E.; Luo, Liqun; Deisseroth, Karl

2017-01-01

SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information. PMID:28521139

Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

PubMed

Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

2014-01-01

Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

Effects of the Brain-Derived Neurotrophic Factor Val66Met polymorphism and resting brain functional connectivity on individual differences in tactile cognitive performance in healthy young adults.

PubMed

Yang, Xuejuan; Xu, Ziliang; Liu, Lin; Liu, Peng; Sun, Jinbo; Jin, Lingmin; Zhu, Yuanqiang; Fei, Ningbo; Qin, Wei

2017-07-28

Cognitive processes involve input from multiple sensory modalities and obvious differences in the level of cognitive function can be observed between individuals. Evidence to date understanding the biological basis of tactile cognitive variability, however, is limited compared with other forms of sensory cognition. Data from auditory and visual cognition research suggest that variations in both genetics and intrinsic brain function might contribute to individual differences in tactile cognitive performance. In the present study, by using the tactual performance test (TPT), a widely used neuropsychological assessment tool, we investigated the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and resting-state brain functional connectivity (FC) on interindividual variability in TPT performance in healthy, young Chinese adults. Our results showed that the BDNF genotypes and resting-state FC had significant effects on the variability in TPT performance, together accounting for 32.5% and 19.1% of the variance on TPT total score and Memory subitem score respectively. Having fewer Met alleles, stronger anticorrelations between left posterior superior temporal gyrus and somatosensory areas (right postcentral gyrus and right parietal operculum cortex), and greater positive correlation between left parietal operculum cortex and left central opercular cortex, all correspond with better performance of TPT task. And FC between left parietal operculum cortex and left central opercular cortex might be a mediator of the relationship between BDNF genotypes and Memory subitem score. These data demonstrate a novel contribution of intrinsic brain function to tactile cognitive capacity, and further confirm the genetic basis of tactile cognition. Our findings might also explain the interindividual differences in cognitive ability observed in those who are blind and/or deaf from a new perspective. Copyright © 2017. Published by Elsevier Ltd.

HCN channels segregate stimulation‐evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

PubMed Central

Farrell, Jordan S.; Palmer, Laura A.; Singleton, Anna C.; Pittman, Quentin J.; Teskey, G. Campbell

2016-01-01

Key points The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task.Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation.Global HCN1KO mice exhibit reduced reaching accuracy and atypical movements during a single‐pellet reaching task relative to wild‐type controls.Acute pharmacological inhibition of HCN channels in forelimb motor cortex decreases reaching accuracy and increases atypical movements during forelimb reaching. Abstract The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short‐duration high‐resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole‐cell patch clamp to substantially reduce I h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all three experimental manipulations in rats or mice. Global HCN1 knockout mice were less successful and exhibited atypical movements on a skilled‐motor learning task relative to wild‐type controls. Furthermore, in reaching‐proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple movement responses within shared networks of motor cortex. This mechanism supports a viewpoint of primary motor cortex as a site of dynamic integration for behavioural output. PMID:27568501

MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage.

PubMed

Sasaki, Kazumasu; Mutoh, Tatsushi; Nakamura, Kazuhiro; Kojima, Ikuho; Taki, Yasuyuki; Suarez, Jose Ignacio; Ishikawa, Tatsuya

2017-07-13

Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n=12; caudate putamen, n=3; hippocampus, n=1) or multiple lesions (cortex and caudate putamen, n=6; cortex and hippocampus, n=2; cortex, hippocampus and thalamus/hypothalamus, n=3; bilateral cortex, n=2). The mortality rate within 24h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P=0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r 2 =0.31, P=0.0002). Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction. Copyright © 2017 Elsevier B.V. All rights reserved.

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex

PubMed Central

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-01-01

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features. DOI: http://dx.doi.org/10.7554/eLife.28611.001 PMID:28682237

Mapping visual cortex in monkeys and humans using surface-based atlases

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

2001-01-01

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Hierarchical representation of shapes in visual cortex-from localized features to figural shape segregation.

PubMed

Tschechne, Stephan; Neumann, Heiko

2014-01-01

Visual structures in the environment are segmented into image regions and those combined to a representation of surfaces and prototypical objects. Such a perceptual organization is performed by complex neural mechanisms in the visual cortex of primates. Multiple mutually connected areas in the ventral cortical pathway receive visual input and extract local form features that are subsequently grouped into increasingly complex, more meaningful image elements. Such a distributed network of processing must be capable to make accessible highly articulated changes in shape boundary as well as very subtle curvature changes that contribute to the perception of an object. We propose a recurrent computational network architecture that utilizes hierarchical distributed representations of shape features to encode surface and object boundary over different scales of resolution. Our model makes use of neural mechanisms that model the processing capabilities of early and intermediate stages in visual cortex, namely areas V1-V4 and IT. We suggest that multiple specialized component representations interact by feedforward hierarchical processing that is combined with feedback signals driven by representations generated at higher stages. Based on this, global configurational as well as local information is made available to distinguish changes in the object's contour. Once the outline of a shape has been established, contextual contour configurations are used to assign border ownership directions and thus achieve segregation of figure and ground. The model, thus, proposes how separate mechanisms contribute to distributed hierarchical cortical shape representation and combine with processes of figure-ground segregation. Our model is probed with a selection of stimuli to illustrate processing results at different processing stages. We especially highlight how modulatory feedback connections contribute to the processing of visual input at various stages in the processing hierarchy.

The brain map of gait variability in aging, cognitive impairment and dementia. A systematic review

PubMed Central

Tian, Qu; Chastan, Nathalie; Bair, Woei-Nan; Resnick, Susan M.; Ferrucci, Luigi; Studenski, Stephanie A.

2017-01-01

While gait variability may reflect subtle changes due to aging or cognitive impairment (CI), associated brain characteristics remain unclear. We summarize structural and functional neuroimaging findings associated with gait variability in older adults with and without CI and dementia. We identified 17 eligible studies; all were cross-sectional; few examined multiple brain areas. In older adults, temporal gait variability was associated with structural differences in medial areas important for lower limb coordination and balance. Both temporal and spatial gait variability were associated with structural and functional differences in hippocampus and primary sensorimotor cortex and structural differences in anterior cingulate cortex, basal ganglia, association tracts, and posterior thalamic radiation. In CI or dementia, some associations were found in primary motor cortex, hippocampus, prefrontal cortex and basal ganglia. In older adults, gait variability may be associated with areas important for sensorimotor integration and coordination. To comprehend the neural basis of gait variability with aging and CI, longitudinal studies of multiple brain areas are needed. PMID:28115194

Intracortical Microstimulation Maps of Motor, Somatosensory, and Posterior Parietal Cortex in Tree Shrews (Tupaia belangeri) Reveal Complex Movement Representations.

PubMed

Baldwin, Mary K L; Cooke, Dylan F; Krubitzer, Leah

2017-02-01

Long-train intracortical microstimulation (LT-ICMS) is a popular method for studying the organization of motor and posterior parietal cortex (PPC) in mammals. In primates, LT-ICMS evokes both multijoint and multiple-body-part movements in primary motor, premotor, and PPC. In rodents, LT-ICMS evokes complex movements of a single limb in motor cortex. Unfortunately, very little is known about motor/PPC organization in other mammals. Tree shrews are closely related to both primates and rodents and could provide insights into the evolution of complex movement domains in primates. The present study investigated the extent of cortex in which movements could be evoked with ICMS and the characteristics of movements elicited using both short train (ST) and LT-ICMS in tree shrews. We demonstrate that LT-ICMS and ST-ICMS maps are similar, with the movements elicited with ST-ICMS being truncated versions of those elicited with LT-ICMS. In addition, LT-ICMS-evoked complex movements within motor cortex similar to those in rodents. More complex movements involving multiple body parts such as the hand and mouth were also elicited in motor cortex and PPC, as in primates. Our results suggest that complex movement networks present in PPC and motor cortex were present in mammals prior to the emergence of primates. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex.

PubMed

Rigas, Pavlos; Adamos, Dimitrios A; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A; Skaliora, Irini

2015-01-01

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models.

Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex

PubMed Central

Rigas, Pavlos; Adamos, Dimitrios A.; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A.; Skaliora, Irini

2015-01-01

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models. PMID:26528142

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines.

PubMed

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca 2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca 2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca 2+ indicators, we recorded the Ca 2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca 2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines

PubMed Central

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors. PMID:29740289

Insights from neuropsychology: pinpointing the role of the posterior parietal cortex in episodic and working memory

PubMed Central

Berryhill, Marian E.

2012-01-01

The role of posterior parietal cortex (PPC) in various forms of memory is a current topic of interest in the broader field of cognitive neuroscience. This large cortical region has been linked with a wide range of mnemonic functions affecting each stage of memory processing: encoding, maintenance, and retrieval. Yet, the precise role of the PPC in memory remains mysterious and controversial. Progress in understanding PPC function will require researchers to incorporate findings in a convergent manner from multiple experimental techniques rather than emphasizing a particular type of data. To facilitate this process, here, we review findings from the human neuropsychological research and examine the consequences to memory following PPC damage. Recent patient-based research findings have investigated two typically disconnected fields: working memory (WM) and episodic memory. The findings from patient participants with unilateral and bilateral PPC lesions performing diverse experimental paradigms are summarized. These findings are then related to findings from other techniques including neurostimulation (TMS and tDCS) and the influential and more abundant functional neuroimaging literature. We then review the strengths and weaknesses of hypotheses proposed to account for PPC function in these forms of memory. Finally, we address what missing evidence is needed to clarify the role(s) of the PPC in memory. PMID:22701406

The cerebellum in action: a simulation and robotics study.

PubMed

Hofstötter, Constanze; Mintz, Matti; Verschure, Paul F M J

2002-10-01

The control or prediction of the precise timing of events are central aspects of the many tasks assigned to the cerebellum. Despite much detailed knowledge of its physiology and anatomy, it remains unclear how the cerebellar circuitry can achieve such an adaptive timing function. We present a computational model pursuing this question for one extensively studied type of cerebellar-mediated learning: the classical conditioning of discrete motor responses. This model combines multiple current assumptions on the function of the cerebellar circuitry and was used to investigate whether plasticity in the cerebellar cortex alone can mediate adaptive conditioned response timing. In particular, we studied the effect of changes in the strength of the synapses formed between parallel fibres and Purkinje cells under the control of a negative feedback loop formed between inferior olive, cerebellar cortex and cerebellar deep nuclei. The learning performance of the model was evaluated at the circuit level in simulated conditioning experiments as well as at the behavioural level using a mobile robot. We demonstrate that the model supports adaptively timed responses under real-world conditions. Thus, in contrast to many other models that have focused on cerebellar-mediated conditioning, we investigated whether and how the suggested underlying mechanisms could give rise to behavioural phenomena.

What’s special about task in dystonia? A voxel-based morphometry and diffusion weighted imaging study

PubMed Central

Ramdhani, Ritesh A.; Kumar, Veena; Velickovic, Miodrag; Frucht, Steven J.; Tagliati, Michele; Simonyan, Kristina

2014-01-01

Background Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well-described phenomenon of task-specificity in dystonia remained limited. Methods We used high-resolution MRI with voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task-specific dystonia forms, writer’s cramp and laryngeal dystonia, and two non-task-specific dystonia forms, cervical dystonia and blepharospasm. Results A direct comparison between the both dystonia forms revealed that characteristic gray matter volumetric changes in task-specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, occipital cortex as well as the striatum and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in non-task-specific group were limited to the left cerebellum (lobule VIIa) only, while white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule and middle cingulate gyrus. Conclusion Distinct microstructural patterns in task-specific and non-task-specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers. PMID:24925463

[The participation of the projection areas of the temporal cortex in the sensory support of certain forms of cognitive processes].

PubMed

Mukhin, E I; Orlova, E I; Teriaeva, N B; Mukhina, Iu K; Nabieva, T N

1993-01-01

In neuropsychophysiological and biochemical experiments was studied the role of the temporal cortex of the cat (AI, AII) in mnemonic, perceptive, gnostic functions, praxis, and the higher cognitive processes. The participation of the temporal fields in the mechanisms forming the gnostic imagery activity was shown.

The Roles of Orbital Frontal Cortex in the Modulation of Antisocial Behavior

ERIC Educational Resources Information Center

Blair, R. J. R.

2004-01-01

This article considers potential roles of orbital frontal cortex in the modulation of antisocial behavior. Two forms of aggression are distinguished: reactive aggression elicited in response to frustration/threat and goal directed, instrumental aggression. It is suggested that orbital frontal cortex is directly involved in the modulation of…

miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity

PubMed Central

Mellios, Nikolaos; Sugihara, Hiroki; Castro, Jorge; Banerjee, Abhishek; Le, Chuong; Kumar, Arooshi; Crawford, Benjamin; Strathmann, Julia; Tropea, Daniela; Levine, Stuart S.; Edbauer, Dieter; Sur, Mriganka

2011-01-01

Using multiple quantitative analyses, we discovered microRNAs (miRNAs) abundantly expressed in visual cortex that respond to dark-rearing (DR) and/or monocular deprivation (MD). The most significantly altered miRNA, miR-132, was rapidly upregulated after eye-opening and delayed by DR. In vivo inhibition of miR-132 prevented ocular dominance plasticity in identified neurons following MD, and affected maturation of dendritic spines, demonstrating its critical role in the plasticity of visual cortex circuits. PMID:21892155

Conjunctive coding in an evolved spiking model of retrosplenial cortex.

PubMed

Rounds, Emily L; Alexander, Andrew S; Nitz, Douglas A; Krichmar, Jeffrey L

2018-06-04

Retrosplenial cortex (RSC) is an association cortex supporting spatial navigation and memory. However, critical issues remain concerning the forms by which its ensemble spiking patterns register spatial relationships that are difficult for experimental techniques to fully address. We therefore applied an evolutionary algorithmic optimization technique to create spiking neural network models that matched electrophysiologically observed spiking dynamics in rat RSC neuronal ensembles. Virtual experiments conducted on the evolved networks revealed a mixed selectivity coding capability that was not built into the optimization method, but instead emerged as a consequence of replicating biological firing patterns. The experiments reveal several important outcomes of mixed selectivity that may subserve flexible navigation and spatial representation: (a) robustness to loss of specific inputs, (b) immediate and stable encoding of novel routes and route locations, (c) automatic resolution of input variable conflicts, and (d) dynamic coding that allows rapid adaptation to changing task demands without retraining. These findings suggest that biological retrosplenial cortex can generate unique, first-trial, conjunctive encodings of spatial positions and actions that can be used by downstream brain regions for navigation and path integration. Moreover, these results are consistent with the proposed role for the RSC in the transformation of representations between reference frames and navigation strategy deployment. Finally, the specific modeling framework used for evolving synthetic retrosplenial networks represents an important advance for computational modeling by which synthetic neural networks can encapsulate, describe, and predict the behavior of neural circuits at multiple levels of function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Feature diagnosticity and task context shape activity in human scene-selective cortex.

PubMed

Lowe, Matthew X; Gallivan, Jason P; Ferber, Susanne; Cant, Jonathan S

2016-01-15

Scenes are constructed from multiple visual features, yet previous research investigating scene processing has often focused on the contributions of single features in isolation. In the real world, features rarely exist independently of one another and likely converge to inform scene identity in unique ways. Here, we utilize fMRI and pattern classification techniques to examine the interactions between task context (i.e., attend to diagnostic global scene features; texture or layout) and high-level scene attributes (content and spatial boundary) to test the novel hypothesis that scene-selective cortex represents multiple visual features, the importance of which varies according to their diagnostic relevance across scene categories and task demands. Our results show for the first time that scene representations are driven by interactions between multiple visual features and high-level scene attributes. Specifically, univariate analysis of scene-selective cortex revealed that task context and feature diagnosticity shape activity differentially across scene categories. Examination using multivariate decoding methods revealed results consistent with univariate findings, but also evidence for an interaction between high-level scene attributes and diagnostic visual features within scene categories. Critically, these findings suggest visual feature representations are not distributed uniformly across scene categories but are shaped by task context and feature diagnosticity. Thus, we propose that scene-selective cortex constructs a flexible representation of the environment by integrating multiple diagnostically relevant visual features, the nature of which varies according to the particular scene being perceived and the goals of the observer. Copyright © 2015 Elsevier Inc. All rights reserved.

Distributed coding of actual and hypothetical outcomes in the orbital and dorsolateral prefrontal cortex

PubMed Central

Abe, Hiroshi; Lee, Daeyeol

2011-01-01

SUMMARY Knowledge about hypothetical outcomes from unchosen actions is beneficial only when such outcomes can be correctly attributed to specific actions. Here, we show that during a simulated rock-paper-scissors game, rhesus monkeys can adjust their choice behaviors according to both actual and hypothetical outcomes from their chosen and unchosen actions, respectively. In addition, neurons in both dorsolateral prefrontal cortex and orbitofrontal cortex encoded the signals related to actual and hypothetical outcomes immediately after they were revealed to the animal. Moreover, compared to the neurons in the orbitofrontal cortex, those in the dorsolateral prefrontal cortex were more likely to change their activity according to the hypothetical outcomes from specific actions. Conjunctive and parallel coding of multiple actions and their outcomes in the prefrontal cortex might enhance the efficiency of reinforcement learning and also contribute to their context-dependent memory. PMID:21609828

Vibrissa motor cortex activity suppresses contralateral whisking behavior.

PubMed

Ebbesen, Christian Laut; Doron, Guy; Lenschow, Constanze; Brecht, Michael

2017-01-01

Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.

Distributed patterns of activity in sensory cortex reflect the precision of multiple items maintained in visual short-term memory.

PubMed

Emrich, Stephen M; Riggall, Adam C; Larocque, Joshua J; Postle, Bradley R

2013-04-10

Traditionally, load sensitivity of sustained, elevated activity has been taken as an index of storage for a limited number of items in visual short-term memory (VSTM). Recently, studies have demonstrated that the contents of a single item held in VSTM can be decoded from early visual cortex, despite the fact that these areas do not exhibit elevated, sustained activity. It is unknown, however, whether the patterns of neural activity decoded from sensory cortex change as a function of load, as one would expect from a region storing multiple representations. Here, we use multivoxel pattern analysis to examine the neural representations of VSTM in humans across multiple memory loads. In an important extension of previous findings, our results demonstrate that the contents of VSTM can be decoded from areas that exhibit a transient response to visual stimuli, but not from regions that exhibit elevated, sustained load-sensitive delay-period activity. Moreover, the neural information present in these transiently activated areas decreases significantly with increasing load, indicating load sensitivity of the patterns of activity that support VSTM maintenance. Importantly, the decrease in classification performance as a function of load is correlated with within-subject changes in mnemonic resolution. These findings indicate that distributed patterns of neural activity in putatively sensory visual cortex support the representation and precision of information in VSTM.

Evidence for unlimited capacity processing of simple features in visual cortex

PubMed Central

White, Alex L.; Runeson, Erik; Palmer, John; Ernst, Zachary R.; Boynton, Geoffrey M.

2017-01-01

Performance in many visual tasks is impaired when observers attempt to divide spatial attention across multiple visual field locations. Correspondingly, neuronal response magnitudes in visual cortex are often reduced during divided compared with focused spatial attention. This suggests that early visual cortex is the site of capacity limits, where finite processing resources must be divided among attended stimuli. However, behavioral research demonstrates that not all visual tasks suffer such capacity limits: The costs of divided attention are minimal when the task and stimulus are simple, such as when searching for a target defined by orientation or contrast. To date, however, every neuroimaging study of divided attention has used more complex tasks and found large reductions in response magnitude. We bridged that gap by using functional magnetic resonance imaging to measure responses in the human visual cortex during simple feature detection. The first experiment used a visual search task: Observers detected a low-contrast Gabor patch within one or four potentially relevant locations. The second experiment used a dual-task design, in which observers made independent judgments of Gabor presence in patches of dynamic noise at two locations. In both experiments, blood-oxygen level–dependent (BOLD) signals in the retinotopic cortex were significantly lower for ignored than attended stimuli. However, when observers divided attention between multiple stimuli, BOLD signals were not reliably reduced and behavioral performance was unimpaired. These results suggest that processing of simple features in early visual cortex has unlimited capacity. PMID:28654964

Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

PubMed

Tucker, Thomas R; Katz, Lawrence C

2003-01-01

To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials. The results indicate that co-activation of multiple sets of horizontal connections recruit strong inhibition from local inhibitory networks, causing marked deviations from simple linear integration.

The Differential Role of Verbal and Spatial Working Memory in the Neural Basis of Arithmetic

PubMed Central

Demir, Özlem Ece; Prado, Jérôme; Booth, James R.

2014-01-01

We examine the relations of verbal and spatial WM ability to the neural bases of arithmetic in school-age children. We independently localize brain regions subserving verbal versus spatial representations. For multiplication, higher verbal WM ability is associated with greater recruitment of the left temporal cortex, identified by the verbal localizer. For multiplication and subtraction, higher spatial WM ability is associated with greater recruitment of right parietal cortex, identified by the spatial localizer. Depending on their WM ability, children engage different neural systems that manipulate different representations to solve arithmetic problems. PMID:25144257

Processing of band-passed noise in the lateral auditory belt cortex of the rhesus monkey.

PubMed

Rauschecker, Josef P; Tian, Biao

2004-06-01

Neurons in the lateral belt areas of rhesus monkey auditory cortex were stimulated with band-passed noise (BPN) bursts of different bandwidths and center frequencies. Most neurons responded much more vigorously to these sounds than to tone bursts of a single frequency, and it thus became possible to elicit a clear response in 85% of lateral belt neurons. Tuning to center frequency and bandwidth of the BPN bursts was analyzed. Best center frequency varied along the rostrocaudal direction, with 2 reversals defining borders between areas. We confirmed the existence of 2 belt areas (AL and ML) that were laterally adjacent to the core areas (R and A1, respectively) and a third area (CL) adjacent to area CM on the supratemporal plane (STP). All 3 lateral belt areas were cochleotopically organized with their frequency gradients collinear to those of the adjacent STP areas. Although A1 neurons responded best to pure tones and their responses decreased with increasing bandwidth, 63% of the lateral belt neurons were tuned to bandwidths between 1/3 and 2 octaves and showed either one or multiple peaks. The results are compared with previous data from visual cortex and are discussed in the context of spectral integration, whereby the lateral belt forms a relatively early stage of processing in the cortical hierarchy, giving rise to parallel streams for the identification of auditory objects and their localization in space.

Lateral Entorhinal Cortex Lesions Impair Local Spatial Frameworks

PubMed Central

Kuruvilla, Maneesh V.; Ainge, James A.

2017-01-01

A prominent theory in the neurobiology of memory processing is that episodic memory is supported by contextually gated spatial representations in the hippocampus formed by combining spatial information from medial entorhinal cortex (MEC) with non-spatial information from lateral entorhinal cortex (LEC). However, there is a growing body of evidence from lesion and single-unit recording studies in rodents suggesting that LEC might have a role in encoding space, particularly the current and previous locations of objects within the local environment. Landmarks, both local and global, have been shown to control the spatial representations hypothesized to underlie cognitive maps. Consequently, it has recently been suggested that information processing within this network might be organized with reference to spatial scale with LEC and MEC providing information about local and global spatial frameworks respectively. In the present study, we trained animals to search for food using either a local or global spatial framework. Animals were re-tested on both tasks after receiving excitotoxic lesions of either the MEC or LEC. LEC lesioned animals were impaired in their ability to learn a local spatial framework task. LEC lesioned animals were also impaired on an object recognition (OR) task involving multiple local features but unimpaired at recognizing a single familiar object. Together, this suggests that LEC is involved in associating features of the local environment. However, neither LEC nor MEC lesions impaired performance on the global spatial framework task. PMID:28567006

Representation of numerosity in posterior parietal cortex

PubMed Central

Roitman, Jamie D.; Brannon, Elizabeth M.; Platt, Michael L.

2012-01-01

Humans and animals appear to share a similar representation of number as an analog magnitude on an internal, subjective scale. Neurological and neurophysiological data suggest that posterior parietal cortex (PPC) is a critical component of the circuits that form the basis of numerical abilities in humans. Patients with parietal lesions are impaired in their ability to access the deep meaning of numbers. Acalculiac patients with inferior parietal damage often have difficulty performing arithmetic (2 + 4?) or number bisection (what is between 3 and 5?) tasks, but are able to recite multiplication tables and read or write numerals. Functional imaging studies of neurologically intact humans performing subtraction, number comparison, and non-verbal magnitude comparison tasks show activity in areas within the intraparietal sulcus (IPS). Taken together, clinical cases and imaging studies support a critical role for parietal cortex in the mental manipulation of numerical quantities. Further, responses of single PPC neurons in non-human primates are sensitive to the numerosity of visual stimuli independent of low-level stimulus qualities. When monkeys are trained to make explicit judgments about the numerical value of such stimuli, PPC neurons encode their cardinal numerical value; without such training PPC neurons appear to encode numerical magnitude in an analog fashion. Here we suggest that the spatial and integrative properties of PPC neurons contribute to their critical role in numerical cognition. PMID:22666194

Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala.

PubMed

Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

2011-09-01

Neural correlates involved in the formation of negative impression from face were investigated using event-related functional magnetic resonance imaging and a partial conditioning paradigm. Eighteen normal volunteers underwent imaging while they viewed the faces of two unfamiliar individuals: one individual's face was partially accompanied by negative emotion but the other's was not. After the volunteers learned the relationship between the faces and the emotion, they formed a more negative impression of the person's face when the emotion was presented. Subtraction analysis of the individuals' neutral faces revealed activation in the dorsal anterior cingulate cortex and superior temporal sulcus, but this activity did not correlate with the change of impression from face. On the other hand, the response in the left amygdala negatively correlated with the change of impression from face in the first run. Time modulation analysis revealed that activity in the dorsomedial prefrontal cortex associated with negative emotion was the largest in the initial part of the acquisition. These results suggest that a negative impression from face may be formed by orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior cingulate cortex and amygdala, and that the activity has a prominent role in the initial acquisition of negative emotion.

How cortical neurons help us see: visual recognition in the human brain

PubMed Central

Blumberg, Julie; Kreiman, Gabriel

2010-01-01

Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex. PMID:20811161

A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application.

PubMed

Ferrari, Marco; Quaresima, Valentina

2012-11-01

This review is aimed at celebrating the upcoming 20th anniversary of the birth of human functional near-infrared spectroscopy (fNIRS). After the discovery in 1992 that the functional activation of the human cerebral cortex (due to oxygenation and hemodynamic changes) can be explored by NIRS, human functional brain mapping research has gained a new dimension. fNIRS or optical topography, or near-infrared imaging or diffuse optical imaging is used mainly to detect simultaneous changes in optical properties of the human cortex from multiple measurement sites and displays the results in the form of a map or image over a specific area. In order to place current fNIRS research in its proper context, this paper presents a brief historical overview of the events that have shaped the present status of fNIRS. In particular, technological progresses of fNIRS are highlighted (i.e., from single-site to multi-site functional cortical measurements (images)), introduction of the commercial multi-channel systems, recent commercial wireless instrumentation and more advanced prototypes. Copyright © 2012 Elsevier Inc. All rights reserved.

The Embryonic Septum and Ventral Pallium, New Sources of Olfactory Cortex Cells

PubMed Central

de Carlos, Juan A.

2012-01-01

The mammalian olfactory cortex is a complex structure located along the rostro-caudal extension of the ventrolateral prosencephalon, which is divided into several anatomically and functionally distinct areas: the anterior olfactory nucleus, piriform cortex, olfactory tubercle, amygdaloid olfactory nuclei, and the more caudal entorhinal cortex. Multiple forebrain progenitor domains contribute to the cellular diversity of the olfactory cortex, which is invaded simultaneously by cells originating in distinct germinal areas in the dorsal and ventral forebrain. Using a combination of dye labeling techniques, we identified two novel areas that contribute cells to the developing olfactory cortices, the septum and the ventral pallium, from which cells migrate along a radial and then a tangential path. We characterized these cell populations by comparing their expression of calretinin, calbindin, reelin and Tbr1 with that of other olfactory cell populations. PMID:22984546

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 subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A passive exoskeleton can push your life up: application on multiple sclerosis patients.

PubMed

Di Russo, Francesco; Berchicci, Marika; Perri, Rinaldo Livio; Ripani, Francesca Romana; Ripani, Maurizio

2013-01-01

In the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity. Multiple sclerosis is a neurological condition characterized by lesions of the myelin sheaths that encapsulate the neurons of the brain, spine and optic nerve, and it causes transient or progressive symptoms and impairments in gait and posture. Up to 50% of multiple sclerosis patients require walking aids and 10% are wheelchair-bound 15 years following the initial diagnosis. We tested the ability of a new orthosis, the "Human Body Posturizer", designed to improve the structural and functional symmetry of the body through proprioception, in multiple sclerosis patients. We observed that a single Human Body Posturizer application improved mobility, ambulation and response accuracy, in all of the tested patients. Most importantly, we associated these clinical observations and behavioral effects to changes in brain activity, particularly in the prefrontal cortex.

Functional dissociations between four basic arithmetic operations in the human posterior parietal cortex: A cytoarchitectonic mapping study

PubMed Central

Rosenberg-Lee, Miriam; Chang, Ting Ting; Young, Christina B; Wu, Sarah; Menon, Vinod

2011-01-01

Although lesion studies over the past several decades have focused on functional dissociations in posterior parietal cortex (PPC) during arithmetic, no consistent view has emerged of its differential involvement in addition, subtraction, multiplication, and division. To circumvent problems with poor anatomical localization, we examined functional overlap and dissociations in cytoarchitectonically-defined subdivisions of the intraparietal sulcus (IPS), superior parietal lobule (SPL) and angular gyrus (AG), across these four operations. Compared to a number identification control task, all operations except addition, showed a consistent profile of left posterior IPS activation and deactivation in the right posterior AG. Multiplication and subtraction differed significantly in right, but not left, IPS and AG activity, challenging the view that the left AG differentially subserves retrieval during multiplication. Although addition and multiplication both rely on retrieval, multiplication evoked significantly greater activation in right posterior IPS, as well as the prefrontal cortex, lingual and fusiform gyri, demonstrating that addition and multiplication engage different brain processes. Comparison of PPC responses to the two pairs of inverse operations: division vs. multiplication and subtraction vs. addition revealed greater activation of left lateral SPL during division, suggesting that processing inverse relations is operation specific. Our findings demonstrate that individual IPS, SPL and AG subdivisions are differentially modulated by the four arithmetic operations and they point to significant functional heterogeneity and individual differences in activation and deactivation within the PPC. Critically, these effects are related to retrieval, calculation and inversion, the three key cognitive processes that are differentially engaged by arithmetic operations. Our findings point to distributed representation of these processes in the human PPC and also help explain why lesion and previous imaging studies have yielded inconsistent findings. PMID:21616086

Functional dissociations between four basic arithmetic operations in the human posterior parietal cortex: a cytoarchitectonic mapping study.

PubMed

Rosenberg-Lee, Miriam; Chang, Ting Ting; Young, Christina B; Wu, Sarah; Menon, Vinod

2011-07-01

Although lesion studies over the past several decades have focused on functional dissociations in posterior parietal cortex (PPC) during arithmetic, no consistent view has emerged of its differential involvement in addition, subtraction, multiplication, and division. To circumvent problems with poor anatomical localization, we examined functional overlap and dissociations in cytoarchitectonically defined subdivisions of the intraparietal sulcus (IPS), superior parietal lobule (SPL) and angular gyrus (AG), across these four operations. Compared to a number identification control task, all operations except addition, showed a consistent profile of left posterior IPS activation and deactivation in the right posterior AG. Multiplication and subtraction differed significantly in right, but not left, IPS and AG activity, challenging the view that the left AG differentially subserves retrieval during multiplication. Although addition and multiplication both rely on retrieval, multiplication evoked significantly greater activation in right posterior IPS, as well as the prefrontal cortex, lingual and fusiform gyri, demonstrating that addition and multiplication engage different brain processes. Comparison of PPC responses to the two pairs of inverse operations: division versus multiplication and subtraction versus addition revealed greater activation of left lateral SPL during division, suggesting that processing inverse relations is operation specific. Our findings demonstrate that individual IPS, SPL and AG subdivisions are differentially modulated by the four arithmetic operations and they point to significant functional heterogeneity and individual differences in activation and deactivation within the PPC. Critically, these effects are related to retrieval, calculation and inversion, the three key cognitive processes that are differentially engaged by arithmetic operations. Our findings point to distribute representation of these processes in the human PPC and also help explain why lesion and previous imaging studies have yielded inconsistent findings. Copyright © 2011 Elsevier Ltd. All rights reserved.

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

PubMed Central

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Homeostatic circuits selectively gate food cue responses in insular cortex

PubMed Central

Livneh, Yoav; Ramesh, Rohan n.; Burgess, christian R.; Levandowski, Kirsten M.; Madara, Joseph c.; Fenselau, henning; Goldey, Glenn J.; Diaz, Veronica E.; Jikomes, nick; Resch, Jon M.; Lowell, Bradford B.; Andermann, Mark L.

2017-01-01

Physiological needs bias perception and attention to relevant sensory cues. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food- cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic ‘hunger neurons’ (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues. PMID:28614299

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

DTIC Science & Technology

2014-09-01

and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI PRINCIPAL INVESTIGATOR: Dr. Caterina Mainero...studies in multiple sclerosis (MS) suggested that cortical demyelinating lesions, which are hardly detected in vivo on conventional magnetic resonance...disease progression in many MS cases. 15. SUBJECT TERMS Multiple sclerosis ; cortex; cortical sulci; neuroinflammation; microglia; cortical

Multiple asynchronous stimulus- and task-dependent hierarchies (STDH) within the visual brain's parallel processing systems.

PubMed

Zeki, Semir

2016-10-01

Results from a variety of sources, some many years old, lead ineluctably to a re-appraisal of the twin strategies of hierarchical and parallel processing used by the brain to construct an image of the visual world. Contrary to common supposition, there are at least three 'feed-forward' anatomical hierarchies that reach the primary visual cortex (V1) and the specialized visual areas outside it, in parallel. These anatomical hierarchies do not conform to the temporal order with which visual signals reach the specialized visual areas through V1. Furthermore, neither the anatomical hierarchies nor the temporal order of activation through V1 predict the perceptual hierarchies. The latter shows that we see (and become aware of) different visual attributes at different times, with colour leading form (orientation) and directional visual motion, even though signals from fast-moving, high-contrast stimuli are among the earliest to reach the visual cortex (of area V5). Parallel processing, on the other hand, is much more ubiquitous than commonly supposed but is subject to a barely noticed but fundamental aspect of brain operations, namely that different parallel systems operate asynchronously with respect to each other and reach perceptual endpoints at different times. This re-assessment leads to the conclusion that the visual brain is constituted of multiple, parallel and asynchronously operating task- and stimulus-dependent hierarchies (STDH); which of these parallel anatomical hierarchies have temporal and perceptual precedence at any given moment is stimulus and task related, and dependent on the visual brain's ability to undertake multiple operations asynchronously. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The neurobiological basis of seeing words

PubMed Central

Wandell, Brian A.

2011-01-01

This review summarizes recent ideas about the cortical circuits for seeing words, an important part of the brain system for reading. Historically, the link between the visual cortex and reading has been contentious. One influential position is that the visual cortex plays a minimal role, limited to identifying contours, and that information about these contours is delivered to cortical regions specialized for reading and language. An alternative position is that specializations for seeing words develop within the visual cortex itself. Modern neuroimaging measurements—including both functional magnetic resonance imaging (fMRI) and diffusion weighted imaging with tractography data—support the position that circuitry for seeing the statistical regularities of word forms develops within the ventral occipitotemporal cortex, which also contains important circuitry for seeing faces, colors, and forms. The review explains new findings about the visual pathways, including visual field maps, as well as new findings about how we see words. The measurements from the two fields are in close cortical proximity, and there are good opportunities for coordinating theoretical ideas about function in the ventral occipitotemporal cortex. PMID:21486296

The neurobiological basis of seeing words.

PubMed

Wandell, Brian A

2011-04-01

This review summarizes recent ideas about the cortical circuits for seeing words, an important part of the brain system for reading. Historically, the link between the visual cortex and reading has been contentious. One influential position is that the visual cortex plays a minimal role, limited to identifying contours, and that information about these contours is delivered to cortical regions specialized for reading and language. An alternative position is that specializations for seeing words develop within the visual cortex itself. Modern neuroimaging measurements-including both functional magnetic resonance imaging (fMRI) and diffusion weighted imaging with tractography (DTI) data-support the position that circuitry for seeing the statistical regularities of word forms develops within the ventral occipitotemporal cortex, which also contains important circuitry for seeing faces, colors, and forms. This review explains new findings about the visual pathways, including visual field maps, as well as new findings about how we see words. The measurements from the two fields are in close cortical proximity, and there are good opportunities for coordinating theoretical ideas about function in the ventral occipitotemporal cortex. © 2011 New York Academy of Sciences.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

PubMed

Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

2011-04-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex.

PubMed

Nixima, Ken'ichi; Okanoya, Kazuo; Ichinohe, Noritaka; Kurotani, Tohru

2017-09-01

Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of inhibition between coronal and horizontal planes. Since deep layers of the GRS receive inputs from the subiculum, GRS circuits may work as an integrator of multiple sources such as sensory and memory information. Copyright © 2017 the American Physiological Society.

Pharmacological tests of hypotheses for acquired pendular nystagmus.

PubMed

Shaikh, Aasef G; Thurtell, Matthew J; Optican, Lance M; Leigh, R John

2011-09-01

Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for their pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus. © 2011 New York Academy of Sciences.

Pharmacological tests of hypotheses for acquired pendular nystagmus

PubMed Central

Shaikh, Aasef G.; Thurtell, Matthew J.; Optican, Lance M.; Leigh, R. John

2011-01-01

Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for the pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus. PMID:21951011

Orientation selectivity in a multi-gated organic electrochemical transistor

NASA Astrophysics Data System (ADS)

Gkoupidenis, Paschalis; Koutsouras, Dimitrios A.; Lonjaret, Thomas; Fairfield, Jessamyn A.; Malliaras, George G.

2016-06-01

Neuromorphic devices offer promising computational paradigms that transcend the limitations of conventional technologies. A prominent example, inspired by the workings of the brain, is spatiotemporal information processing. Here we demonstrate orientation selectivity, a spatiotemporal processing function of the visual cortex, using a poly(3,4ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) organic electrochemical transistor with multiple gates. Spatially distributed inputs on a gate electrode array are found to correlate with the output of the transistor, leading to the ability to discriminate between different stimuli orientations. The demonstration of spatiotemporal processing in an organic electronic device paves the way for neuromorphic devices with new form factors and a facile interface with biology.

The Left Occipitotemporal Cortex Does Not Show Preferential Activity for Words

PubMed Central

Petersen, Steven E.; Schlaggar, Bradley L.

2012-01-01

Regions in left occipitotemporal (OT) cortex, including the putative visual word form area, are among the most commonly activated in imaging studies of single-word reading. It remains unclear whether this part of the brain is more precisely characterized as specialized for words and/or letters or contains more general-use visual regions having properties useful for processing word stimuli, among others. In Analysis 1, we found no evidence of greater activity in left OT regions for words or letter strings relative to other high–spatial frequency high-contrast stimuli, including line drawings and Amharic strings (which constitute the Ethiopian writing system). In Analysis 2, we further investigated processing characteristics of OT cortex potentially useful in reading. Analysis 2 showed that a specific part of OT cortex 1) is responsive to visual feature complexity, measured by the number of strokes forming groups of letters or Amharic strings and 2) processes learned combinations of characters, such as those in words and pseudowords, as groups but does not do so in consonant and Amharic strings. Together, these results indicate that while regions of left OT cortex are not specialized for words, at least part of OT cortex has properties particularly useful for processing words and letters. PMID:22235035

The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543

Multimodal representation of limb endpoint position in the posterior parietal cortex.

PubMed

Shi, Ying; Apker, Gregory; Buneo, Christopher A

2013-04-01

Understanding the neural representation of limb position is important for comprehending the control of limb movements and the maintenance of body schema, as well as for the development of neuroprosthetic systems designed to replace lost limb function. Multiple subcortical and cortical areas contribute to this representation, but its multimodal basis has largely been ignored. Regarding the parietal cortex, previous results suggest that visual information about arm position is not strongly represented in area 5, although these results were obtained under conditions in which animals were not using their arms to interact with objects in their environment, which could have affected the relative weighting of relevant sensory signals. Here we examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and actively maintained their arm position at multiple locations in a frontal plane. On half of the trials both visual and nonvisual feedback of the endpoint of the arm were available, while on the other trials visual feedback was withheld. Many neurons were tuned to arm position, while a smaller number were modulated by the presence/absence of visual feedback. Visual modulation generally took the form of a decrease in both firing rate and variability with limb vision and was associated with more accurate decoding of position at the population level under these conditions. These findings support a multimodal representation of limb endpoint position in the SPL but suggest that visual signals are relatively weakly represented in this area, and only at the population level.

Different forms of effective connectivity in primate frontotemporal pathways.

PubMed

Petkov, Christopher I; Kikuchi, Yukiko; Milne, Alice E; Mishkin, Mortimer; Rauschecker, Josef P; Logothetis, Nikos K

2015-01-23

It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.

Different forms of effective connectivity in primate frontotemporal pathways

PubMed Central

Petkov, Christopher I.; Kikuchi, Yukiko; Milne, Alice E.; Mishkin, Mortimer; Rauschecker, Josef P.; Logothetis, Nikos K.

2015-01-01

It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex. PMID:25613079

Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy.

PubMed

Wang, Po-Shan; Wu, Hsiu-Mei; Lin, Ching-Po; Soong, Bing-Wen

2011-07-01

We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P < 0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications.

Cortical Representations of Speech in a Multitalker Auditory Scene.

PubMed

Puvvada, Krishna C; Simon, Jonathan Z

2017-09-20

The ability to parse a complex auditory scene into perceptual objects is facilitated by a hierarchical auditory system. Successive stages in the hierarchy transform an auditory scene of multiple overlapping sources, from peripheral tonotopically based representations in the auditory nerve, into perceptually distinct auditory-object-based representations in the auditory cortex. Here, using magnetoencephalography recordings from men and women, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in distinct hierarchical stages of the auditory cortex. Using systems-theoretic methods of stimulus reconstruction, we show that the primary-like areas in the auditory cortex contain dominantly spectrotemporal-based representations of the entire auditory scene. Here, both attended and ignored speech streams are represented with almost equal fidelity, and a global representation of the full auditory scene with all its streams is a better candidate neural representation than that of individual streams being represented separately. We also show that higher-order auditory cortical areas, by contrast, represent the attended stream separately and with significantly higher fidelity than unattended streams. Furthermore, the unattended background streams are more faithfully represented as a single unsegregated background object rather than as separated objects. Together, these findings demonstrate the progression of the representations and processing of a complex acoustic scene up through the hierarchy of the human auditory cortex. SIGNIFICANCE STATEMENT Using magnetoencephalography recordings from human listeners in a simulated cocktail party environment, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in separate hierarchical stages of the auditory cortex. We show that the primary-like areas in the auditory cortex use a dominantly spectrotemporal-based representation of the entire auditory scene, with both attended and unattended speech streams represented with almost equal fidelity. We also show that higher-order auditory cortical areas, by contrast, represent an attended speech stream separately from, and with significantly higher fidelity than, unattended speech streams. Furthermore, the unattended background streams are represented as a single undivided background object rather than as distinct background objects. Copyright © 2017 the authors 0270-6474/17/379189-08$15.00/0.

Hierarchical Organization of Auditory and Motor Representations in Speech Perception: Evidence from Searchlight Similarity Analysis

PubMed Central

Evans, Samuel; Davis, Matthew H.

2015-01-01

How humans extract the identity of speech sounds from highly variable acoustic signals remains unclear. Here, we use searchlight representational similarity analysis (RSA) to localize and characterize neural representations of syllables at different levels of the hierarchically organized temporo-frontal pathways for speech perception. We asked participants to listen to spoken syllables that differed considerably in their surface acoustic form by changing speaker and degrading surface acoustics using noise-vocoding and sine wave synthesis while we recorded neural responses with functional magnetic resonance imaging. We found evidence for a graded hierarchy of abstraction across the brain. At the peak of the hierarchy, neural representations in somatomotor cortex encoded syllable identity but not surface acoustic form, at the base of the hierarchy, primary auditory cortex showed the reverse. In contrast, bilateral temporal cortex exhibited an intermediate response, encoding both syllable identity and the surface acoustic form of speech. Regions of somatomotor cortex associated with encoding syllable identity in perception were also engaged when producing the same syllables in a separate session. These findings are consistent with a hierarchical account of how variable acoustic signals are transformed into abstract representations of the identity of speech sounds. PMID:26157026

The subthalamic nucleus during decision-making with multiple alternatives.

PubMed

Keuken, Max C; Van Maanen, Leendert; Bogacz, Rafal; Schäfer, Andreas; Neumann, Jane; Turner, Robert; Forstmann, Birte U

2015-10-01

Several prominent neurocomputational models predict that an increase of choice alternatives is modulated by increased activity in the subthalamic nucleus (STN). In turn, increased STN activity allows prolonged accumulation of information. At the same time, areas in the medial frontal cortex such as the anterior cingulate cortex (ACC) and the pre-SMA are hypothesized to influence the information processing in the STN. This study set out to test concrete predictions of STN activity in multiple-alternative decision-making using a multimodal combination of 7 Tesla structural and functional Magnetic Resonance Imaging, and ancestral graph (AG) modeling. The results are in line with the predictions in that increased STN activity was found with an increasing amount of choice alternatives. In addition, our study shows that activity in the ACC is correlated with activity in the STN without directly modulating it. This result sheds new light on the information processing streams between medial frontal cortex and the basal ganglia. © 2015 Wiley Periodicals, Inc.

Cortex-based inter-subject analysis of iEEG and fMRI data sets: application to sustained task-related BOLD and gamma responses.

PubMed

Esposito, Fabrizio; Singer, Neomi; Podlipsky, Ilana; Fried, Itzhak; Hendler, Talma; Goebel, Rainer

2013-02-01

Linking regional metabolic changes with fluctuations in the local electromagnetic fields directly on the surface of the human cerebral cortex is of tremendous importance for a better understanding of detailed brain processes. Functional magnetic resonance imaging (fMRI) and intra-cranial electro-encephalography (iEEG) measure two technically unrelated but spatially and temporally complementary sets of functional descriptions of human brain activity. In order to allow fine-grained spatio-temporal human brain mapping at the population-level, an effective comparative framework for the cortex-based inter-subject analysis of iEEG and fMRI data sets is needed. We combined fMRI and iEEG recordings of the same patients with epilepsy during alternated intervals of passive movie viewing and music listening to explore the degree of local spatial correspondence and temporal coupling between blood oxygen level dependent (BOLD) fMRI changes and iEEG spectral power modulations across the cortical surface after cortex-based inter-subject alignment. To this purpose, we applied a simple model of the iEEG activity spread around each electrode location and the cortex-based inter-subject alignment procedure to transform discrete iEEG measurements into cortically distributed group patterns by establishing a fine anatomic correspondence of many iEEG cortical sites across multiple subjects. Our results demonstrate the feasibility of a multi-modal inter-subject cortex-based distributed analysis for combining iEEG and fMRI data sets acquired from multiple subjects with the same experimental paradigm but with different iEEG electrode coverage. The proposed iEEG-fMRI framework allows for improved group statistics in a common anatomical space and preserves the dynamic link between the temporal features of the two modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.

PubMed

Meijer, Kim A; Eijlers, Anand J C; Geurts, Jeroen J G; Schoonheim, Menno M

2018-02-01

Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sensorimotor Rhythm BCI with Simultaneous High Definition-Transcranial Direct Current Stimulation Alters Task Performance.

PubMed

Baxter, Bryan S; Edelman, Bradley J; Nesbitt, Nicholas; He, Bin

Transcranial direct current stimulation (tDCS) has been used to alter the excitability of neurons within the cerebral cortex. Improvements in motor learning have been found in multiple studies when tDCS was applied to the motor cortex before or during task learning. The motor cortex is also active during the performance of motor imagination, a cognitive task during which a person imagines, but does not execute, a movement. Motor imagery can be used with noninvasive brain computer interfaces (BCIs) to control virtual objects in up to three dimensions, but to master control of such devices requires long training times. To evaluate the effect of high-definition tDCS on the performance and underlying electrophysiology of motor imagery based BCI. We utilize high-definition tDCS to investigate the effect of stimulation on motor imagery-based BCI performance across and within sessions over multiple training days. We report a decreased time-to-hit with anodal stimulation both within and across sessions. We also found differing electrophysiological changes of the stimulated sensorimotor cortex during online BCI task performance for left vs. right trials. Cathodal stimulation led to a decrease in alpha and beta band power during task performance compared to sham stimulation for right hand imagination trials. These results suggest that unilateral tDCS over the sensorimotor motor cortex differentially affects cortical areas based on task specific neural activation. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of functional and morphological deficits in the rat after gestational exposure to ionizing radiation

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

Norton, S.; Kimler, B.F.

1988-07-01

Ionizing radiation is a precise tool for altering formation of the developing cerebral cortex of the fetal rat. Whole body exposure of the pregnant rat on gestational day 13, 15 or 17 to 1.0 Gy of gamma radiation resulted in maximum thinning of the cortex on days 15 and 17. In the preweaning period, functional tests (negative geotaxis, reflex suspension, continuous corridor and gait) were most affected by irradiation gestational day 15, as was body weight. When a lower dose of radiation (0.75 Gy) was used on gestational day 15, the damage to the cortex was much less but behavioralmore » changes were still present. Frontal, parietal and occipital areas of the cortex were approximately equally affected. Using stepwise multiple regression analysis, the linkage of functional tests and cortical thickness was examined. Functional variables which were most commonly included as predictors of frontal and parietal cortex were negative geotaxis and continuous corridor. Occipital cortical layers were not predicted by behavioral variables. In predicting function using cortical variables, frontal cortex was better than parietal and occipital cortex was the poorest predictor.« less

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

PubMed Central

Juric-Sekhar, Gordana; Kapur, Raj P.; Glass, Ian A.; Murray, Mitzi L.; Parnell, Shawn E.

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

Segregated Fronto-Cerebellar Circuits Revealed by Intrinsic Functional Connectivity

PubMed Central

Buckner, Randy L.

2009-01-01

Multiple, segregated fronto-cerebellar circuits have been characterized in nonhuman primates using transneuronal tracing techniques including those that target prefrontal areas. Here, we used functional connectivity MRI (fcMRI) in humans (n = 40) to identify 4 topographically distinct fronto-cerebellar circuits that target 1) motor cortex, 2) dorsolateral prefrontal cortex, 3) medial prefrontal cortex, and 4) anterior prefrontal cortex. All 4 circuits were replicated and dissociated in an independent data set (n = 40). Direct comparison of right- and left-seeded frontal regions revealed contralateral lateralization in the cerebellum for each of the segregated circuits. The presence of circuits that involve prefrontal regions confirms that the cerebellum participates in networks important to cognition including a specific fronto-cerebellar circuit that interacts with the default network. Overall, the extent of the cerebellum associated with prefrontal cortex included a large portion of the posterior hemispheres consistent with a prominent role of the cerebellum in nonmotor functions. We conclude by providing a provisional map of the topography of the cerebellum based on functional correlations with the frontal cortex. PMID:19592571

Structural and functional analyses of human cerebral cortex using a surface-based atlas

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Drury, H. A.

1997-01-01

We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

Acoustic and higher-level representations of naturalistic auditory scenes in human auditory and frontal cortex.

PubMed

Hausfeld, Lars; Riecke, Lars; Formisano, Elia

2018-06-01

Often, in everyday life, we encounter auditory scenes comprising multiple simultaneous sounds and succeed to selectively attend to only one sound, typically the most relevant for ongoing behavior. Studies using basic sounds and two-talker stimuli have shown that auditory selective attention aids this by enhancing the neural representations of the attended sound in auditory cortex. It remains unknown, however, whether and how this selective attention mechanism operates on representations of auditory scenes containing natural sounds of different categories. In this high-field fMRI study we presented participants with simultaneous voices and musical instruments while manipulating their focus of attention. We found an attentional enhancement of neural sound representations in temporal cortex - as defined by spatial activation patterns - at locations that depended on the attended category (i.e., voices or instruments). In contrast, we found that in frontal cortex the site of enhancement was independent of the attended category and the same regions could flexibly represent any attended sound regardless of its category. These results are relevant to elucidate the interacting mechanisms of bottom-up and top-down processing when listening to real-life scenes comprised of multiple sound categories. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

PubMed Central

Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

2016-01-01

The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

Functional Topography of Human Auditory Cortex

PubMed Central

Rauschecker, Josef P.

2016-01-01

Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior–posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or “periodotopy,” are also addressed. Although isolated subregions show a preference for high rates of amplitude-modulated white noise (AMWN) in our data, large-scale “periodotopic” organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex. SIGNIFICANCE STATEMENT In this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds. PMID:26818527

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

PubMed

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

2018-02-01

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parallel, multi-stage processing of colors, faces and shapes in macaque inferior temporal cortex

PubMed Central

Lafer-Sousa, Rosa; Conway, Bevil R.

2014-01-01

Visual-object processing culminates in inferior temporal (IT) cortex. To assess the organization of IT, we measured fMRI responses in alert monkey to achromatic images (faces, fruit, bodies, places) and colored gratings. IT contained multiple color-biased regions, which were typically ventral to face patches and, remarkably, yoked to them, spaced regularly at four locations predicted by known anatomy. Color and face selectivity increased for more anterior regions, indicative of a broad hierarchical arrangement. Responses to non-face shapes were found across IT, but were stronger outside color-biased regions and face patches, consistent with multiple parallel streams. IT also contained multiple coarse eccentricity maps: face patches overlapped central representations; color-biased regions spanned mid-peripheral representations; and place-biased regions overlapped peripheral representations. These results suggest that IT comprises parallel, multi-stage processing networks subject to one organizing principle. PMID:24141314

A neuroimaging investigation of attribute framing and individual differences

PubMed Central

Murch, Kevin B.

2014-01-01

Functional magnetic resonance imaging was used to evaluate the neural basis of framing effects. We tested the reflexive and reflective systems model of social cognition as it relates to framing. We also examined the relationships among frame susceptibility, intelligence and personality measures. Participants evaluated whether personal attributes applied to themselves from multiple perspectives and in positive and negative frames. Participants rated whether each statement was descriptive or not and endorsed positive frames more than negative frames. Individual differences on frame decisions enabled us to form high and low frame susceptibility groups. Endorsement of frame-consistent attributes was associated with personality factors, cognitive reflection and intelligence. Reflexive brain regions were associated with positive frames while reflective areas were associated with negative frames. Region of Interest analyses showed that frame-inconsistent responses were associated with increased activation within reflective cognitive control regions including the left dorsolateral prefrontal cortex (PFC), dorsomedial PFC and left ventrolateral PFC. Frame-consistent responses were associated with increased activation in the right orbitofrontal cortex. These results demonstrate that individual differences in frame susceptibility influence personal attribute evaluations. Overall, this study clarifies the neural correlates of the reflective and reflexive systems of social cognition as applied to decisions about social attributions. PMID:23988759

Auditory Cortex Is Required for Fear Potentiation of Gap Detection

PubMed Central

Weible, Aldis P.; Liu, Christine; Niell, Cristopher M.

2014-01-01

Auditory cortex is necessary for the perceptual detection of brief gaps in noise, but is not necessary for many other auditory tasks such as frequency discrimination, prepulse inhibition of startle responses, or fear conditioning with pure tones. It remains unclear why auditory cortex should be necessary for some auditory tasks but not others. One possibility is that auditory cortex is causally involved in gap detection and other forms of temporal processing in order to associate meaning with temporally structured sounds. This predicts that auditory cortex should be necessary for associating meaning with gaps. To test this prediction, we developed a fear conditioning paradigm for mice based on gap detection. We found that pairing a 10 or 100 ms gap with an aversive stimulus caused a robust enhancement of gap detection measured 6 h later, which we refer to as fear potentiation of gap detection. Optogenetic suppression of auditory cortex during pairing abolished this fear potentiation, indicating that auditory cortex is critically involved in associating temporally structured sounds with emotionally salient events. PMID:25392510

Reward-Based Learning Drives Rapid Sensory Signals in Medial Prefrontal Cortex and Dorsal Hippocampus Necessary for Goal-Directed Behavior.

PubMed

Le Merre, Pierre; Esmaeili, Vahid; Charrière, Eloïse; Galan, Katia; Salin, Paul-A; Petersen, Carl C H; Crochet, Sylvain

2018-01-03

The neural circuits underlying learning and execution of goal-directed behaviors remain to be determined. Here, through electrophysiological recordings, we investigated fast sensory processing across multiple cortical areas as mice learned to lick a reward spout in response to a brief deflection of a single whisker. Sensory-evoked signals were absent from medial prefrontal cortex and dorsal hippocampus in naive mice, but developed with task learning and correlated with behavioral performance in mice trained in the detection task. The sensory responses in medial prefrontal cortex and dorsal hippocampus occurred with short latencies of less than 50 ms after whisker deflection. Pharmacological and optogenetic inactivation of medial prefrontal cortex or dorsal hippocampus impaired behavioral performance. Neuronal activity in medial prefrontal cortex and dorsal hippocampus thus appears to contribute directly to task performance, perhaps providing top-down control of learned, context-dependent transformation of sensory input into goal-directed motor output. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

PubMed Central

Winter, Mark R.; Liu, Mo; Monteleone, David; Melunis, Justin; Hershberg, Uri; Goderie, Susan K.; Temple, Sally; Cohen, Andrew R.

2015-01-01

Summary Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex. PMID:26344906

Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

PubMed Central

Righart, Ruthger; Biberacher, Viola; Jonkman, Laura E.; Klaver, Roel; Schmidt, Paul; Buck, Dorothea; Berthele, Achim; Kirschke, Jan S.; Zimmer, Claus; Hemmer, Bernhard; Geurts, Jeroen J. G.

2017-01-01

Objective In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Methods Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Results Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. Interpretation The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529 PMID:28833433

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

Disease-specific molecular events in cortical multiple sclerosis lesions

PubMed Central

Wimmer, Isabella; Höftberger, Romana; Gerlach, Susanna; Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Mahad, Don; Binder, Christoph J.; Krumbholz, Markus; Bauer, Jan; Bradl, Monika

2013-01-01

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen’s encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer’s disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis. PMID:23687122

Does the Sound of a Barking Dog Activate its Corresponding Visual Form? An fMRI Investigation of Modality-Specific Semantic Access

PubMed Central

Reilly, Jamie; Garcia, Amanda; Binney, Richard J.

2016-01-01

Much remains to be learned about the neural architecture underlying word meaning. Fully distributed models of semantic memory predict that the sound of a barking dog will conjointly engage a network of distributed sensorimotor spokes. An alternative framework holds that modality-specific features additionally converge within transmodal hubs. Participants underwent functional MRI while covertly naming familiar objects versus newly learned novel objects from only one of their constituent semantic features (visual form, characteristic sound, or point-light motion representation). Relative to the novel object baseline, familiar concepts elicited greater activation within association regions specific to that presentation modality. Furthermore, visual form elicited activation within high-level auditory association cortex. Conversely, environmental sounds elicited activation in regions proximal to visual association cortex. Both conditions commonly engaged a putative hub region within lateral anterior temporal cortex. These results support hybrid semantic models in which local hubs and distributed spokes are dually engaged in service of semantic memory. PMID:27289210

Hierarchical Organization of Auditory and Motor Representations in Speech Perception: Evidence from Searchlight Similarity Analysis.

PubMed

Evans, Samuel; Davis, Matthew H

2015-12-01

How humans extract the identity of speech sounds from highly variable acoustic signals remains unclear. Here, we use searchlight representational similarity analysis (RSA) to localize and characterize neural representations of syllables at different levels of the hierarchically organized temporo-frontal pathways for speech perception. We asked participants to listen to spoken syllables that differed considerably in their surface acoustic form by changing speaker and degrading surface acoustics using noise-vocoding and sine wave synthesis while we recorded neural responses with functional magnetic resonance imaging. We found evidence for a graded hierarchy of abstraction across the brain. At the peak of the hierarchy, neural representations in somatomotor cortex encoded syllable identity but not surface acoustic form, at the base of the hierarchy, primary auditory cortex showed the reverse. In contrast, bilateral temporal cortex exhibited an intermediate response, encoding both syllable identity and the surface acoustic form of speech. Regions of somatomotor cortex associated with encoding syllable identity in perception were also engaged when producing the same syllables in a separate session. These findings are consistent with a hierarchical account of how variable acoustic signals are transformed into abstract representations of the identity of speech sounds. © The Author 2015. Published by Oxford University Press.

Sleep promotes branch-specific formation of dendritic spines after learning

PubMed Central

Yang, Guang; Lai, Cora Sau Wan; Cichon, Joseph; Ma, Lei; Li, Wei; Gan, Wen-Biao

2015-01-01

How sleep helps learning and memory remains unknown. We report in mouse motor cortex that sleep after motor learning promotes the formation of postsynaptic dendritic spines on a subset of branches of individual layer V pyramidal neurons. New spines are formed on different sets of dendritic branches in response to different learning tasks and are protected from being eliminated when multiple tasks are learned. Neurons activated during learning of a motor task are reactivated during subsequent non-rapid eye movement sleep, and disrupting this neuronal reactivation prevents branch-specific spine formation. These findings indicate that sleep has a key role in promoting learning-dependent synapse formation and maintenance on selected dendritic branches, which contribute to memory storage. PMID:24904169

Extinction Circuits for Fear and Addiction Overlap in Prefrontal Cortex

ERIC Educational Resources Information Center

Peters, Jamie; Kalivas, Peter W.; Quirk, Gregory J.

2009-01-01

Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is…

Neurotoxic lesions of ventrolateral prefrontal cortex impair object-in-place scene memory

PubMed Central

Wilson, Charles R E; Gaffan, David; Mitchell, Anna S; Baxter, Mark G

2007-01-01

Disconnection of the frontal lobe from the inferotemporal cortex produces deficits in a number of cognitive tasks that require the application of memory-dependent rules to visual stimuli. The specific regions of frontal cortex that interact with the temporal lobe in performance of these tasks remain undefined. One capacity that is impaired by frontal–temporal disconnection is rapid learning of new object-in-place scene problems, in which visual discriminations between two small typographic characters are learned in the context of different visually complex scenes. In the present study, we examined whether neurotoxic lesions of ventrolateral prefrontal cortex in one hemisphere, combined with ablation of inferior temporal cortex in the contralateral hemisphere, would impair learning of new object-in-place scene problems. Male macaque monkeys learned 10 or 20 new object-in-place problems in each daily test session. Unilateral neurotoxic lesions of ventrolateral prefrontal cortex produced by multiple injections of a mixture of ibotenate and N-methyl-d-aspartate did not affect performance. However, when disconnection from inferotemporal cortex was completed by ablating this region contralateral to the neurotoxic prefrontal lesion, new learning was substantially impaired. Sham disconnection (injecting saline instead of neurotoxin contralateral to the inferotemporal lesion) did not affect performance. These findings support two conclusions: first, that the ventrolateral prefrontal cortex is a critical area within the frontal lobe for scene memory; and second, the effects of ablations of prefrontal cortex can be confidently attributed to the loss of cell bodies within the prefrontal cortex rather than to interruption of fibres of passage through the lesioned area. PMID:17445247

Structural and functional changes across the visual cortex of a patient with visual form agnosia.

PubMed

Bridge, Holly; Thomas, Owen M; Minini, Loredana; Cavina-Pratesi, Cristiana; Milner, A David; Parker, Andrew J

2013-07-31

Loss of shape recognition in visual-form agnosia occurs without equivalent losses in the use of vision to guide actions, providing support for the hypothesis of two visual systems (for "perception" and "action"). The human individual DF received a toxic exposure to carbon monoxide some years ago, which resulted in a persisting visual-form agnosia that has been extensively characterized at the behavioral level. We conducted a detailed high-resolution MRI study of DF's cortex, combining structural and functional measurements. We present the first accurate quantification of the changes in thickness across DF's occipital cortex, finding the most substantial loss in the lateral occipital cortex (LOC). There are reduced white matter connections between LOC and other areas. Functional measures show pockets of activity that survive within structurally damaged areas. The topographic mapping of visual areas showed that ordered retinotopic maps were evident for DF in the ventral portions of visual cortical areas V1, V2, V3, and hV4. Although V1 shows evidence of topographic order in its dorsal portion, such maps could not be found in the dorsal parts of V2 and V3. We conclude that it is not possible to understand fully the deficits in object perception in visual-form agnosia without the exploitation of both structural and functional measurements. Our results also highlight for DF the cortical routes through which visual information is able to pass to support her well-documented abilities to use visual information to guide actions.

Advances in the behavioural testing and network imaging of rodent recognition memory

PubMed Central

Kinnavane, Lisa; Albasser, Mathieu M.; Aggleton, John P.

2015-01-01

Research into object recognition memory has been galvanised by the introduction of spontaneous preference tests for rodents. The standard task, however, contains a number of inherent shortcomings that reduce its power. Particular issues include the problem that individual trials are time consuming, so limiting the total number of trials in any condition. In addition, the spontaneous nature of the behaviour and the variability between test objects add unwanted noise. To combat these issues, the ‘bow-tie maze’ was introduced. Although still based on the spontaneous preference of novel over familiar stimuli, the ability to give multiple trials within a session without handling the rodents, as well as using the same objects as both novel and familiar samples on different trials, overcomes key limitations in the standard task. Giving multiple trials within a single session also creates new opportunities for functional imaging of object recognition memory. A series of studies are described that examine the expression of the immediate-early gene, c-fos. Object recognition memory is associated with increases in perirhinal cortex and area Te2 c-fos activity. When rats explore novel objects the pathway from the perirhinal cortex to lateral entorhinal cortex, and then to the dentate gyrus and CA3, is engaged. In contrast, when familiar objects are explored the pathway from the perirhinal cortex to lateral entorhinal cortex, and then to CA1, takes precedence. The switch to the perforant pathway (novel stimuli) from the temporoammonic pathway (familiar stimuli) may assist the enhanced associative learning promoted by novel stimuli. PMID:25106740

Multiple parietal-frontal pathways mediate grasping in macaque monkeys

PubMed Central

Gharbawie, Omar A.; Stepniewska, Iwona; Qi, Huixin; Kaas, Jon H.

2011-01-01

The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, respectively in parietal and frontal cortex, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in M1, PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and S2/PV, and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal-frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal-frontal pathways likely coordinate their respective functions into an accurate grasp. PMID:21832196

Brain connectivity and psychiatric comorbidity in adolescents with Internet gaming disorder.

PubMed

Han, Doug Hyun; Kim, Sun Mi; Bae, Sujin; Renshaw, Perry F; Anderson, Jeffrey S

2017-05-01

Prolonged Internet video game play may have multiple and complex effects on human cognition and brain development in both negative and positive ways. There is not currently a consensus on the principle effects of video game play neither on brain development nor on the relationship to psychiatric comorbidity. In this study, 78 adolescents with Internet gaming disorder (IGD) and 73 comparison subjects without IGD, including subgroups with no other psychiatric comorbid disease, with major depressive disorder and with attention deficit hyperactivity disorder (ADHD), were included in a 3 T resting state functional magnetic resonance imaging analysis. The severity of Internet gaming disorder, depression, anxiety and ADHD symptoms were assessed with the Young Internet Addiction Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Korean ADHD rating scales, respectively. Patients with IGD showed an increased functional correlation between seven pairs of regions, all satisfying q < 0.05 False discovery rates in light of multiple statistical tests: left frontal eye field to dorsal anterior cingulate, left frontal eye field to right anterior insula, left dorsolateral prefrontal cortex (DLPFC) to left temporoparietal junction (TPJ), right DLPFC to right TPJ, right auditory cortex to right motor cortex, right auditory cortex to supplementary motor area and right auditory cortex to dorsal anterior cingulate. These findings may represent a training effect of extended game play and suggest a risk or predisposition in game players for over-connectivity of the default mode and executive control networks that may relate to psychiatric comorbidity. © 2015 Society for the Study of Addiction.

Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

PubMed Central

Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.

2013-01-01

Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior based on changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining brain regions contributing to the encoding, maintenance and retrieval of overlapping identity information during working memory using a delayed match-to-sample (DMS) task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the non-overlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and non-overlapping condition at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the DMS task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory while the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses. PMID:23640112

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PubMed

Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

2017-05-01

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

PubMed

Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

2010-02-01

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Perceptual grouping in the human brain: common processing of different cues.

PubMed

Seymour, Kiley; Karnath, Hans-Otto; Himmelbach, Marc

2008-12-03

The perception of global scenes and objects consisting of multiple constituents is based on the integration of local elements or features. Gestalt grouping cues, such as proximity or similarity, can aid this process. Using functional MRI we investigated whether grouping guided by different gestalt cues rely on distinct networks in the brain or share a common network. Our study revealed that gestalt grouping involved the inferior parietal cortex, middle temporal gyrus and prefrontal cortex irrespective of the specific cue used. These findings agree with observations in neurological patients, which suggest that inferior parietal regions may aid the integration of local features into a global gestalt. Damage to this region results in simultanagnosia, a deficit in perceiving multiple objects and global scenes.

Competition between Visual Events Modulates the Influence of Salience during Free-Viewing of Naturalistic Videos

PubMed Central

Nardo, Davide; Console, Paola; Reverberi, Carlo; Macaluso, Emiliano

2016-01-01

In daily life the brain is exposed to a large amount of external signals that compete for processing resources. The attentional system can select relevant information based on many possible combinations of goal-directed and stimulus-driven control signals. Here, we investigate the behavioral and physiological effects of competition between distinctive visual events during free-viewing of naturalistic videos. Nineteen healthy subjects underwent functional magnetic resonance imaging (fMRI) while viewing short video-clips of everyday life situations, without any explicit goal-directed task. Each video contained either a single semantically-relevant event on the left or right side (Lat-trials), or multiple distinctive events in both hemifields (Multi-trials). For each video, we computed a salience index to quantify the lateralization bias due to stimulus-driven signals, and a gaze index (based on eye-tracking data) to quantify the efficacy of the stimuli in capturing attention to either side. Behaviorally, our results showed that stimulus-driven salience influenced spatial orienting only in presence of multiple competing events (Multi-trials). fMRI results showed that the processing of competing events engaged the ventral attention network, including the right temporoparietal junction (R TPJ) and the right inferior frontal cortex. Salience was found to modulate activity in the visual cortex, but only in the presence of competing events; while the orienting efficacy of Multi-trials affected activity in both the visual cortex and posterior parietal cortex (PPC). We conclude that in presence of multiple competing events, the ventral attention system detects semantically-relevant events, while regions of the dorsal system make use of saliency signals to select relevant locations and guide spatial orienting. PMID:27445760

Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders

PubMed Central

Folsom, Timothy D.; Thuras, Paul D.; Fatemi, S. Hossein

2016-01-01

Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33 kDa forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders. PMID:25956630

Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders.

PubMed

Folsom, Timothy D; Thuras, Paul D; Fatemi, S Hossein

2015-07-01

Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33k Da forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Monoaminergic Modulation of Motor Cortex Function

PubMed Central

Vitrac, Clément; Benoit-Marand, Marianne

2017-01-01

Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions. PMID:29062274

Developmental dissociation in the neural responses to simple multiplication and subtraction problems

PubMed Central

Prado, Jérôme; Mutreja, Rachna; Booth, James R.

2014-01-01

Mastering single-digit arithmetic during school years is commonly thought to depend upon an increasing reliance on verbally memorized facts. An alternative model, however, posits that fluency in single-digit arithmetic might also be achieved via the increasing use of efficient calculation procedures. To test between these hypotheses, we used a cross-sectional design to measure the neural activity associated with single-digit subtraction and multiplication in 34 children from 2nd to 7th grade. The neural correlates of language and numerical processing were also identified in each child via localizer scans. Although multiplication and subtraction were undistinguishable in terms of behavior, we found a striking developmental dissociation in their neural correlates. First, we observed grade-related increases of activity for multiplication, but not for subtraction, in a language-related region of the left temporal cortex. Second, we found grade-related increases of activity for subtraction, but not for multiplication, in a region of the right parietal cortex involved in the procedural manipulation of numerical quantities. The present results suggest that fluency in simple arithmetic in children may be achieved by both increasing reliance on verbal retrieval and by greater use of efficient quantity-based procedures, depending on the operation. PMID:25089323

Biased and unbiased perceptual decision-making on vocal emotions.

PubMed

Dricu, Mihai; Ceravolo, Leonardo; Grandjean, Didier; Frühholz, Sascha

2017-11-24

Perceptual decision-making on emotions involves gathering sensory information about the affective state of another person and forming a decision on the likelihood of a particular state. These perceptual decisions can be of varying complexity as determined by different contexts. We used functional magnetic resonance imaging and a region of interest approach to investigate the brain activation and functional connectivity behind two forms of perceptual decision-making. More complex unbiased decisions on affective voices recruited an extended bilateral network consisting of the posterior inferior frontal cortex, the orbitofrontal cortex, the amygdala, and voice-sensitive areas in the auditory cortex. Less complex biased decisions on affective voices distinctly recruited the right mid inferior frontal cortex, pointing to a functional distinction in this region following decisional requirements. Furthermore, task-induced neural connectivity revealed stronger connections between these frontal, auditory, and limbic regions during unbiased relative to biased decision-making on affective voices. Together, the data shows that different types of perceptual decision-making on auditory emotions have distinct patterns of activations and functional coupling that follow the decisional strategies and cognitive mechanisms involved during these perceptual decisions.

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

PubMed

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

2017-01-24

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

The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive.

PubMed

Goldman-Rakic, P S

1996-10-29

The functional architecture of prefrontal cortex is central to our understanding of human mentation and cognitive prowess. This region of the brain is often treated as an undifferentiated structure, on the one hand, or as a mosaic of psychological faculties, on the other. This paper focuses on the working memory processor as a specialization of prefrontal cortex and argues that the different areas within prefrontal cortex represent iterations of this function for different information domains, including spatial cognition, object cognition and additionally, in humans, semantic processing. According to this parallel processing architecture, the 'central executive' could be considered an emergent property of multiple domain-specific processors operating interactively. These processors are specializations of different prefrontal cortical areas, each interconnected both with the domain-relevant long-term storage sites in posterior regions of the cortex and with appropriate output pathways.

Co-localisation of abnormal brain structure and function in specific language impairment

PubMed Central

Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

2012-01-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys

PubMed Central

Procyk, Emmanuel; Wilson, Charles R. E.; Stoll, Frederic M.; Faraut, Maïlys C. M.; Petrides, Michael; Amiez, Céline

2016-01-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. PMID:25217467

A radial map of multi-whisker correlation selectivity in the rat barrel cortex

PubMed Central

Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E.; Bourdieu, Laurent; Léger, Jean- François

2016-01-01

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel–septal borders, forming rings of multi-whisker synchrony-preferring cells. PMID:27869114

A radial map of multi-whisker correlation selectivity in the rat barrel cortex.

PubMed

Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E; Bourdieu, Laurent; Léger, Jean-François

2016-11-21

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel-septal borders, forming rings of multi-whisker synchrony-preferring cells.

Cache Sharing and Isolation Tradeoffs in Multicore Mixed-Criticality Systems

DTIC Science & Technology

2015-05-01

of lockdown registers, to provide way-based partitioning. These alternatives are illustrated in Fig. 1 with respect to a quad-core ARM Cortex A9...presented a cache-partitioning scheme that allows multiple tasks to share the same cache partition on a single processor (as we do for Level-A and...sets and determined the fraction that were schedulable on our target hardware platform, the quad-core ARM Cortex A9 machine mentioned earlier, the LLC

Wnt6 activates endoderm in the sea urchin gene regulatory network

PubMed Central

Croce, Jenifer; Range, Ryan; Wu, Shu-Yu; Miranda, Esther; Lhomond, Guy; Peng, Jeff Chieh-fu; Lepage, Thierry; McClay, David R.

2011-01-01

In the sea urchin, entry of β-catenin into the nuclei of the vegetal cells at 4th and 5th cleavages is necessary for activation of the endomesoderm gene regulatory network. Beyond that, little is known about how the embryo uses maternal information to initiate specification. Here, experiments establish that of the three maternal Wnts in the egg, Wnt6 is necessary for activation of endodermal genes in the endomesoderm GRN. A small region of the vegetal cortex is shown to be necessary for activation of the endomesoderm GRN. If that cortical region of the egg is removed, addition of Wnt6 rescues endoderm. At a molecular level, the vegetal cortex region contains a localized concentration of Dishevelled (Dsh) protein, a transducer of the canonical Wnt pathway; however, Wnt6 mRNA is not similarly localized. Ectopic activation of the Wnt pathway, through the expression of an activated form of β-catenin, of a dominant-negative variant of GSK-3β or of Dsh itself, rescues endomesoderm specification in eggs depleted of the vegetal cortex. Knockdown experiments in whole embryos show that absence of Wnt6 produces embryos that lack endoderm, but those embryos continue to express a number of mesoderm markers. Thus, maternal Wnt6 plus a localized vegetal cortical molecule, possibly Dsh, is necessary for endoderm specification; this has been verified in two species of sea urchin. The data also show that Wnt6 is only one of what are likely to be multiple components that are necessary for activation of the entire endomesoderm gene regulatory network. PMID:21750039

Selective functional interactions between excitatory and inhibitory cortical neurons and differential contribution to persistent activity of the slow oscillation.

PubMed

Tahvildari, Babak; Wölfel, Markus; Duque, Alvaro; McCormick, David A

2012-08-29

The neocortex depends upon a relative balance of recurrent excitation and inhibition for its operation. During spontaneous Up states, cortical pyramidal cells receive proportional barrages of excitatory and inhibitory synaptic potentials. Many of these synaptic potentials arise from the activity of nearby neurons, although the identity of these cells is relatively unknown, especially for those underlying the generation of inhibitory synaptic events. To address these fundamental questions, we developed an in vitro submerged slice preparation of the mouse entorhinal cortex that generates robust and regular spontaneous recurrent network activity in the form of the slow oscillation. By performing whole-cell recordings from multiple cell types identified with green fluorescent protein expression and electrophysiological and/or morphological properties, we show that distinct functional subpopulations of neurons exist in the entorhinal cortex, with large variations in contribution to the generation of balanced excitation and inhibition during the slow oscillation. The most active neurons during the slow oscillation are excitatory pyramidal and inhibitory fast spiking interneurons, receiving robust barrages of both excitatory and inhibitory synaptic potentials. Weak action potential activity was observed in stellate excitatory neurons and somatostatin-containing interneurons. In contrast, interneurons containing neuropeptide Y, vasoactive intestinal peptide, or the 5-hydroxytryptamine (serotonin) 3a receptor, were silent. Our data demonstrate remarkable functional specificity in the interactions between different excitatory and inhibitory cortical neuronal subtypes, and suggest that it is the large recurrent interaction between pyramidal neurons and fast spiking interneurons that is responsible for the generation of persistent activity that characterizes the depolarized states of the cortex.

Motor activation in patients with Pantothenate-Kinase Associated Neurodegeneration: a functional magnetic resonance imaging study.

PubMed

Stoeter, P; Rodriguez-Raecke, R; Vilchez, C; Perez-Then, E; Speckter, H; Oviedo, J; Roa-Sanchez, P

2012-11-01

In a variety of dystonias, functional magnetic resonance imaging has shown deviations of cortical and basal ganglia activations within the motor network, which might cause the movement disturbances. Because these investigations have never been performed in secondary dystonia due to Pantothenate-Kinase Associated Neurodegeneration, we report our results in a small group of such patients from the Dominican Republic. Functional magnetic resonance imaging was carried out in 7 patients with a genetically confirmed mutation of the PANK2 gene and a non-affected control group (matched pairs) using an event-related motor activation paradigm (hand movements). Compared to the control group (p ≤ 0.01), patients showed a larger amount of activated voxels starting in the contralateral cerebellum and contralateral premotor cortex 2 s before the actual hand movement. Whereas these "hyperactivations" gradually diminished over time, activations in the contralateral primary motor cortex and the supplementary motor area peaked during the next second and those of the contralateral putamen at the time of the actual hand movement. In a multiple regression analysis, all these areas correlated positively with the degree of dystonia of the contralateral arm as judged by the Burke-Fahn-Marsden-scale (p ≤ 0.001). As in other forms of dystonia, the increased activations of the motor system found in our patients could be related to the origin of the dystonic movements. Because in this condition the primary lesion affects the pallidum, a defect of the feed-back control mechanism between basal ganglia and cortex might be the responsible factor. © 2012 Elsevier Ltd. All rights reserved.

Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study

PubMed Central

Moseley, Graham Lorimer; Berna, Chantal; Ploner, Markus; Tracey, Irene

2014-01-01

The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings. PMID:25502237

Juvenile social experience and differential age-related changes in the dendritic morphologies of subareas of the prefrontal cortex in rats.

PubMed

Himmler, Brett T; Mychasiuk, Richelle; Nakahashi, Ayuno; Himmler, Stephanie M; Pellis, Sergio M; Kolb, Bryan

2018-04-01

Juvenile social interactions have been shown to influence the dendritic complexity of neurons in the prefrontal cortex (PFC). In particular, social play induces pruning of the cells in the medial prefrontal cortex (mPFC), whereas interacting with multiple partners, whether those interactions involve play or not, increases the complexity of cells in the orbital frontal cortex (OFC). Previous studies suggest that these changes differ in their stability during adulthood. In the present study, rats were reared in groups of either four (quads) or two (pairs) and the brains of the rats from each rearing condition were then harvested at 60 days (i.e., shortly after sexual maturity) and 100 days (i.e., fully adult). The rats housed with multiple partners had more complex neurons of the OFC at 60 days and this complexity declined to a comparable level to that of pair housed rats by 100 days. In contrast, the play-induced changes of the mPFC remained similar at both ages. These findings suggest that the changes in the PFC induced by different social experiences in the juvenile period differ in how long they are maintained in adulthood. Differences in the functions regulated by the OFC and the mPFC are considered with regard to these differences in the stability of juvenile-induced neural changes. © 2017 Wiley Periodicals, Inc.

A meta-analysis of neuroimaging studies on divergent thinking using activation likelihood estimation.

PubMed

Wu, Xin; Yang, Wenjing; Tong, Dandan; Sun, Jiangzhou; Chen, Qunlin; Wei, Dongtao; Zhang, Qinglin; Zhang, Meng; Qiu, Jiang

2015-07-01

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability). © 2015 Wiley Periodicals, Inc.

Speech comprehension aided by multiple modalities: behavioural and neural interactions

PubMed Central

McGettigan, Carolyn; Faulkner, Andrew; Altarelli, Irene; Obleser, Jonas; Baverstock, Harriet; Scott, Sophie K.

2014-01-01

Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources – e.g. voice, face, gesture, linguistic context – to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with increased activation in left inferior frontal gyrus and left posterior STS. The current multimodal speech comprehension paradigm demonstrates recruitment of a wide comprehension network in the brain, in which posterior STS and fusiform gyrus form sites for convergence of auditory, visual and linguistic information, while left-dominant sites in temporal and frontal cortex support successful comprehension. PMID:22266262

Speech comprehension aided by multiple modalities: behavioural and neural interactions.

PubMed

McGettigan, Carolyn; Faulkner, Andrew; Altarelli, Irene; Obleser, Jonas; Baverstock, Harriet; Scott, Sophie K

2012-04-01

Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources - e.g. voice, face, gesture, linguistic context - to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with increased activation in left inferior frontal gyrus and left posterior STS. The current multimodal speech comprehension paradigm demonstrates recruitment of a wide comprehension network in the brain, in which posterior STS and fusiform gyrus form sites for convergence of auditory, visual and linguistic information, while left-dominant sites in temporal and frontal cortex support successful comprehension. Copyright © 2012 Elsevier Ltd. All rights reserved.

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia

PubMed Central

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B.; Geary, David C.; Menon, Vinod

2014-01-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. PMID:25098903

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia.

PubMed

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B; Geary, David C; Menon, Vinod

2015-05-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. © 2014 John Wiley & Sons Ltd.

Origins of the specialization for letters and numbers in ventral occipitotemporal cortex.

PubMed

Hannagan, Thomas; Amedi, Amir; Cohen, Laurent; Dehaene-Lambertz, Ghislaine; Dehaene, Stanislas

2015-07-01

Deep in the occipitotemporal cortex lie two functional regions, the visual word form area (VWFA) and the number form area (NFA), which are thought to play a special role in letter and number recognition, respectively. We review recent progress made in characterizing the origins of these symbol form areas in children or adults, sighted or blind subjects, and humans or monkeys. We propose two non-mutually-exclusive hypotheses on the origins of the VWFA and NFA: the presence of a connectivity bias, and a sensitivity to shape features. We assess the explanatory power of these hypotheses, describe their consequences, and offer several experimental tests. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurotoxicological effects of nicotine on the embryonic development of cerebellar cortex of chick embryo during various stages of incubation.

PubMed

El-Beltagy, Abd El-Fattah B M; Abou-El-Naga, Amoura M; Sabry, Dalia M

2015-10-01

Long-acting nicotine is known to exert pathological effects on almost all tissues including the cerebellar cortex. The present work was designed to elucidate the effect of nicotine on the development of cerebellar cortex of chick embryo during incubation period. The fertilized eggs of hen (Gallus gallus domesticus) were injected into the air space by a single dose of long acting nicotine (1.6 mg/kg/egg) at the 4th day of incubation. The embryos were taken out of the eggs on days 8, 12 and 16 of incubation. The cerebellum of the control and treated embryos at above ages were processed for histopathological examination. The TEM were examined at 16th day of incubation. The results of the present study revealed that, exposure to long-acting nicotine markedly influence the histogenesis of cerebellar cortex of chick embryo during the incubation period. At 8th day of incubation, nicotine delayed the differentiation of the cerebellar analge; especially the external granular layer (EGL) and inner cortical layer (ICL). Furthermore, at 12th day of incubation, the cerebellar foliation was irregular and the Purkinje cells not recognized. By 16th day of incubation, the cerebellar foliations were irregular with interrupted cerebellar cortex and irregular arrangement of Purkinje cells. Immunohistochemical analysis for antibody P53 protein revealed that the cerebellar cortex in all stages of nicotine treated groups possessed a moderate to weak reaction for P53 protein however; this reaction was markedly stronger in the cerebellar cortex of control groups. Moreover, the flow cytometric analysis confirmed that the percentage of apoptosis in control group was significantly higher compared with that of nicotine treated group. At the TEM level, the cerebellar Purkinje cells of 16th day of treated groups showed multiple subcellular alterations in compared with those of the corresponding control group. Such changes represented by appearing of vacuolated mitochondria, cisternal fragmentation of RER, irregular grooves of Golgi tubules. Also, multiple cytoplasmic vacuoles and aggregation of Nissl granules were recorded around pyknotic nucleus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory

PubMed Central

Kitamura, Takashi; Sun, Chen; Martin, Jared; Kitch, Lacey J; Schnitzer, Mark J; Tonegawa, Susumu

2016-01-01

Summary Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II projecting into DG and CA3, rapidly form a distinct representation of a novel context and drive context-specific activation of downstream CA3 cells as well as context-specific fear memory. In contrast, Island cells, excitatory pyramidal neurons in the medial EC layer II projecting into CA1, are indifferent to context-specific encoding or memory. On the other hand, Ocean cells are dispensable for temporal association learning, for which Island cells are crucial. Together, the two excitatory medial EC layer II inputs to the hippocampus have complementary roles in episodic memory. PMID:26402611

Widespread Increases in Malondialdehyde Immunoreactivity in Dopamine-Rich and Dopamine-Poor Regions of Rat Brain Following Multiple, High Doses of Methamphetamine

PubMed Central

Horner, Kristen A.; Gilbert, Yamiece E.; Cline, Susan D.

2011-01-01

Treatment with multiple high doses of methamphetamine (METH) can induce oxidative damage, including dopamine (DA)-mediated reactive oxygen species (ROS) formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu) and substantia nigra pars compacta (SNpc). Malondialdehyde (MDA), a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg) every 2 h for 6 h, sacrificed 1 week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir) in the CPu, SNpc, cortex, and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area and nucleus accumbens. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system. PMID:21602916

Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

PubMed

Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

2008-07-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

Cerebellar Modulation of Frontal Cortex Dopamine Efflux in Mice: Relevance to Autism and Schizophrenia

PubMed Central

MITTLEMAN, GUY; GOLDOWITZ, DANIEL; HECK, DETLEF H.; BLAHA, CHARLES D.

2013-01-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 μA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked pre-frontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders. PMID:18435424

Motor cortex is required for learning but not for executing a motor skill.

PubMed

Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu L; Dhawale, Ashesh K; Kampff, Adam R; Ölveczky, Bence P

2015-05-06

Motor cortex is widely believed to underlie the acquisition and execution of motor skills, but its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex's established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in "tutoring" these circuits during learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Neural coding strategies in auditory cortex.

PubMed

Wang, Xiaoqin

2007-07-01

In contrast to the visual system, the auditory system has longer subcortical pathways and more spiking synapses between the peripheral receptors and the cortex. This unique organization reflects the needs of the auditory system to extract behaviorally relevant information from a complex acoustic environment using strategies different from those used by other sensory systems. The neural representations of acoustic information in auditory cortex can be characterized by three types: (1) isomorphic (faithful) representations of acoustic structures; (2) non-isomorphic transformations of acoustic features and (3) transformations from acoustical to perceptual dimensions. The challenge facing auditory neurophysiologists is to understand the nature of the latter two transformations. In this article, I will review recent studies from our laboratory regarding temporal discharge patterns in auditory cortex of awake marmosets and cortical representations of time-varying signals. Findings from these studies show that (1) firing patterns of neurons in auditory cortex are dependent on stimulus optimality and context and (2) the auditory cortex forms internal representations of sounds that are no longer faithful replicas of their acoustic structures.

The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.

PubMed

Courtiol, Emmanuelle; Wilson, Donald A

2017-01-01

Olfactory perception and its underlying neural mechanisms are not fixed, but rather vary over time, dependent on various parameters such as state, task, or learning experience. In olfaction, one of the primary sensory areas beyond the olfactory bulb is the piriform cortex. Due to an increasing number of functions attributed to the piriform cortex, it has been argued to be an associative cortex rather than a simple primary sensory cortex. In fact, the piriform cortex plays a key role in creating olfactory percepts, helping to form configural odor objects from the molecular features extracted in the nose. Moreover, its dynamic interactions with other olfactory and nonolfactory areas are also critical in shaping the olfactory percept and resulting behavioral responses. In this brief review, we will describe the key role of the piriform cortex in the larger olfactory perceptual network, some of the many actors of this network, and the importance of the dynamic interactions among the piriform-trans-thalamic and limbic pathways.

Cross-Modal Attention Effects in the Vestibular Cortex during Attentive Tracking of Moving Objects.

PubMed

Frank, Sebastian M; Sun, Liwei; Forster, Lisa; Tse, Peter U; Greenlee, Mark W

2016-12-14

The midposterior fundus of the Sylvian fissure in the human brain is central to the cortical processing of vestibular cues. At least two vestibular areas are located at this site: the parietoinsular vestibular cortex (PIVC) and the posterior insular cortex (PIC). It is now well established that activity in sensory systems is subject to cross-modal attention effects. Attending to a stimulus in one sensory modality enhances activity in the corresponding cortical sensory system, but simultaneously suppresses activity in other sensory systems. Here, we wanted to probe whether such cross-modal attention effects also target the vestibular system. To this end, we used a visual multiple-object tracking task. By parametrically varying the number of tracked targets, we could measure the effect of attentional load on the PIVC and the PIC while holding the perceptual load constant. Participants performed the tracking task during functional magnetic resonance imaging. Results show that, compared with passive viewing of object motion, activity during object tracking was suppressed in the PIVC and enhanced in the PIC. Greater attentional load, induced by increasing the number of tracked targets, was associated with a corresponding increase in the suppression of activity in the PIVC. Activity in the anterior part of the PIC decreased with increasing load, whereas load effects were absent in the posterior PIC. Results of a control experiment show that attention-induced suppression in the PIVC is stronger than any suppression evoked by the visual stimulus per se. Overall, our results suggest that attention has a cross-modal modulatory effect on the vestibular cortex during visual object tracking. In this study we investigate cross-modal attention effects in the human vestibular cortex. We applied the visual multiple-object tracking task because it is known to evoke attentional load effects on neural activity in visual motion-processing and attention-processing areas. Here we demonstrate a load-dependent effect of attention on the activation in the vestibular cortex, despite constant visual motion stimulation. We find that activity in the parietoinsular vestibular cortex is more strongly suppressed the greater the attentional load on the visual tracking task. These findings suggest cross-modal attentional modulation in the vestibular cortex. Copyright © 2016 the authors 0270-6474/16/3612720-09$15.00/0.

SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

PubMed

Saud, K; Cánovas, J; Lopez, C I; Berndt, F A; López, E; Maass, J C; Barriga, A; Kukuljan, M

2017-04-01

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Attention to Multiple Objects Facilitates Their Integration in Prefrontal and Parietal Cortex.

PubMed

Kim, Yee-Joon; Tsai, Jeffrey J; Ojemann, Jeffrey; Verghese, Preeti

2017-05-10

Selective attention is known to interact with perceptual organization. In visual scenes, individual objects that are distinct and discriminable may occur on their own, or in groups such as a stack of books. The main objective of this study is to probe the neural interaction that occurs between individual objects when attention is directed toward one or more objects. Here we record steady-state visual evoked potentials via electrocorticography to directly assess the responses to individual stimuli and to their interaction. When human participants attend to two adjacent stimuli, prefrontal and parietal cortex shows a selective enhancement of only the neural interaction between stimuli, but not the responses to individual stimuli. When only one stimulus is attended, the neural response to that stimulus is selectively enhanced in prefrontal and parietal cortex. In contrast, early visual areas generally manifest responses to individual stimuli and to their interaction regardless of attentional task, although a subset of the responses is modulated similarly to prefrontal and parietal cortex. Thus, the neural representation of the visual scene as one progresses up the cortical hierarchy becomes more highly task-specific and represents either individual stimuli or their interaction, depending on the behavioral goal. Attention to multiple objects facilitates an integration of objects akin to perceptual grouping. SIGNIFICANCE STATEMENT Individual objects in a visual scene are seen as distinct entities or as parts of a whole. Here we examine how attention to multiple objects affects their neural representation. Previous studies measured single-cell or fMRI responses and obtained only aggregate measures that combined the activity to individual stimuli as well as their potential interaction. Here, we directly measure electrocorticographic steady-state responses corresponding to individual objects and to their interaction using a frequency-tagging technique. Attention to two stimuli increases the interaction component that is a hallmark for perceptual integration of stimuli. Furthermore, this stimulus-specific interaction is represented in prefrontal and parietal cortex in a task-dependent manner. Copyright © 2017 the authors 0270-6474/17/374942-12$15.00/0.

Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

PubMed

Morales, A M; Kohno, M; Robertson, C L; Dean, A C; Mandelkern, M A; London, E D

2015-06-01

Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders.

Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

PubMed

Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

2016-01-01

Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

Major depressive episodes over the course of 7 years and hippocampal subfield volumes at 7 tesla MRI: the PREDICT-MR study.

PubMed

Wisse, L E M; Biessels, G J; Stegenga, B T; Kooistra, M; van der Veen, P H; Zwanenburg, J J M; van der Graaf, Y; Geerlings, M I

2015-04-01

Smaller hippocampal volumes have been associated with major depressive disorder (MDD). The hippocampus consists of several subfields that may be differentially related to MDD. We investigated the association of occurrence of major depressive episodes (MDEs), assessed five times over seven years, with hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. In this prospective study of randomly selected general practice attendees, MDEs according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and 84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was obtained in 47 participants (60±10 years). The subiculum, cornu ammonis (CA) 1 to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented according a published protocol. Of the 47 participants, 13 had one MDE and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and intracranial volume, revealed no significant differences in hippocampal subfield or entorhinal cortex volumes between participants with and without an MDE in the preceding 84 months. Multiple episodes were associated with smaller subiculum volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume. A limitation of this study is the small sample size which makes replication necessary. In this exploratory study, we found that an increasing number of major depressive episodes was associated with smaller subiculum volumes in middle-aged and older persons, but not with smaller volumes in other hippocampal subfields or the entorhinal cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

Gray-Matter Volume, Midbrain Dopamine D2/D3 Receptors and Drug Craving in Methamphetamine Users

PubMed Central

Morales, Angelica A.; Kohno, Milky; Robertson, Chelsea L.; Dean, Andy C.; Mandelkern, Mark A.; London, Edythe D.

2015-01-01

Dysfunction of the mesocorticolimbic system plays a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [18F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, p<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum, and thalamus (p<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance use disorders. PMID:25896164

Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

PubMed

Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

2018-06-01

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

Linguistic processing in visual and modality-nonspecific brain areas: PET recordings during selective attention.

PubMed

Vorobyev, Victor A; Alho, Kimmo; Medvedev, Svyatoslav V; Pakhomov, Sergey V; Roudas, Marina S; Rutkovskaya, Julia M; Tervaniemi, Mari; Van Zuijen, Titia L; Näätänen, Risto

2004-07-01

Positron emission tomography (PET) was used to investigate the neural basis of selective processing of linguistic material during concurrent presentation of multiple stimulus streams ("cocktail-party effect"). Fifteen healthy right-handed adult males were to attend to one of three simultaneously presented messages: one presented visually, one to the left ear, and one to the right ear. During the control condition, subjects attended to visually presented consonant letter strings and ignored auditory messages. This paper reports the modality-nonspecific language processing and visual word-form processing, whereas the auditory attention effects have been reported elsewhere [Cogn. Brain Res. 17 (2003) 201]. The left-hemisphere areas activated by both the selective processing of text and speech were as follows: the inferior prefrontal (Brodmann's area, BA 45, 47), anterior temporal (BA 38), posterior insular (BA 13), inferior (BA 20) and middle temporal (BA 21), occipital (BA 18/30) cortices, the caudate nucleus, and the amygdala. In addition, bilateral activations were observed in the medial occipito-temporal cortex and the cerebellum. Decreases of activation during both text and speech processing were found in the parietal (BA 7, 40), frontal (BA 6, 8, 44) and occipito-temporal (BA 37) regions of the right hemisphere. Furthermore, the present data suggest that the left occipito-temporal cortex (BA 18, 20, 37, 21) can be subdivided into three functionally distinct regions in the posterior-anterior direction on the basis of their activation during attentive processing of sublexical orthography, visual word form, and supramodal higher-level aspects of language.

Motor cortex is required for learning but not executing a motor skill

PubMed Central

Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu; Dhawale, Ashesh; Kampff, Adam R.; Ölveczky, Bence P.

2018-01-01

Motor cortex is widely believed to underlie the acquisition and execution of motor skills, yet its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex’s established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in ‘tutoring’ these circuits during learning. PMID:25892304

Proteins YlaJ and YhcN contribute to the efficiency of spore germination in Bacillus subtilis.

PubMed

Johnson, Christian L; Moir, Anne

2017-04-01

The YlaJ and YhcN spore lipoproteins of Bacillus subtilis contain a common domain, and are of unknown function. Homologues of YlaJ or YhcN are widespread in Bacilli and are also encoded in those Clostridia that use cortex lytic enzymes SleB and CwlJ for cortex hydrolysis during germination. In B. subtilis, we report that single and double mutants lacking YlaJ and/or YhcN show a reduced rate of spore germination in L-alanine, with a delay in loss of heat resistance, release of dipicolinic acid and OD fall. If B. subtilis spores lack the cortex lytic enzyme CwlJ, spore cortex degradation and subsequent outgrowth to form colonies is strictly dependent on the other cortex lytic enzyme SleB, allowing a test of SleB function; in a cwlJ mutant background, the combined loss of both ylaJ and yhcN genes resulted in a spore population in which only 20% of spores germinated and outgrew to form colonies, suggesting that SleB activity is compromised. YlaJ and YhcN have a role in germination that is not yet well defined, but these proteins are likely to contribute, directly or indirectly, to early events in germination, including effective SleB function. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Intrinsic frequency biases and profiles across human cortex.

PubMed

Mellem, Monika S; Wohltjen, Sophie; Gotts, Stephen J; Ghuman, Avniel Singh; Martin, Alex

2017-11-01

Recent findings in monkeys suggest that intrinsic periodic spiking activity in selective cortical areas occurs at timescales that follow a sensory or lower order-to-higher order processing hierarchy (Murray JD, Bernacchia A, Freedman DJ, Romo R, Wallis JD, Cai X, Padoa-Schioppa C, Pasternak T, Seo H, Lee D, Wang XJ. Nat Neurosci 17: 1661-1663, 2014). It has not yet been fully explored if a similar timescale hierarchy is present in humans. Additionally, these measures in the monkey studies have not addressed findings that rhythmic activity within a brain area can occur at multiple frequencies. In this study we investigate in humans if regions may be biased toward particular frequencies of intrinsic activity and if a full cortical mapping still reveals an organization that follows this hierarchy. We examined the spectral power in multiple frequency bands (0.5-150 Hz) from task-independent data using magnetoencephalography (MEG). We compared standardized power across bands to find regional frequency biases. Our results demonstrate a mix of lower and higher frequency biases across sensory and higher order regions. Thus they suggest a more complex cortical organization that does not simply follow this hierarchy. Additionally, some regions do not display a bias for a single band, and a data-driven clustering analysis reveals a regional organization with high standardized power in multiple bands. Specifically, theta and beta are both high in dorsal frontal cortex, whereas delta and gamma are high in ventral frontal cortex and temporal cortex. Occipital and parietal regions are biased more narrowly toward alpha power, and ventral temporal lobe displays specific biases toward gamma. Thus intrinsic rhythmic neural activity displays a regional organization but one that is not necessarily hierarchical. NEW & NOTEWORTHY The organization of rhythmic neural activity is not well understood. Whereas it has been postulated that rhythms are organized in a hierarchical manner across brain regions, our novel analysis allows comparison of full cortical maps across different frequency bands, which demonstrate that the rhythmic organization is more complex. Additionally, data-driven methods show that rhythms of multiple frequencies or timescales occur within a particular region and that this nonhierarchical organization is widespread. Copyright © 2017 the American Physiological Society.

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function.

PubMed

Kealy, John; Commins, Sean

2011-04-01

The perirhinal cortex is located in a pivotal position to influence the flow of information into and out of the hippocampal formation. In this review, we examine the anatomical, physiological and functional properties of the rat perirhinal cortex. Firstly, we review the properties of the perirhinal cortex itself, we describe how it can be separated into two distinct subregions and consider how it differs from other neighbouring regions in terms of cell type, cellular organisation and its afferent and efferent projections. We review the forms of neurotransmission present in the perirhinal cortex and the morphological, electrophysiological and plastic properties of its neurons. Secondly, we review the perirhinal cortex in the context of its connections with other brain areas; focussing on the projections to cortical, subcortical and hippocampal/parahippocampal regions. Particular attention is paid the anatomical and electrophysiological properties of these projections. Thirdly, we review the main functions of the perirhinal cortex; its roles in perception, recognition memory, spatial and contextual memory and fear conditioning are explored. Finally, we discuss the idea of anatomical, electrophysiological and functional segregation within the perirhinal cortex itself and as part of a hippocampal-parahippocampal network and suggest that understanding this segregation is of critical importance in understanding the role and contributions made by the perirhinal cortex in general. Copyright © 2011 Elsevier Ltd. All rights reserved.

Higher Media Multi-Tasking Activity Is Associated with Smaller Gray-Matter Density in the Anterior Cingulate Cortex

PubMed Central

Loh, Kep Kee; Kanai, Ryota

2014-01-01

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences. PMID:25250778

Mapping multisensory parietal face and body areas in humans.

PubMed

Huang, Ruey-Song; Chen, Ching-fu; Tran, Alyssa T; Holstein, Katie L; Sereno, Martin I

2012-10-30

Detection and avoidance of impending obstacles is crucial to preventing head and body injuries in daily life. To safely avoid obstacles, locations of objects approaching the body surface are usually detected via the visual system and then used by the motor system to guide defensive movements. Mediating between visual input and motor output, the posterior parietal cortex plays an important role in integrating multisensory information in peripersonal space. We used functional MRI to map parietal areas that see and feel multisensory stimuli near or on the face and body. Tactile experiments using full-body air-puff stimulation suits revealed somatotopic areas of the face and multiple body parts forming a higher-level homunculus in the superior posterior parietal cortex. Visual experiments using wide-field looming stimuli revealed retinotopic maps that overlap with the parietal face and body areas in the postcentral sulcus at the most anterior border of the dorsal visual pathway. Starting at the parietal face area and moving medially and posteriorly into the lower-body areas, the median of visual polar-angle representations in these somatotopic areas gradually shifts from near the horizontal meridian into the lower visual field. These results suggest the parietal face and body areas fuse multisensory information in peripersonal space to guard an individual from head to toe.

Separate channels for processing form, texture, and color: evidence from FMRI adaptation and visual object agnosia.

PubMed

Cavina-Pratesi, C; Kentridge, R W; Heywood, C A; Milner, A D

2010-10-01

Previous neuroimaging research suggests that although object shape is analyzed in the lateral occipital cortex, surface properties of objects, such as color and texture, are dealt with in more medial areas, close to the collateral sulcus (CoS). The present study sought to determine whether there is a single medial region concerned with surface properties in general or whether instead there are multiple foci independently extracting different surface properties. We used stimuli varying in their shape, texture, or color, and tested healthy participants and 2 object-agnosic patients, in both a discrimination task and a functional MR adaptation paradigm. We found a double dissociation between medial and lateral occipitotemporal cortices in processing surface (texture or color) versus geometric (shape) properties, respectively. In Experiment 2, we found that the medial occipitotemporal cortex houses separate foci for color (within anterior CoS and lingual gyrus) and texture (caudally within posterior CoS). In addition, we found that areas selective for shape, texture, and color individually were quite distinct from those that respond to all of these features together (shape and texture and color). These latter areas appear to correspond to those associated with the perception of complex stimuli such as faces and places.

A neuroimaging investigation of attribute framing and individual differences.

PubMed

Murch, Kevin B; Krawczyk, Daniel C

2014-10-01

Functional magnetic resonance imaging was used to evaluate the neural basis of framing effects. We tested the reflexive and reflective systems model of social cognition as it relates to framing. We also examined the relationships among frame susceptibility, intelligence and personality measures. Participants evaluated whether personal attributes applied to themselves from multiple perspectives and in positive and negative frames. Participants rated whether each statement was descriptive or not and endorsed positive frames more than negative frames. Individual differences on frame decisions enabled us to form high and low frame susceptibility groups. Endorsement of frame-consistent attributes was associated with personality factors, cognitive reflection and intelligence. Reflexive brain regions were associated with positive frames while reflective areas were associated with negative frames. Region of Interest analyses showed that frame-inconsistent responses were associated with increased activation within reflective cognitive control regions including the left dorsolateral prefrontal cortex (PFC), dorsomedial PFC and left ventrolateral PFC. Frame-consistent responses were associated with increased activation in the right orbitofrontal cortex. These results demonstrate that individual differences in frame susceptibility influence personal attribute evaluations. Overall, this study clarifies the neural correlates of the reflective and reflexive systems of social cognition as applied to decisions about social attributions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

An anatomical and functional topography of human auditory cortical areas

PubMed Central

Moerel, Michelle; De Martino, Federico; Formisano, Elia

2014-01-01

While advances in magnetic resonance imaging (MRI) throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla). Importantly, we illustrate that—whereas a group-based approach to analyze functional (tonotopic) maps is appropriate to highlight the main tonotopic axis—the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e., myelination) as well as of functional properties (e.g., broadness of frequency tuning) is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post-mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions. PMID:25120426

The role of the medial prefrontal cortex in trace fear extinction

PubMed Central

Kwapis, Janine L.; Jarome, Timothy J.

2015-01-01

The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that supports extinction of this memory has received very little attention. Recent research has indicated that trace fear extinction requires a different neural circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ. PMID:25512576

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

PubMed Central

Li, Xiao; Yu, Kai; Zhang, Zicong; Sun, Wenjian; Yang, Zhou; Feng, Jingyu; Chen, Xi; Liu, Chun-Hua; Wang, Haitao; Guo, Yi Ping; He, Jufang

2014-01-01

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex. PMID:24343575

Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

PubMed

Morrill, Ryan J; Hasenstaub, Andrea R

2018-03-14

The cerebral cortex is a major hub for the convergence and integration of signals from across the sensory modalities; sensory cortices, including primary regions, are no exception. Here we show that visual stimuli influence neural firing in the auditory cortex of awake male and female mice, using multisite probes to sample single units across multiple cortical layers. We demonstrate that visual stimuli influence firing in both primary and secondary auditory cortex. We then determine the laminar location of recording sites through electrode track tracing with fluorescent dye and optogenetic identification using layer-specific markers. Spiking responses to visual stimulation occur deep in auditory cortex and are particularly prominent in layer 6. Visual modulation of firing rate occurs more frequently at areas with secondary-like auditory responses than those with primary-like responses. Auditory cortical responses to drifting visual gratings are not orientation-tuned, unlike visual cortex responses. The deepest cortical layers thus appear to be an important locus for cross-modal integration in auditory cortex. SIGNIFICANCE STATEMENT The deepest layers of the auditory cortex are often considered its most enigmatic, possessing a wide range of cell morphologies and atypical sensory responses. Here we show that, in mouse auditory cortex, these layers represent a locus of cross-modal convergence, containing many units responsive to visual stimuli. Our results suggest that this visual signal conveys the presence and timing of a stimulus rather than specifics about that stimulus, such as its orientation. These results shed light on both how and what types of cross-modal information is integrated at the earliest stages of sensory cortical processing. Copyright © 2018 the authors 0270-6474/18/382854-09$15.00/0.

Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis.

PubMed

Marshall, Randolph S; Asllani, Iris; Pavol, Marykay A; Cheung, Ying-Kuen; Lazar, Ronald M

2017-01-01

Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascular disease is unknown. We investigated the association between regional cortical blood flow and regional cortical thickness in patients with asymptomatic unilateral high-grade internal carotid artery disease without stroke. Twenty-nine patients underwent high resolution anatomical and single-delay, pseudocontinuous arterial spin labeling magnetic resonance imaging with partial volume correction to assess gray matter baseline flow. Cortical thickness was estimated using Freesurfer software, followed by co-registration onto each patient's cerebral blood flow image space. Paired t-tests assessed regional cerebral blood flow in motor cortex (supplied by the carotid artery) and visual cortex (indirectly supplied by the carotid) on the occluded and unoccluded side. Pearson correlations were calculated between cortical thickness and regional cerebral blood flow, along with age, hypertension, diabetes and white matter hyperintensity volume. Multiple regression and generalized estimating equation were used to predict cortical thickness bilaterally and in each hemisphere separately. Cortical blood flow correlated with thickness in motor cortex bilaterally (p = 0.0002), and in the occluded and unoccluded sides individually; age (p = 0.002) was also a predictor of cortical thickness in the motor cortex. None of the variables predicted cortical thickness in visual cortex. Blood flow was significantly lower on the occluded versus unoccluded side in the motor cortex (p<0.0001) and in the visual cortex (p = 0.018). On average, cortex was thinner on the side of occlusion in motor but not in visual cortex. The association between cortical blood flow and cortical thickness in carotid arterial territory with greater thinning on the side of the carotid occlusion suggests that altered cerebral hemodynamics is a factor in cortical thinning.

Alterations of brain activity in fibromyalgia patients.

PubMed

Sawaddiruk, Passakorn; Paiboonworachat, Sahattaya; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-04-01

Fibromyalgia is a chronic pain syndrome, characterized by widespread musculoskeletal pain with diffuse tenderness at multiple tender points. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Evidence shows that it could be due to changes in either the peripheral or central nervous system (CNS). For the CNS changes, alterations in the high brain area of fibromyalgia patients have been investigated but the definite mechanisms are still unclear. Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance (fMRI) have been used to gather evidence regarding the changes of brain morphologies and activities in fibromyalgia patients. Nevertheless, due to few studies, limited knowledge for alterations in brain activities in fibromyalgia is currently available. In this review, the changes in brain activity in various brain areas obtained from reports in fibromyalgia patients are comprehensively summarized. Changes of the grey matter in multiple regions such as the superior temporal gyrus, posterior thalamus, amygdala, basal ganglia, cerebellum, cingulate cortex, SII, caudate and putamen from the MRI as well as the increase of brain activities in the cerebellum, prefrontal cortex, anterior cingulate cortex, thalamus, somatosensory cortex, insula in fMRI studies are presented and discussed. Moreover, evidence from pharmacological interventions offering benefits for fibromyalgia patients by reducing brain activity is presented. Because of limited knowledge regarding the roles of brain activity alterations in fibromyalgia, this summarized review will encourage more future studies to elucidate the underlying mechanisms involved in the brains of these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

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

Encoding of Natural Sounds at Multiple Spectral and Temporal Resolutions in the Human Auditory Cortex

PubMed Central

Santoro, Roberta; Moerel, Michelle; De Martino, Federico; Goebel, Rainer; Ugurbil, Kamil; Yacoub, Essa; Formisano, Elia

2014-01-01

Functional neuroimaging research provides detailed observations of the response patterns that natural sounds (e.g. human voices and speech, animal cries, environmental sounds) evoke in the human brain. The computational and representational mechanisms underlying these observations, however, remain largely unknown. Here we combine high spatial resolution (3 and 7 Tesla) functional magnetic resonance imaging (fMRI) with computational modeling to reveal how natural sounds are represented in the human brain. We compare competing models of sound representations and select the model that most accurately predicts fMRI response patterns to natural sounds. Our results show that the cortical encoding of natural sounds entails the formation of multiple representations of sound spectrograms with different degrees of spectral and temporal resolution. The cortex derives these multi-resolution representations through frequency-specific neural processing channels and through the combined analysis of the spectral and temporal modulations in the spectrogram. Furthermore, our findings suggest that a spectral-temporal resolution trade-off may govern the modulation tuning of neuronal populations throughout the auditory cortex. Specifically, our fMRI results suggest that neuronal populations in posterior/dorsal auditory regions preferably encode coarse spectral information with high temporal precision. Vice-versa, neuronal populations in anterior/ventral auditory regions preferably encode fine-grained spectral information with low temporal precision. We propose that such a multi-resolution analysis may be crucially relevant for flexible and behaviorally-relevant sound processing and may constitute one of the computational underpinnings of functional specialization in auditory cortex. PMID:24391486

Population responses in primary auditory cortex simultaneously represent the temporal envelope and periodicity features in natural speech.

PubMed

Abrams, Daniel A; Nicol, Trent; White-Schwoch, Travis; Zecker, Steven; Kraus, Nina

2017-05-01

Speech perception relies on a listener's ability to simultaneously resolve multiple temporal features in the speech signal. Little is known regarding neural mechanisms that enable the simultaneous coding of concurrent temporal features in speech. Here we show that two categories of temporal features in speech, the low-frequency speech envelope and periodicity cues, are processed by distinct neural mechanisms within the same population of cortical neurons. We measured population activity in primary auditory cortex of anesthetized guinea pig in response to three variants of a naturally produced sentence. Results show that the envelope of population responses closely tracks the speech envelope, and this cortical activity more closely reflects wider bandwidths of the speech envelope compared to narrow bands. Additionally, neuronal populations represent the fundamental frequency of speech robustly with phase-locked responses. Importantly, these two temporal features of speech are simultaneously observed within neuronal ensembles in auditory cortex in response to clear, conversation, and compressed speech exemplars. Results show that auditory cortical neurons are adept at simultaneously resolving multiple temporal features in extended speech sentences using discrete coding mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams.

PubMed

Beetz, M Jerome; Hechavarría, Julio C; Kössl, Manfred

2016-10-27

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical "default mode" that allows selectively focusing on close obstacle even without active attention from the animals.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams

PubMed Central

Beetz, M. Jerome; Hechavarría, Julio C.; Kössl, Manfred

2016-01-01

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical “default mode” that allows selectively focusing on close obstacle even without active attention from the animals. PMID:27786252

Hierarchical representation of shapes in visual cortex—from localized features to figural shape segregation

PubMed Central

Tschechne, Stephan; Neumann, Heiko

2014-01-01

Visual structures in the environment are segmented into image regions and those combined to a representation of surfaces and prototypical objects. Such a perceptual organization is performed by complex neural mechanisms in the visual cortex of primates. Multiple mutually connected areas in the ventral cortical pathway receive visual input and extract local form features that are subsequently grouped into increasingly complex, more meaningful image elements. Such a distributed network of processing must be capable to make accessible highly articulated changes in shape boundary as well as very subtle curvature changes that contribute to the perception of an object. We propose a recurrent computational network architecture that utilizes hierarchical distributed representations of shape features to encode surface and object boundary over different scales of resolution. Our model makes use of neural mechanisms that model the processing capabilities of early and intermediate stages in visual cortex, namely areas V1–V4 and IT. We suggest that multiple specialized component representations interact by feedforward hierarchical processing that is combined with feedback signals driven by representations generated at higher stages. Based on this, global configurational as well as local information is made available to distinguish changes in the object's contour. Once the outline of a shape has been established, contextual contour configurations are used to assign border ownership directions and thus achieve segregation of figure and ground. The model, thus, proposes how separate mechanisms contribute to distributed hierarchical cortical shape representation and combine with processes of figure-ground segregation. Our model is probed with a selection of stimuli to illustrate processing results at different processing stages. We especially highlight how modulatory feedback connections contribute to the processing of visual input at various stages in the processing hierarchy. PMID:25157228

Classifying multiple types of hand motions using electrocorticography during intraoperative awake craniotomy and seizure monitoring processes—case studies

PubMed Central

Xie, Tao; Zhang, Dingguo; Wu, Zehan; Chen, Liang; Zhu, Xiangyang

2015-01-01

In this work, some case studies were conducted to classify several kinds of hand motions from electrocorticography (ECoG) signals during intraoperative awake craniotomy & extraoperative seizure monitoring processes. Four subjects (P1, P2 with intractable epilepsy during seizure monitoring and P3, P4 with brain tumor during awake craniotomy) participated in the experiments. Subjects performed three types of hand motions (Grasp, Thumb-finger motion and Index-finger motion) contralateral to the motor cortex covered with ECoG electrodes. Two methods were used for signal processing. Method I: autoregressive (AR) model with burg method was applied to extract features, and additional waveform length (WL) feature has been considered, finally the linear discriminative analysis (LDA) was used as the classifier. Method II: stationary subspace analysis (SSA) was applied for data preprocessing, and the common spatial pattern (CSP) was used for feature extraction before LDA decoding process. Applying method I, the three-class accuracy of P1~P4 were 90.17, 96.00, 91.77, and 92.95% respectively. For method II, the three-class accuracy of P1~P4 were 72.00, 93.17, 95.22, and 90.36% respectively. This study verified the possibility of decoding multiple hand motion types during an awake craniotomy, which is the first step toward dexterous neuroprosthetic control during surgical implantation, in order to verify the optimal placement of electrodes. The accuracy during awake craniotomy was comparable to results during seizure monitoring. This study also indicated that ECoG was a promising approach for precise identification of eloquent cortex during awake craniotomy, and might form a promising BCI system that could benefit both patients and neurosurgeons. PMID:26483627

Neuropsychology of prefrontal cortex

PubMed Central

Siddiqui, Shazia Veqar; Chatterjee, Ushri; Kumar, Devvarta; Siddiqui, Aleem; Goyal, Nishant

2008-01-01

The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different functional operations within the PFC. The specification of the component ‘executive’ processes and their localization to particular regions of PFC have been implicated in a wide variety of psychiatric disorders. PMID:19742233

Computational Models of Cognitive Control

PubMed Central

O’Reilly, Randall C.; Herd, Seth A.; Pauli, Wolfgang M.

2010-01-01

Cognitive control refers to the ability to perform task-relevant processing in the face of other distractions or other forms of interference, in the absence of strong environmental support. It depends on the integrity of the prefrontal cortex and associated biological structures (e.g., the basal ganglia). Computational models have played an influential role in developing our understanding of this system, and we review current developments in three major areas: dynamic gating of prefrontal representations, hierarchies in the prefrontal cortex, and reward, motivation, and goal-related processing in prefrontal cortex. Models in these and other areas are advancing the field further forward. PMID:20185294

Dipicolinic Acid Release by Germinating Clostridium difficile Spores Occurs through a Mechanosensing Mechanism.

PubMed

Francis, Michael B; Sorg, Joseph A

2016-01-01

Classically, dormant endospores are defined by their resistance properties, particularly their resistance to heat. Much of the heat resistance is due to the large amount of dipicolinic acid (DPA) stored within the spore core. During spore germination, DPA is released and allows for rehydration of the otherwise-dehydrated core. In Bacillus subtilis , 7 proteins are encoded by the spoVA operon and are important for DPA release. These proteins receive a signal from the activated germinant receptor and release DPA. This DPA activates the cortex lytic enzyme CwlJ, and cortex degradation begins. In Clostridium difficile , spore germination is initiated in response to certain bile acids and amino acids. These bile acids interact with the CspC germinant receptor, which then transfers the signal to the CspB protease. Activated CspB cleaves the cortex lytic enzyme, pro-SleC, to its active form. Subsequently, DPA is released from the core. C. difficile encodes orthologues of spoVAC , spoVAD , and spoVAE . Of these, the B. subtilis SpoVAC protein was shown to be capable of mechanosensing. Because cortex degradation precedes DPA release during C. difficile spore germination (opposite of what occurs in B. subtilis ), we hypothesized that cortex degradation would relieve the osmotic constraints placed on the inner spore membrane and permit DPA release. Here, we assayed germination in the presence of osmolytes, and we found that they can delay DPA release from germinating C. difficile spores while still permitting cortex degradation. Together, our results suggest that DPA release during C. difficile spore germination occurs though a mechanosensing mechanism. IMPORTANCE Clostridium difficile is transmitted between hosts in the form of a dormant spore, and germination by C. difficile spores is required to initiate infection, because the toxins that are necessary for disease are not deposited on the spore form. Importantly, the C. difficile spore germination pathway represents a novel pathway for bacterial spore germination. Prior work has shown that the order of events during C. difficile spore germination (cortex degradation and DPA release) is flipped compared to the events during B. subtilis spore germination, a model organism. Here, we further characterize the C. difficile spore germination pathway and summarize our findings indicating that DPA release by germinating C. difficile spores occurs through a mechanosensing mechanism in response to the degradation of the spore cortex.

Capturing the temporal evolution of choice across prefrontal cortex

PubMed Central

Hunt, Laurence T; Behrens, Timothy EJ; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

2015-01-01

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi.org/10.7554/eLife.11945.001 PMID:26653139

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys.

PubMed

Procyk, Emmanuel; Wilson, Charles R E; Stoll, Frederic M; Faraut, Maïlys C M; Petrides, Michael; Amiez, Céline

2016-02-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Co-localisation of abnormal brain structure and function in specific language impairment.

PubMed

Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

2012-03-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

The gene cortex controls mimicry and crypsis in butterflies and moths.

PubMed

Nadeau, Nicola J; Pardo-Diaz, Carolina; Whibley, Annabel; Supple, Megan A; Saenko, Suzanne V; Wallbank, Richard W R; Wu, Grace C; Maroja, Luana; Ferguson, Laura; Hanly, Joseph J; Hines, Heather; Salazar, Camilo; Merrill, Richard M; Dowling, Andrea J; ffrench-Constant, Richard H; Llaurens, Violaine; Joron, Mathieu; McMillan, W Owen; Jiggins, Chris D

2016-06-02

The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and whether this control shows any commonality across the 160,000 moth and 17,000 butterfly species. Here, we use fine-scale mapping with population genomics and gene expression analyses to identify a gene, cortex, that regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast-evolving subfamily of the otherwise highly conserved fizzy family of cell-cycle regulators, suggesting that it probably regulates pigmentation patterning by regulating scale cell development. In parallel with findings in the peppered moth (Biston betularia), our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects.

Underlying neural mechanisms of mirror therapy: Implications for motor rehabilitation in stroke.

PubMed

Arya, Kamal Narayan

2016-01-01

Mirror therapy (MT) is a valuable method for enhancing motor recovery in poststroke hemiparesis. The technique utilizes the mirror-illusion created by the movement of sound limb that is perceived as the paretic limb. MT is a simple and economical technique than can stimulate the brain noninvasively. The intervention unquestionably has neural foundation. But the underlying neural mechanisms inducing motor recovery are still unclear. In this review, the neural-modulation due to MT has been explored. Multiple areas of the brain such as the occipital lobe, dorsal frontal area and corpus callosum are involved during the simple MT regime. Bilateral premotor cortex, primary motor cortex, primary somatosensory cortex, and cerebellum also get reorganized to enhance the function of the damaged brain. The motor areas of the lesioned hemisphere receive visuo-motor processing information through the parieto-occipital lobe. The damaged motor cortex responds variably to the MT and may augment true motor recovery. Mirror neurons may also play a possible role in the cortico-stimulatory mechanisms occurring due to the MT.

Learning and recall of form discriminations during reversible cooling deactivation of ventral-posterior suprasylvian cortex in the cat.

PubMed Central

Lomber, S G; Payne, B R; Cornwell, P

1996-01-01

Extrastriate visual cortex of the ventral-posterior suprasylvian gyrus (vPS cortex) of freely behaving cats was reversibly deactivated with cooling to determine its role in performance on a battery of simple or masked two-dimensional pattern discriminations, and three-dimensional object discriminations. Deactivation of vPS cortex by cooling profoundly impaired the ability of the cats to recall the difference between all previously learned pattern and object discriminations. However, the cats' ability to learn or relearn pattern and object discriminations while vPS was deactivated depended upon the nature of the pattern or object and the cats' prior level of exposure to them. During cooling of vPS cortex, the cats could neither learn the novel object discriminations nor relearn a highly familiar masked or partially occluded pattern discrimination, although they could relearn both the highly familiar object and simple pattern discriminations. These cooling-induced deficits resemble those induced by cooling of the topologically equivalent inferotemporal cortex of monkeys and provides evidence that the equivalent regions contribute to visual processing in similar ways. Images Fig. 1 Fig. 3 PMID:8643686

Color opponent receptive fields self-organize in a biophysical model of visual cortex via spike-timing dependent plasticity

PubMed Central

Eguchi, Akihiro; Neymotin, Samuel A.; Stringer, Simon M.

2014-01-01

Although many computational models have been proposed to explain orientation maps in primary visual cortex (V1), it is not yet known how similar clusters of color-selective neurons in macaque V1/V2 are connected and develop. In this work, we address the problem of understanding the cortical processing of color information with a possible mechanism of the development of the patchy distribution of color selectivity via computational modeling. Each color input is decomposed into a red, green, and blue representation and transmitted to the visual cortex via a simulated optic nerve in a luminance channel and red–green and blue–yellow opponent color channels. Our model of the early visual system consists of multiple topographically-arranged layers of excitatory and inhibitory neurons, with sparse intra-layer connectivity and feed-forward connectivity between layers. Layers are arranged based on anatomy of early visual pathways, and include a retina, lateral geniculate nucleus, and layered neocortex. Each neuron in the V1 output layer makes synaptic connections to neighboring neurons and receives the three types of signals in the different channels from the corresponding photoreceptor position. Synaptic weights are randomized and learned using spike-timing-dependent plasticity (STDP). After training with natural images, the neurons display heightened sensitivity to specific colors. Information-theoretic analysis reveals mutual information between particular stimuli and responses, and that the information reaches a maximum with fewer neurons in the higher layers, indicating that estimations of the input colors can be done using the output of fewer cells in the later stages of cortical processing. In addition, cells with similar color receptive fields form clusters. Analysis of spiking activity reveals increased firing synchrony between neurons when particular color inputs are presented or removed (ON-cell/OFF-cell). PMID:24659956

Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits?

PubMed Central

Aggleton, John P.; Nelson, Andrew J.D.

2015-01-01

Lesions of the rodent anterior thalamic nuclei cause severe deficits to multiple spatial learning tasks. Possible explanations for these effects are examined, with particular reference to T-maze alternation. Anterior thalamic lesions not only impair allocentric place learning but also disrupt other spatial processes, including direction learning, path integration, and relative length discriminations, as well as aspects of nonspatial learning, e.g., temporal discriminations. Working memory tasks, such as T-maze alternation, appear particularly sensitive as they combine an array of these spatial and nonspatial demands. This sensitivity partly reflects the different functions supported by individual anterior thalamic nuclei, though it is argued that anterior thalamic lesion effects also arise from covert pathology in sites distal to the thalamus, most critically in the retrosplenial cortex and hippocampus. This two-level account, involving both local and distal lesion effects, explains the range and severity of the spatial deficits following anterior thalamic lesions. These findings highlight how the anterior thalamic nuclei form a key component in a series of interdependent systems that support multiple spatial functions. PMID:25195980

Synchronous activity in cat visual cortex encodes collinear and cocircular contours.

PubMed

Samonds, Jason M; Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2006-04-01

We explored how contour information in primary visual cortex might be embedded in the simultaneous activity of multiple cells recorded with a 100-electrode array. Synchronous activity in cat visual cortex was more selective and predictable in discriminating between drifting grating and concentric ring stimuli than changes in firing rate. Synchrony was found even between cells with wholly different orientation preferences when their receptive fields were circularly aligned, and membership in synchronous groups was orientation and curvature dependent. The existence of synchrony between cocircular cells reinforces its role as a general mechanism for contour integration and shape detection as predicted by association field concepts. Our data suggest that cortical synchrony results from common and synchronous input from earlier visual areas and that it could serve to shape extrastriate response selectivity.

Impairment in judgement of the moral emotion guilt following orbitofrontal cortex damage.

PubMed

Funayama, Michitaka; Koreki, Akihiro; Muramatsu, Taro; Mimura, Masaru; Kato, Motoichiro; Abe, Takayuki

2018-04-19

Although neuroimaging studies have provided evidence for an association between moral emotions and the orbitofrontal cortex, studies on patients with focal lesions using experimental probes of moral emotions are scarce. Here, we addressed this topic by presenting a moral emotion judgement task to patients with focal brain damage. Four judgement tasks in a simple pairwise choice paradigm were given to 72 patients with cerebrovascular disease. These tasks consisted of a perceptual line judgement task as a control task; the objects' preference task as a basic preference judgement task; and two types of moral emotion judgement task, an anger task and a guilt task. A multiple linear regression analysis was performed on each set of task performance scores to take into account potential confounders. Performance on the guilt emotion judgement task negatively correlated with the orbitofrontal cortex damage, but not with the other variables. Results for the other judgement tasks did not reach statistical significance. The close association between orbitofrontal cortex damage and a decrease in guilt emotion judgement consistency might suggest that the orbitofrontal cortex plays a key role in the sense of guilt, a hallmark of morality. © 2018 The British Psychological Society.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

PubMed

Teixeira, Francisco B; de Oliveira, Ana C A; Leão, Luana K R; Fagundes, Nathália C F; Fernandes, Rafael M; Fernandes, Luanna M P; da Silva, Márcia C F; Amado, Lilian L; Sagica, Fernanda E S; de Oliveira, Edivaldo H C; Crespo-Lopez, Maria E; Maia, Cristiane S F; Lima, Rafael R

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

PubMed Central

Teixeira, Francisco B.; de Oliveira, Ana C. A.; Leão, Luana K. R.; Fagundes, Nathália C. F.; Fernandes, Rafael M.; Fernandes, Luanna M. P.; da Silva, Márcia C. F.; Amado, Lilian L.; Sagica, Fernanda E. S.; de Oliveira, Edivaldo H. C.; Crespo-Lopez, Maria E.; Maia, Cristiane S. F.; Lima, Rafael R.

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats. PMID:29867340

Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

NASA Astrophysics Data System (ADS)

Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

1980-12-01

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

3D topology of orientation columns in visual cortex revealed by functional optical coherence tomography.

PubMed

Nakamichi, Yu; Kalatsky, Valery A; Watanabe, Hideyuki; Sato, Takayuki; Rajagopalan, Uma Maheswari; Tanifuji, Manabu

2018-04-01

Orientation tuning is a canonical neuronal response property of six-layer visual cortex that is encoded in pinwheel structures with center orientation singularities. Optical imaging of intrinsic signals enables us to map these surface two-dimensional (2D) structures, whereas lack of appropriate techniques has not allowed us to visualize depth structures of orientation coding. In the present study, we performed functional optical coherence tomography (fOCT), a technique capable of acquiring a 3D map of the intrinsic signals, to study the topology of orientation coding inside the cat visual cortex. With this technique, for the first time, we visualized columnar assemblies in orientation coding that had been predicted from electrophysiological recordings. In addition, we found that the columnar structures were largely distorted around pinwheel centers: center singularities were not rigid straight lines running perpendicularly to the cortical surface but formed twisted string-like structures inside the cortex that turned and extended horizontally through the cortex. Looping singularities were observed with their respective termini accessing the same cortical surface via clockwise and counterclockwise orientation pinwheels. These results suggest that a 3D topology of orientation coding cannot be fully anticipated from 2D surface measurements. Moreover, the findings demonstrate the utility of fOCT as an in vivo mesoscale imaging method for mapping functional response properties of cortex in the depth axis. NEW & NOTEWORTHY We used functional optical coherence tomography (fOCT) to visualize three-dimensional structure of the orientation columns with millimeter range and micrometer spatial resolution. We validated vertically elongated columnar structure in iso-orientation domains. The columnar structure was distorted around pinwheel centers. An orientation singularity formed a string with tortuous trajectories inside the cortex and connected clockwise and counterclockwise pinwheel centers in the surface orientation map. The results were confirmed by comparisons with conventional optical imaging and electrophysiological recordings.

Functional connectivity of visual cortex in the blind follows retinotopic organization principles

PubMed Central

Ovadia-Caro, Smadar; Caramazza, Alfonso; Margulies, Daniel S.; Villringer, Arno

2015-01-01

Is visual input during critical periods of development crucial for the emergence of the fundamental topographical mapping of the visual cortex? And would this structure be retained throughout life-long blindness or would it fade as a result of plastic, use-based reorganization? We used functional connectivity magnetic resonance imaging based on intrinsic blood oxygen level-dependent fluctuations to investigate whether significant traces of topographical mapping of the visual scene in the form of retinotopic organization, could be found in congenitally blind adults. A group of 11 fully and congenitally blind subjects and 18 sighted controls were studied. The blind demonstrated an intact functional connectivity network structural organization of the three main retinotopic mapping axes: eccentricity (centre-periphery), laterality (left-right), and elevation (upper-lower) throughout the retinotopic cortex extending to high-level ventral and dorsal streams, including characteristic eccentricity biases in face- and house-selective areas. Functional connectivity-based topographic organization in the visual cortex was indistinguishable from the normally sighted retinotopic functional connectivity structure as indicated by clustering analysis, and was found even in participants who did not have a typical retinal development in utero (microphthalmics). While the internal structural organization of the visual cortex was strikingly similar, the blind exhibited profound differences in functional connectivity to other (non-visual) brain regions as compared to the sighted, which were specific to portions of V1. Central V1 was more connected to language areas but peripheral V1 to spatial attention and control networks. These findings suggest that current accounts of critical periods and experience-dependent development should be revisited even for primary sensory areas, in that the connectivity basis for visual cortex large-scale topographical organization can develop without any visual experience and be retained through life-long experience-dependent plasticity. Furthermore, retinotopic divisions of labour, such as that between the visual cortex regions normally representing the fovea and periphery, also form the basis for topographically-unique plastic changes in the blind. PMID:25869851

Dopamine D1 Receptors in the Anterior Cingulate Cortex Regulate Effort-Based Decision Making

ERIC Educational Resources Information Center

Schweimer, Judith; Hauber, Wolfgang

2006-01-01

The anterior cingulate cortex (ACC) has been implicated in encoding whether or not an action is worth performing in view of the expected benefit and the cost of performing the action. Dopamine input to the ACC may be critical for this form of effort-based decision making; however, the role of distinct ACC dopamine receptors is yet unknown.…

Sympathetic sprouting in visual cortex stimulated by cholinergic denervation rescues expression of two forms of long-term depression at layer 2/3 synapses.

PubMed

McCoy, P A; McMahon, L L

2010-07-14

Cholinergic innervation of hippocampus and cortex is required for some forms of learning and memory. Several reports have shown that activation of muscarinic m1 receptors induces a long-term depression (mLTD) at glutamate synapses in hippocampus and in several areas of cortex, including perirhinal and visual cortices. This plasticity likely contributes to cognitive function dependent upon the cholinergic system. In rodent models, degeneration of hippocampal cholinergic innervation following lesion of the medial septum stimulates sprouting of adrenergic sympathetic axons, originating from the superior cervical ganglia (SCG), into denervated hippocampal subfields. We previously reported that this adrenergic sympathetic sprouting occurs simultaneously with a reappearance of cholinergic fibers in hippocampus and rescue of mLTD at CA3-CA1 synapses. Because cholinergic neurons throughout basal forebrain degenerate in aging and Alzheimer's disease, it is critical to determine if this compensatory sprouting occurs in other regions impacted by cholinergic cell loss. To this end, we investigated whether lesion of the nucleus basalis magnocellularis (NbM) to cholinergically denervate cortex stimulates adrenergic sympathetic sprouting and the accompanying increase in cholinergic innervation. Further, we assessed whether the presence of sprouting positively correlates with the ability of glutamate synapses in acute visual cortex slices to express mLTD and low frequency stimulation induced LTD (LFS LTD), another cholinergic dependent form of plasticity in visual cortex. We found that both mLTD and LFS LTD are absent in animals when NbM lesion is combined with bilateral removal of the SCG to prevent possible compensatory sprouting. In contrast, when the SCG remain intact to permit sprouting in animals with NbM lesion, cholinergic fiber density is increased concurrently with adrenergic sympathetic sprouting, and mLTD and LFS LTD are preserved. Our findings suggest that autonomic compensation for central cholinergic degeneration is not specific to hippocampus, but is a general repair mechanism occurring in other brain regions important for normal cognitive function. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

An Evolutionary Perspective on Learning Disability in Mathematics

PubMed Central

Geary, David C.

2015-01-01

A distinction between potentially evolved, or biologically-primary forms of cognition, and the culturally-specific, or biologically-secondary forms of cognition that are built from primary systems is used to explore mathematical learning disability (MLD). Using this model, MLD could result from deficits in the brain and cognitive systems that support biologically-primary mathematical competencies, or from the brain and cognitive systems that support the modification of primary systems for the creation of secondary knowledge and secondary cognitive competencies. The former include visuospatial long-term and working memory and the intraparietal sulcus, whereas the latter include the central executive component of working memory and the anterior cingulate cortex and lateral prefrontal cortex. Different forms of MLD are discussed as related to each of the cognitive and brain systems. PMID:17650991

Visual priming within and across symbolic format using a tachistoscopic picture identification task: a PET study.

PubMed

Lebreton, K; Desgranges, B; Landeau, B; Baron, J C; Eustache, F

2001-07-01

The present work was aimed at characterizing picture priming effects from two complementary behavioral and functional neuroimaging (positron emission tomography, PET) studies. In two experiments, we used the same line drawings of common living/nonliving objects in a tachistoscopic identification task to contrast two forms of priming. In the within-format priming condition (picture-picture), subjects were instructed to perform a perceptual encoding task in the study phase, whereas in the cross-format priming condition (word-picture), they were instructed to perform a semantic encoding task. In Experiment 1, we showed significant priming effects in both priming conditions. However, the magnitude of priming effects in the same-format/perceptual encoding condition was higher than that in the different-format/semantic encoding condition, while the recognition performance did not differ between the two conditions. This finding supports the existence of two forms of priming that may be subserved by different systems. Consistent with these behavioral findings, the PET data for Experiment 2 revealed distinct priming-related patterns of regional cerebral blood flow (rCBF) decreases for the two priming conditions when primed items were compared to unprimed items. The same-format priming condition involved reductions in cerebral activity particularly in the right extrastriate cortex and left cerebellum, while the different-format priming condition was associated with rCBF decreases in the left inferior temporo-occipital cortex, left frontal regions, and the right cerebellum. These results suggest that the extrastriate cortex may subserve general aspects of perceptual priming, independent of the kind of stimuli, and that the right part of this cortex could underlie the same-format-specific system for pictures. These data also support the idea that the cross-format/semantic encoding priming for pictures represents a form of lexico-semantic priming subserved by a semantic neural network extending from left temporo-occipital cortex to left frontal regions. These results reinforce the distinction between perceptual and conceptual priming for pictures, indicating that different cerebral processes and systems are implicated in these two forms of picture priming.

Lateral prefrontal cortex is organized into parallel dorsal and ventral streams along the rostro-caudal axis.

PubMed

Blumenfeld, Robert S; Nomura, Emi M; Gratton, Caterina; D'Esposito, Mark

2013-10-01

Anatomical connectivity differences between the dorsal and ventral lateral prefrontal cortex (PFC) of the non-human primate strongly suggests that these regions support different functions. However, after years of study, it remains unclear whether these regions are functionally distinct. In contrast, there has been a groundswell of recent studies providing evidence for a rostro-caudal functional organization, along the lateral as well as dorsomedial frontal cortex. Thus, it is not known whether dorsal and ventral regions of lateral PFC form distinct functional networks and how to reconcile any dorso-ventral organization with the medio-lateral and rostro-caudal axes. Here, we used resting-state connectivity data to identify parallel dorsolateral and ventrolateral streams of intrinsic connectivity with the dorsomedial frontal cortex. Moreover, we show that this connectivity follows a rostro-caudal gradient. Our results provide evidence for a novel framework for the intrinsic organization of the frontal cortex that incorporates connections between medio-lateral, dorso-ventral, and rostro-caudal axes.

[Studies on HPLC chromatogram of phenolic constituents of Cortex Magnoliae Officinalis].

PubMed

Huang, Wen-hua; Guo, Bao-lin; Si, Jin-ping

2005-07-01

To study the chemical characteristic, to identify the different forms and to establish the new standard for the quality control of Cortex Magnoliae Officinalis. HPLC method was used with acetonitrile-water (63:37) as the mobile phase at room temperature. The chromatographic column was Lichrospher 100 RP-18e (4.6 mm x 250 mm, 5 microm). The flow rate was 1 mL x min(-1), and the detection wavelength was 294 nm. The chromatograms of 45 individuals from 13 seed resources of Cortex Magnolia Officinalis were recorded. The chemical characteristics analysis and comparability' s calculation of seed resources were made. It was proposed that the area ratio of peak 5 to 6 (characteristic I) and the area ratio of peak 5 and 6 to the total peak areas (characteristic II) are the identification characteristics for different seed resources of Cortex Magnoliae Officinalis. This method can be used effectively to identify the high quality seed resource of Cortex Magnoliae Officinalis.

Void and pore formation inside the hair cortex by a denaturation and super-contraction process occurring during hair setting with hot irons.

PubMed

Gamez-Garcia, Manuel

2011-01-01

An analysis of hair fibers from donors that frequently use hot irons for hair straightening showed the presence of multiple pores and voids (φ approximately 0.1-1.5 μm) that extend from the cuticle sheath to regions inside the hair cortex. Pore formation in the cortex was found to be confined at its periphery and could be reproduced in the laboratory with virgin hair fibers after the application of various hot-iron straightening cycles. The appearance of pores and voids in the cortex was found to be associated to the production of hot water vapor while the fiber is undergoing mechanical elongation or contraction. The number of pores was seen to rapidly increase with temperature in the range from 190 to 220°C and also with the number of straightening cycles. Larger hair voids (φ approximately 2-5 μm) were also detected in the cortex. The small pores found at the cortex periphery appear to occur by the simultaneous occurrence of rearrangement of hair proteins, fiber mechanical contraction/expansion, and the flow of super-heated steam. Hot irons create, thus, the conditions for the onset of pore formation as the high temperatures produce superheated steam and soften the native state of hair proteins by a process involving denaturation and changes in the crystalline regions.

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

Reward value-based gain control: divisive normalization in parietal cortex.

PubMed

Louie, Kenway; Grattan, Lauren E; Glimcher, Paul W

2011-07-20

The representation of value is a critical component of decision making. Rational choice theory assumes that options are assigned absolute values, independent of the value or existence of other alternatives. However, context-dependent choice behavior in both animals and humans violates this assumption, suggesting that biological decision processes rely on comparative evaluation. Here we show that neurons in the monkey lateral intraparietal cortex encode a relative form of saccadic value, explicitly dependent on the values of the other available alternatives. Analogous to extra-classical receptive field effects in visual cortex, this relative representation incorporates target values outside the response field and is observed in both stimulus-driven activity and baseline firing rates. This context-dependent modulation is precisely described by divisive normalization, indicating that this standard form of sensory gain control may be a general mechanism of cortical computation. Such normalization in decision circuits effectively implements an adaptive gain control for value coding and provides a possible mechanistic basis for behavioral context-dependent violations of rationality.

Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

NASA Astrophysics Data System (ADS)

Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

2009-04-01

Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

Reduced Global Functional Connectivity of the Medial Prefrontal Cortex in Major Depressive Disorder

PubMed Central

Murrough, James W.; Abdallah, Chadi G.; Anticevic, Alan; Collins, Katherine A.; Geha, Paul; Averill, Lynnette A.; Schwartz, Jaclyn; DeWilde, Kaitlin E.; Averill, Christopher; Yang, Genevieve Jia-wei; Wong, Edmund; Tang, Cheuk Y.; Krystal, John H.; Iosifescu, Dan V.; Charney, Dennis S.

2016-01-01

Background Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity. Methods A total of 82 subjects, including medication-free patients with major depression (n=57) and healthy volunteers (n=25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel’s time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation. Results Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges’ g = −1.48, p<0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = −0.47, p=0.0005). Conclusions Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. PMID:27144347

Interplay of hippocampus and prefrontal cortex in memory

PubMed Central

Preston, Alison R.; Eichenbaum, Howard

2013-01-01

Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

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

PubMed Central

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis. PMID:26097452

Developmental remodeling of corticocortical feedback circuits in ferret visual cortex

PubMed Central

Khalil, Reem; Levitt, Jonathan B.

2014-01-01

Visual cortical areas in the mammalian brain are linked through a system of interareal feedforward and feedback connections, which presumably underlie different visual functions. We characterized the refinement of feedback projections to primary visual cortex (V1) from multiple sources in juvenile ferrets ranging in age from four to ten weeks postnatal. We studied whether the refinement of different aspects of feedback circuitry from multiple visual cortical areas proceeds at a similar rate in all areas. We injected the neuronal tracer cholera toxin B (CTb) into V1, and mapped the areal and laminar distribution of retrogradely labeled cells in extrastriate cortex. Around the time of eye opening at four weeks postnatal, the retinotopic arrangement of feedback appears essentially adultlike; however, Suprasylvian cortex supplies the greatest proportion of feedback, whereas area 18 supplies the greatest proportion in the adult. The density of feedback cells and the ratio of supragranular/infragranular feedback contribution declined in this period at a similar rate in all cortical areas. We also find significant feedback to V1 from layer IV of all extrastriate areas. The regularity of cell spacing, the proportion of feedback arising from layer IV, and the tangential extent of feedback in each area all remained essentially unchanged during this period, except for the infragranular feedback source in area 18 which expanded. Thus, while much of the basic pattern of cortical feedback to V1 is present before eye opening, there is major synchronous reorganization after eye opening, suggesting a crucial role for visual experience in this remodeling process. PMID:24665018

Developmental remodeling of corticocortical feedback circuits in ferret visual cortex.

PubMed

Khalil, Reem; Levitt, Jonathan B

2014-10-01

Visual cortical areas in the mammalian brain are linked through a system of interareal feedforward and feedback connections, which presumably underlie different visual functions. We characterized the refinement of feedback projections to primary visual cortex (V1) from multiple sources in juvenile ferrets ranging in age from 4-10 weeks postnatal. We studied whether the refinement of different aspects of feedback circuitry from multiple visual cortical areas proceeds at a similar rate in all areas. We injected the neuronal tracer cholera toxin B (CTb) into V1 and mapped the areal and laminar distribution of retrogradely labeled cells in extrastriate cortex. Around the time of eye opening at 4 weeks postnatal, the retinotopic arrangement of feedback appears essentially adult-like; however, suprasylvian cortex supplies the greatest proportion of feedback, whereas area 18 supplies the greatest proportion in the adult. The density of feedback cells and the ratio of supragranular/infragranular feedback contribution declined in this period at a similar rate in all cortical areas. We also found significant feedback to V1 from layer IV of all extrastriate areas. The regularity of cell spacing, the proportion of feedback arising from layer IV, and the tangential extent of feedback in each area all remained essentially unchanged during this period, except for the infragranular feedback source in area 18, which expanded. Thus, while much of the basic pattern of cortical feedback to V1 is present before eye opening, there is major synchronous reorganization after eye opening, suggesting a crucial role for visual experience in this remodeling process. © 2014 Wiley Periodicals, Inc.

Cortical travelling waves: mechanisms and computational principles

PubMed Central

Muller, Lyle; Chavane, Frédéric; Reynolds, John

2018-01-01

Multichannel recording technologies have revealed travelling waves of neural activity in multiple sensory, motor and cognitive systems. These waves can be spontaneously generated by recurrent circuits or evoked by external stimuli. They travel along brain networks at multiple scales, transiently modulating spiking and excitability as they pass. Here, we review recent experimental findings that have found evidence for travelling waves at single-area (mesoscopic) and whole-brain (macroscopic) scales. We place these findings in the context of the current theoretical understanding of wave generation and propagation in recurrent networks. During the large low-frequency rhythms of sleep or the relatively desynchronized state of the awake cortex, travelling waves may serve a variety of functions, from long-term memory consolidation to processing of dynamic visual stimuli. We explore new avenues for experimental and computational understanding of the role of spatiotemporal activity patterns in the cortex. PMID:29563572

Learning-Induced Plasticity in Medial Prefrontal Cortex Predicts Preference Malleability

PubMed Central

Garvert, Mona M.; Moutoussis, Michael; Kurth-Nelson, Zeb; Behrens, Timothy E.J.; Dolan, Raymond J.

2015-01-01

Summary Learning induces plasticity in neuronal networks. As neuronal populations contribute to multiple representations, we reasoned plasticity in one representation might influence others. We used human fMRI repetition suppression to show that plasticity induced by learning another individual’s values impacts upon a value representation for oneself in medial prefrontal cortex (mPFC), a plasticity also evident behaviorally in a preference shift. We show this plasticity is driven by a striatal “prediction error,” signaling the discrepancy between the other’s choice and a subject’s own preferences. Thus, our data highlight that mPFC encodes agent-independent representations of subjective value, such that prediction errors simultaneously update multiple agents’ value representations. As the resulting change in representational similarity predicts interindividual differences in the malleability of subjective preferences, our findings shed mechanistic light on complex human processes such as the powerful influence of social interaction on beliefs and preferences. PMID:25611512

Mapping Resting-State Brain Networks in Conscious Animals

PubMed Central

Zhang, Nanyin; Rane, Pallavi; Huang, Wei; Liang, Zhifeng; Kennedy, David; Frazier, Jean A.; King, Jean

2010-01-01

In the present study we mapped brain functional connectivity in the conscious rat at the “resting state” based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models. PMID:20382183

Prestimulus Network Integration of Auditory Cortex Predisposes Near-Threshold Perception Independently of Local Excitability

PubMed Central

Leske, Sabine; Ruhnau, Philipp; Frey, Julia; Lithari, Chrysa; Müller, Nadia; Hartmann, Thomas; Weisz, Nathan

2015-01-01

An ever-increasing number of studies are pointing to the importance of network properties of the brain for understanding behavior such as conscious perception. However, with regards to the influence of prestimulus brain states on perception, this network perspective has rarely been taken. Our recent framework predicts that brain regions crucial for a conscious percept are coupled prior to stimulus arrival, forming pre-established pathways of information flow and influencing perceptual awareness. Using magnetoencephalography (MEG) and graph theoretical measures, we investigated auditory conscious perception in a near-threshold (NT) task and found strong support for this framework. Relevant auditory regions showed an increased prestimulus interhemispheric connectivity. The left auditory cortex was characterized by a hub-like behavior and an enhanced integration into the brain functional network prior to perceptual awareness. Right auditory regions were decoupled from non-auditory regions, presumably forming an integrated information processing unit with the left auditory cortex. In addition, we show for the first time for the auditory modality that local excitability, measured by decreased alpha power in the auditory cortex, increases prior to conscious percepts. Importantly, we were able to show that connectivity states seem to be largely independent from local excitability states in the context of a NT paradigm. PMID:26408799

Progression of regional grey matter atrophy in multiple sclerosis

PubMed Central

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis. PMID:29741648

Progression of regional grey matter atrophy in multiple sclerosis.

PubMed

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

Ventral aspect of the visual form pathway is not critical for the perception of biological motion

PubMed Central

Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

2015-01-01

Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults

PubMed Central

Hayes, Scott M.; Hayes, Jasmeet P.; Williams, Victoria J.; Liu, Huiting; Verfaellie, Mieke

2017-01-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO2) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. PMID:28161031

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults.

PubMed

Hayes, Scott M; Hayes, Jasmeet P; Williams, Victoria J; Liu, Huiting; Verfaellie, Mieke

2017-06-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO 2 ) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO 2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO 2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. Published by Elsevier Ltd.

Interpretation of the function of the striate cortex

NASA Astrophysics Data System (ADS)

Garner, Bernardette M.; Paplinski, Andrew P.

2000-04-01

Biological neural networks do not require retraining every time objects move in the visual field. Conventional computer neural networks do not share this shift-invariance. The brain compensates for movements in the head, body, eyes and objects by allowing the sensory data to be tracked across the visual field. The neurons in the striate cortex respond to objects moving across the field of vision as is seen in many experiments. It is proposed, that the neurons in the striate cortex allow continuous angle changes needed to compensate for changes in orientation of the head, eyes and the motion of objects in the field of vision. It is hypothesized that the neurons in the striate cortex form a system that allows for the translation, some rotation and scaling of objects and provides a continuity of objects as they move relative to other objects. The neurons in the striate cortex respond to features which are fundamental to sight, such as orientation of lines, direction of motion, color and contrast. The neurons that respond to these features are arranged on the cortex in a way that depends on the features they are responding to and on the area of the retina from which they receive their inputs.

Heterosynaptic modulation of evoked synaptic potentials in layer II of the entorhinal cortex by activation of the parasubiculum

PubMed Central

Sparks, Daniel W.

2016-01-01

The superficial layers of the entorhinal cortex receive sensory and associational cortical inputs and provide the hippocampus with the majority of its cortical sensory input. The parasubiculum, which receives input from multiple hippocampal subfields, sends its single major output projection to layer II of the entorhinal cortex, suggesting that it may modulate processing of synaptic inputs to the entorhinal cortex. Indeed, stimulation of the parasubiculum can enhance entorhinal responses to synaptic input from the piriform cortex in vivo. Theta EEG activity contributes to spatial and mnemonic processes in this region, and the current study assessed how stimulation of the parasubiculum with either single pulses or short, five-pulse, theta-frequency trains may modulate synaptic responses in layer II entorhinal stellate neurons evoked by stimulation of layer I afferents in vitro. Parasubicular stimulation pulses or trains suppressed responses to layer I stimulation at intervals of 5 ms, and parasubicular stimulation trains facilitated layer I responses at a train-pulse interval of 25 ms. This suggests that firing of parasubicular neurons during theta activity may heterosynaptically enhance incoming sensory inputs to the entorhinal cortex. Bath application of the hyperpolarization-activated cation current (Ih) blocker ZD7288 enhanced the facilitation effect, suggesting that cholinergic inhibition of Ih may contribute. In addition, repetitive pairing of parasubicular trains and layer I stimulation induced a lasting depression of entorhinal responses to layer I stimulation. These findings provide evidence that theta activity in the parasubiculum may promote heterosynaptic modulation effects that may alter sensory processing in the entorhinal cortex. PMID:27146979

Cultural differences in human brain activity: a quantitative meta-analysis.

PubMed

Han, Shihui; Ma, Yina

2014-10-01

Psychologists have been trying to understand differences in cognition and behavior between East Asian and Western cultures within a single cognitive framework such as holistic versus analytic or interdependent versus independent processes. However, it remains unclear whether cultural differences in multiple psychological processes correspond to the same or different neural networks. We conducted a quantitative meta-analysis of 35 functional MRI studies to examine cultural differences in brain activity engaged in social and non-social processes. We showed that social cognitive processes are characterized by stronger activity in the dorsal medial prefrontal cortex, lateral frontal cortex and temporoparietal junction in East Asians but stronger activity in the anterior cingulate, ventral medial prefrontal cortex and bilateral insula in Westerners. Social affective processes are associated with stronger activity in the right dorsal lateral frontal cortex in East Asians but greater activity in the left insula and right temporal pole in Westerners. Non-social processes induce stronger activity in the left inferior parietal cortex, left middle occipital and left superior parietal cortex in East Asians but greater activations in the right lingual gyrus, right inferior parietal cortex and precuneus in Westerners. The results suggest that cultural differences in social and non-social processes are mediated by distinct neural networks. Moreover, East Asian cultures are associated with increased neural activity in the brain regions related to inference of others' mind and emotion regulation whereas Western cultures are associated with enhanced neural activity in the brain areas related to self-relevance encoding and emotional responses during social cognitive/affective processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Perirhinal Cortex Lesions in Rats: Novelty Detection and Sensitivity to Interference

PubMed Central

2015-01-01

Rats with perirhinal cortex lesions received multiple object recognition trials within a continuous session to examine whether they show false memories. Experiment 1 focused on exploration patterns during the first object recognition test postsurgery, in which each trial contained 1 novel and 1 familiar object. The perirhinal cortex lesions reduced time spent exploring novel objects, but did not affect overall time spent exploring the test objects (novel plus familiar). Replications with subsequent cohorts of rats (Experiments 2, 3, 4.1) repeated this pattern of results. When all recognition memory data were combined (Experiments 1–4), giving totals of 44 perirhinal lesion rats and 40 surgical sham controls, the perirhinal cortex lesions caused a marginal reduction in total exploration time. That decrease in time with novel objects was often compensated by increased exploration of familiar objects. Experiment 4 also assessed the impact of proactive interference on recognition memory. Evidence emerged that prior object experience could additionally impair recognition performance in rats with perirhinal cortex lesions. Experiment 5 examined exploration levels when rats were just given pairs of novel objects to explore. Despite their perirhinal cortex lesions, exploration levels were comparable with those of control rats. While the results of Experiment 4 support the notion that perirhinal lesions can increase sensitivity to proactive interference, the overall findings question whether rats lacking a perirhinal cortex typically behave as if novel objects are familiar, that is, show false recognition. Rather, the rats retain a signal of novelty but struggle to discriminate the identity of that signal. PMID:26030425

Brain morphology of childhood aggressive behavior: A multi-informant study in school-age children.

PubMed

Thijssen, Sandra; Ringoot, Ank P; Wildeboer, Andrea; Bakermans-Kranenburg, Marian J; El Marroun, Hanan; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; van IJzendoorn, Marinus H; White, Tonya

2015-09-01

Few studies have focused on the neuroanatomy of aggressive behavior in children younger than 10 years. Here, we explored the neuroanatomical correlates of aggression in a population-based sample of 6- to 9-year-old children using a multiple-informant approach. Magnetic resonance (MR) scans were acquired from 566 children from the Generation R study who participated in the Berkeley Puppet Interview and whose parents had completed the Child Behavior Checklist. Linear regression analyses were used to examine associations between aggression and amygdala and hippocampal volume. We performed surface-based analyses to study the association between aggression and cortical thickness, surface area, and gyrification. Aggressive behavior was associated with smaller amygdala (p < .05) but not hippocampal volume. Aggression was associated with a thinner cortex in the left precentral cortex (p < .01) and in a cluster including the right inferior parietal, supramarginal, and postcentral cortex (p < .001). Gender moderated the association between aggression and cortical thickness in the right medial posterior cortex (p = .001) and the right prefrontal cortex (p < .001). Aggression was associated with decreased gyrification in a large cluster including the right precentral, postcentral, frontal, and parietal cortex (p = .01). Moreover, aggression was associated with decreased gyrification in the right occipital and parietal cortex (p = .02). We found novel evidence that childhood aggressive behavior is related to decreased amygdala volume, decreased sensorimotor cortical thickness, and decreased global right hemisphere gyrification. Aggression is related to cortical thickness in regions associated with the default mode network, with negative associations in boys and positive associations in girls.

Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry

PubMed Central

2015-01-01

Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex. PMID:26719085

Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity

PubMed Central

Richner, Thomas J.; Thongpang, Sanitta; Brodnick, Sarah K.; Schendel, Amelia A.; Falk, Ryan W.; Krugner-Higby, Lisa A.; Pashaie, Ramin; Williams, Justin C.

2014-01-01

Objective Spatial localization of neural activity from within the brain with electrocorticography (ECoG) and electroencephalography (EEG) remains a challenge in clinical and research settings, and while microfabricated ECoG (micro-ECoG) array technology continues to improve, complimentary methods to simultaneously modulate cortical activity while recording are needed. Approach We developed a neural interface utilizing optogenetics, cranial windowing, and micro-ECoG arrays fabricated on a transparent polymer. This approach enabled us to directly modulate neural activity at known locations around micro-ECoG arrays in mice expressing Channelrhodopsin-2 (ChR2). We applied photostimuli varying in time, space and frequency to the cortical surface, and we targeted multiple depths within the cortex using an optical fiber while recording micro-ECoG signals. Main Results Negative potentials of up to 1.5 mV were evoked by photostimuli applied to the entire cortical window, while focally applied photostimuli evoked spatially localized micro-ECoG potentials. Two simultaneously applied focal stimuli could be separated, depending on the distance between them. Photostimuli applied within the cortex with an optical fiber evoked more complex micro-ECoG potentials with multiple positive and negative peaks whose relative amplitudes depended on the depth of the fiber. Significance Optogenetic ECoG has potential applications in the study of epilepsy, cortical dynamics, and neuroprostheses. PMID:24445482

A specific area of olfactory cortex involved in stress hormone responses to predator odours.

PubMed

Kondoh, Kunio; Lu, Zhonghua; Ye, Xiaolan; Olson, David P; Lowell, Bradford B; Buck, Linda B

2016-04-07

Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising <5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.

All for one but not one for all: how multiple number representations are recruited in one numerical task.

PubMed

Wood, Guilherme; Nuerk, Hans-Christoph; Moeller, Korbinian; Geppert, Barbara; Schnitker, Ralph; Weber, Jochen; Willmes, Klaus

2008-01-02

Number processing recruits a complex network of multiple numerical representations. Usually the components of this network are examined in a between-task approach with the disadvantage of relying upon different instructions, tasks, and inhomogeneous stimulus sets across different studies. A within-task approach may avoid these disadvantages and access involved numerical representations more specifically. In the present study we employed a within-task approach to investigate numerical representations activated in the number bisection task (NBT) using parametric rapid event-related fMRI. Participants were to judge whether the central number of a triplet was also its arithmetic mean (e.g. 23_26_29) or not (e.g. 23_25_29). Activation in the left inferior parietal cortex was associated with the deployment of arithmetic fact knowledge, while activation of the intraparietal cortex indicated more intense magnitude processing, instrumental aspects of calculation and integration of the base-10 structure of two-digit numbers. These results replicate evidence from the literature. Furthermore, activation in the dorsolateral and ventrolateral prefrontal cortex revealed mechanisms of feature monitoring and inhibition as well as allocation of cognitive resources recruited to solve a specific triplet. We conclude that the network of numerical representations should rather be studied in a within-task approach than in varying between-task approaches.

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

PubMed

Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

2008-02-01

To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I =

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

PubMed

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug's side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing.

PubMed

Wagner, Dylan D; Kelley, William M; Haxby, James V; Heatherton, Todd F

2016-06-29

Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven "reverse correlation" approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics. Copyright © 2016 the authors 0270-6474/16/366917-09$15.00/0.

The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing

PubMed Central

Kelley, William M.; Haxby, James V.; Heatherton, Todd F.

2016-01-01

Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven “reverse correlation” approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. SIGNIFICANCE STATEMENT Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics. PMID:27358450

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making

PubMed Central

Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.

2008-01-01

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more ‘bankruptcies’. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage. PMID:18390562

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.

PubMed

Clark, L; Bechara, A; Damasio, H; Aitken, M R F; Sahakian, B J; Robbins, T W

2008-05-01

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.

Somatic sensory cortex (SmI) of the prosimian primate Galago crassicaudatus: organization of mechanoreceptive input from the hand in relation to cytoarchitecture.

PubMed

Carlson, M; Welt, C

1980-01-15

Mechanoreceptive input from the hand to the somatic sensory cortex (SmI) of the prosimian primate Galago crassicaudatus was examined with microelectrode mapping methods. In anesthetized animals, low threshold cutaneous input from the hand projects to SmI cortex in a single, complete, somatotopically organized pattern. Within this single pattern, cells with receptive fields on the glabrous skin of the palm, digits and digit tips are located in the rostral half, and cells with RFs on the hairy skin of the dorsal hand and digits are located in the caudal half of the hand areas. The cutaneous hand area is coextensive with the densely granular architectonic region of SmI. Studies of single cells in this region of awake galagos reveal the same pattern of cutaneous input and, in addition, demonstrate the presence of cells responding to joint movement not detected in anesthetized animals. Cells responsive to joint movement are arranged in vertically oriented columns located adjacent to cutaneous columns with receptive fields on the same part of the hand. In anesthetized animals, cells rostral to the granular region, in an area typified by increasing numbers of pyramidal cells in layer V and decreasing numbers of granular cells in upper layers, respond to high threshold stimulation of large areas of the hand. The few cells isolated in this area in awake animals respond to either active or passive hand movements. In such animals, cells caudal to the granular region, in an area characterized as agranular and alaminar cortex, respond to either passive stimulation of single or multiple joints or to active hand movements. These results, together with similar findings in a related prosimian, Nycticebus coucang, emphasize the generality of a single cutaneous hand area in SmI of prosimian species. The demonstration of multiple hand areas corresponding to multiple cytoarchitectonic subdivisions in SmI of Old and New World simians illustrates the increased degree of SmI differentiation from the prosimian to the simian grade of organization. The present results further suggest that determination of the homologues of multiple areas or subdivisions within and surrounding SmI in primates will require comparisons of somatotopy, submodality, sulcal patterns, cytoarchitecture, and connectivity in representative members of prosimian and simian families.

Age-Related Differences in Memory and Executive Functions in Healthy "APOE"[epsilon]4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

ERIC Educational Resources Information Center

Bender, Andrew R.; Raz, Naftali

2012-01-01

Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of…

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain

PubMed Central

Haider, Lukas; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang

2016-01-01

Abstract Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. PMID:26912645

Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization.

PubMed

Beckmann, Matthias; Johansen-Berg, Heidi; Rushworth, Matthew F S

2009-01-28

Whole-brain neuroimaging studies have demonstrated regional variations in function within human cingulate cortex. At the same time, regional variations in cingulate anatomical connections have been found in animal models. It has, however, been difficult to estimate the relationship between connectivity and function throughout the whole cingulate cortex within the human brain. In this study, magnetic resonance diffusion tractography was used to investigate cingulate probabilistic connectivity in the human brain with two approaches. First, an algorithm was used to search for regional variations in the probabilistic connectivity profiles of all cingulate cortex voxels with the whole of the rest of the brain. Nine subregions with distinctive connectivity profiles were identified. It was possible to characterize several distinct areas in the dorsal cingulate sulcal region. Several distinct regions were also found in subgenual and perigenual cortex. Second, the probabilities of connection between cingulate cortex and 11 predefined target regions of interest were calculated. Cingulate voxels with a high probability of connection with the different targets formed separate clusters within cingulate cortex. Distinct connectivity fingerprints characterized the likelihood of connections between the extracingulate target regions and the nine cingulate subregions. Last, a meta-analysis of 171 functional studies reporting cingulate activation was performed. Seven different cognitive conditions were selected and peak activation coordinates were plotted to create maps of functional localization within the cingulate cortex. Regional functional specialization was found to be related to regional differences in probabilistic anatomical connectivity.

Complex neural codes in rat prelimbic cortex are stable across days on a spatial decision task

PubMed Central

Powell, Nathaniel J.; Redish, A. David

2014-01-01

The rodent prelimbic cortex has been shown to play an important role in cognitive processing, and has been implicated in encoding many different parameters relevant to solving decision-making tasks. However, it is not known how the prelimbic cortex represents all these disparate variables, and if they are simultaneously represented when the task requires it. In order to investigate this question, we trained rats to run the Multiple-T Left Right Alternate (MT-LRA) task and recorded multi-unit ensembles from their prelimbic regions. Significant populations of cells in the prelimbic cortex represented the strategy controlling reward receipt on a given lap, whether the animal chose to go right or left on a given lap, and whether the animal made a correct decision or an error on a given lap. These populations overlapped in the cells recorded, with several cells demonstrating differential firing to all three variables. The spatial and strategic firing patterns of individual prelimbic cells were highly conserved across several days of running this task, indicating that each cell encoded the same information across days. PMID:24795579

Integrating Information from Different Senses in the Auditory Cortex

PubMed Central

King, Andrew J.; Walker, Kerry M.M.

2015-01-01

Multisensory integration was once thought to be the domain of brain areas high in the cortical hierarchy, with early sensory cortical fields devoted to unisensory processing of inputs from their given set of sensory receptors. More recently, a wealth of evidence documenting visual and somatosensory responses in auditory cortex, even as early as the primary fields, has changed this view of cortical processing. These multisensory inputs may serve to enhance responses to sounds that are accompanied by other sensory cues, effectively making them easier to hear, but may also act more selectively to shape the receptive field properties of auditory cortical neurons to the location or identity of these events. We discuss the new, converging evidence that multiplexing of neural signals may play a key role in informatively encoding and integrating signals in auditory cortex across multiple sensory modalities. We highlight some of the many open research questions that exist about the neural mechanisms that give rise to multisensory integration in auditory cortex, which should be addressed in future experimental and theoretical studies. PMID:22798035

Elevated expression of pleiotrophin in pilocarpine-induced seizures of immature rats and in pentylenetetrazole-induced hippocampal astrocytes in vitro.

PubMed

Zhang, Shuqin; Liang, Feng; Wang, Bing; Le, Yuan; Wang, Hua

2014-03-01

Pleiotrophin (PTN) is a secreted extracellular matrix (ECM)-associated cytokine that has emerged as an important neuromodulator with multiple neuronal functions. In the present study, we detected and compared the dynamic expression of PTN in the hippocampus and adjacent cortex of immature rats with pilocarpine-induced epilepsy. Moreover, we also confirmed the results by examining PTN expression in hippocampal astrocytes cultured in the presence of pentylenetetrazole (PTZ). Immunohistochemistry showed faint immunostaining of PTN in the control hippocampus and adjacent cortex. Notably, PTN immunoreactivity began to increase in relatively small cells in the hippocampus and adjacent cortex at 2h and 3 weeks after seizures, and the labeling intensity reached the maximum level in the hippocampus and adjacent cortex at 8 weeks after seizures. Furthermore, we also found that PTZ treatment significantly reduced astrocytic viability in a dose-dependent manner and time-dependently increased expression levels of PTN in hippocampal astrocytes. In conclusion, our data suggest that increased expression of PTN in the brain tissues may be involved in epileptogenesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Basic level category structure emerges gradually across human ventral visual cortex.

PubMed

Iordan, Marius Cătălin; Greene, Michelle R; Beck, Diane M; Fei-Fei, Li

2015-07-01

Objects can be simultaneously categorized at multiple levels of specificity ranging from very broad ("natural object") to very distinct ("Mr. Woof"), with a mid-level of generality (basic level: "dog") often providing the most cognitively useful distinction between categories. It is unknown, however, how this hierarchical representation is achieved in the brain. Using multivoxel pattern analyses, we examined how well each taxonomic level (superordinate, basic, and subordinate) of real-world object categories is represented across occipitotemporal cortex. We found that, although in early visual cortex objects are best represented at the subordinate level (an effect mostly driven by low-level feature overlap between objects in the same category), this advantage diminishes compared to the basic level as we move up the visual hierarchy, disappearing in object-selective regions of occipitotemporal cortex. This pattern stems from a combined increase in within-category similarity (category cohesion) and between-category dissimilarity (category distinctiveness) of neural activity patterns at the basic level, relative to both subordinate and superordinate levels, suggesting that successive visual areas may be optimizing basic level representations.

Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway.

PubMed

Ruggiero, Rafael N; Rossignoli, Matheus T; Lopes-Aguiar, Cleiton; Leite, João P; Bueno-Junior, Lezio S; Romcy-Pereira, Rodrigo N

2018-06-01

Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1. Either of two forms of synaptic plasticity, long-term potentiation (LTP) or depression (LTD), were induced during pilocarpine effects, which were monitored in real time through local field potentials. We found that lithium attenuates the muscarinic potentiation of cortical LTP (<20 min) but enhances the muscarinic potentiation of LTD maintenance (>80 min). Moreover, lithium treatment promoted significant cross-frequency coupling between CA1 theta (3-5 Hz) and mPFC low-gamma (30-55 Hz) oscillations. Interestingly, lithium by itself did not affect any of these measures. Thus, lithium pretreatment and muscarinic activation synergistically modulate the hippocampal-prefrontal connectivity. Because these alterations varied with time, oscillatory parameters, and type of synaptic plasticity, our study suggests that lithium influences prefrontal-related circuits through intricate dynamics, informing future experiments on mood disorders. Copyright © 2018. Published by Elsevier Inc.

Short term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior

PubMed Central

Ramanathan, Lalini; Hu, Shuxin; Frautschy, Sally A.; Siegel, Jerome M.

2009-01-01

Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5–11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short term (6 h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory. PMID:19850085

Cortical mechanisms for the segregation and representation of acoustic textures.

PubMed

Overath, Tobias; Kumar, Sukhbinder; Stewart, Lauren; von Kriegstein, Katharina; Cusack, Rhodri; Rees, Adrian; Griffiths, Timothy D

2010-02-10

Auditory object analysis requires two fundamental perceptual processes: the definition of the boundaries between objects, and the abstraction and maintenance of an object's characteristic features. Although it is intuitive to assume that the detection of the discontinuities at an object's boundaries precedes the subsequent precise representation of the object, the specific underlying cortical mechanisms for segregating and representing auditory objects within the auditory scene are unknown. We investigated the cortical bases of these two processes for one type of auditory object, an "acoustic texture," composed of multiple frequency-modulated ramps. In these stimuli, we independently manipulated the statistical rules governing (1) the frequency-time space within individual textures (comprising ramps with a given spectrotemporal coherence) and (2) the boundaries between textures (adjacent textures with different spectrotemporal coherences). Using functional magnetic resonance imaging, we show mechanisms defining boundaries between textures with different coherences in primary and association auditory cortices, whereas texture coherence is represented only in association cortex. Furthermore, participants' superior detection of boundaries across which texture coherence increased (as opposed to decreased) was reflected in a greater neural response in auditory association cortex at these boundaries. The results suggest a hierarchical mechanism for processing acoustic textures that is relevant to auditory object analysis: boundaries between objects are first detected as a change in statistical rules over frequency-time space, before a representation that corresponds to the characteristics of the perceived object is formed.

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

PubMed Central

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

2010-01-01

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

Effects of acute phencyclidine administration on arginine metabolism in the hippocampus and prefrontal cortex in rats.

PubMed

Knox, Logan T; Jing, Yu; Collie, Nicola D; Zhang, Hu; Liu, Ping

2014-06-01

Phencyclidine (PCP), a non-competitive N-methyl-d-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the sub-regions of the hippocampus and prefrontal cortex in male young adult Sprague-Dawley rats. Animals' general behaviour was assessed in the open field apparatus 30 min after the treatment, and the brain tissues were collected at the time point of 60 min post-treatment. Behaviourally, PCP resulted in reduced exploratory activity in a dose-dependent manner, and severe stereotype behaviour and ataxia at the highest dose. Neurochemically, PCP significantly altered the nitric oxide synthase and arginase activities, the l-arginine, agmatine, spermine, glutamate and GABA levels, and the glutamine/glutamate and glutamate/GABA ratios in a dose-dependent and/or region-specific manner. Cluster analyses showed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which changed as a function of PCP mainly in the hippocampus. Multiple regression analysis revealed significant neurochemical-behavioural correlations. These results demonstrate, for the first time, that a single acute administration of PCP affects animals' behaviour and arginine metabolism in the brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.

PubMed

Rowan, Sheldon; Chang, Min-Lee; Reznikov, Natalie; Taylor, Allen

2017-03-01

The eye lens is unique among tissues: it is transparent, does not form tumors, and the majority of its cells degrade their organelles, including their cell nuclei. A mystery for over a century, there has been considerable recent progress in elucidating mechanisms of lens fiber cell denucleation (LFCD). In contrast to the disassembly and reassembly of the cell nucleus during mitosis, LFCD is a unidirectional process that culminates in destruction of the fiber cell nucleus. Whereas p27 Kip1 , the cyclin-dependent kinase inhibitor, is upregulated during formation of LFC in the outermost cortex, in the inner cortex, in the nascent organelle free zone, p27 Kip1 is degraded, markedly activating cyclin-dependent kinase 1 (Cdk1). This process results in phosphorylation of nuclear Lamins, dissociation of the nuclear membrane, and entry of lysosomes that liberate DNaseIIβ (DLAD) to cleave chromatin. Multiple cellular pathways, including the ubiquitin proteasome system and the unfolded protein response, converge on post-translational regulation of p27 Kip1 . Mutations that impair these pathways are associated with congenital cataracts and loss of LFCD. These findings highlight new regulatory nodes in the lens and suggest that we are close to understanding this fascinating terminal differentiation process. Such knowledge may offer a new means to confront proliferative diseases including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders

NASA Astrophysics Data System (ADS)

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-01

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds’ Glx, Cho, Cr in the ACC and HCs’ mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds’ Glx and Cr in the PC and HCs’ mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders.

PubMed

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-21

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds' Glx, Cho, Cr in the ACC and HCs' mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds' Glx and Cr in the PC and HCs' mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex.

PubMed

Reillo, Isabel; de Juan Romero, Camino; García-Cabezas, Miguel Ángel; Borrell, Víctor

2011-07-01

The cerebral cortex of large mammals undergoes massive surface area expansion and folding during development. Specific mechanisms to orchestrate the growth of the cortex in surface area rather than in thickness are likely to exist, but they have not been identified. Analyzing multiple species, we have identified a specialized type of progenitor cell that is exclusive to mammals with a folded cerebral cortex, which we named intermediate radial glia cell (IRGC). IRGCs express Pax6 but not Tbr2, have a radial fiber contacting the pial surface but not the ventricular surface, and are found in both the inner subventricular zone and outer subventricular zone (OSVZ). We find that IRGCs are massively generated in the OSVZ, thus augmenting the numbers of radial fibers. Fanning out of this expanding radial fiber scaffold promotes the tangential dispersion of radially migrating neurons, allowing for the growth in surface area of the cortical sheet. Accordingly, the tangential expansion of particular cortical regions was preceded by high proliferation in the underlying OSVZ, whereas the experimental reduction of IRGCs impaired the tangential dispersion of neurons and resulted in a smaller cortical surface. Thus, the generation of IRGCs plays a key role in the tangential expansion of the mammalian cerebral cortex.

Single-unit analysis of somatosensory processing in the core auditory cortex of hearing ferrets.

PubMed

Meredith, M Alex; Allman, Brian L

2015-03-01

The recent findings in several species that the primary auditory cortex processes non-auditory information have largely overlooked the possibility of somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior auditory field and primary auditory cortex) for tactile responsivity. Multiple single-unit recordings from anesthetised ferret cortex yielded histologically verified neurons (n = 311) tested with electronically controlled auditory, visual and tactile stimuli, and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory-tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in the core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in the auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing, and indicate that crossmodal plasticity following deafness may unmask these existing non-auditory functions. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Abstract memory representations in the ventromedial prefrontal cortex and hippocampus support concept generalization.

PubMed

Bowman, Caitlin R; Zeithamova, Dagmar

2018-02-07

Memory function involves both the ability to remember details of individual experiences and the ability to link information across events to create new knowledge. Prior research has identified the ventromedial prefrontal cortex (VMPFC) and the hippocampus as important for integrating across events in service of generalization in episodic memory. The degree to which these memory integration mechanisms contribute to other forms of generalization, such as concept learning, is unclear. The present study used a concept-learning task in humans (both sexes) coupled with model-based fMRI to test whether VMPFC and hippocampus contribute to concept generalization, and whether they do so by maintaining specific category exemplars or abstract category representations. Two formal categorization models were fit to individual subject data: a prototype model that posits abstract category representations and an exemplar model that posits category representations based on individual category members. Latent variables from each of these models were entered into neuroimaging analyses to determine whether VMPFC and the hippocampus track prototype or exemplar information during concept generalization. Behavioral model fits indicated that almost three quarters of the subjects relied on prototype information when making judgments about new category members. Paralleling prototype dominance in behavior, correlates of the prototype model were identified in VMPFC and the anterior hippocampus with no significant exemplar correlates. These results indicate that the VMPFC and portions of the hippocampus play a broad role in memory generalization and that they do so by representing abstract information integrated from multiple events. SIGNIFICANCE STATEMENT Whether people represent concepts as a set of individual category members or by deriving generalized concept representations abstracted across exemplars has been debated. In episodic memory, generalized memory representations have been shown to arise through integration across events supported by the ventromedial prefrontal cortex (VMPFC) and hippocampus. The current study combined formal categorization models with fMRI data analysis to show that the VMPFC and anterior hippocampus represent abstract prototype information during concept generalization, contributing novel evidence of generalized concept representations in the brain. Results indicate that VMPFC-hippocampal memory integration mechanisms contribute to knowledge generalization across multiple cognitive domains, with the degree of abstraction of memory representations varying along the long axis of the hippocampus. Copyright © 2018 the authors.

Memory retrieval and the parietal cortex: a review of evidence from a dual-process perspective.

PubMed

Vilberg, Kaia L; Rugg, Michael D

2008-01-01

Although regions of the parietal cortex have been consistently implicated in episodic memory retrieval, the functional roles of these regions remain poorly understood. The present review presents a meta-analysis of findings from event-related fMRI studies reporting the loci of retrieval effects associated with familiarity- and recollection-related recognition judgments. The results of this analysis support previous suggestions that retrieval-related activity in lateral parietal cortex dissociates between superior regions, where activity likely reflects the task relevance of different classes of recognition test items, and more inferior regions where retrieval-related activity appears closely linked to successful recollection. It is proposed that inferior lateral parietal cortex forms part of a neural network supporting the 'episodic buffer' [Baddeley, A. D. (2000). The episodic buffer: A new component of working memory? Trends in Cognitive Sciences, 4, 417-423].

Auditory spatial processing in the human cortex.

PubMed

Salminen, Nelli H; Tiitinen, Hannu; May, Patrick J C

2012-12-01

The auditory system codes spatial locations in a way that deviates from the spatial representations found in other modalities. This difference is especially striking in the cortex, where neurons form topographical maps of visual and tactile space but where auditory space is represented through a population rate code. In this hemifield code, sound source location is represented in the activity of two widely tuned opponent populations, one tuned to the right and the other to the left side of auditory space. Scientists are only beginning to uncover how this coding strategy adapts to various spatial processing demands. This review presents the current understanding of auditory spatial processing in the cortex. To this end, the authors consider how various implementations of the hemifield code may exist within the auditory cortex and how these may be modulated by the stimulation and task context. As a result, a coherent set of neural strategies for auditory spatial processing emerges.

SINGLE NEURON ACTIVITY AND THETA MODULATION IN POSTRHINAL CORTEX DURING VISUAL OBJECT DISCRIMINATION

PubMed Central

Furtak, Sharon C.; Ahmed, Omar J.; Burwell, Rebecca D.

2012-01-01

Postrhinal cortex, the rodent homolog of the primate parahippocampal cortex, processes spatial and contextual information. Our hypothesis of postrhinal function is that it serves to encode context, in part, by forming representations that link objects to places. We recorded postrhinal neuronal activity and local field potentials (LFPs) in rats trained on a two-choice, visual discrimination task. As predicted, a large proportion of postrhinal neurons signaled object-location conjunctions. In addition, postrhinal LFPs exhibited strong oscillatory rhythms in the theta band, and many postrhinal neurons were phase locked to theta. Although correlated with running speed, theta power was lower than predicted by speed alone immediately before and after choice. However, theta power was significantly increased following incorrect decisions, suggesting a role in signaling error. These findings provide evidence that postrhinal cortex encodes representations that link objects to places and suggest that postrhinal theta modulation extends to cognitive as well as spatial functions. PMID:23217745

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

PubMed

Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Theory of Synaptic Plasticity in Visual Cortex

DTIC Science & Technology

1993-01-20

Science, 255:730-733. 15 Hubel, D. H. and Wiesel, T. N. (1959). Integrative action in the cat’s lateral geniculate body . J. Physiol, 148:574-591. Hubel...neuron in striate cortex receives thousands of afferents from other cells. Most of these afferents derive from the lateral geniculate nucleus (LGN) and...locally available to the junction mi but is physically connected to the junction by the cell body itself-thus necessitating some form of internal

[Macro- and microscopic systematization of cerebral cortex malformations in children].

PubMed

Milovanov, A P; Milovanova, O A

2011-01-01

For the first time in pediatric pathologicoanatomic practice the complete systematization of cerebral cortex malformations is represented. Organ, macroscopic forms: microencephaly, macroencephaly, micropolygyria, pachygyria, schizencephaly, porencephaly, lissencephaly. Histic microdysgenesis of cortex: type I includes isolated abnormalities such as radial (IA) and tangential (I B) subtypes of cortical dislamination; type II includes sublocal cortical dislamination with immature dysmorphic neurons (II A) and balloon cells (II B); type III are the combination focal cortical dysplasia with tuberous sclerosis of the hippocampus (III A), tumors (III B) and malformations of vessels, traumatic and hypoxic disorders (III C). Band heterotopias. Subependimal nodular heterotopias. Tuberous sclerosis. Cellular typification of cortical dysplasia: immature neurons and balloon cells.

Novel Experience Induces Persistent Sleep-Dependent Plasticity in the Cortex but not in the Hippocampus

PubMed Central

Ribeiro, Sidarta; Shi, Xinwu; Engelhard, Matthew; Zhou, Yi; Zhang, Hao; Gervasoni, Damien; Lin, Shi-Chieh; Wada, Kazuhiro; Lemos, Nelson A.M.

2007-01-01

Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS) and rapid eye movement (REM) sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP), and expression levels of plasticity-related immediate-early genes (IEG) arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours) than in the hippocampus (minutes). During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10–14 Hz) but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time. PMID:18982118

Responses of primate frontal cortex neurons during natural vocal communication.

PubMed

Miller, Cory T; Thomas, A Wren; Nummela, Samuel U; de la Mothe, Lisa A

2015-08-01

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. Copyright © 2015 the American Physiological Society.

Responses of primate frontal cortex neurons during natural vocal communication

PubMed Central

Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

2015-01-01

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. PMID:26084912

Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators

PubMed Central

Whittington, Miles A.; Kopell, Nancy J.

2015-01-01

The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID:26558772

Incorporation of physical constraints in optimal surface search for renal cortex segmentation

NASA Astrophysics Data System (ADS)

Li, Xiuli; Chen, Xinjian; Yao, Jianhua; Zhang, Xing; Tian, Jie

2012-02-01

In this paper, we propose a novel approach for multiple surfaces segmentation based on the incorporation of physical constraints in optimal surface searching. We apply our new approach to solve the renal cortex segmentation problem, an important but not sufficiently researched issue. In this study, in order to better restrain the intensity proximity of the renal cortex and renal column, we extend the optimal surface search approach to allow for varying sampling distance and physical separation constraints, instead of the traditional fixed sampling distance and numerical separation constraints. The sampling distance of each vertex-column is computed according to the sparsity of the local triangular mesh. Then the physical constraint learned from a priori renal cortex thickness is applied to the inter-surface arcs as the separation constraints. Appropriate varying sampling distance and separation constraints were learnt from 6 clinical CT images. After training, the proposed approach was tested on a test set of 10 images. The manual segmentation of renal cortex was used as the reference standard. Quantitative analysis of the segmented renal cortex indicates that overall segmentation accuracy was increased after introducing the varying sampling distance and physical separation constraints (the average true positive volume fraction (TPVF) and false positive volume fraction (FPVF) were 83.96% and 2.80%, respectively, by using varying sampling distance and physical separation constraints compared to 74.10% and 0.18%, respectively, by using fixed sampling distance and numerical separation constraints). The experimental results demonstrated the effectiveness of the proposed approach.

Theoretical Limitations on Functional Imaging Resolution in Auditory Cortex

PubMed Central

Chen, Thomas L.; Watkins, Paul V.; Barbour, Dennis L.

2010-01-01

Functional imaging can reveal detailed organizational structure in cerebral cortical areas, but neuronal response features and local neural interconnectivity can influence the resulting images, possibly limiting the inferences that can be drawn about neural function. Discerning the fundamental principles of organizational structure in the auditory cortex of multiple species has been somewhat challenging historically both with functional imaging and with electrophysiology. A possible limitation affecting any methodology using pooled neuronal measures may be the relative distribution of response selectivity throughout the population of auditory cortex neurons. One neuronal response type inherited from the cochlea, for example, exhibits a receptive field that increases in size (i.e., decreases in selectivity) at higher stimulus intensities. Even though these neurons appear to represent a minority of auditory cortex neurons, they are likely to contribute disproportionately to the activity detected in functional images, especially if intense sounds are used for stimulation. To evaluate the potential influence of neuronal subpopulations upon functional images of primary auditory cortex, a model array representing cortical neurons was probed with virtual imaging experiments under various assumptions about the local circuit organization. As expected, different neuronal subpopulations were activated preferentially under different stimulus conditions. In fact, stimulus protocols that can preferentially excite selective neurons, resulting in a relatively sparse activation map, have the potential to improve the effective resolution of functional auditory cortical images. These experimental results also make predictions about auditory cortex organization that can be tested with refined functional imaging experiments. PMID:20079343

Twelfth annual meeting of the International Society for the History of the Neurosciences. June 19-23, 2007.

PubMed

2008-01-01

Christian Baumann (Justus-Liebig-University, Giessen, Germany): Wilbrand's ideas of the visual cortex. Hermann Wilbrand (1851-1935) is considered one of the founders of neuro-opthalmology. He is best known for the monumental handbook, Die Neurologie des Auges (Wilbrand &Saenger, 1898-1922). Prior to this encyclopedic work, Wilbrand published three clinical monographs on the diagnosis of brain diseases with the help of ophthalmological examinations(Wilbrand 1881, 1884, 1890). But Wilbrand not only treated clinical aspects but also supplied evidence for the localization of the optical center in the calcarine fissure of the occipital cortex. Moreover, he worked out theories of the organization of the visual cortex that, as he postulated, must contain subdivisions corresponding to the qualities of visual sensation such as light, form, and color. Wilbrand also considered the binocular input of the visual cortex and put forward a detailed scheme of the projection of the two retinae to the occipital cortex that anticipated modern concepts of ocular dominance columns. His ideas are critically reviewed in the light of current opinions about his topics.

Medial prefrontal cortex subserves diverse forms of self-reflection.

PubMed

Jenkins, Adrianna C; Mitchell, Jason P

2011-01-01

The ability to think about oneself--to self--reflect--is one of the defining features of the human mind. Recent research has suggested that this ability may be subserved by a particular brain region: the medial prefrontal cortex (MPFC). However, although humans can contemplate a variety of different aspects of themselves, including their stable personality traits, current feelings, and physical attributes, no research has directly examined the extent to which these different forms of self-reflection are subserved by common mechanisms. To address this question, participants were scanned using functional magnetic resonance imaging (fMRI) while making judgments about their own personality traits, current mental states, and physical attributes as well as those of another person. Whereas some brain regions responded preferentially during only one form of self-reflection, a robust region of MPFC was engaged preferentially during self-reflection across all three types of judgment. These results suggest that--although dissociable--diverse forms of self-referential thought draw on a shared cognitive process subserved by MPFC.

Functional connectivity of visual cortex in the blind follows retinotopic organization principles.

PubMed

Striem-Amit, Ella; Ovadia-Caro, Smadar; Caramazza, Alfonso; Margulies, Daniel S; Villringer, Arno; Amedi, Amir

2015-06-01

Is visual input during critical periods of development crucial for the emergence of the fundamental topographical mapping of the visual cortex? And would this structure be retained throughout life-long blindness or would it fade as a result of plastic, use-based reorganization? We used functional connectivity magnetic resonance imaging based on intrinsic blood oxygen level-dependent fluctuations to investigate whether significant traces of topographical mapping of the visual scene in the form of retinotopic organization, could be found in congenitally blind adults. A group of 11 fully and congenitally blind subjects and 18 sighted controls were studied. The blind demonstrated an intact functional connectivity network structural organization of the three main retinotopic mapping axes: eccentricity (centre-periphery), laterality (left-right), and elevation (upper-lower) throughout the retinotopic cortex extending to high-level ventral and dorsal streams, including characteristic eccentricity biases in face- and house-selective areas. Functional connectivity-based topographic organization in the visual cortex was indistinguishable from the normally sighted retinotopic functional connectivity structure as indicated by clustering analysis, and was found even in participants who did not have a typical retinal development in utero (microphthalmics). While the internal structural organization of the visual cortex was strikingly similar, the blind exhibited profound differences in functional connectivity to other (non-visual) brain regions as compared to the sighted, which were specific to portions of V1. Central V1 was more connected to language areas but peripheral V1 to spatial attention and control networks. These findings suggest that current accounts of critical periods and experience-dependent development should be revisited even for primary sensory areas, in that the connectivity basis for visual cortex large-scale topographical organization can develop without any visual experience and be retained through life-long experience-dependent plasticity. Furthermore, retinotopic divisions of labour, such as that between the visual cortex regions normally representing the fovea and periphery, also form the basis for topographically-unique plastic changes in the blind. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Reconstructing Perceived and Retrieved Faces from Activity Patterns in Lateral Parietal Cortex.

PubMed

Lee, Hongmi; Kuhl, Brice A

2016-06-01

Recent findings suggest that the contents of memory encoding and retrieval can be decoded from the angular gyrus (ANG), a subregion of posterior lateral parietal cortex. However, typical decoding approaches provide little insight into the nature of ANG content representations. Here, we tested whether complex, multidimensional stimuli (faces) could be reconstructed from ANG by predicting underlying face components from fMRI activity patterns in humans. Using an approach inspired by computer vision methods for face recognition, we applied principal component analysis to a large set of face images to generate eigenfaces. We then modeled relationships between eigenface values and patterns of fMRI activity. Activity patterns evoked by individual faces were then used to generate predicted eigenface values, which could be transformed into reconstructions of individual faces. We show that visually perceived faces were reliably reconstructed from activity patterns in occipitotemporal cortex and several lateral parietal subregions, including ANG. Subjective assessment of reconstructed faces revealed specific sources of information (e.g., affect and skin color) that were successfully reconstructed in ANG. Strikingly, we also found that a model trained on ANG activity patterns during face perception was able to successfully reconstruct an independent set of face images that were held in memory. Together, these findings provide compelling evidence that ANG forms complex, stimulus-specific representations that are reflected in activity patterns evoked during perception and remembering. Neuroimaging studies have consistently implicated lateral parietal cortex in episodic remembering, but the functional contributions of lateral parietal cortex to memory remain a topic of debate. Here, we used an innovative form of fMRI pattern analysis to test whether lateral parietal cortex actively represents the contents of memory. Using a large set of human face images, we first extracted latent face components (eigenfaces). We then used machine learning algorithms to predict face components from fMRI activity patterns and, ultimately, to reconstruct images of individual faces. We show that activity patterns in a subregion of lateral parietal cortex, the angular gyrus, supported successful reconstruction of perceived and remembered faces, confirming a role for this region in actively representing remembered content. Copyright © 2016 the authors 0270-6474/16/366069-14$15.00/0.

Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

PubMed Central

de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

2015-01-01

Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825

Double dissociation of value computations in orbitofrontal and anterior cingulate neurons

PubMed Central

Kennerley, Steven W.; Behrens, Timothy E. J.; Wallis, Jonathan D.

2011-01-01

Damage to prefrontal cortex (PFC) impairs decision-making, but the underlying value computations that might cause such impairments remain unclear. Here we report that value computations are doubly dissociable within PFC neurons. While many PFC neurons encoded chosen value, they used opponent encoding schemes such that averaging the neuronal population eliminated value coding. However, a special population of neurons in anterior cingulate cortex (ACC) - but not orbitofrontal cortex (OFC) - multiplex chosen value across decision parameters using a unified encoding scheme, and encoded reward prediction errors. In contrast, neurons in OFC - but not ACC - encoded chosen value relative to the recent history of choice values. Together, these results suggest complementary valuation processes across PFC areas: OFC neurons dynamically evaluate current choices relative to recent choice values, while ACC neurons encode choice predictions and prediction errors using a common valuation currency reflecting the integration of multiple decision parameters. PMID:22037498

Three-way ROC validation of rs-fMRI visual information propagation transfer functions used to differentiate between RRMS and CIS optic neuritis patients.

PubMed

Farahani, Ehsan Shahrabi; Choudhury, Samiul H; Cortese, Filomeno; Costello, Fiona; Goodyear, Bradley; Smith, Michael R

2017-07-01

Resting-state fMRI (rs-fMRI) measures the temporal synchrony between different brain regions while the subject is at rest. We present an investigation using visual information propagation transfer functions as potential optic neuritis (ON) markers for the pathways between the lateral geniculate nuclei, the primary visual cortex, the lateral occipital cortex and the superior parietal cortex. We investigate marker reliability in differentiating between healthy controls and ON patients with clinically isolated syndrome (CIS), and relapsing-remitting multiple sclerosis (RRMS) using a three-way receiver operating characteristics analysis. We identify useful and reliable three-way ON related metrics in the rs-fMRI low-frequency band 0.0 Hz to 0.1 Hz, with potential markers associated with the higher frequency harmonics of these signals in the 0.1 Hz to 0.2 Hz and 0.2 Hz to 0.3 Hz bands.

Theta coupling between V4 and prefrontal cortex predicts visual short-term memory performance.

PubMed

Liebe, Stefanie; Hoerzer, Gregor M; Logothetis, Nikos K; Rainer, Gregor

2012-01-29

Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3-9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.

Decoding Multiple Sound Categories in the Human Temporal Cortex Using High Resolution fMRI

PubMed Central

Zhang, Fengqing; Wang, Ji-Ping; Kim, Jieun; Parrish, Todd; Wong, Patrick C. M.

2015-01-01

Perception of sound categories is an important aspect of auditory perception. The extent to which the brain’s representation of sound categories is encoded in specialized subregions or distributed across the auditory cortex remains unclear. Recent studies using multivariate pattern analysis (MVPA) of brain activations have provided important insights into how the brain decodes perceptual information. In the large existing literature on brain decoding using MVPA methods, relatively few studies have been conducted on multi-class categorization in the auditory domain. Here, we investigated the representation and processing of auditory categories within the human temporal cortex using high resolution fMRI and MVPA methods. More importantly, we considered decoding multiple sound categories simultaneously through multi-class support vector machine-recursive feature elimination (MSVM-RFE) as our MVPA tool. Results show that for all classifications the model MSVM-RFE was able to learn the functional relation between the multiple sound categories and the corresponding evoked spatial patterns and classify the unlabeled sound-evoked patterns significantly above chance. This indicates the feasibility of decoding multiple sound categories not only within but across subjects. However, the across-subject variation affects classification performance more than the within-subject variation, as the across-subject analysis has significantly lower classification accuracies. Sound category-selective brain maps were identified based on multi-class classification and revealed distributed patterns of brain activity in the superior temporal gyrus and the middle temporal gyrus. This is in accordance with previous studies, indicating that information in the spatially distributed patterns may reflect a more abstract perceptual level of representation of sound categories. Further, we show that the across-subject classification performance can be significantly improved by averaging the fMRI images over items, because the irrelevant variations between different items of the same sound category are reduced and in turn the proportion of signals relevant to sound categorization increases. PMID:25692885

Decoding multiple sound categories in the human temporal cortex using high resolution fMRI.

PubMed

Zhang, Fengqing; Wang, Ji-Ping; Kim, Jieun; Parrish, Todd; Wong, Patrick C M

2015-01-01

Perception of sound categories is an important aspect of auditory perception. The extent to which the brain's representation of sound categories is encoded in specialized subregions or distributed across the auditory cortex remains unclear. Recent studies using multivariate pattern analysis (MVPA) of brain activations have provided important insights into how the brain decodes perceptual information. In the large existing literature on brain decoding using MVPA methods, relatively few studies have been conducted on multi-class categorization in the auditory domain. Here, we investigated the representation and processing of auditory categories within the human temporal cortex using high resolution fMRI and MVPA methods. More importantly, we considered decoding multiple sound categories simultaneously through multi-class support vector machine-recursive feature elimination (MSVM-RFE) as our MVPA tool. Results show that for all classifications the model MSVM-RFE was able to learn the functional relation between the multiple sound categories and the corresponding evoked spatial patterns and classify the unlabeled sound-evoked patterns significantly above chance. This indicates the feasibility of decoding multiple sound categories not only within but across subjects. However, the across-subject variation affects classification performance more than the within-subject variation, as the across-subject analysis has significantly lower classification accuracies. Sound category-selective brain maps were identified based on multi-class classification and revealed distributed patterns of brain activity in the superior temporal gyrus and the middle temporal gyrus. This is in accordance with previous studies, indicating that information in the spatially distributed patterns may reflect a more abstract perceptual level of representation of sound categories. Further, we show that the across-subject classification performance can be significantly improved by averaging the fMRI images over items, because the irrelevant variations between different items of the same sound category are reduced and in turn the proportion of signals relevant to sound categorization increases.

Neuroinflammatory component of gray matter pathology in multiple sclerosis.

PubMed

Herranz, Elena; Giannì, Costanza; Louapre, Céline; Treaba, Constantina A; Govindarajan, Sindhuja T; Ouellette, Russell; Loggia, Marco L; Sloane, Jacob A; Madigan, Nancy; Izquierdo-Garcia, David; Ward, Noreen; Mangeat, Gabriel; Granberg, Tobias; Klawiter, Eric C; Catana, Ciprian; Hooker, Jacob M; Taylor, Norman; Ionete, Carolina; Kinkel, Revere P; Mainero, Caterina

2016-11-01

In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios. Relative to controls, MS subjects exhibited abnormally high 11 C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790. © 2016 American Neurological Association.

Abnormalities in Functional Connectivity in Collegiate Football Athletes with and without a Concussion History: Implications and Role of Neuroactive Kynurenine Pathway Metabolites.

PubMed

Meier, Timothy B; Lancaster, Melissa A; Mayer, Andrew R; Teague, T Kent; Savitz, Jonathan

2017-02-15

There is a great need to identify potential long-term consequences of contact sport exposure and to identify molecular pathways that may be associated with these changes. We tested the hypothesis that football players with (Ath-mTBI) (n = 25) and without a concussion history (Ath) (n = 24) have altered resting state functional connectivity in regions with previously documented structural changes relative to healthy controls without football or concussion history (HC) (n = 27). As a secondary aim, we tested the hypothesis that group differences in functional connectivity are moderated by the relative ratio of neuroprotective to neurotoxic metabolites of the kynurenine pathway. Ath-mTBI had significantly increased connectivity of motor cortex to the supplementary motor area relative to Ath and HC. In contrast, both Ath-mTBI and Ath had increased connectivity between the left orbital frontal cortex and the right lateral frontal cortex, and between the left cornu ammonis areas 2 and 3/dentate gyrus (CA2-3/DG) of the hippocampus and the middle and posterior cingulate cortices, relative to HC. The relationship between the ratio of plasma concentrations of kynurenic acid to quinolinic acid (KYNA/QUIN) and left pregenual anterior cingulate cortex connectivity to multiple regions as well as KYNA/QUIN and right CA2-3/DG connectivity to multiple regions differed significantly according to football and concussion history. The results suggest that football exposure with and without concussion history can have a significant effect on intrinsic brain connectivity and implicate the kynurenine metabolic pathway as one potential moderator of functional connectivity dependent on football exposure and concussion history.

Multimap formation in visual cortex

PubMed Central

Jain, Rishabh; Millin, Rachel; Mel, Bartlett W.

2015-01-01

An extrastriate visual area such as V2 or V4 contains neurons selective for a multitude of complex shapes, all sharing a common topographic organization. Simultaneously developing multiple interdigitated maps—hereafter a “multimap”—is challenging in that neurons must compete to generate a diversity of response types locally, while cooperating with their dispersed same-type neighbors to achieve uniform visual field coverage for their response type at all orientations, scales, etc. Previously proposed map development schemes have relied on smooth spatial interaction functions to establish both topography and columnar organization, but by locally homogenizing cells' response properties, local smoothing mechanisms effectively rule out multimap formation. We found in computer simulations that the key requirements for multimap development are that neurons are enabled for plasticity only within highly active regions of cortex designated “learning eligibility regions” (LERs), but within an LER, each cell's learning rate is determined only by its activity level with no dependence on location. We show that a hybrid developmental rule that combines spatial and activity-dependent learning criteria in this way successfully produces multimaps when the input stream contains multiple distinct feature types, or in the degenerate case of a single feature type, produces a V1-like map with “salt-and-pepper” structure. Our results support the hypothesis that cortical maps containing a fine mixture of different response types, whether in monkey extrastriate cortex, mouse V1 or elsewhere in the cortex, rather than signaling a breakdown of map formation mechanisms at the fine scale, are a product of a generic cortical developmental scheme designed to map cells with a diversity of response properties across a shared topographic space. PMID:26641946

Functional magnetic resonance imaging examination of two modular architectures for switching multiple internal models.

PubMed

Imamizu, Hiroshi; Kuroda, Tomoe; Yoshioka, Toshinori; Kawato, Mitsuo

2004-02-04

An internal model is a neural mechanism that can mimic the input-output properties of a controlled object such as a tool. Recent research interests have moved on to how multiple internal models are learned and switched under a given context of behavior. Two representative computational models for task switching propose distinct neural mechanisms, thus predicting different brain activity patterns in the switching of internal models. In one model, called the mixture-of-experts architecture, switching is commanded by a single executive called a "gating network," which is different from the internal models. In the other model, called the MOSAIC (MOdular Selection And Identification for Control), the internal models themselves play crucial roles in switching. Consequently, the mixture-of-experts model predicts that neural activities related to switching and internal models can be temporally and spatially segregated, whereas the MOSAIC model predicts that they are closely intermingled. Here, we directly examined the two predictions by analyzing functional magnetic resonance imaging activities during the switching of one common tool (an ordinary computer mouse) and two novel tools: a rotated mouse, the cursor of which appears in a rotated position, and a velocity mouse, the cursor velocity of which is proportional to the mouse position. The switching and internal model activities temporally and spatially overlapped each other in the cerebellum and in the parietal cortex, whereas the overlap was very small in the frontal cortex. These results suggest that switching mechanisms in the frontal cortex can be explained by the mixture-of-experts architecture, whereas those in the cerebellum and the parietal cortex are explained by the MOSAIC model.

Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets

PubMed Central

Ryali, Srikanth; Chen, Tianwen; Li, Chiang-Shan R.

2014-01-01

The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control. PMID:25355218

Training-Dependent Associative Learning Induced Neocortical Structural Plasticity: A Trace Eyeblink Conditioning Analysis

PubMed Central

Chau, Lily S.; Prakapenka, Alesia V.; Zendeli, Liridon; Davis, Ashley S.; Galvez, Roberto

2014-01-01

Studies utilizing general learning and memory tasks have suggested the importance of neocortical structural plasticity for memory consolidation. However, these learning tasks typically result in learning of multiple different tasks over several days of training, making it difficult to determine the synaptic time course mediating each learning event. The current study used trace-eyeblink conditioning to determine the time course for neocortical spine modification during learning. With eyeblink conditioning, subjects are presented with a neutral, conditioned stimulus (CS) paired with a salient, unconditioned stimulus (US) to elicit an unconditioned response (UR). With multiple CS-US pairings, subjects learn to associate the CS with the US and exhibit a conditioned response (CR) when presented with the CS. Trace conditioning is when there is a stimulus free interval between the CS and the US. Utilizing trace-eyeblink conditioning with whisker stimulation as the CS (whisker-trace-eyeblink: WTEB), previous findings have shown that primary somatosensory (barrel) cortex is required for both acquisition and retention of the trace-association. Additionally, prior findings demonstrated that WTEB acquisition results in an expansion of the cytochrome oxidase whisker representation and synaptic modification in layer IV of barrel cortex. To further explore these findings and determine the time course for neocortical learning-induced spine modification, the present study utilized WTEB conditioning to examine Golgi-Cox stained neurons in layer IV of barrel cortex. Findings from this study demonstrated a training-dependent spine proliferation in layer IV of barrel cortex during trace associative learning. Furthermore, findings from this study showing that filopodia-like spines exhibited a similar pattern to the overall spine density further suggests that reorganization of synaptic contacts set the foundation for learning-induced neocortical modifications through the different neocortical layers. PMID:24760074

Myosin II dynamics are regulated by tension in intercalating cells.

PubMed

Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

2009-11-01

Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

A corticothalamic switch: controlling the thalamus with dynamic synapses

PubMed Central

Crandall, Shane R.; Cruikshank, Scott J.; Connors, Barry W.

2015-01-01

SUMMARY Corticothalamic neurons provide massive input to the thalamus. This top-down projection may allow cortex to regulate sensory processing by modulating the excitability of thalamic cells. Layer 6 corticothalamic neurons monosynaptically excite thalamocortical cells, but also indirectly inhibit them by driving inhibitory cells of the thalamic reticular nucleus. Whether corticothalamic activity generally suppresses or excites the thalamus remains unclear. Here we show that the corticothalamic influence is dynamic, with the excitatory-inhibitory balance shifting in an activity-dependent fashion. During low-frequency activity corticothalamic effects are mainly suppressive, whereas higher frequency activity (even a short bout of gamma frequency oscillations) converts the corticothalamic influence to enhancement. The mechanism of this switching depends upon distinct forms of short-term synaptic plasticity across multiple corticothalamic circuit components. Our results reveal an activity-dependent mechanism by which corticothalamic neurons can bidirectionally switch the excitability and sensory throughput of the thalamus, possibly to meet changing behavioral demands. PMID:25913856

Rapid learning in visual cortical networks.

PubMed

Wang, Ye; Dragoi, Valentin

2015-08-26

Although changes in brain activity during learning have been extensively examined at the single neuron level, the coding strategies employed by cell populations remain mysterious. We examined cell populations in macaque area V4 during a rapid form of perceptual learning that emerges within tens of minutes. Multiple single units and LFP responses were recorded as monkeys improved their performance in an image discrimination task. We show that the increase in behavioral performance during learning is predicted by a tight coordination of spike timing with local population activity. More spike-LFP theta synchronization is correlated with higher learning performance, while high-frequency synchronization is unrelated with changes in performance, but these changes were absent once learning had stabilized and stimuli became familiar, or in the absence of learning. These findings reveal a novel mechanism of plasticity in visual cortex by which elevated low-frequency synchronization between individual neurons and local population activity accompanies the improvement in performance during learning.

Combined diffusion-weighted and functional magnetic resonance imaging reveals a temporal-occipital network involved in auditory-visual object processing

PubMed Central

Beer, Anton L.; Plank, Tina; Meyer, Georg; Greenlee, Mark W.

2013-01-01

Functional magnetic resonance imaging (MRI) showed that the superior temporal and occipital cortex are involved in multisensory integration. Probabilistic fiber tracking based on diffusion-weighted MRI suggests that multisensory processing is supported by white matter connections between auditory cortex and the temporal and occipital lobe. Here, we present a combined functional MRI and probabilistic fiber tracking study that reveals multisensory processing mechanisms that remained undetected by either technique alone. Ten healthy participants passively observed visually presented lip or body movements, heard speech or body action sounds, or were exposed to a combination of both. Bimodal stimulation engaged a temporal-occipital brain network including the multisensory superior temporal sulcus (msSTS), the lateral superior temporal gyrus (lSTG), and the extrastriate body area (EBA). A region-of-interest (ROI) analysis showed multisensory interactions (e.g., subadditive responses to bimodal compared to unimodal stimuli) in the msSTS, the lSTG, and the EBA region. Moreover, sounds elicited responses in the medial occipital cortex. Probabilistic tracking revealed white matter tracts between the auditory cortex and the medial occipital cortex, the inferior occipital cortex (IOC), and the superior temporal sulcus (STS). However, STS terminations of auditory cortex tracts showed limited overlap with the msSTS region. Instead, msSTS was connected to primary sensory regions via intermediate nodes in the temporal and occipital cortex. Similarly, the lSTG and EBA regions showed limited direct white matter connections but instead were connected via intermediate nodes. Our results suggest that multisensory processing in the STS is mediated by separate brain areas that form a distinct network in the lateral temporal and inferior occipital cortex. PMID:23407860

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.

PubMed

Fiorentino, Maria; Sapone, Anna; Senger, Stefania; Camhi, Stephanie S; Kadzielski, Sarah M; Buie, Timothy M; Kelly, Deanna L; Cascella, Nicola; Fasano, Alessio

2016-01-01

Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. Claudin ( CLDN )-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3 , tricellulin , and MMP-9 were higher in the ASD cortex. IL-8 , tPA , and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components ( CLDN-1 , OCLN , TRIC ), whereas 66% had increased pore-forming CLDNs ( CLDN-2 , -10 , -15 ) compared to controls. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

PubMed

Mohedano-Moriano, Alicia; Muñoz-López, Mónica; Sanz-Arigita, Ernesto; Pró-Sistiaga, Palma; Martínez-Marcos, Alino; Legidos-Garcia, María Ester; Insausti, Ana María; Cebada-Sánchez, Sandra; Arroyo-Jiménez, María Del Mar; Marcos, Pilar; Artacho-Pérula, Emilio; Insausti, Ricardo

2015-12-01

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. © 2015 Wiley Periodicals, Inc.

Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume.

PubMed

Dalwani, Manish S; McMahon, Mary Agnes; Mikulich-Gilbertson, Susan K; Young, Susan E; Regner, Michael F; Raymond, Kristen M; McWilliams, Shannon K; Banich, Marie T; Tanabe, Jody L; Crowley, Thomas J; Sakai, Joseph T

2015-01-01

Structural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum). We conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold. Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls. Female adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women.

PubMed

García-Casares, Natalia; Bernal-López, María R; Roé-Vellvé, Nuria; Gutiérrez-Bedmar, Mario; Fernández-García, Jose C; García-Arnés, Juan A; Ramos-Rodriguez, José R; Alfaro, Francisco; Santamaria-Fernández, Sonia; Steward, Trevor; Jiménez-Murcia, Susana; Garcia-Garcia, Isabel; Valdivielso, Pedro; Fernández-Aranda, Fernando; Tinahones, Francisco J; Gómez-Huelgas, Ricardo

2017-07-01

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m²) was 38.15 ± 4.7 vs. 34.18 ± 4.5 ( p < 0.02), and body weight (kg) was 98.5 ± 13.1 vs. 88.28 ± 12.2 ( p < 0.03). All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex ( p < 0.001), left posterior cingulate ( p < 0.001), and right posterior cingulate ( p < 0.03); decreased connectivity between the left superior frontal gyrus and the right temporal cortex ( p < 0.01); decreased connectivity between the prefrontal cortex and the somatosensory cortex ( p < 0.025); and decreased connectivity between the left and right posterior cingulate ( p < 0.04). Results were considered significant at a voxel-wise threshold of p ≤ 0.05, and a cluster-level family-wise error correction for multiple comparisons of p ≤ 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity (the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex) may be modified by a weight loss program including a Mediterranean diet and physical exercise.

The possibility of left dominant activation of the sensorimotor cortex during lip protrusion in men.

PubMed

Fukunaga, Atsushi; Ohira, Takayuki; Kamba, Masayuki; Ogawa, Seiji; Akiyama, Takenori; Kawase, Takeshi

2009-09-01

Lip protrusion requires bilateral symmetrical movements of the facial muscles, but the laterality of the activated sensorimotor cortex corresponding to the area of the face activated during lip protrusion remains under discussion. In this study, blood-oxygenation-level-dependent (BOLD) responses in the sensorimotor cortex during non-verbal lip protrusion were evaluated in a 3T magnetic field in twenty healthy right-handed subjects. The results showed that the activated sensorimotor area on the left side was larger than that on the right side, and there was a statistically significant difference in the number of activated voxels between the left and right sensorimotor cortex in an individual study of the male group, although approximately symmetrical motor action potentials of facial muscles were recorded during lip protrusion. There was a statistically significant difference in interaction between the hemisphere (right and left) and sex (men and women) and multiple comparison test showed statistical significant differences between "men and right" and "men and left", and between "men and left" and "women and left". The peak value of the percent changes in BOLD signal responses on the left side was approximately twice as high as that on the right side in the males of the group, though the bilateral sensorimotor cortex was almost equally activated in the females in the group. In addition, the left primary sensory area related to the face area was significantly activated as a region where Male was more active than Female in a general linear model (multi-study, multisubject) analysis. This study revealed the possibility that the left sensorimotor cortex was more closely involved in non-verbal mouth movement in men, suggesting sex-related differences in sensorimotor cortex activation.

Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning

PubMed Central

Wise, Richard J.S.; Geranmayeh, Fatemeh; Hampshire, Adam

2017-01-01

It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword–object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary. SIGNIFICANCE STATEMENT Learning a task involves the brain system within which that specific task becomes established. Therefore, successfully learning a new vocabulary establishes the novel words in the language system. However, there is evidence that in the early stages of learning, networks within multiple-demand cortex (MDC), which control higher cognitive functions, such as working memory, attention, and monitoring of performance, become active. This activity declines once the task is learnt. The present study demonstrated that a node within MDC, located in midline frontal cortex, becomes active during the early stage of learning a novel vocabulary. Importantly, noninvasive brain stimulation of this node improved performance during this stage of learning. This observation demonstrated that MDC activity is important for learning. PMID:28676576

Seeing Is Not Feeling: Posterior Parietal But Not Somatosensory Cortex Engagement During Touch Observation

PubMed Central

Baker, Chris I.

2015-01-01

Observing touch has been reported to elicit activation in human primary and secondary somatosensory cortices and is suggested to underlie our ability to interpret other's behavior and potentially empathy. However, despite these reports, there are a large number of inconsistencies in terms of the precise topography of activation, the extent of hemispheric lateralization, and what aspects of the stimulus are necessary to drive responses. To address these issues, we investigated the localization and functional properties of regions responsive to observed touch in a large group of participants (n = 40). Surprisingly, even with a lenient contrast of hand brushing versus brushing alone, we did not find any selective activation for observed touch in the hand regions of somatosensory cortex but rather in superior and inferior portions of neighboring posterior parietal cortex, predominantly in the left hemisphere. These regions in the posterior parietal cortex required the presence of both brush and hand to elicit strong responses and showed some selectivity for the form of the object or agent of touch. Furthermore, the inferior parietal region showed nonspecific tactile and motor responses, suggesting some similarity to area PFG in the monkey. Collectively, our findings challenge the automatic engagement of somatosensory cortex when observing touch, suggest mislocalization in previous studies, and instead highlight the role of posterior parietal cortex. PMID:25632124

Auditory pathways: anatomy and physiology.

PubMed

Pickles, James O

2015-01-01

This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described. © 2015 Elsevier B.V. All rights reserved.

Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.

PubMed

Liu, Jianbo; Khalil, Hassan K; Oweiss, Karim G

2011-10-01

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

[Neural Mechanisms Underlying the Processing of Temporal Information in Episodic Memory and Its Disturbance].

PubMed

Iwata, Saeko; Tsukiura, Takashi

2017-11-01

Episodic memory is defined as memory for personally experienced events, and includes memory content and contextual information of time and space. Previous neuroimaging and neuropsychological studies have demonstrated three possible roles of the temporal context in episodic memory. First, temporal information contributes to the arrangement of temporal order for sequential events in episodic memory, and this process is involved in the lateral prefrontal cortex. The second possible role of temporal information in episodic memory is the segregation between memories of multiple events, which are segregated by cues of different time information. The role of segregation is associated with the orbitofrontal regions including the orbitofrontal cortex and basal forebrain region. Third, temporal information in episodic memory plays an important role in the integration of multiple components into a coherent episodic memory, in which episodic components in the different modalities are combined by temporal information as an index. The role of integration is mediated by the medial temporal lobe including the hippocampus and parahippocampal gyrus. Thus, temporal information in episodic memory could be represented in multiple stages, which are involved in a network of the lateral prefrontal, orbitofrontal, and medial temporal lobe regions.

Damage to the ventromedial prefrontal cortex reduces interpersonal disgust.

PubMed

Ciaramelli, Elisa; Sperotto, Rebecca G; Mattioli, Flavia; di Pellegrino, Giuseppe

2013-02-01

Disgust for contaminating objects (core disgust), immoral behaviors (moral disgust) and unsavory others (interpersonal disgust), have been assumed to be closely related. It is not clear, however, whether different forms of disgust are mediated by overlapping or specific neural substrates. We report that 10 patients with damage to the ventromedial prefrontal cortex (vmPFC) avoided behaviors that normally elicit interpersonal disgust (e.g. using the scarf of a busker) less frequently than healthy and brain-damaged controls, whereas they avoided core and moral disgust elicitors at normal rates. These results indicate that different forms of disgust are dissociated neurally. We propose that the vmPFC is causally (and selectively) involved in mediating interpersonal disgust, shaping patterns of social avoidance and approach.

Damage to the ventromedial prefrontal cortex reduces interpersonal disgust

PubMed Central

Ciaramelli, Elisa; Sperotto, Rebecca G.; Mattioli, Flavia

2013-01-01

Disgust for contaminating objects (core disgust), immoral behaviors (moral disgust) and unsavory others (interpersonal disgust), have been assumed to be closely related. It is not clear, however, whether different forms of disgust are mediated by overlapping or specific neural substrates. We report that 10 patients with damage to the ventromedial prefrontal cortex (vmPFC) avoided behaviors that normally elicit interpersonal disgust (e.g. using the scarf of a busker) less frequently than healthy and brain-damaged controls, whereas they avoided core and moral disgust elicitors at normal rates. These results indicate that different forms of disgust are dissociated neurally. We propose that the vmPFC is causally (and selectively) involved in mediating interpersonal disgust, shaping patterns of social avoidance and approach. PMID:22842816

(±)3,4-Methylenedioxymethamphetamine (“Ecstasy”) Treatment Modulates Expression of Neurotrophins and Their Receptors in Multiple Regions of Adult Rat Brain

PubMed Central

Hemmerle, Ann M.; Dickerson, Jonathan W.; Herring, Nicole R.; Schaefer, Tori L.; Vorhees, Charles V.; Williams, Michael T.; Seroogy, Kim B.

2014-01-01

(±)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high-affinity receptors, tropomyosin receptor kinase (trk)B and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg × 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats, and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB, and trkC were analyzed by using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB, and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased NT-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta, and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in the learning and memory deficits seen following MDMA treatment. PMID:22237931

The Multiple Correspondence Analysis Method and Brain Functional Connectivity: Its Application to the Study of the Non-linear Relationships of Motor Cortex and Basal Ganglia.

PubMed

Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Rodriguez, Manuel

2017-01-01

The complexity of basal ganglia (BG) interactions is often condensed into simple models mainly based on animal data and that present BG in closed-loop cortico-subcortical circuits of excitatory/inhibitory pathways which analyze the incoming cortical data and return the processed information to the cortex. This study was aimed at identifying functional relationships in the BG motor-loop of 24 healthy-subjects who provided written, informed consent and whose BOLD-activity was recorded by MRI methods. The analysis of the functional interaction between these centers by correlation techniques and multiple linear regression showed non-linear relationships which cannot be suitably addressed with these methods. The multiple correspondence analysis (MCA), an unsupervised multivariable procedure which can identify non-linear interactions, was used to study the functional connectivity of BG when subjects were at rest. Linear methods showed different functional interactions expected according to current BG models. MCA showed additional functional interactions which were not evident when using lineal methods. Seven functional configurations of BG were identified with MCA, two involving the primary motor and somatosensory cortex, one involving the deepest BG (external-internal globus pallidum, subthalamic nucleus and substantia nigral), one with the input-output BG centers (putamen and motor thalamus), two linking the input-output centers with other BG (external pallidum and subthalamic nucleus), and one linking the external pallidum and the substantia nigral. The results provide evidence that the non-linear MCA and linear methods are complementary and should be best used in conjunction to more fully understand the nature of functional connectivity of brain centers.

Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

PubMed

Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

2017-04-01

Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

An evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats.

PubMed

Goto, Takakuni; Hatanaka, Rieko; Ogawa, Takeshi; Sumiyoshi, Akira; Riera, Jorge; Kawashima, Ryuta

2010-12-01

Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

Emerging feed-forward inhibition allows the robust formation of direction selectivity in the developing ferret visual cortex

PubMed Central

Escobar, Gina M.; Maffei, Arianna; Miller, Paul

2014-01-01

The computation of direction selectivity requires that a cell respond to joint spatial and temporal characteristics of the stimulus that cannot be separated into independent components. Direction selectivity in ferret visual cortex is not present at the time of eye opening but instead develops in the days and weeks following eye opening in a process that requires visual experience with moving stimuli. Classic Hebbian or spike timing-dependent modification of excitatory feed-forward synaptic inputs is unable to produce direction-selective cells from unselective or weakly directionally biased initial conditions because inputs eventually grow so strong that they can independently drive cortical neurons, violating the joint spatial-temporal activation requirement. Furthermore, without some form of synaptic competition, cells cannot develop direction selectivity in response to training with bidirectional stimulation, as cells in ferret visual cortex do. We show that imposing a maximum lateral geniculate nucleus (LGN)-to-cortex synaptic weight allows neurons to develop direction-selective responses that maintain the requirement for joint spatial and temporal activation. We demonstrate that a novel form of inhibitory plasticity, postsynaptic activity-dependent long-term potentiation of inhibition (POSD-LTPi), which operates in the developing cortex at the time of eye opening, can provide synaptic competition and enables robust development of direction-selective receptive fields with unidirectional or bidirectional stimulation. We propose a general model of the development of spatiotemporal receptive fields that consists of two phases: an experience-independent establishment of initial biases, followed by an experience-dependent amplification or modification of these biases via correlation-based plasticity of excitatory inputs that compete against gradually increasing feed-forward inhibition. PMID:24598528

Multiple forebrain systems converge on motor neurons innervating the thyroarytenoid muscle

PubMed Central

Van Daele, Douglas J.; Cassell, Martin D.

2009-01-01

The present study investigated the central connections of motor neurons innervating the thyroarytenoid laryngeal muscle that is active in swallowing, respiration and vocalization. In both intact and sympathectomized rats, the pseudorabies virus (PRV) was inoculated into the muscle. After initial infection of laryngomotor neurons in the ipsilateral loose division of the nucleus ambiguous (NA) by 3 days post-inoculation., PRV spread to the ipsilateral compact portion of the NA, the central and intermediate divisions of the nucleus tractus solitarii (NTS), the Botzinger complex, and the parvocellular reticular formation by 4 days. Infection was subsequently expanded to include the ipsilateral granular and dysgranular parietal insular cortex, the ipsilateral medial division of the central nucleus of the amygdala, the lateral, paraventricular, ventrolateral and medial preoptic nuclei of the hypothalamus (generally bilaterally), the lateral periaqueductal gray, the A7 and oral and caudal pontine nuclei. At the latest time points sampled post-inoculation (5 days), infected neurons were identified in the ipsilateral agranular insular cortex, the caudal parietal insular cortex, the anterior cingulate cortex, and the contralateral motor cortex. In the amygdala, infection had spread to the lateral central nucleus and the parvocellular portion of the basolateral nucleus. Hypothalamic infection was largely characterized by an increase in the number of infected cells in earlier infected regions though the posterior, dorsomedial, tuberomammillary and mammillary nuclei contained infected cells. Comparison with previous connectional data suggest PRV followed three interconnected systems originating in the forebrain; a bilateral system including the ventral anterior cingulate cortex, periaqueductal gray and ventral respiratory group; an ipsilateral system involving the parietal insular cortex, central nucleus of the amygdala and parvicellular reticular formation, and a minor contralateral system originating in motor cortex. Hypothalamic innervation involved several functionally specific nuclei. Overall, the data imply complex central nervous system control over the multi-functional thyroarytenoid muscle.[297 words] PMID:19426785

Unravelling the development of the visual cortex: implications for plasticity and repair

PubMed Central

Bourne, James A

2010-01-01

The visual cortex comprises over 50 areas in the human, each with a specified role and distinct physiology, connectivity and cellular morphology. How these individual areas emerge during development still remains something of a mystery and, although much attention has been paid to the initial stages of the development of the visual cortex, especially its lamination, very little is known about the mechanisms responsible for the arealization and functional organization of this region of the brain. In recent years we have started to discover that it is the interplay of intrinsic (molecular) and extrinsic (afferent connections) cues that are responsible for the maturation of individual areas, and that there is a spatiotemporal sequence in the maturation of the primary visual cortex (striate cortex, V1) and the multiple extrastriate/association areas. Studies in both humans and non-human primates have started to highlight the specific neural underpinnings responsible for the maturation of the visual cortex, and how experience-dependent plasticity and perturbations to the visual system can impact upon its normal development. Furthermore, damage to specific nuclei of the visual cortex, such as the primary visual cortex (V1), is a common occurrence as a result of a stroke, neurotrauma, disease or hypoxia in both neonates and adults alike. However, the consequences of a focal injury differ between the immature and adult brain, with the immature brain demonstrating a higher level of functional resilience. With better techniques for examining specific molecular and connectional changes, we are now starting to uncover the mechanisms responsible for the increased neural plasticity that leads to significant recovery following injury during this early phase of life. Further advances in our understanding of postnatal development/maturation and plasticity observed during early life could offer new strategies to improve outcomes by recapitulating aspects of the developmental program in the adult brain. PMID:20722872

Simultaneous Top-down Modulation of the Primary Somatosensory Cortex and Thalamic Nuclei during Active Tactile Discrimination

PubMed Central

Pais-Vieira, Miguel; Lebedev, Mikhail A.; Wiest, Michael C.; Nicolelis, Miguel A.L.

2013-01-01

The rat somatosensory system contains multiple thalamocortical loops (TCL) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial (VPM) and the posterior medial (POM) thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations prior to the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal’s discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal’s performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system. PMID:23447616

Enhanced accumulation of Kir4.1 protein, but not mRNA, in a murine model of cuprizone-induced demyelination.

PubMed

Nakajima, Mitsunari; Kawamura, Takuya; Tokui, Ryuji; Furuta, Kohei; Sugino, Mami; Nakanishi, Masayuki; Okuyama, Satoshi; Furukawa, Yoshiko

2013-11-06

Two channel proteins, inwardly rectifying potassium channel 4.1 (Kir4.1) and water channel aquaporin-4 (AQP4), were recently identified as targets of an autoantibody response in patients with multiple sclerosis and neuromyelitis optica, respectively. In the present study, we examined the expression patterns of Kir4.1 and AQP4 in a mouse model of demyelination induced by cuprizone, a copper chelator. Demyelination was confirmed by immunohistochemistry using an anti-proteolipid protein antibody in various brain regions, including the corpus callosum, of cuprizone-fed mice. Activation of microglial and astroglial cells was also confirmed by immunohistochemistry, using an anti-ionized calcium binding adapter molecule and a glial fibrillary acidic protein antibody. Western blot analysis revealed the induction of Kir4.1 protein, but not AQP4, in the cortex of cuprizone-fed mice. Immunohistochemical analysis confirmed the Kir4.1 protein induction in microvessels of the cerebral cortex. Real-time polymerase chain reaction analysis revealed that mRNA levels of Kir4.1 and AQP4 in the cortex did not change during cuprizone administration. These findings suggest that enhanced accumulation of Kir4.1 protein in the brain with an inflammatory condition facilitates the autoantibody formation against Kir4.1 in patients with multiple sclerosis. © 2013 Published by Elsevier B.V.

Estrogen Restores Multisynaptic Boutons in the Dorsolateral Prefrontal Cortex while Promoting Working Memory in Aged Rhesus Monkeys.

PubMed

Hara, Yuko; Yuk, Frank; Puri, Rishi; Janssen, William G M; Rapp, Peter R; Morrison, John H

2016-01-20

Humans and nonhuman primates are vulnerable to age- and menopause- related decline in working memory, a cognitive function reliant on area 46 of the dorsolateral prefrontal cortex (dlPFC). We showed previously that presynaptic mitochondrial number and morphology in monkey dlPFC neurons correlate with working memory performance. The current study tested the hypothesis that the types of synaptic connections these boutons form are altered with aging and menopause in rhesus monkeys and that these metrics may be coupled with mitochondrial measures and working memory. Using serial section electron microscopy, we examined the frequencies and characteristics of nonsynaptic, single-synaptic, and multisynaptic boutons (MSBs) in the dlPFC. In contrast to our previous observations in the monkey hippocampal dentate gyrus, where MSBs comprised ∼40% of boutons, the vast majority of dlPFC boutons were single-synaptic, whereas MSBs constituted a mere 10%. The frequency of MSBs was not altered by normal aging, but decreased by over 50% with surgical menopause induced by ovariectomy in aged monkeys. Cyclic estradiol treatment in aged ovariectomized animals restored MSB frequencies to levels comparable to young and aged premenopausal monkeys. Notably, the frequency of MSBs positively correlated with working memory scores, as measured by the average accuracy on the delayed response (DR) test. Furthermore, MSB incidence positively correlated with the number of healthy straight mitochondria in dlPFC boutons and inversely correlated with the number of pathological donut-shaped mitochondria. Together, our data suggest that MSBs are coupled to cognitive function and mitochondrial health and are sensitive to estrogen. Significance statement: Many aged menopausal individuals experience deficits in working memory, an executive function reliant on recurrent firing of prefrontal cortex (PFC) neurons. However, little is known about the organization of presynaptic inputs to these neurons and how they may be altered with aging and menopause. Multisynaptic boutons (MSBs) were of particular interest, because they form multiple synapses and can enhance coupling between presynaptic and postsynaptic neurons. We found that higher MSB frequency correlated with better working memory performance in rhesus monkeys. Additionally, aged surgically menopausal monkeys experienced a 50% loss of MSBs that was restored with cyclic estradiol treatment. Together, our findings suggest that hormone replacement therapy benefits cognitive aging, in part by retaining complex synaptic organizations in the PFC. Copyright © 2016 the authors 0270-6474/16/360902-10$15.00/0.

Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

PubMed Central

Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

2015-01-01

Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted −10.86 (95% confidence intervals −16.786 to −4.482) decrease in grip strength (kg force) (P < 0.001) and −8.74 (95% confidence intervals −13.943 to −3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis. See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. PMID:26304151

Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior.

PubMed

Siniscalchi, Michael J; Phoumthipphavong, Victoria; Ali, Farhan; Lozano, Marc; Kwan, Alex C

2016-09-01

The ability to shift between repetitive and goal-directed actions is a hallmark of cognitive control. Previous studies have reported that adaptive shifts in behavior are accompanied by changes of neural activity in frontal cortex. However, neural and behavioral adaptations can occur at multiple time scales, and their relationship remains poorly defined. Here we developed an adaptive sensorimotor decision-making task for head-fixed mice, requiring them to shift flexibly between multiple auditory-motor mappings. Two-photon calcium imaging of secondary motor cortex (M2) revealed different ensemble activity states for each mapping. When adapting to a conditional mapping, transitions in ensemble activity were abrupt and occurred before the recovery of behavioral performance. By contrast, gradual and delayed transitions accompanied shifts toward repetitive responding. These results demonstrate distinct ensemble signatures associated with the start versus end of sensory-guided behavior and suggest that M2 leads in engaging goal-directed response strategies that require sensorimotor associations.

Learning Enhances Sensory and Multiple Non-sensory Representations in Primary Visual Cortex

PubMed Central

Poort, Jasper; Khan, Adil G.; Pachitariu, Marius; Nemri, Abdellatif; Orsolic, Ivana; Krupic, Julija; Bauza, Marius; Sahani, Maneesh; Keller, Georg B.; Mrsic-Flogel, Thomas D.; Hofer, Sonja B.

2015-01-01

Summary We determined how learning modifies neural representations in primary visual cortex (V1) during acquisition of a visually guided behavioral task. We imaged the activity of the same layer 2/3 neuronal populations as mice learned to discriminate two visual patterns while running through a virtual corridor, where one pattern was rewarded. Improvements in behavioral performance were closely associated with increasingly distinguishable population-level representations of task-relevant stimuli, as a result of stabilization of existing and recruitment of new neurons selective for these stimuli. These effects correlated with the appearance of multiple task-dependent signals during learning: those that increased neuronal selectivity across the population when expert animals engaged in the task, and those reflecting anticipation or behavioral choices specifically in neuronal subsets preferring the rewarded stimulus. Therefore, learning engages diverse mechanisms that modify sensory and non-sensory representations in V1 to adjust its processing to task requirements and the behavioral relevance of visual stimuli. PMID:26051421

Perirhinal cortex and temporal lobe epilepsy

PubMed Central

Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

2013-01-01

The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

Abnormalities in cortical gray matter density in borderline personality disorder

PubMed Central

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

2015-01-01

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

Cache Sharing and Isolation Tradeoffs in Multicore Mixed-Criticality Systems

DTIC Science & Technology

2015-05-01

form of lockdown registers, to provide way-based partitioning. These alternatives are illustrated in Fig. 1 with respect to a quad-core ARM Cortex A9... processor (as we do for Level-A and -B tasks), but they did not consider MC systems. Altmeyer et al. [1] considered uniprocessor scheduling on a system with a...framework. We randomly generated task sets and determined the fraction that were schedulable on our target hardware platform, the quad-core ARM Cortex A9

[Mental Space Navigation and Mental Time Travel].

PubMed

Kawamura, Mitsuru

2017-11-01

We examined patients with mental space navigation or mental time travel disorder to identify regions in the brain that may play a critical role in mental time travel in terms of clinical neuropsychology. These regions included the precneus, posterior cingulate gyrus, retrosplenial cortex, and hippocampus, as well as the orbitofrontal cortex: the anterior and posterior medial areas were both shown to be important in this process. Further studies are required to define whether these form a network for mental time travel.

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

PubMed

Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

2016-03-01

Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Traumatic Brain Injury and Neuronal Functionality Changes in Sensory Cortex

PubMed Central

Carron, Simone F.; Alwis, Dasuni S.; Rajan, Ramesh

2016-01-01

Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat’s exploratory and discriminative tactile system, the large face macrovibrissae, which feeds to the so-called “barrel cortex” of somatosensory cortex. In this review we describe the short-term and long-term changes in the barrel cortex encoding of whisker motion modeling naturalistic whisker movement undertaken by rats engaged in a variety of tasks. We demonstrate that the most common form of TBI results in persistent neuronal hyperexcitation specifically in the upper cortical layers, likely due to changes in inhibition. We describe the types of cortical inhibitory neurons and their roles and how selective effects on some of these could produce the particular forms of neuronal encoding changes described in TBI, and then generalize to compare the effects on inhibition seen in other forms of brain injury. From these findings we make specific predictions as to how non-invasive extra-cranial electrophysiology can be used to provide the high-precision information needed to monitor and understand the temporal evolution of changes in neuronal functionality in humans suffering TBI. Such detailed understanding of the specific changes in an individual patient’s cortex can allow for treatment to be tailored to the neuronal changes in that particular patient’s brain in TBI, a precision that is currently unavailable with any technique. PMID:27313514

Superior parietal lobule dysfunction in a homogeneous group of dyslexic children with a visual attention span disorder.

PubMed

Peyrin, C; Démonet, J F; N'Guyen-Morel, M A; Le Bas, J F; Valdois, S

2011-09-01

A visual attention (VA) span disorder has been reported in dyslexic children as potentially responsible for their poor reading outcome. The purpose of the current paper was to identify the cerebral correlates of this VA span disorder. For this purpose, 12 French dyslexic children with severe reading and VA span disorders and 12 age-matched control children were engaged in a categorisation task under fMRI. Two flanked and isolated conditions were designed which both involved multiple-element simultaneous visual processing but taxed visual attention differently. For skilled readers, flanked stimuli processing activated a large bilateral cortical network comprising the superior and inferior parietal cortex, the inferior temporal cortex, the striate and extrastriate visual cortex, the middle frontal cortex and the anterior cingulate cortex while the less attention-demanding task of isolated stimuli only activated the inferior occipito-temporal cortex bilaterally. With respect to controls, the dyslexic children showed significantly reduced activation within bilateral parietal and temporal areas during flanked processing, but no difference during the isolated condition. The neural correlates of the processes involved in attention-demanding multi-element processing tasks were more specifically addressed by contrasting the flanked and the isolated conditions. This contrast elicited activation of the left precuneus/superior parietal lobule in the controls, but not in the dyslexic children. These findings provide new insights on the role of parietal regions, in particular the left superior parietal lobule, in the visual attention span and in developmental dyslexia. Copyright © 2010 Elsevier Inc. All rights reserved.

Sweet and bitter taste in the brain of awake behaving animals

PubMed Central

Peng, Yueqing; Gillis-Smith, Sarah; Jin, Hao; Tränkner, Dimitri; Ryba, Nicholas J. P.; Zuker, Charles S.

2015-01-01

Taste is responsible for evaluating the nutritious content of food, guiding essential appetitive behaviors, preventing the ingestion of toxic substances, and helping ensure the maintenance of a healthy diet. Sweet and bitter are two of the most salient sensory percepts for humans and other animals; sweet taste permits the identification of energy-rich nutrients while bitter warns against the intake of potentially noxious chemicals1. In mammals, information from taste receptor cells in the tongue is transmitted through multiple neural stations to the primary gustatory cortex in the brain2. Recent imaging studies have shown that sweet and bitter are represented in the primary gustatory cortex by neurons organized in a spatial map3,4, with each taste quality encoded by distinct cortical fields4. Here we demonstrate that by manipulating the brain fields representing sweet and bitter taste we directly control an animal’s internal representation, sensory perception, and behavioral actions. These results substantiate the segregation of taste qualities in the cortex, expose the innate nature of appetitive and aversive taste responses, and illustrate the ability of gustatory cortex to recapitulate complex behaviors in the absence of sensory input. PMID:26580015

Sex differences in structural brain asymmetry predict overt aggression in early adolescents.

PubMed

Visser, Troy A W; Ohan, Jeneva L; Whittle, Sarah; Yücel, Murat; Simmons, Julian G; Allen, Nicholas B

2014-04-01

The devastating social, emotional and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e. left vs right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here, we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.

Functional heterogeneity of conflict, error, task-switching, and unexpectedness effects within medial prefrontal cortex.

PubMed

Nee, Derek Evan; Kastner, Sabine; Brown, Joshua W

2011-01-01

The last decade has seen considerable discussion regarding a theoretical account of medial prefrontal cortex (mPFC) function with particular focus on the anterior cingulate cortex. The proposed theories have included conflict detection, error likelihood prediction, volatility monitoring, and several distinct theories of error detection. Arguments for and against particular theories often treat mPFC as functionally homogeneous, or at least nearly so, despite some evidence for distinct functional subregions. Here we used functional magnetic resonance imaging (fMRI) to simultaneously contrast multiple effects of error, conflict, and task-switching that have been individually construed in support of various theories. We found overlapping yet functionally distinct subregions of mPFC, with activations related to dominant error, conflict, and task-switching effects successively found along a rostral-ventral to caudal-dorsal gradient within medial prefrontal cortex. Activations in the rostral cingulate zone (RCZ) were strongly correlated with the unexpectedness of outcomes suggesting a role in outcome prediction and preparing control systems to deal with anticipated outcomes. The results as a whole support a resolution of some ongoing debates in that distinct theories may each pertain to corresponding distinct yet overlapping subregions of mPFC. Copyright © 2010 Elsevier Inc. All rights reserved.

Role of medio-dorsal frontal and posterior parietal neurons during auditory detection performance in rats.

PubMed

Bohon, Kaitlin S; Wiest, Michael C

2014-01-01

To further characterize the role of frontal and parietal cortices in rat cognition, we recorded action potentials simultaneously from multiple sites in the medio-dorsal frontal cortex and posterior parietal cortex of rats while they performed a two-choice auditory detection task. We quantified neural correlates of task performance, including response movements, perception of a target tone, and the differentiation between stimuli with distinct features (different pitches or durations). A minority of units--15% in frontal cortex, 23% in parietal cortex--significantly distinguished hit trials (successful detections, response movement to the right) from correct rejection trials (correct leftward response to the absence of the target tone). Estimating the contribution of movement-related activity to these responses suggested that more than half of these units were likely signaling correct perception of the auditory target, rather than merely movement direction. In addition, we found a smaller and mostly not overlapping population of units that differentiated stimuli based on task-irrelevant details. The detection-related spiking responses we observed suggest that correlates of perception in the rat are sparsely represented among neurons in the rat's frontal-parietal network, without being concentrated preferentially in frontal or parietal areas.

Neural dynamics of object-based multifocal visual spatial attention and priming: Object cueing, useful-field-of-view, and crowding

PubMed Central

Foley, Nicholas C.; Grossberg, Stephen; Mingolla, Ennio

2015-01-01

How are spatial and object attention coordinated to achieve rapid object learning and recognition during eye movement search? How do prefrontal priming and parietal spatial mechanisms interact to determine the reaction time costs of intra-object attention shifts, inter-object attention shifts, and shifts between visible objects and covertly cued locations? What factors underlie individual differences in the timing and frequency of such attentional shifts? How do transient and sustained spatial attentional mechanisms work and interact? How can volition, mediated via the basal ganglia, influence the span of spatial attention? A neural model is developed of how spatial attention in the where cortical stream coordinates view-invariant object category learning in the what cortical stream under free viewing conditions. The model simulates psychological data about the dynamics of covert attention priming and switching requiring multifocal attention without eye movements. The model predicts how “attentional shrouds” are formed when surface representations in cortical area V4 resonate with spatial attention in posterior parietal cortex (PPC) and prefrontal cortex (PFC), while shrouds compete among themselves for dominance. Winning shrouds support invariant object category learning, and active surface-shroud resonances support conscious surface perception and recognition. Attentive competition between multiple objects and cues simulates reaction-time data from the two-object cueing paradigm. The relative strength of sustained surface-driven and fast-transient motion-driven spatial attention controls individual differences in reaction time for invalid cues. Competition between surface-driven attentional shrouds controls individual differences in detection rate of peripheral targets in useful-field-of-view tasks. The model proposes how the strength of competition can be mediated, though learning or momentary changes in volition, by the basal ganglia. A new explanation of crowding shows how the cortical magnification factor, among other variables, can cause multiple object surfaces to share a single surface-shroud resonance, thereby preventing recognition of the individual objects. PMID:22425615

Neural dynamics of object-based multifocal visual spatial attention and priming: object cueing, useful-field-of-view, and crowding.

PubMed

Foley, Nicholas C; Grossberg, Stephen; Mingolla, Ennio

2012-08-01

How are spatial and object attention coordinated to achieve rapid object learning and recognition during eye movement search? How do prefrontal priming and parietal spatial mechanisms interact to determine the reaction time costs of intra-object attention shifts, inter-object attention shifts, and shifts between visible objects and covertly cued locations? What factors underlie individual differences in the timing and frequency of such attentional shifts? How do transient and sustained spatial attentional mechanisms work and interact? How can volition, mediated via the basal ganglia, influence the span of spatial attention? A neural model is developed of how spatial attention in the where cortical stream coordinates view-invariant object category learning in the what cortical stream under free viewing conditions. The model simulates psychological data about the dynamics of covert attention priming and switching requiring multifocal attention without eye movements. The model predicts how "attentional shrouds" are formed when surface representations in cortical area V4 resonate with spatial attention in posterior parietal cortex (PPC) and prefrontal cortex (PFC), while shrouds compete among themselves for dominance. Winning shrouds support invariant object category learning, and active surface-shroud resonances support conscious surface perception and recognition. Attentive competition between multiple objects and cues simulates reaction-time data from the two-object cueing paradigm. The relative strength of sustained surface-driven and fast-transient motion-driven spatial attention controls individual differences in reaction time for invalid cues. Competition between surface-driven attentional shrouds controls individual differences in detection rate of peripheral targets in useful-field-of-view tasks. The model proposes how the strength of competition can be mediated, though learning or momentary changes in volition, by the basal ganglia. A new explanation of crowding shows how the cortical magnification factor, among other variables, can cause multiple object surfaces to share a single surface-shroud resonance, thereby preventing recognition of the individual objects. Copyright © 2012 Elsevier Inc. All rights reserved.

The Neural Correlates of Emotion Regulation by Implementation Intentions

PubMed Central

Hallam, Glyn P.; Webb, Thomas L.; Sheeran, Paschal; Miles, Eleanor; Wilkinson, Iain D.; Hunter, Michael D.; Barker, Anthony T.; Woodruff, Peter W. R.; Totterdell, Peter; Lindquist, Kristen A.; Farrow, Tom F. D.

2015-01-01

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency. PMID:25798822

Brain Activity During the Encoding, Retention, and Retrieval of Stimulus Representations

PubMed Central

de Zubicaray, Greig I.; McMahon, Katie; Wilson, Stephen J.; Muthiah, Santhi

2001-01-01

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory. PMID:11584070

Reciprocal neural response within lateral and ventral medial prefrontal cortex during hot and cold reasoning.

PubMed

Goel, Vinod; Dolan, Raymond J

2003-12-01

Logic is widely considered the basis of rationality. Logical choices, however, are often influenced by emotional responses, sometimes to our detriment, sometimes to our advantage. To understand the neural basis of emotionally neutral ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using event-related fMRI, as they made logical judgments about arguments that varied in emotional saliency. Despite identical logical form and content categories across "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal cortex showed reciprocal response patterns as a function of emotional saliency of content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in enhanced activation in VMPFC and suppression of activation in L/DLPFC. This reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural system for reasoning, the configuration of which is strongly influenced by emotional saliency.

Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

PubMed Central

Naimark, Ari; Barkai, Edi; Matar, Michael A.; Kaplan, Zeev; Kozlovsky, Nitzan; Cohen, Hagit

2007-01-01

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks. PMID:17710248

Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula

PubMed Central

Castro, Daniel C.; Berridge, Kent C.

2017-01-01

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

Role of cerebellum in learning postural tasks.

PubMed

Ioffe, M E; Chernikova, L A; Ustinova, K I

2007-01-01

For a long time, the cerebellum has been known to be a structure related to posture and equilibrium control. According to the anatomic structure of inputs and internal structure of the cerebellum, its role in learning was theoretically reasoned and experimentally proved. The hypothesis of an inverse internal model based on feedback-error learning mechanism combines feedforward control by the cerebellum and feedback control by the cerebral motor cortex. The cerebellar cortex is suggested to acquire internal models of the body and objects in the external world. During learning of a new tool the motor cortex receives feedback from the realized movement while the cerebellum produces only feedforward command. To realize a desired movement without feedback of the realized movement, the cerebellum needs to form an inverse model of the hand/arm system. This suggestion was supported by FMRi data. The role of cerebellum in learning new postural tasks mainly concerns reorganization of natural synergies. A learned postural pattern in dogs has been shown to be disturbed after lesions of the cerebral motor cortex or cerebellar nuclei. In humans, learning voluntary control of center of pressure position is greatly disturbed after cerebellar lesions. However, motor cortex and basal ganglia are also involved in the feedback learning postural tasks.

Excessive Astrocyte-Derived Neurotrophin-3 Contributes to the Abnormal Neuronal Dendritic Development in a Mouse Model of Fragile X Syndrome

PubMed Central

Guo, Yan-yan; Liu, Shui-bing; Wu, Yu-mei; Li, Xiao-qiang; Zhao, Ming-gao

2012-01-01

Fragile X syndrome (FXS) is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene. Recent studies suggest a role of astrocytes in neuronal development. However, the mechanisms involved in the regulation process of astrocytes from FXS remain unclear. In this study, we found that astrocytes derived from a Fragile X model, the Fmr1 knockout (KO) mouse which lacks FMRP expression, inhibited the proper elaboration of dendritic processes of neurons in vitro. Furthermore, astrocytic conditioned medium (ACM) from KO astrocytes inhibited proper dendritic growth of both wild-type (WT) and KO neurons. Inducing expression of FMRP by transfection of FMRP vectors in KO astrocytes restored dendritic morphology and levels of synaptic proteins. Further experiments revealed elevated levels of the neurotrophin-3 (NT-3) in KO ACM and the prefrontal cortex of Fmr1 KO mice. However, the levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were normal. FMRP has multiple RNA–binding motifs and is involved in translational regulation. RNA–binding protein immunoprecipitation (RIP) showed the NT-3 mRNA interacted with FMRP in WT astrocytes. Addition of high concentrations of exogenous NT-3 to culture medium reduced the dendrites of neurons and synaptic protein levels, whereas these measures were ameliorated by neutralizing antibody to NT-3 or knockdown of NT-3 expression in KO astrocytes through short hairpin RNAs (shRNAs). Prefrontal cortex microinjection of WT astrocytes or NT-3 shRNA infected KO astrocytes rescued the deficit of trace fear memory in KO mice, concomitantly decreased the NT-3 levels in the prefrontal cortex. This study indicates that excessive NT-3 from astrocytes contributes to the abnormal neuronal dendritic development and that astrocytes could be a potential therapeutic target for FXS. PMID:23300470

Expanding the spectrum of neuronal pathology in multiple system atrophy

PubMed Central

Cykowski, Matthew D.; Coon, Elizabeth A.; Powell, Suzanne Z.; Jenkins, Sarah M.; Benarroch, Eduardo E.; Low, Phillip A.; Schmeichel, Ann M.

2015-01-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. See Halliday (doi:10.1093/brain/awv151) for a scientific commentary on this article. PMID:25981961

Psychophysical and neuroimaging responses to moving stimuli in a patient with the Riddoch phenomenon due to bilateral visual cortex lesions.

PubMed

Arcaro, Michael J; Thaler, Lore; Quinlan, Derek J; Monaco, Simona; Khan, Sarah; Valyear, Kenneth F; Goebel, Rainer; Dutton, Gordon N; Goodale, Melvyn A; Kastner, Sabine; Culham, Jody C

2018-05-09

Patients with injury to early visual cortex or its inputs can display the Riddoch phenomenon: preserved awareness for moving but not stationary stimuli. We provide a detailed case report of a patient with the Riddoch phenomenon, MC. MC has extensive bilateral lesions to occipitotemporal cortex that include most early visual cortex and complete blindness in visual field perimetry testing with static targets. Nevertheless, she shows a remarkably robust preserved ability to perceive motion, enabling her to navigate through cluttered environments and perform actions like catching moving balls. Comparisons of MC's structural magnetic resonance imaging (MRI) data to a probabilistic atlas based on controls reveals that MC's lesions encompass the posterior, lateral, and ventral early visual cortex bilaterally (V1, V2, V3A/B, LO1/2, TO1/2, hV4 and VO1 in both hemispheres) as well as more extensive damage to right parietal (inferior parietal lobule) and left ventral occipitotemporal cortex (VO1, PHC1/2). She shows some sparing of anterior occipital cortex, which may account for her ability to see moving targets beyond ~15 degrees eccentricity during perimetry. Most strikingly, functional and structural MRI revealed robust and reliable spared functionality of the middle temporal motion complex (MT+) bilaterally. Moreover, consistent with her preserved ability to discriminate motion direction in psychophysical testing, MC also shows direction-selective adaptation in MT+. A variety of tests did not enable us to discern whether input to MT+ was driven by her spared anterior occipital cortex or subcortical inputs. Nevertheless, MC shows rich motion perception despite profoundly impaired static and form vision, combined with clear preservation of activation in MT+, thus supporting the role of MT+ in the Riddoch phenomenon. Copyright © 2018 Elsevier Ltd. All rights reserved.

The organization of plasticity in the cerebellar cortex: from synapses to control.

PubMed

D'Angelo, Egidio

2014-01-01

The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Amyloid deposition in the hippocampus and entorhinal cortex: Quantitative analysis of a transgenic mouse model

PubMed Central

Reilly, John F.; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2003-01-01

Various transgenic mouse models of Alzheimer's disease (AD) have been developed that overexpress mutant forms of amyloid precursor protein in an effort to elucidate more fully the potential role of β-amyloid (Aβ) in the etiopathogenesis of the disease. The present study represents the first complete 3D reconstruction of Aβ in the hippocampus and entorhinal cortex of PDAPP transgenic mice. Aβ deposits were detected by immunostaining and thioflavin fluorescence, and quantified by using high-throughput digital image acquisition and analysis. Quantitative analysis of amyloid load in hippocampal subfields showed a dramatic increase between 12 and 15 months of age, with little or no earlier detectable deposition. Three-dimensional reconstruction in the oldest brains visualized previously unrecognized sheets of Aβ coursing through the hippocampus and cerebral cortex. In contrast with previous hypotheses, compact plaques form before significant deposition of diffuse Aβ, suggesting that different mechanisms are involved in the deposition of diffuse amyloid and the aggregation into plaques. The dentate gyrus was the hippocampal subfield with the greatest amyloid burden. Sublaminar distribution of Aβ in the dentate gyrus correlated most closely with the termination of afferent projections from the lateral entorhinal cortex, mirroring the selective vulnerability of this circuit in human AD. This detailed temporal and spatial analysis of Aβ and compact amyloid deposition suggests that specific corticocortical circuits express selective, but late, vulnerability to the pathognomonic markers of amyloid deposition, and can provide a basis for detecting prior vulnerability factors. PMID:12697936

Evaluation of Techniques Used to Estimate Cortical Feature Maps

PubMed Central

Katta, Nalin; Chen, Thomas L.; Watkins, Paul V.; Barbour, Dennis L.

2011-01-01

Functional properties of neurons are often distributed nonrandomly within a cortical area and form topographic maps that reveal insights into neuronal organization and interconnection. Some functional maps, such as in visual cortex, are fairly straightforward to discern with a variety of techniques, while other maps, such as in auditory cortex, have resisted easy characterization. In order to determine appropriate protocols for establishing accurate functional maps in auditory cortex, artificial topographic maps were probed under various conditions, and the accuracy of estimates formed from the actual maps was quantified. Under these conditions, low-complexity maps such as sound frequency can be estimated accurately with as few as 25 total samples (e.g., electrode penetrations or imaging pixels) if neural responses are averaged together. More samples are required to achieve the highest estimation accuracy for higher complexity maps, and averaging improves map estimate accuracy even more than increasing sampling density. Undersampling without averaging can result in misleading map estimates, while undersampling with averaging can lead to the false conclusion of no map when one actually exists. Uniform sample spacing only slightly improves map estimation over nonuniform sample spacing typical of serial electrode penetrations. Tessellation plots commonly used to visualize maps estimated using nonuniform sampling are always inferior to linearly interpolated estimates, although differences are slight at higher sampling densities. Within primary auditory cortex, then, multiunit sampling with at least 100 samples would likely result in reasonable feature map estimates for all but the highest complexity maps and the highest variability that might be expected. PMID:21889537

Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer's disease.

PubMed

Shu, Liqi; Sun, Wenjia; Li, Liping; Xu, Zihui; Lin, Li; Xie, Pei; Shen, Hui; Huang, Luoxiu; Xu, Qi; Jin, Peng; Li, Xuekun

2016-05-20

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder that leads to a decline in cognitive function. In AD, aggregates of amyloid β peptide precede the accumulation of neurofibrillary tangles, both of which are hallmarks of the disease. The great majority (>90 %) of the AD cases are not originated from genetic defects, therefore supporting the central roles of epigenetic modifications that are acquired progressively during the life span. Strong evidences have indicated the implication of epigenetic modifications, including histone modification and DNA methylation, in AD. Recent studies revealed that 5-hydroxymethylcytosine (5hmC) is dynamically regulated during neurodevelopment and aging. We show that amyloid peptide 1-42 (Aβ1-42) could significantly reduce the overall level of 5hmC in vitro. We found that the level of 5hmC displayed differential response to the pathogenesis in different brain regions, including the cortex, cerebellum, and hippocampus of APP-PSEN1 double transgenic (DTg) mice. We observed a significant decrease of overall 5hmC in hippocampus, but not in cortex and cerebellum, as the DTg mice aged. Genome-wide profiling identified differential hydroxymethylation regions (DhMRs) in DTg mice, which are highly enriched in introns, exons and intergenic regions. Gene ontology analyses indicated that DhMR-associated genes are highly enriched in multiple signaling pathways involving neuronal development/differentiation and neuronal function/survival. 5hmC-mediated epigenetic regulation could potentially be involved in the pathogenesis of AD.

Sight and sound converge to form modality-invariant representations in temporo-parietal cortex

PubMed Central

Man, Kingson; Kaplan, Jonas T.; Damasio, Antonio; Meyer, Kaspar

2013-01-01

People can identify objects in the environment with remarkable accuracy, irrespective of the sensory modality they use to perceive them. This suggests that information from different sensory channels converges somewhere in the brain to form modality-invariant representations, i.e., representations that reflect an object independently of the modality through which it has been apprehended. In this functional magnetic resonance imaging study of human subjects, we first identified brain areas that responded to both visual and auditory stimuli and then used crossmodal multivariate pattern analysis to evaluate the neural representations in these regions for content-specificity (i.e., do different objects evoke different representations?) and modality-invariance (i.e., do the sight and the sound of the same object evoke a similar representation?). While several areas became activated in response to both auditory and visual stimulation, only the neural patterns recorded in a region around the posterior part of the superior temporal sulcus displayed both content-specificity and modality-invariance. This region thus appears to play an important role in our ability to recognize objects in our surroundings through multiple sensory channels and to process them at a supra-modal (i.e., conceptual) level. PMID:23175818

The development of psychopathy.

PubMed

Blair, R J R; Peschardt, K S; Budhani, S; Mitchell, D G V; Pine, D S

2006-01-01

The current review focuses on the construct of psychopathy, conceptualized as a clinical entity that is fundamentally distinct from a heterogeneous collection of syndromes encompassed by the term 'conduct disorder'. We will provide an account of the development of psychopathy at multiple levels: ultimate causal (the genetic or social primary cause), molecular, neural, cognitive and behavioral. The following main claims will be made: (1) that there is a stronger genetic as opposed to social ultimate cause to this disorder. The types of social causes proposed (e.g., childhood sexual/physical abuse) should elevate emotional responsiveness, not lead to the specific form of reduced responsiveness seen in psychopathy; (2) The genetic influence leads to the emotional dysfunction that is the core of psychopathy; (3) The genetic influence at the molecular level remains unknown. However, it appears to impact the functional integrity of the amygdala and orbital/ventrolateral frontal cortex (and possibly additional systems); (4) Disruption within these two neural systems leads to impairment in the ability to form stimulus-reinforcement associations and to alter stimulus-response associations as a function of contingency change. These impairments disrupt the impact of standard socialization techniques and increase the risk for frustration-induced reactive aggression respectively.

Rat immunoreactive cholecystokinin (CCK): characterization using two chromatographic techniques.

PubMed

Bacarese-Hamilton, A J; Adrian, T E; Chohan, P; Bloom, S R

1985-06-01

Acid and neutral extracts of rat cerebral cortex and upper small intestine were prepared and the endogenous concentrations of cholecystokinin-like immunoreactivity (CCK-LI) measured by three new CCK-specific radioimmunoassays. The characterization of the immunoreactive CCK molecular forms was undertaken using gel permeation chromatography in the presence of 6 M urea to minimise problems relating to peptide adsorption or aggregation. Reverse-phase high-performance liquid chromatography (HPLC) was also performed on the rat tissue extracts. Rat cortex contained 268 +/- 12 pmol/g CCK-LI, and over 90% resembled the sulphated CCK-8, which was preferentially extracted at neutral pH. In contrast, the rat upper small intestine (97 +/- 8 pmol/g of CCK-LI) contained less than 20% CCK-8, the majority of immunoreactive CCK being of larger molecular size and being preferentially extracted at acid pH. In the small intestine the predominant molecular form(s) was intermediate in size between CCK-33 and CCK-8. Large amounts of CCK-33 and of a molecular form larger than CCK-33 were also detected. It is concluded that post-translational cleavage of CCK differs in rat brain and gut.

Effect of Different Forms of Hypokinesia on the Ultrastructure of Limbic, Extrapyramidal and Neocortical Areas of the Rat Brain: Electron Microscopic Study

NASA Astrophysics Data System (ADS)

Zhvania, Mzia G.; Japaridze, Nadezhda J.; Ksovreli, Mariam G.

The effect of chronic restraint stress and chronic hypokinesia "without stress" on the ultrastructure of central and lateral nuclei of amygdala, CA1 and CA3 area of the hippocampus, cingular cortex, nucleus caudatus and motor cortex of adult male rats were elucidated. In some neurons and synapses of abovementioned regions pathological modifications were revealed. More significant alterations provokes chronic restraint stress. Alterations are mostly concentrated: first—in the nuclei of amygdala, then in the CA1 and CA3 areas. Moderate alterations were observed in cingular cortex and nucleus caudatus. In comparing with it, hypokinesia "without stress" provokes only moderate modifications: predominantly in the nucleus caudatus, in lesser degree—in the hippocampus and amygdalae.

Attenuating illusory binding with TMS of the right parietal cortex

PubMed Central

Esterman, Michael; Verstynen, Timothy; Robertson, Lynn C.

2007-01-01

A number of neuroimaging and neuropsychology studies have implicated various regions of parietal cortex as playing a critical role in the binding of color and form into conjunctions. The current study investigates the role of two such regions by examining how parietal transcranial magnetic stimulation (TMS) influences binding errors known as ‘illusory conjunctions.’ Participants made fewer binding errors after 1 Hz rTMS of the right intraparietal sulcus (IPS), while basic perception of features (colors and shape) was unaffected. No perceptual effects were found following left IPS stimulation, or stimulation of the right angular gyrus at the junction of the transverse occipital sulcus (IPS/TOS). These results support a role for the parietal cortex in feature binding but in ways that may require rethinking. PMID:17336097

Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

PubMed

Mitchell, D G V; Fine, C; Richell, R A; Newman, C; Lumsden, J; Blair, K S; Blair, R J R

2006-05-01

Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. Copyright (c) 2006 APA, all rights reserved.

Electrophysiological correlates of cocktail-party listening.

PubMed

Lewald, Jörg; Getzmann, Stephan

2015-10-01

Detecting, localizing, and selectively attending to a particular sound source of interest in complex auditory scenes composed of multiple competing sources is a remarkable capacity of the human auditory system. The neural basis of this so-called "cocktail-party effect" has remained largely unknown. Here, we studied the cortical network engaged in solving the "cocktail-party" problem, using event-related potentials (ERPs) in combination with two tasks demanding horizontal localization of a naturalistic target sound presented either in silence or in the presence of multiple competing sound sources. Presentation of multiple sound sources, as compared to single sources, induced an increased P1 amplitude, a reduction in N1, and a strong N2 component, resulting in a pronounced negativity in the ERP difference waveform (N2d) around 260 ms after stimulus onset. About 100 ms later, the anterior contralateral N2 subcomponent (N2ac) occurred in the multiple-sources condition, as computed from the amplitude difference for targets in the left minus right hemispaces. Cortical source analyses of the ERP modulation, resulting from the contrast of multiple vs. single sources, generally revealed an initial enhancement of electrical activity in right temporo-parietal areas, including auditory cortex, by multiple sources (at P1) that is followed by a reduction, with the primary sources shifting from right inferior parietal lobule (at N1) to left dorso-frontal cortex (at N2d). Thus, cocktail-party listening, as compared to single-source localization, appears to be based on a complex chronology of successive electrical activities within a specific cortical network involved in spatial hearing in complex situations. Copyright © 2015 Elsevier B.V. All rights reserved.

Neural Correlates of Olfactory Learning: Critical Role of Centrifugal Neuromodulation

ERIC Educational Resources Information Center

Fletcher, Max L.; Chen, Wei R.

2010-01-01

The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of…

Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

PubMed

Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

2013-11-01

The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

[Inhibitory effects of extracts from Moutan Cortex on formation of advanced glycation end-products (AGEs) in vitro and specificity screening of its potential active components].

PubMed

Chen, Juan; Zhang, Li; Zhang, Ming-Hua; Zhao, Di; Yuan, Jia-Rui; Feng, Liang; Jia, Xiao-Bin

2016-03-01

In this study, bovine serum albumin (BSA)/methylglyoxal (MGO) non-enzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects of Moutan Cortex extracts on the formation of AGEs. The HPLC-LC-ESI-MS/MS technology was adopted to test and indentify active components in Moutan Cortex against AGEs formation. The different concentrations of extracts (crude herb concentration 50, 100, 150, 200, 250 g•L⁻¹) from Moutan Cortexwas determined by fluorospectrophotometry, indicating an activity against AGEs formation in different concentrations of extracts, the inhibition ratio were (36.2±5.3)%, (43.5±6.2)%, (55.4±7.8)%, (68.6±6.7)%, (70.4±8.2)%, respectively after 6-day reaction in a dose dependent manner. Besides, the forming speed of AGEs tended to be steady after 24 h reaction. The HPLC technology was used to analyze chromatograms before and after the incubation of Moutan Cortex and methylglyoxal, identify changes in five chromatographic peaks and show decrease or increase in chromatographic peaks. These substances were trigalloyl glucose, tetragalloyl glucose, galloylpaeoniflorin, hexagalloyl glucose and benzoylpaeoniflorin after LC-ESI-MS/MS identification. Extracts from Moutan Cortex showed the remarkable inhibitory effects against formation of AGEs in BSA/glucose system. Furthermore, these potential active components might be associated with the efficacy of Moutan Cortex on treatment of diabetic nephropathy, which enriches basic studies for Moutan Cortex and provides ideas and reference basis for subsequent studies. Copyright© by the Chinese Pharmaceutical Association.

Multiple Neural Mechanisms of Decision Making and Their Competition under Changing Risk Pressure

PubMed Central

Kolling, Nils; Wittmann, Marco; Rushworth, Matthew F.S.

2014-01-01

Summary Sometimes when a choice is made, the outcome is not guaranteed and there is only a probability of its occurrence. Each individual’s attitude to probability, sometimes called risk proneness or aversion, has been assumed to be static. Behavioral ecological studies, however, suggest such attitudes are dynamically modulated by the context an organism finds itself in; in some cases, it may be optimal to pursue actions with a low probability of success but which are associated with potentially large gains. We show that human subjects rapidly adapt their use of probability as a function of current resources, goals, and opportunities for further foraging. We demonstrate that dorsal anterior cingulate cortex (dACC) carries signals indexing the pressure to pursue unlikely choices and signals related to the taking of such choices. We show that dACC exerts this control over behavior when it, rather than ventromedial prefrontal cortex, interacts with posterior cingulate cortex. PMID:24607236

A major gene controls mimicry and crypsis in butterflies and moths

PubMed Central

Nadeau, Nicola J.; Pardo-Diaz, Carolina; Whibley, Annabel; Supple, Megan; Saenko, Suzanne V.; Wallbank, Richard W. R.; Wu, Grace C.; Maroja, Luana; Ferguson, Laura; Hanly, Joseph J.; Hines, Heather; Salazar, Camilo; Merrill, Richard; Dowling, Andrea; ffrench-Constant, Richard; Llaurens, Violaine; Joron, Mathieu; McMillan, W. Owen; Jiggins, Chris D.

2016-01-01

The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection1,2. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and if there is any commonality across the 160,000 moth and 17,000 butterfly species. Here, we identify a gene, cortex, through fine-scale mapping using population genomics and gene expression analyses, which regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast evolving subfamily of the otherwise highly conserved fizzy family of cell cycle regulators3, suggesting that it most likely regulates pigmentation patterning through regulation of scale cell development. In parallel with findings in the peppered moth (Biston betularia)4, our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects. PMID:27251285

Increasing contextual demand modulates anterior and lateral prefrontal brain regions associated with proactive interference.

PubMed

Wolf, Robert Christian; Walter, Henrik; Vasic, Nenad

2010-01-01

Using a parametric version of a modified item-recognition paradigm with three different load levels and by means of event-related functional magnetic resonance imaging, this study tested the hypothesis that cerebral activation associated with intratrial proactive interference (PI) during working memory retrieval is influenced by increased context processing. We found activation of left BA 45 during interference trials across all levels of cognitive processing, and left lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared with high susceptibility to PI, low susceptibility was associated with activation of the left DLPFC. These results suggest that an intratrial PI effect can be modulated by increasing context processing of a transiently relevant stimulus set. Moreover, PI resolution associated with increasing context load involves multiple prefrontal regions including the ventro- and dorsolateral prefrontal cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI might be influenced by increased executive control exerted by the DLPFC.

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome.

PubMed

Huang, Wen-Chin; Chen, Youjun; Page, Damon T

2016-11-15

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten +/- ), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten +/- mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC-BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling.

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome

PubMed Central

Huang, Wen-Chin; Chen, Youjun; Page, Damon T.

2016-01-01

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten+/−), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten+/− mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC–BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling. PMID:27845329

Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.

PubMed

Teles-Grilo Ruivo, Leonor M; Baker, Keeley L; Conway, Michael W; Kinsley, Peter J; Gilmour, Gary; Phillips, Keith G; Isaac, John T R; Lowry, John P; Mellor, Jack R

2017-01-24

Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states. We found that tonic levels of acetylcholine release were coordinated between the prefrontal cortex and hippocampus and maximal during training on a rewarded working memory task. Tonic release also increased during REM sleep but was contingent on subsequent wakefulness. In contrast, coordinated phasic acetylcholine release occurred only during the memory task and was strongly localized to reward delivery areas without being contingent on trial outcome. These results show that coordinated acetylcholine release between the prefrontal cortex and hippocampus is associated with reward and arousal on distinct timescales, providing dual mechanisms to support learned behavior acquisition during cognitive task performance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A review of reward processing and motivational impairment in schizophrenia.

PubMed

Strauss, Gregory P; Waltz, James A; Gold, James M

2014-03-01

This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopamine-mediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia

PubMed Central

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy. PMID:27891079

Plasticity and stability of visual field maps in adult primary visual cortex

PubMed Central

Wandell, Brian A.; Smirnakis, Stelios M.

2010-01-01

Preface It is important to understand the balance between cortical plasticity and stability in various systems and spatial scales in the adult brain. We review measurements of adult plasticity in primary visual cortex (V1), a structure that has a key role in distributing visual information. There are claims of plasticity at multiple spatial scales in adult V1, but many inconsistencies in the data raise questions about the extent and nature of such plasticity. Understanding is further limited by a lack of quantitative models to guide the interpretation of the data. These problems limit efforts to translate research findings about adult cortical plasticity into significant clinical, educational and policy applications. PMID:19904279

Parallel Processing Strategies of the Primate Visual System

PubMed Central

Nassi, Jonathan J.; Callaway, Edward M.

2009-01-01

Preface Incoming sensory information is sent to the brain along modality-specific channels corresponding to the five senses. Each of these channels further parses the incoming signals into parallel streams to provide a compact, efficient input to the brain. Ultimately, these parallel input signals must be elaborated upon and integrated within the cortex to provide a unified and coherent percept. Recent studies in the primate visual cortex have greatly contributed to our understanding of how this goal is accomplished. Multiple strategies including retinal tiling, hierarchical and parallel processing and modularity, defined spatially and by cell type-specific connectivity, are all used by the visual system to recover the rich detail of our visual surroundings. PMID:19352403

Functional connectivity of task context representations in prefrontal nodes of the multiple demand network.

PubMed

Stiers, Peter; Goulas, Alexandros

2018-06-01

A subset of regions in the lateral and medial prefrontal cortex and the anterior insula increase their activity level whenever a cognitive task becomes more demanding, regardless of the specific nature of this demand. During execution of a task, these areas and the surrounding cortex temporally encode aspects of the task context in spatially distributed patterns of activity. It is not clear whether these patterns reflect underlying anatomical subnetworks that still exist when task execution has finished. We use fMRI in 12 participants performing alternating blocks of three cognitive tasks to address this question. A first data set is used to define multiple demand regions in each participant. A second dataset from the same participants is used to determine multiple demand voxel assemblies with a preference for one task over the others. We then show that these voxels remain functionally coupled during execution of non-preferred tasks and that they exhibit stronger functional connectivity during rest. This indicates that the assemblies of task preference sharing voxels reflect patterns of underlying anatomical connections. Moreover, we show that voxels preferring the same task have more similar whole brain functional connectivity profiles that are consistent across participants. This suggests that voxel assemblies differ in patterns of input-output connections, most likely reflecting task demand-specific information exchange.

Coordinated learning of grid cell and place cell spatial and temporal properties: multiple scales, attention and oscillations.

PubMed

Grossberg, Stephen; Pilly, Praveen K

2014-02-05

A neural model proposes how entorhinal grid cells and hippocampal place cells may develop as spatial categories in a hierarchy of self-organizing maps (SOMs). The model responds to realistic rat navigational trajectories by learning both grid cells with hexagonal grid firing fields of multiple spatial scales, and place cells with one or more firing fields, that match neurophysiological data about their development in juvenile rats. Both grid and place cells can develop by detecting, learning and remembering the most frequent and energetic co-occurrences of their inputs. The model's parsimonious properties include: similar ring attractor mechanisms process linear and angular path integration inputs that drive map learning; the same SOM mechanisms can learn grid cell and place cell receptive fields; and the learning of the dorsoventral organization of multiple spatial scale modules through medial entorhinal cortex to hippocampus (HC) may use mechanisms homologous to those for temporal learning through lateral entorhinal cortex to HC ('neural relativity'). The model clarifies how top-down HC-to-entorhinal attentional mechanisms may stabilize map learning, simulates how hippocampal inactivation may disrupt grid cells, and explains data about theta, beta and gamma oscillations. The article also compares the three main types of grid cell models in the light of recent data.

A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse

PubMed Central

Radulovic, Jelena

2016-01-01

Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2–6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control. SIGNIFICANCE STATEMENT Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the “map”) to sensorimotor networks involved the control of movement (the “motor”). PMID:27605612

Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI.

PubMed

Tumati, Shankar; Opmeer, Esther M; Marsman, Jan-Bernard C; Martens, Sander; Reesink, Fransje E; De Deyn, Peter P; Aleman, André

2018-01-01

Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI) and is associated with an increased risk of progression to Alzheimer's disease (AD). The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy ( 1 H-MRS). Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1 H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (DACC), right dorsolateral prefrontal cortex (DLPFC), and right temporo-parietal cortex (TPC). Apathy was measured with the Apathy Evaluation Scale (AES). Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA) were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI) in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA)/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx) levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

Spatial attention improves reliability of fMRI retinotopic mapping signals in occipital and parietal cortex

PubMed Central

Bressler, David W.; Silver, Michael A.

2010-01-01

Spatial attention improves visual perception and increases the amplitude of neural responses in visual cortex. In addition, spatial attention tasks and fMRI have been used to discover topographic visual field representations in regions outside visual cortex. We therefore hypothesized that requiring subjects to attend to a retinotopic mapping stimulus would facilitate the characterization of visual field representations in a number of cortical areas. In our study, subjects attended either a central fixation point or a wedge-shaped stimulus that rotated about the fixation point. Response reliability was assessed by computing coherence between the fMRI time series and a sinusoid with the same frequency as the rotating wedge stimulus. When subjects attended to the rotating wedge instead of ignoring it, the reliability of retinotopic mapping signals increased by approximately 50% in early visual cortical areas (V1, V2, V3, V3A/B, V4) and ventral occipital cortex (VO1) and by approximately 75% in lateral occipital (LO1, LO2) and posterior parietal (IPS0, IPS1 and IPS2) cortical areas. Additionally, one 5-minute run of retinotopic mapping in the attention-to-wedge condition produced responses as reliable as the average of three to five (early visual cortex) or more than five (lateral occipital, ventral occipital, and posterior parietal cortex) attention-to-fixation runs. These results demonstrate that allocating attention to the retinotopic mapping stimulus substantially reduces the amount of scanning time needed to determine the visual field representations in occipital and parietal topographic cortical areas. Attention significantly increased response reliability in every cortical area we examined and may therefore be a general mechanism for improving the fidelity of neural representations of sensory stimuli at multiple levels of the cortical processing hierarchy. PMID:20600961

Avalanche Analysis from Multielectrode Ensemble Recordings in Cat, Monkey, and Human Cerebral Cortex during Wakefulness and Sleep

PubMed Central

Dehghani, Nima; Hatsopoulos, Nicholas G.; Haga, Zach D.; Parker, Rebecca A.; Greger, Bradley; Halgren, Eric; Cash, Sydney S.; Destexhe, Alain

2012-01-01

Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep, and REM sleep, using high density electrode arrays in cat motor cortex (96 electrodes), monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes) in epileptic patients. In neuronal avalanches defined from units (up to 160 single units), the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs) and in particular LFP negative peaks (nLFPs) among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and premotor cortices). In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP) peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF) and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey, and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man. PMID:22934053

Effect of light on the activity of motor cortex neurons during locomotion

PubMed Central

Armer, Madison C.; Nilaweera, Wijitha U.; Rivers, Trevor J.; Dasgupta, Namrata M.; Beloozerova, Irina N.

2013-01-01

The motor cortex plays a critical role in accurate visually guided movements such as reaching and target stepping. However, the manner in which vision influences the movement-related activity of neurons in the motor cortex is not well understood. In this study we have investigated how the locomotion-related activity of neurons in the motor cortex is modified when subjects switch between walking in the darkness and in light. Three adult cats were trained to walk through corridors of an experimental chamber for a food reward. On randomly selected trials, lights were extinguished for approximately four seconds when the cat was in a straight portion of the chamber's corridor. Discharges of 146 neurons from layer V of the motor cortex, including 51 pyramidal tract cells (PTNs), were recorded and compared between light and dark conditions. It was found that while cats’ movements during locomotion in light and darkness were similar (as judged from the analysis of three-dimensional limb kinematics and the activity of limb muscles), the firing behavior of 49% (71/146) of neurons was different between the two walking conditions. This included differences in the mean discharge rate (19%, 28/146 of neurons), depth of stride-related frequency modulation (24%, 32/131), duration of the period of elevated firing ([PEF], 19%, 25/131), and number of PEFs among stride-related neurons (26%, 34/131). 20% of responding neurons exhibited more than one type of change. We conclude that visual input plays a very significant role in determining neuronal activity in the motor cortex during locomotion by altering one, or occasionally multiple, parameters of locomotion-related discharges of its neurons. PMID:23680161

Effect of light on the activity of motor cortex neurons during locomotion.

PubMed

Armer, Madison C; Nilaweera, Wijitha U; Rivers, Trevor J; Dasgupta, Namrata M; Beloozerova, Irina N

2013-08-01

The motor cortex plays a critical role in accurate visually guided movements such as reaching and target stepping. However, the manner in which vision influences the movement-related activity of neurons in the motor cortex is not well understood. In this study we have investigated how the locomotion-related activity of neurons in the motor cortex is modified when subjects switch between walking in the darkness and in light. Three adult cats were trained to walk through corridors of an experimental chamber for a food reward. On randomly selected trials, lights were extinguished for approximately 4s when the cat was in a straight portion of the chamber's corridor. Discharges of 146 neurons from layer V of the motor cortex, including 51 pyramidal tract cells (PTNs), were recorded and compared between light and dark conditions. It was found that while cats' movements during locomotion in light and darkness were similar (as judged from the analysis of three-dimensional limb kinematics and the activity of limb muscles), the firing behavior of 49% (71/146) of neurons was different between the two walking conditions. This included differences in the mean discharge rate (19%, 28/146 of neurons), depth of stride-related frequency modulation (24%, 32/131), duration of the period of elevated firing ([PEF], 19%, 25/131), and number of PEFs among stride-related neurons (26%, 34/131). 20% of responding neurons exhibited more than one type of change. We conclude that visual input plays a very significant role in determining neuronal activity in the motor cortex during locomotion by altering one, or occasionally multiple, parameters of locomotion-related discharges of its neurons. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Early sensitivity of left perisylvian cortex to relationality in nouns and verbs.

PubMed

Williams, Adina; Reddigari, Samir; Pylkkänen, Liina

2017-06-01

The ability to track the relationality of concepts, i.e., their capacity to encode a relationship between entities, is one of the core semantic abilities humans possess. In language processing, we systematically leverage this ability when computing verbal argument structure, in order to link participants to the events they participate in. Previous work has converged on a large region of left posterior perisylvian cortex as a locus for such processing, but the wide range of experimental stimuli and manipulations has yielded an unclear picture of the region's exact role(s). Importantly, there is a tendency for effects of relationality in single-word studies to localize to posterior temporo-parietal cortex, while argument structure effects in sentences appear in left superior temporal cortex. To characterize these sensitivities, we designed two MEG experiments that cross the factors relationality and eventivity. The first used minimal noun phrases and tested for an effect of semantic composition, while the second employed full sentences and a manipulation of grammatical category. The former identified a region of the left inferior parietal lobe sensitive to relationality, but not eventivity or combination, beginning at 170ms. The latter revealed a similarly-timed effect of relationality in left mid-superior temporal cortex, independent of eventivity and category. The results suggest that i) multiple sub-regions of perisylvian cortex are sensitive to the relationality carried by concepts even in the absence of arguments, ii) linguistic context modulates the locus of this sensitivity, consistent with prior studies, and iii) relationality information is accessed early - before 200ms - regardless of the concept's event status or syntactic category. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inflow-vascular space occupancy (iVASO) reproducibility in the hippocampus and cortex at different blood water nulling times.

PubMed

Rane, Swati; Talati, Pratik; Donahue, Manus J; Heckers, Stephan

2016-06-01

Inflow-vascular space occupancy (iVASO) measures arterial cerebral blood volume (aCBV) using accurate blood water nulling (inversion time [TI]) when arterial blood reaches the capillary, i.e., at the arterial arrival time. This work assessed the reproducibility of iVASO measurements in the hippocampus and cortex at multiple TIs. The iVASO approach was implemented at multiple TIs in 10 healthy volunteers at 3 Tesla. aCBV values were measured at each TI in the left and right hippocampus, and the cortex. Reproducibility of aCBV measurements within scans (same day) and across sessions (different days) was assessed using the intraclass correlation coefficient (ICC). Overall hippocampal aCBV was significantly higher than cortical aCBV, likely due to higher gray matter volume. Hippocampal ICC values were high at short TIs (≤914 ms; intrascan values = 0.80-0.96, interscan values = 0.61-0.91). Cortically, high ICC values were observed at intermediate TIs of 914 (intra: 0.93, inter: 0.87) and 1034 ms (intra: 0.96, inter: 0.86). The ICC values were comparable to established contrast-based CBV measures. iVASO measurements are reproducible within and across sessions. TIs for iVASO measurements should be chosen carefully, taking into account heterogeneous arterial arrival times in different brain regions. Magn Reson Med 75:2379-2387, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Processes in arithmetic strategy selection: a fMRI study.

PubMed

Taillan, Julien; Ardiale, Eléonore; Anton, Jean-Luc; Nazarian, Bruno; Félician, Olivier; Lemaire, Patrick

2015-01-01

This neuroimaging (functional magnetic resonance imaging) study investigated neural correlates of strategy selection. Young adults performed an arithmetic task in two different conditions. In both conditions, participants had to provide estimates of two-digit multiplication problems like 54 × 78. In the choice condition, participants had to select the better of two available rounding strategies, rounding-up (RU) strategy (i.e., doing 60 × 80 = 4,800) or rounding-down (RD) strategy (i.e., doing 50 × 70 = 3,500 to estimate product of 54 × 78). In the no-choice condition, participants did not have to select strategy on each problem but were told which strategy to use; they executed RU and RD strategies each on a series of problems. Participants also had a control task (i.e., providing correct products of multiplication problems like 40 × 50). Brain activations and performance were analyzed as a function of these conditions. Participants were able to frequently choose the better strategy in the choice condition; they were also slower when they executed the difficult RU than the easier RD. Neuroimaging data showed greater brain activations in right anterior cingulate cortex (ACC), dorso-lateral prefrontal cortex (DLPFC), and angular gyrus (ANG), when selecting (relative to executing) the better strategy on each problem. Moreover, RU was associated with more parietal cortex activation than RD. These results suggest an important role of fronto-parietal network in strategy selection and have important implications for our further understanding and modeling cognitive processes underlying strategy selection.

Processes in arithmetic strategy selection: a fMRI study

PubMed Central

Taillan, Julien; Ardiale, Eléonore; Anton, Jean-Luc; Nazarian, Bruno; Félician, Olivier; Lemaire, Patrick

2015-01-01

This neuroimaging (functional magnetic resonance imaging) study investigated neural correlates of strategy selection. Young adults performed an arithmetic task in two different conditions. In both conditions, participants had to provide estimates of two-digit multiplication problems like 54 × 78. In the choice condition, participants had to select the better of two available rounding strategies, rounding-up (RU) strategy (i.e., doing 60 × 80 = 4,800) or rounding-down (RD) strategy (i.e., doing 50 × 70 = 3,500 to estimate product of 54 × 78). In the no-choice condition, participants did not have to select strategy on each problem but were told which strategy to use; they executed RU and RD strategies each on a series of problems. Participants also had a control task (i.e., providing correct products of multiplication problems like 40 × 50). Brain activations and performance were analyzed as a function of these conditions. Participants were able to frequently choose the better strategy in the choice condition; they were also slower when they executed the difficult RU than the easier RD. Neuroimaging data showed greater brain activations in right anterior cingulate cortex (ACC), dorso-lateral prefrontal cortex (DLPFC), and angular gyrus (ANG), when selecting (relative to executing) the better strategy on each problem. Moreover, RU was associated with more parietal cortex activation than RD. These results suggest an important role of fronto-parietal network in strategy selection and have important implications for our further understanding and modeling cognitive processes underlying strategy selection. PMID:25698995

Frontolimbic Neural Circuit Changes in Emotional Processing and Inhibitory Control Associated With Clinical Improvement Following Transference-Focused Psychotherapy in Borderline Personality Disorder

PubMed Central

Perez, David L.; Vago, David R.; Pan, Hong; Root, James; Tuescher, Oliver; Fuchs, Benjamin H.; Leung, Lorene; Epstein, Jane; Cain, Nicole M.; Clarkin, John F.; Lenzenweger, Mark F.; Kernberg, Otto F.; Levy, Kenneth N.; Silbersweig, David A.; Stern, Emily

2015-01-01

Aim Borderline personality disorder (BPD) is characterized by self-regulation deficits, including impulsivity and affective lability. Transference-Focused Psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms across multiple cognitive-emotional domains in BPD. This pilot study aims to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP. Methods BPD subjects (N=10) were scanned pre- and post-TFP treatment using a within-subjects design. A disorder-specific emotional-linguistic go/no-go fMRI paradigm was used to probe the interaction between negative emotional processing and inhibitory control. Results Analyses demonstrated significant treatment-related effects with relative increased dorsal prefrontal (dorsal anterior cingulate, dorsolateral prefrontal, and frontopolar cortices) activation, and relative decreased ventrolateral prefrontal cortex and hippocampal activation following treatment. Clinical improvement in constraint correlated positively with relative increased left dorsal anterior cingulate cortex activation. Clinical improvement in affective lability correlated positively with left posterior-medial orbitofrontal cortex/ventral striatum activation, and negatively with right amygdala/parahippocampal activation. Post-treatment improvements in constraint were predicted by pre-treatment right dorsal anterior cingulate cortex hypoactivation, and pre-treatment left posterior-medial orbitofrontal cortex/ventral striatum hypoactivation predicted improvements in affective lability. Conclusions These preliminary findings demonstrate potential TFP-associated alterations in frontolimbic circuitry and begin to identify neural mechanisms associated with a psychodynamically-oriented psychotherapy. PMID:26289141

Lateral prefrontal cortex: architectonic and functional organization

PubMed Central

Petrides, Michael

2005-01-01

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral–caudal axis and a dorsal–ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal–ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information. PMID:15937012

Homeostatic Regulation of Memory Systems and Adaptive Decisions

PubMed Central

Mizumori, Sheri JY; Jo, Yong Sang

2013-01-01

While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The “multiple memory systems of the brain” have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:23929788

Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving

PubMed Central

Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

2015-01-01

Objectives In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Results Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Conclusions Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions. PMID:25993263

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women

PubMed Central

García-Casares, Natalia; Bernal-López, María R.; Roé-Vellvé, Nuria; Gutiérrez-Bedmar, Mario; García-Arnés, Juan A.; Ramos-Rodriguez, José R.; Alfaro, Francisco; Santamaria-Fernández, Sonia; Jiménez-Murcia, Susana; Garcia-Garcia, Isabel; Valdivielso, Pedro; Fernández-Aranda, Fernando; Tinahones, Francisco J.; Gómez-Huelgas, Ricardo

2017-01-01

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m2) was 38.15 ± 4.7 vs. 34.18 ± 4.5 (p < 0.02), and body weight (kg) was 98.5 ± 13.1 vs. 88.28 ± 12.2 (p < 0.03). All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex (p < 0.001), left posterior cingulate (p < 0.001), and right posterior cingulate (p < 0.03); decreased connectivity between the left superior frontal gyrus and the right temporal cortex (p < 0.01); decreased connectivity between the prefrontal cortex and the somatosensory cortex (p < 0.025); and decreased connectivity between the left and right posterior cingulate (p < 0.04). Results were considered significant at a voxel-wise threshold of p ≤ 0.05, and a cluster-level family-wise error correction for multiple comparisons of p ≤ 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity (the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex) may be modified by a weight loss program including a Mediterranean diet and physical exercise. PMID:28671558

Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving.

PubMed

Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

2015-01-01

In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

Homeostatic regulation of memory systems and adaptive decisions.

PubMed

Mizumori, Sheri J Y; Jo, Yong Sang

2013-11-01

While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The "multiple memory systems of the brain" have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. Copyright © 2013 Wiley Periodicals, Inc.

Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days.

PubMed

Schild, Laura J; Divi, Rao L; Beland, Frederick A; Churchwell, Mona I; Doerge, Daniel R; Gamboa da Costa, Gonçalo; Marques, M Matilde; Poirier, Miriam C

2003-09-15

The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides), whereas brain cortex DNA contained lower adduct levels (0.6-4.8 adducts/10(8) nucleotides) and the lowest levels were measured in the kidney (0.2-0.4 adducts/10(8) nucleotides). This study indicates that cynomolgus monkeys are capable of metabolizing TAM to genotoxic intermediates that form TAM-DNA adducts in multiple tissues.

Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex.

PubMed

Olulade, O A; Flowers, D L; Napoliello, E M; Eden, G F

2015-01-01

fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called "visual word form area", VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report absence of an IFC gradient and connectivity between the lateral aspect of the IFC and the anterior occipito-temporal cortex in the dyslexic children. Together, our results provide insights into the source of the anomalies reported in previous studies of dyslexia and add to the growing evidence of an orthographic role of IFC in reading.

The Neural Basis of Obligatory Decomposition of Suffixed Words

ERIC Educational Resources Information Center

Lewis, Gwyneth; Solomyak, Olla; Marantz, Alec

2011-01-01

Recent neurolinguistic studies present somewhat conflicting evidence concerning the role of the inferior temporal cortex (IT) in visual word recognition within the first 200 ms after presentation. On the one hand, fMRI studies of the Visual Word Form Area (VWFA) suggest that the IT might recover representations of the orthographic form of words.…

A Putative Multiple-Demand System in the Macaque Brain.

PubMed

Mitchell, Daniel J; Bell, Andrew H; Buckley, Mark J; Mitchell, Anna S; Sallet, Jerome; Duncan, John

2016-08-17

In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex. Copyright © 2016 Mitchell et al.

Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis.

PubMed

Cawley, Niamh; Solanky, Bhavana S; Muhlert, Nils; Tur, Carmen; Edden, Richard A E; Wheeler-Kingshott, Claudia A M; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2015-09-01

Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = -0.403 mM, 95% confidence intervals -0.792, -0.014, P = 0.043) and sensorimotor cortex (adjusted difference = -0.385 mM, 95% confidence intervals -0.667, -0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted -10.86 (95% confidence intervals -16.786 to -4.482) decrease in grip strength (kg force) (P < 0.001) and -8.74 (95% confidence intervals -13.943 to -3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis.See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

PubMed

Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

2015-01-01

Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

Preferential stabilization of newly formed dendritic spines in motor cortex during manual skill learning predicts performance gains, but not memory endurance.

PubMed

Clark, Taylor A; Fu, Min; Dunn, Andrew K; Zuo, Yi; Jones, Theresa A

2018-07-01

Previous findings that skill learning is associated with the formation and preferential stabilization of new dendritic spines in cortex have raised the possibility that this preferential stabilization is a mechanism for lasting skill memory. We investigated this possibility in adult mice using in vivo two-photon imaging to monitor spine dynamics on superficial apical dendrites of layer V pyramidal neurons in motor cortex during manual skill learning. Spine formation increased over the first 3 days of training on a skilled reaching task, followed by increased spine elimination. A greater proportion of spines formed during the first 3 training days were lost if training stopped after 3, compared with 15 days. However, performance gains achieved in 3 training days persisted, indicating that preferential new spine stabilization was non-essential for skill retention. Consistent with a role in ongoing skill refinement, the persistence of spines formed early in training strongly predicted performance improvements. Finally, while we observed no net spine density change on superficial dendrites, the density of spines on deeper apical branches of the same neuronal population was increased regardless of training duration, suggestive of a potential role in the retention of the initial skill memory. Together, these results indicate dendritic subpopulation-dependent variation in spine structural responses to skill learning, which potentially reflect distinct contributions to the refinement and retention of newly acquired motor skills. Copyright © 2018 Elsevier Inc. All rights reserved.

Neural correlates of abnormal sensory discrimination in laryngeal dystonia.

PubMed

Termsarasab, Pichet; Ramdhani, Ritesh A; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J; Reilly, Richard B; Hutchinson, Michael; Ozelius, Laurie J; Simonyan, Kristina

2016-01-01

Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

The harmonic organization of auditory cortex.

PubMed

Wang, Xiaoqin

2013-12-17

A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds.

Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function.

PubMed

Curado, Marco; Fritsch, Brita; Reis, Janine

2016-02-04

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

Hemispherical map for the human brain cortex

NASA Astrophysics Data System (ADS)

Tosun, Duygu; Prince, Jerry L.

2001-07-01

Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex.

PubMed

Mejias, Jorge F; Murray, John D; Kennedy, Henry; Wang, Xiao-Jing

2016-11-01

Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions.

Neural Substrates Underlying Effort, Time, and Risk-Based Decision Making in Motivated Behavior

PubMed Central

Bailey, Matthew R.; Simpson, Eleanor H.; Balsam, Peter D

2016-01-01

All mobile organisms rely on adaptive motivated behavior to overcome the challenges of living in an environment in which essential resources may be limited. A variety of influences ranging from an organism’s environment, experiential history, and physiological state all influence a cost-benefit analysis which allows motivation to energize behavior and direct it toward specific goals. Here we review the substantial amount of research aimed at discovering the interconnected neural circuits which allow organisms to carry-out the cost-benefit computations which allow them to behave in adaptive ways. We specifically focus on how the brain deals with different types of costs, including effort requirements, delays to reward and payoff riskiness. An examination of this broad literature highlights the importance of the extended neural circuits which enable organisms to make decisions about these different types of costs. This involves Cortical Structures, including the Anterior Cingulate Cortex (ACC), the Orbital Frontal Cortex (OFC), the Infralimbic Cortex (IL), and prelimbic Cortex (PL), as well as the Baso-Lateral Amygdala (BLA), the Nucleus Accumbens (Nacc), the Ventral Pallidal (VP), the Sub Thalamic Nucleus (STN) among others. Some regions are involved in multiple aspects of cost-benefit computations while the involvement of other regions is restricted to information relating to specific types of costs. PMID:27427327

Neural substrates underlying effort, time, and risk-based decision making in motivated behavior.

PubMed

Bailey, Matthew R; Simpson, Eleanor H; Balsam, Peter D

2016-09-01

All mobile organisms rely on adaptive motivated behavior to overcome the challenges of living in an environment in which essential resources may be limited. A variety of influences ranging from an organism's environment, experiential history, and physiological state all influence a cost-benefit analysis which allows motivation to energize behavior and direct it toward specific goals. Here we review the substantial amount of research aimed at discovering the interconnected neural circuits which allow organisms to carry-out the cost-benefit computations which allow them to behave in adaptive ways. We specifically focus on how the brain deals with different types of costs, including effort requirements, delays to reward and payoff riskiness. An examination of this broad literature highlights the importance of the extended neural circuits which enable organisms to make decisions about these different types of costs. This involves Cortical Structures, including the Anterior Cingulate Cortex (ACC), the Orbital Frontal Cortex (OFC), the Infralimbic Cortex (IL), and prelimbic Cortex (PL), as well as the Baso-Lateral Amygdala (BLA), the Nucleus Accumbens (NAcc), the Ventral Pallidal (VP), the Sub Thalamic Nucleus (STN) among others. Some regions are involved in multiple aspects of cost-benefit computations while the involvement of other regions is restricted to information relating to specific types of costs. Copyright © 2016 Elsevier Inc. All rights reserved.

Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex

PubMed Central

Mejias, Jorge F.; Murray, John D.; Kennedy, Henry; Wang, Xiao-Jing

2016-01-01

Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions. PMID:28138530

Spatio-Temporal Patterning in Primary Motor Cortex at Movement Onset.

PubMed

Best, Matthew D; Suminski, Aaron J; Takahashi, Kazutaka; Brown, Kevin A; Hatsopoulos, Nicholas G

2017-02-01

Voluntary movement initiation involves the engagement of large populations of motor cortical neurons around movement onset. Despite knowledge of the temporal dynamics that lead to movement, the spatial structure of these dynamics across the cortical surface remains unknown. In data from 4 rhesus macaques, we show that the timing of attenuation of beta frequency local field potential oscillations, a correlate of locally activated cortex, forms a spatial gradient across primary motor cortex (MI). We show that these spatio-temporal dynamics are recapitulated in the engagement order of ensembles of MI neurons. We demonstrate that these patterns are unique to movement onset and suggest that movement initiation requires a precise spatio-temporal sequential activation of neurons in MI. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Large-Scale Brain Networks Supporting Divided Attention across Spatial Locations and Sensory Modalities

PubMed Central

Santangelo, Valerio

2018-01-01

Higher-order cognitive processes were shown to rely on the interplay between large-scale neural networks. However, brain networks involved with the capability to split attentional resource over multiple spatial locations and multiple stimuli or sensory modalities have been largely unexplored to date. Here I re-analyzed data from Santangelo et al. (2010) to explore the causal interactions between large-scale brain networks during divided attention. During fMRI scanning, participants monitored streams of visual and/or auditory stimuli in one or two spatial locations for detection of occasional targets. This design allowed comparing a condition in which participants monitored one stimulus/modality (either visual or auditory) in two spatial locations vs. a condition in which participants monitored two stimuli/modalities (both visual and auditory) in one spatial location. The analysis of the independent components (ICs) revealed that dividing attentional resources across two spatial locations necessitated a brain network involving the left ventro- and dorso-lateral prefrontal cortex plus the posterior parietal cortex, including the intraparietal sulcus (IPS) and the angular gyrus, bilaterally. The analysis of Granger causality highlighted that the activity of lateral prefrontal regions were predictive of the activity of all of the posteriors parietal nodes. By contrast, dividing attention across two sensory modalities necessitated a brain network including nodes belonging to the dorsal frontoparietal network, i.e., the bilateral frontal eye-fields (FEF) and IPS, plus nodes belonging to the salience network, i.e., the anterior cingulated cortex and the left and right anterior insular cortex (aIC). The analysis of Granger causality highlights a tight interdependence between the dorsal frontoparietal and salience nodes in trials requiring divided attention between different sensory modalities. The current findings therefore highlighted a dissociation among brain networks implicated during divided attention across spatial locations and sensory modalities, pointing out the importance of investigating effective connectivity of large-scale brain networks supporting complex behavior. PMID:29535614

Large-Scale Brain Networks Supporting Divided Attention across Spatial Locations and Sensory Modalities.

PubMed

Santangelo, Valerio

2018-01-01

Higher-order cognitive processes were shown to rely on the interplay between large-scale neural networks. However, brain networks involved with the capability to split attentional resource over multiple spatial locations and multiple stimuli or sensory modalities have been largely unexplored to date. Here I re-analyzed data from Santangelo et al. (2010) to explore the causal interactions between large-scale brain networks during divided attention. During fMRI scanning, participants monitored streams of visual and/or auditory stimuli in one or two spatial locations for detection of occasional targets. This design allowed comparing a condition in which participants monitored one stimulus/modality (either visual or auditory) in two spatial locations vs. a condition in which participants monitored two stimuli/modalities (both visual and auditory) in one spatial location. The analysis of the independent components (ICs) revealed that dividing attentional resources across two spatial locations necessitated a brain network involving the left ventro- and dorso-lateral prefrontal cortex plus the posterior parietal cortex, including the intraparietal sulcus (IPS) and the angular gyrus, bilaterally. The analysis of Granger causality highlighted that the activity of lateral prefrontal regions were predictive of the activity of all of the posteriors parietal nodes. By contrast, dividing attention across two sensory modalities necessitated a brain network including nodes belonging to the dorsal frontoparietal network, i.e., the bilateral frontal eye-fields (FEF) and IPS, plus nodes belonging to the salience network, i.e., the anterior cingulated cortex and the left and right anterior insular cortex (aIC). The analysis of Granger causality highlights a tight interdependence between the dorsal frontoparietal and salience nodes in trials requiring divided attention between different sensory modalities. The current findings therefore highlighted a dissociation among brain networks implicated during divided attention across spatial locations and sensory modalities, pointing out the importance of investigating effective connectivity of large-scale brain networks supporting complex behavior.

Zinc histochemistry reveals circuit refinement and distinguishes visual areas in the developing ferret cerebral cortex.

PubMed

Khalil, Reem; Levitt, Jonathan B

2013-09-01

A critical question in brain development is whether different brain circuits mature concurrently or with different timescales. To characterize the anatomical and functional development of different visual cortical areas, one must be able to distinguish these areas. Here, we show that zinc histochemistry, which reveals a subset of glutamatergic processes, can be used to reliably distinguish visual areas in juvenile and adult ferret cerebral cortex, and that the postnatal decline in levels of synaptic zinc follows a broadly similar developmental trajectory in multiple areas of ferret visual cortex. Zinc staining in all areas examined (17, 18, 19, 21, and Suprasylvian) is greater in the 5-week-old than in the adult. Furthermore, there is less laminar variation in zinc staining in the 5-week-old visual cortex than in the adult. Despite differences in staining intensity, areal boundaries can be discerned in the juvenile as in the adult. By 6 weeks of age, we observe a significant decline in visual cortical synaptic zinc; this decline was most pronounced in layer IV of areas 17 and 18, with much less change in higher-order extrastriate areas during the important period in visual cortical development following eye opening. By 10 weeks of age, the laminar pattern of zinc staining in all visual areas is essentially adultlike. The decline in synaptic zinc in the supra- and infragranular layers in all areas proceeds at the same rate, though the decline in layer IV does not. These results suggest that the timecourse of synaptic zinc decline is lamina specific, and further confirm and extend the notion that at least some aspects of cortical maturation follow a similar developmental timecourse in multiple areas. The postnatal decline in synaptic zinc we observe during the second postnatal month begins after eye opening, consistent with evidence that synaptic zinc is regulated by sensory experience.

Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex.

PubMed

López-Ramos, Juan Carlos; Guerra-Narbona, Rafael; Delgado-García, José M

2015-01-01

Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex (mPFC) is identified in rodents by its dense connectivity with the mediodorsal (MD) thalamus, and because of its inputs from other sites, such as hippocampus and amygdala (Amyg). The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials (fPSPs) evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the MD thalamus, the hippocampal CA1 area, or the basolateral amygdala (BLA), and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. FPSPs evoked at the mPFC from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals' avoidance of the reward. FPSPs collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation) when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations.

Parcellation of left parietal tool representations by functional connectivity

PubMed Central

Garcea, Frank E.; Z. Mahon, Bradford

2014-01-01

Manipulating a tool according to its function requires the integration of visual, conceptual, and motor information, a process subserved in part by left parietal cortex. How these different types of information are integrated and how their integration is reflected in neural responses in the parietal lobule remains an open question. Here, participants viewed images of tools and animals during functional magnetic resonance imaging (fMRI). K-means clustering over time series data was used to parcellate left parietal cortex into subregions based on functional connectivity to a whole brain network of regions involved in tool processing. One cluster, in the inferior parietal cortex, expressed privileged functional connectivity to the left ventral premotor cortex. A second cluster, in the vicinity of the anterior intraparietal sulcus, expressed privileged functional connectivity with the left medial fusiform gyrus. A third cluster in the superior parietal lobe expressed privileged functional connectivity with dorsal occipital cortex. Control analyses using Monte Carlo style permutation tests demonstrated that the clustering solutions were outside the range of what would be observed based on chance ‘lumpiness’ in random data, or mere anatomical proximity. Finally, hierarchical clustering analyses were used to formally relate the resulting parcellation scheme of left parietal tool representations to previous work that has parcellated the left parietal lobule on purely anatomical grounds. These findings demonstrate significant heterogeneity in the functional organization of manipulable object representations in left parietal cortex, and outline a framework that generates novel predictions about the causes of some forms of upper limb apraxia. PMID:24892224

High-Definition Transcranial Direct Current Stimulation Enhances Conditioned Pain Modulation in Healthy Volunteers: A Randomized Trial.

PubMed

Flood, Andrew; Waddington, Gordon; Cathcart, Stuart

2016-05-01

Transcranial direct current stimulation (tDCS) is a form of brain stimulation that allows for the selective increase or decrease in the cortical excitability of a targeted region. When applied over the motor cortex it has been shown to induce changes in cortical and subcortical brain regions involved in descending pain inhibition or conditioned pain modulation (CPM). The aim of the current study was to assess whether activation of pain inhibitory pathways via tDCS of the motor cortex facilitates the CPM response. Elevated CPM after active tDCS of the motor cortex was hypothesized. Thirty healthy male volunteers attended 2 experimental sessions separated by 7 days. Both sessions consisted of CPM assessment after 20 minutes of either active or sham (placebo) tDCS over the motor cortex. CPM capacity was assessed via the pain-inhibits-pain protocol; CPM responses were shown to be elevated after active compared with sham tDCS. This report concludes that tDCS of the motor cortex enhances the CPM response in healthy men. This finding supports the potential utility of tDCS interventions in clinical pain treatment. The use of noninvasive brain stimulation over the motor cortex was shown to enhance the CPM effect. This finding supports the use of tDCS in the treatment of chronic pain, particularly in sufferers exhibiting maladaptive CPM. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex

PubMed Central

López-Ramos, Juan Carlos; Guerra-Narbona, Rafael; Delgado-García, José M.

2015-01-01

Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex (mPFC) is identified in rodents by its dense connectivity with the mediodorsal (MD) thalamus, and because of its inputs from other sites, such as hippocampus and amygdala (Amyg). The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials (fPSPs) evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the MD thalamus, the hippocampal CA1 area, or the basolateral amygdala (BLA), and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. FPSPs evoked at the mPFC from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals’ avoidance of the reward. FPSPs collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation) when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations. PMID:25688195

Harmonic template neurons in primate auditory cortex underlying complex sound processing

PubMed Central

Feng, Lei

2017-01-01

Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it has remained largely unknown what neural mechanisms are used by the primate auditory cortex to extract these biologically important acoustic structures. In this study, we discovered a unique class of harmonic template neurons in the core region of auditory cortex of a highly vocal New World primate, the common marmoset (Callithrix jacchus), across the entire hearing frequency range. Marmosets have a rich vocal repertoire and a similar hearing range to that of humans. Responses of these neurons show nonlinear facilitation to harmonic complex sounds over inharmonic sounds, selectivity for particular harmonic structures beyond two-tone combinations, and sensitivity to harmonic number and spectral regularity. Our findings suggest that the harmonic template neurons in auditory cortex may play an important role in processing sounds with harmonic structures, such as animal vocalizations, human speech, and music. PMID:28096341

Motor Deficits Are Produced By Removing Some Cortical Transplants Grafted Into Injured Sensorimotor Cortex of Neonatal Rats

PubMed Central

Sandor, Rick; Gonzalez, Manuel F.; Moseley, Michael; Sharp, Frank R.

1991-01-01

Fetal frontal cortex was transplanted into cavities formed in the right, motor cortex of neonatal rats. As adults, the animals were trained to press two levers in rapid succession with their left forelimb to receive food rewards. Once they had reached an optimal level of performance, the effect of removing their transplants was assessed. Surgical removal of transplants significantly impaired the performance of 2 of 4 subjects. Placing a crossstrain skin graft to induce the immunological rejection of the transplants produced a behavioral deficit in 1 of 2 subjects with complete transplant removal. Skin grafts produced no behavioral effects in four subjects that had surviving transplants. Since the motor deficit produced by transplant removal resembled those observed following the removal of normal motor cortex, we propose that these three transplants functioned within the host brain. Histology Showed that the procedures used to remove cortical grafts did not injure any host brains. Therefore, host brain damage is unlikely to account for the behavioral deterioration that followed transplant removals. PMID:1782254

Coding the presence of visual objects in a recurrent neural network of visual cortex.

PubMed

Zwickel, Timm; Wachtler, Thomas; Eckhorn, Reinhard

2007-01-01

Before we can recognize a visual object, our visual system has to segregate it from its background. This requires a fast mechanism for establishing the presence and location of objects independently of their identity. Recently, border-ownership neurons were recorded in monkey visual cortex which might be involved in this task [Zhou, H., Friedmann, H., von der Heydt, R., 2000. Coding of border ownership in monkey visual cortex. J. Neurosci. 20 (17), 6594-6611]. In order to explain the basic mechanisms required for fast coding of object presence, we have developed a neural network model of visual cortex consisting of three stages. Feed-forward and lateral connections support coding of Gestalt properties, including similarity, good continuation, and convexity. Neurons of the highest area respond to the presence of an object and encode its position, invariant of its form. Feedback connections to the lowest area facilitate orientation detectors activated by contours belonging to potential objects, and thus generate the experimentally observed border-ownership property. This feedback control acts fast and significantly improves the figure-ground segregation required for the consecutive task of object recognition.

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset

PubMed Central

Jackson, Stacey A. W.; Horst, Nicole K.; Pears, Andrew; Robbins, Trevor W.; Roberts, Angela C.

2016-01-01

Two learning mechanisms contribute to decision-making: goal-directed actions and the “habit” system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. PMID:27130662

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

2001-06-01

Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

Sparse bursts optimize information transmission in a multiplexed neural code.

PubMed

Naud, Richard; Sprekeler, Henning

2018-06-22

Many cortical neurons combine the information ascending and descending the cortical hierarchy. In the classical view, this information is combined nonlinearly to give rise to a single firing-rate output, which collapses all input streams into one. We analyze the extent to which neurons can simultaneously represent multiple input streams by using a code that distinguishes spike timing patterns at the level of a neural ensemble. Using computational simulations constrained by experimental data, we show that cortical neurons are well suited to generate such multiplexing. Interestingly, this neural code maximizes information for short and sparse bursts, a regime consistent with in vivo recordings. Neurons can also demultiplex this information, using specific connectivity patterns. The anatomy of the adult mammalian cortex suggests that these connectivity patterns are used by the nervous system to maintain sparse bursting and optimal multiplexing. Contrary to firing-rate coding, our findings indicate that the physiology and anatomy of the cortex may be interpreted as optimizing the transmission of multiple independent signals to different targets. Copyright © 2018 the Author(s). Published by PNAS.

Ecstatic Epileptic Seizures: A Glimpse into the Multiple Roles of the Insula.

PubMed

Gschwind, Markus; Picard, Fabienne

2016-01-01

Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds of these seizures, ecstatic auras provoke feelings of well-being, intense serenity, bliss, and "enhanced self-awareness." They are associated with the impression of time dilation, and can be described as a mystic experience by some patients. The functional neuroanatomy of ecstatic seizures is still debated. During recent years several patients presenting with ecstatic auras have been reported by others and us (in total n = 52); a few of them in the setting of presurgical evaluation including electrical brain stimulation. According to the recently recognized functions of the insula, and the results of nuclear brain imaging and electrical stimulation, the ecstatic symptoms in these patients seem to localize to a functional network centered around the anterior insular cortex, where we thus propose to locate this rare ictal phenomenon. Here we summarize the role of the multiple sensory, autonomic, affective, and cognitive functions of the insular cortex, which are integrated into the creation of self-awareness, and we suggest how this system may become dysfunctional on several levels during ecstatic aura.

Effects of transcranial random noise stimulation (tRNS) on affect, pain and attention in multiple sclerosis.

PubMed

Palm, Ulrich; Chalah, Moussa A; Padberg, Frank; Al-Ani, Tarik; Abdellaoui, Mohamed; Sorel, Marc; Dimitri, Dalia; Créange, Alain; Lefaucheur, Jean-Pascal; Ayache, Samar S

2016-01-01

Pain and cognitive impairment are frequent symptoms in patients with multiple sclerosis (MS). Neglecting experimental pain and paying attention to demanding tasks is reported to decrease the pain intensity. Little is known about the interaction between chronic neuropathic pain and attention disorders in MS. Recently, transcranial direct current stimulation (tDCS) was used to modulate various cognitive and motor symptoms in MS. We aimed to study the effects of transcranial random noise stimulation (tRNS), a form of transcranial electric stimulation, over the left dorsolateral prefrontal cortex (DLPFC) on attention and neuropathic pain in MS patients. 16 MS patients were included in a randomized, sham-controlled, cross-over study. Each patient randomly received two tRNS blocks, separated by three weeks of washout interval. Each block consisted of three consecutive daily sessions of either active or sham tRNS. The patients were evaluated for pain, attention and mood and further underwent an electrophysiological evaluation. Compared to sham, tRNS showed a trend to decrease the N2-P2 amplitudes of pain related evoked potentials and improve pain ratings. Attention performance and mood scales did not change after stimulations. This study suggests the role of tRNS in pain modulation, which could have been more evident with longer stimulation protocols.

Background and stimulus-induced patterns of high metabolic activity in the visual cortex (area 17) of the squirrel and macaque monkey

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

Humphrey, A.L.; Hendrickson, A.E.

1983-02-01

We have used 2-deoxy-D-(/sup 14/C)glucose (2-DG) autoradiography and cytochrome oxidase histochemistry to examine background and stimulus-induced patterns of metabolic activity in monkey striate cortex. In squirrel monkeys (Saimiri sciureus) that binocularly or monocularly viewed diffuse white light or binocularly viewed bars of many orientations and spatial frequencies, 2-DG consumption was not uniform across the cortex but consisted of regularly spaced radial zones of high uptake. The zones extended through all laminae except IVc beta and, when viewed tangentially, formed separate patches 500 microns apart. The cytochrome oxidase stain in these animals also revealed patches of high metabolism which coincided withmore » the 2-DG patches. Squirrel monkeys binocularly viewing vertical stripes showed parallel bands of increased 2-DG uptake in the cortex, while the cytochrome label in these animals remained patchy. When monkeys were kept in the dark during 2-DG exposure, 2-DG-labeled patches were not seen but cytochrome oxidase-positive patches remained. In macaque (Macaca nemestrina) monkeys, binocular stimulation with many orientations and spatial frequencies produced radial zones of high 2-DG uptake in layers I to IVa and VI. When viewed tangentially, these zones formed a dots-in-rows pattern with a spacing of 350 X 500 microns; cytochrome oxidase staining produced an identical pattern. Macaca differed from Saimiri in that monocular stimulation labeled alternate rows. These results indicate that there are radial zones of high background metabolism across squirrel and macaque monkey striate cortex. In Saimiri these zones do not appear to be related to an eye dominance system, while in Macaca they do. The presence of these zones of high metabolism may complicate the interpretation of 2-DG autoradiographs that result from specific visual stimuli.« less

Inter-cortical Modulation from Premotor to Motor Plasticity.

PubMed

Huang, Ying-Zu; Chen, Rou-Shayn; Fong, Po-Yu; Rothwell, John C; Chuang, Wen-Li; Weng, Yi-Hsin; Lin, Wey-Yil; Lu, Chin-Song

2018-06-11

Plasticity is involved in daily activities but abnormal plasticity may be deleterious. In this study, we found that motor plasticity could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Such changes in motor plasticity were associated with reduced learning of a simple motor task. We postulate that the premotor cortex adjusts the amount of motor plasticity to modulate motor learning through heterosynaptic metaplasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. This concept could be employed to intervene in diseases with abnormal plasticity. Primary motor cortex (M1) plasticity is known to be influenced by the excitability and prior activation history of M1 itself. However, little is known about how its plasticity is influenced by other areas of the brain. In the present study on humans of either sex who were known to respond to theta burst stimulation from previous studies, we found plasticity of M1 could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Motor plasticity was distorted and disappeared 30 min and 120 min respectively after premotor excitability was suppressed. Further evaluation revealed that such changes in motor plasticity were associated with impaired learning of a simple motor task. We postulate that the premotor cortex modulates the amount of plasticity within M1 through heterosynaptic metaplasticity, and that this may impact on learning of a simple motor task previously shown to be directly affected by M1 plasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. Furthermore, such concepts could be translated into therapeutic approaches for diseases with aberrant plasticity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prenatal stress decreases glycogen synthase kinase-3 phosphorylation in the rat frontal cortex.

PubMed

Szymańska, Magdalena; Suska, Anna; Budziszewska, Bogusława; Jaworska-Feil, Lucylla; Basta-Kaim, Agnieszka; Leśkiewicz, Monika; Kubera, Marta; Gergont, Aleksandra; Kroczka, Sławomir; Kaciński, Marek; Lasoń, Władysław

2009-01-01

It has been postulated that hyperactive glycogen synthase kinase-3 (GSK-3) is an important factor in the pathogenesis of depression, and that this enzyme also contributes to the mechanism of antidepressant drug action. In the present study, we investigated the effect of prenatal stress (an animal model of depression) and long-term treatment with antidepressant drugs on the concentration of GSK-3beta and its main regulating protein kinase B (PKB, Akt). The concentration of GSK-3beta, its inactive form (phospho-Ser9-GSK-3beta), and the amounts of active (phospho-Akt) and total Akt were determined in the hippocampus and frontal cortex in rats. In order to verify our animal model of depression, immobility time in the forced swim test (Porsolt test) was also determined.We found that prenatally stressed rats display a high level of immobility in the Porsolt test and chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine normalize this change. Western blot analysis demonstrated that GSK-3beta levels were significantly elevated in the frontal cortex, but not in the hippocampus, of prenatally stressed rats. The concentration of its non-active form (phospho-Ser9-GSK-3beta) was decreased only in the former brain structure. No changes were found in the amounts of active (phospho-Akt) and total Akt in both studied brain structures. Chronic treatment with antidepressant drugs diminished stress-induced alterations in GSK-3beta and phospho-GSK-3beta the frontal cortex, but had no effect on the concentration of these enzymes in the hippocampus. Moreover, levels of Akt and phospho-Akt in all experimental groups remained unchanged. Since our animal model of depression is connected with hyperactivity of the HPA axis, our results suggest that GSK-3beta is an important intracellular target for maladaptive glucocorticoid action on frontal cortex neurons and in antidepressant drug effects. Furthermore, the influence of stress and antidepressant drugs on GSK-3beta does not appear to impact the kinase activity of Akt.

Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction.

PubMed

Libé-Philippot, Baptiste; Michel, Vincent; Boutet de Monvel, Jacques; Le Gal, Sébastien; Dupont, Typhaine; Avan, Paul; Métin, Christine; Michalski, Nicolas; Petit, Christine

2017-07-25

Many genetic forms of congenital deafness affect the sound reception antenna of cochlear sensory cells, the hair bundle. The resulting sensory deprivation jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should revive this process. Nevertheless, this view assumes that no intrinsic AC deficits coexist with the cochlear ones, a possibility as yet unexplored. We show here that many GABAergic interneurons, from their generation in the medial ganglionic eminence up to their settlement in the AC, express two cadherin-related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links gating the mechanoelectrical transduction channels. Mutant mice lacking either protein showed a major decrease in the number of parvalbumin interneurons specifically in the AC, and displayed audiogenic reflex seizures. Cdhr15 - and Cdhr23 -expressing interneuron precursors in Cdhr23 -/- and Cdhr15 -/- mouse embryos, respectively, failed to enter the embryonic cortex and were scattered throughout the subpallium, consistent with the cell polarity abnormalities we observed in vitro. In the absence of adhesion G protein-coupled receptor V1 (adgrv1), another hair bundle link protein, the entry of Cdhr23 - and Cdhr15 -expressing interneuron precursors into the embryonic cortex was also impaired. Our results demonstrate that a population of newborn interneurons is endowed with specific cdhr proteins necessary for these cells to reach the developing AC. We suggest that an "early adhesion code" targets populations of interneuron precursors to restricted neocortical regions belonging to the same functional area. These findings open up new perspectives for auditory rehabilitation and cortical therapies in patients.

Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN)

PubMed Central

2018-01-01

Abstract The neocortex is composed of many distinct subtypes of neurons that must form precise subtype-specific connections to enable the cortex to perform complex functions. Callosal projection neurons (CPN) are the broad population of commissural neurons that connect the cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We identify in mouse that the lipid-bound scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal projections to premotor cortex. CAV1 is expressed by over 80% of these dual projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking early postnatally as axonal and dendritic targets are being reached and refined. CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of neurons that shares information both between hemispheres and with premotor cortex, suggesting function during postmitotic development and refinement of these neurons, rather than in their specification. Consistent with this, we find that Cav1 function is not necessary for the early specification of CPN/FPN, or for projecting to their dual axonal targets. CPN subtype-specific expression of Cav1 identifies and characterizes a first molecular component that distinguishes this functionally unique projection neuron population, a population that expands in primates, and is prototypical of additional dual and higher-order projection neuron subtypes. PMID:29379878

Importance of magnesium depletion with hypofunction of the biological clock in the pathophysiology of headhaches with photophobia, sudden infant death and some clinical forms of multiple sclerosis.

PubMed

Durlach, J; Pagès, N; Bac, P; Bara, M; Guiet-Bara, A

2004-12-01

Mg depletion is a type of Mg deficit due to a dysregulation of the Mg status. It cannot be corrected through nutritional supplementation only, but requires the most specific correction of the dysregulating mechanism. Among those, Biological Clock (BC) dysrhythmias are to be considered. The aim of this study is to analyze the clinical forms of Mg depletion with hypofunction of the Biological Clock (hBC). hBC may be due to either Primary disorders of BC [Suprachiasmatic Nuclei (SCN) and pineal gland (PG)] or Secondary with homeostatic response [reactive Photophobia (Pphi] to light neurostimulating effects [Nervous Hyper Excitability (NHE)]. The symptomatology is mainly diurnal and observed during fair weather (Spring,Summer). The elective marker of hBC is represented by a decrease in melatonin and in its metabolites in various fluids. The clinical forms of NHE due to Mg depletion with hBC are central and peripheral. The central forms associate anxiety, headaches and dyssomnia. The peripheral manifestations are neuromuscular: photosensitive epilepsia mainly. Three chronopathological forms of Mg depletion with hBC have been highlighted: 1. Headaches with Pphi: mainly migraine; 2. Sudden Infant Death Syndrome (SIDS); 3. Multiple Sclerosis (MS).- Headaches with Pphi, migraine particularly. These cephalalgias are diurnal with Pphi and are aggravated during the fair seasons (particularly during midnight sun-summer). Migraine is their typical form with its dishabituation to visual stimuli and its occipital cortex hyperexcitability. Comorbidity with anxiety is frequent. In 2/3 of the cases, it appears first.- SIDS might be linked to an impaired maturation of both photoendocrine system and brown adipose tissue. MS may be associated with primary disorders of BC Clinical forms of Mg depletion with hBC in MS present diurnal exacerbations and relapses during fair seasons. They have been underestimated because they disagree with the dogma of the < latitude gradient >, presently questioned. Comorbidities with anxiety and migraine are frequent.hBC may be treated by using darkness therapy with a balanced Mg status. Absolute light deprivation should only be used only in acute indications and is time-limited. Partial substitutive therapy and chromatotherapy have not been validated yet and are still uncertain.

A theory about a role of the hyper direct pathway in pattern expression by the basal ganglia.

PubMed

Jourdan, Ivan; Barttfeld, Pablo; Zanutto, B Silvano

2010-01-01

The Basal Ganglia (BG) are a group of nuclei, in the brain of mammalians and other vertebrates, strongly connected with the cerebral cortex, thalamus and other brain areas. The BG are associated with several brain functions including learning and motor control. When there is cortical activation, there is a strong synchronization between BG and cortex, i.e. when a given task is being executed or in the case of Parkinson disease[1], [2]. If we consider the internal segment of the Globus Pallidus (GPi) there is synchronism between GPi-cortex at frequencies as low as 3Hz to as high as 85Hz [1], [3]. In the other hand, in a delta sleep or in an anesthetized case, a very low frequency correlation is observed (1-10 Hz), but no high frequency correlation between GPi-cortex [1], [2], [3]. It is unknown why this decorrelation happens. But It is agreement that when there is no pattern to select, like in delta sleep or with an anesthetized model, the BG network would maintain the GPi and cortex decorrelated at high frequencies. Many thalamus-BG and thalamus-BG-cortex loops are modulators of the BG activity. Particularly there exists an anatomic thalamus-BG loop, formed by GPi, intralaminar thalamic nuclei (IL) and Subthalamic Nucleus (STN) [4]. Using a computational model, based on an "Integrate and Fire" neural network, we analyzed the IL nucleus as a modulator of the so-called hyper direct pathway. Our results show that, in an anesthetic case, this thalamic path could be relevant to allow a high frequency decorrelated state between the GPi and cortex.

Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex.

PubMed

Winter, Shawn S; Mehlman, Max L; Clark, Benjamin J; Taube, Jeffrey S

2015-10-05

Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal's movements. These signals include grid cells, which fire at multiple locations, forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz electroencephalogram (EEG) oscillation that is modulated by the animals' movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall head-direction (HD) cell characteristics, but abolished both velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity, which may be used as a speed signal to generate the repeating pattern of grid cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

PubMed

Okumura, Akihisa; Lee, Tsubasa; Ikeno, Mitsuru; Shimojima, Keiko; Kajino, Kazunori; Inoue, Yuka; Yoshikawa, Naomi; Suganuma, Hiroki; Suzuki, Mitsuyoshi; Hisata, Ken; Shoji, Hiromichi; Takanashi, Jun-ichi; Barkovich, A James; Shimizu, Toshiaki; Yamamoto, Toshiyuki; Hayashi, Masaharu

2012-11-01

Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Regional Homogeneity Predicts Creative Insight: A Resting-State fMRI Study.

PubMed

Lin, Jiabao; Cui, Xuan; Dai, Xiaoying; Mo, Lei

2018-01-01

Creative insight plays an important role in our daily life. Previous studies have investigated the neural correlates of creative insight by functional magnetic resonance imaging (fMRI), however, the intrinsic resting-state brain activity associated with creative insight is still unclear. In the present study, we used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in creative insight, which was compued by the response time (RT) of creative Chinese character chunk decomposition. The findings indicated that ReHo in the anterior cingulate cortex (ACC)/caudate nucleus (CN) and angular gyrus (AG)/superior temporal gyrus (STG)/inferior parietal lobe (IPL) negatively predicted creative insight. Furthermore, these findings suggested that spontaneous brain activity in multiple regions related to breaking and establishing mental sets, goal-directed solutions exploring, shifting attention, forming new associations and emotion experience contributes to creative insight. In conclusion, the present study provides new evidence to further understand the cognitive processing and neural correlates of creative insight.

Early Exposure to Haloperidol or Olanzapine Induces Long-Term Alterations of Dendritic Form

PubMed Central

Frost, Douglas O.; Page, Stephanie Cerceo; Carroll, Cathy; Kolb, Bryan

2009-01-01

Exposure of the developing brain to a wide variety of drugs of abuse (eg., stimulants, opioids, ethanol, etc.) can induce life-long changes in behavior and neural circuitry. However, the long-term effects of exposure to therapeutic, psychotropic drugs have only recently begun to be appreciated. Antipsychotic drugs are little studied in this regard. Here we quantitatively analyzed dendritic architecture in adult mice treated with paradigmatic typical- (haloperidol) or atypical (olanzapine) antipsychotic drugs at developmental stages corresponding to fetal or fetal plus early childhood stages in humans. In layer 3 pyramidal cells of the medial and orbital prefrontal cortices and the parietal cortex and in spiny neurons of the core of the nucleus accumbens, both drugs induced significant changes (predominantly reductions) in the amount and complexity of dendritic arbor and the density of dendritic spines. The drug-induced plasticity of dendritic architecture suggests changes in patterns of neuronal connectivity in multiple brain regions that are likely to be functionally significant. PMID:19862684

Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex

PubMed Central

Winter, Shawn S.; Mehlman, Max L.; Clark, Benjamin J.; Taube, Jeffrey S.

2015-01-01

Summary Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal’s movements. These signals include grid cells, which fire at multiple locations forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz EEG oscillation that is modulated by the animals’ movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall HD cell characteristics, and abolished velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity. Velocity modulation of theta may be used as a speed signal to generate the repeating pattern of grid cells. PMID:26387719

[The motor organization of cerebral cortex and the role of the mirror neuron system. Clinical impact for rehabilitation].

PubMed

Sallés, Laia; Gironès, Xavier; Lafuente, José Vicente

2015-01-06

The basic characteristics of Penfield homunculus (somatotopy and unique representation) have been questioned. The existence of a defined anatomo-functional organization within different segments of the same region is controversial. The presence of multiple motor representations in the primary motor area and in the parietal lobe interconnected by parieto-frontal circuits, which are widely overlapped, form a complex organization. Both features support the recovery of functions after brain injury. Regarding the movement organization, it is possible to yield a relevant impact through the understanding of actions and intentions of others, which is mediated by the activation of mirror-neuron systems. The implementation of cognitive functions (observation, image of the action and imitation) from the acute treatment phase allows the activation of motor representations without having to perform the action and it plays an important role in learning motor patterns. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Are memory traces localized or distributed?

PubMed

Thompson, R F

1991-01-01

Evidence supports the view that "memory traces" are formed in the hippocampus and in the cerebellum in classical conditioning of discrete behavioral responses (e.g. eyeblink conditioning). In the hippocampus, learning results in long-lasting increases in excitability of pyramidal neurons that appear to be localized to these neurons (i.e. changes in membrane properties and receptor function). However, these learning-altered pyramidal neurons are distributed widely throughout CA3 and CA1. Although it plays a key role in certain aspects of classical conditioning, the hippocampus is not necessary for learning and memory of the basic conditioned responses. The cerebellum and its associated brain stem circuitry, on the other hand, does appear to be essential (necessary and sufficient) for learning and memory of the conditioned response. Evidence to date is most consistent with a localized trace in the interpositus nucleus and multiple localized traces in cerebellar cortex, each involving relatively large ensembles of neurons. Perhaps "procedural" memory traces are relatively localized and "declarative" traces more widely distributed.

The Convallis Rule for Unsupervised Learning in Cortical Networks

PubMed Central

Yger, Pierre; Harris, Kenneth D.

2013-01-01

The phenomenology and cellular mechanisms of cortical synaptic plasticity are becoming known in increasing detail, but the computational principles by which cortical plasticity enables the development of sensory representations are unclear. Here we describe a framework for cortical synaptic plasticity termed the “Convallis rule”, mathematically derived from a principle of unsupervised learning via constrained optimization. Implementation of the rule caused a recurrent cortex-like network of simulated spiking neurons to develop rate representations of real-world speech stimuli, enabling classification by a downstream linear decoder. Applied to spike patterns used in in vitro plasticity experiments, the rule reproduced multiple results including and beyond STDP. However STDP alone produced poorer learning performance. The mathematical form of the rule is consistent with a dual coincidence detector mechanism that has been suggested by experiments in several synaptic classes of juvenile neocortex. Based on this confluence of normative, phenomenological, and mechanistic evidence, we suggest that the rule may approximate a fundamental computational principle of the neocortex. PMID:24204224

Expanding the spectrum of neuronal pathology in multiple system atrophy.

PubMed

Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

2015-08-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perceptual learning and adult cortical plasticity.

PubMed

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

2009-06-15

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

PROBING HUMAN AND MONKEY ANTERIOR CINGULATE CORTEX IN VARIABLE ENVIRONMENTS

PubMed Central

Walton, Mark E.; Mars, Rogier B.

2008-01-01

Previous research has identified the anterior cingulate cortex (ACC) as an important node in the neural network underlying decision making in primates. Decision making can, however, be studied under large variety of circumstances, ranging from the standard well-controlled lab situation to more natural, stochastic settings during which multiple agents interact. Here, we illustrate how these different varieties of decision making studied can influence theories of ACC function in monkeys. Converging evidence from unit recordings and lesions studies now suggest that the ACC is important for interpreting outcome information according to the current task context to guide future action selection. We then apply this framework to the study of human ACC function and discuss its potential implications. PMID:18189014

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

PubMed Central

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

2013-01-01

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

Parallel processing and learning in simple systems. Annual report, 10 January 1987-9 January 1988

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

Mpitsos, G.J.

1988-03-11

To date it has been demonstrated that an experimental animal, the sea slug Pleurobranchaea, is capable of one-trial food-aversion learning, and that the muscarinic antagonist scopolamine in low doses causes an enhancement of learning. Pharmacologic binding studies using a new, /sup 125/I-form of quinuclidinyl benzilate, in addition to studies using the /sup 3/H form of this ligand, have uncovered not only the classical types of muscarinic receptors that are typical of vertebrate cortex, but also a new form that is not found in other invertebrates tested. Usually muscarinic receptors are found in low densities in invertebrate neural membranes, but themore » density of the new form in this animal's neural membranes is similar to the density of the classic receptors in mammalian cortex. Neurophysiological studies of individual neurons in small groups of identifiable neurons have shown that their activity is variable, as is the behavior that they take part in generating, and that the variability fits the definition of low-dimensional chaos. Findings show that such variability is an important feature of the emergence of adaptive responses arising from parallel, distributed neural networks in biological systems.« less

Histological comparison of long-bone cortex between 11-year-old giant cow with dermal dysplasia and the child cow aged 8.5 years.

PubMed

Mori, Ryoichi; Kodaka, Tetsuo; Naito, Yoshihisa

2012-02-01

Young calves are known to be formed with laminar bone in long-bone cortex during growing periods and the osteon formation begins later. Previously, we reported that an 11-year-old giant Holstein cow with dermal dysplasia showed a delayed osteon formation. An 8.5-year-old cow, born from the giant Holstein cow, also showed some dermal dysplasia and the outer-half layer of the child almost retained laminar bone similar to that of the mother, although the body weight was approximately normal. The mother had formed the inner circumferential lamella and the child was going to form the inner circumferential lamella, but their outer circumferential lamellas were not formed yet in both of them, when compared with a 12-years-old cow as a control of the mother. Therefore, we suggest on long-bone formation pattern that the child resembled the mother rather than the control, and that the child had more or less succeeded to the mother genes of delayed osteon formation as well as dermal dysplasia which seemed to be genetic collagen disorder, although there were mild gene appearances.

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

PubMed

Jonas, Jacques; Frismand, Solène; Vignal, Jean-Pierre; Colnat-Coulbois, Sophie; Koessler, Laurent; Vespignani, Hervé; Rossion, Bruno; Maillard, Louis

2014-07-01

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Copyright © 2013 Wiley Periodicals, Inc.

How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex

PubMed Central

Cooke, Sam F.; Bear, Mark F.

2014-01-01

Donald Hebb chose visual learning in primary visual cortex (V1) of the rodent to exemplify his theories of how the brain stores information through long-lasting homosynaptic plasticity. Here, we revisit V1 to consider roles for bidirectional ‘Hebbian’ plasticity in the modification of vision through experience. First, we discuss the consequences of monocular deprivation (MD) in the mouse, which have been studied by many laboratories over many years, and the evidence that synaptic depression of excitatory input from the thalamus is a primary contributor to the loss of visual cortical responsiveness to stimuli viewed through the deprived eye. Second, we describe a less studied, but no less interesting form of plasticity in the visual cortex known as stimulus-selective response potentiation (SRP). SRP results in increases in the response of V1 to a visual stimulus through repeated viewing and bears all the hallmarks of perceptual learning. We describe evidence implicating an important role for potentiation of thalamo-cortical synapses in SRP. In addition, we present new data indicating that there are some features of this form of plasticity that cannot be fully accounted for by such feed-forward Hebbian plasticity, suggesting contributions from intra-cortical circuit components. PMID:24298166

Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects.

PubMed

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-06-15

Studies in schizophrenic patients have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus, and cortex that have been related to positive symptoms and cognitive impairments. [(18)F]fallypride positron emission tomography studies were performed in off-medication or never-medicated schizophrenic subjects (n = 11, 6 men, 5 women; mean age of 30.5 +/- 8.0 [SD] years; 4 drug-naive) and age-matched healthy subjects (n = 11, 5 men, 6 women, mean age of 31.6 +/- 9.2 [SD]) to examine dopamine D(2) receptor (DA D(2)r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. In schizophrenic subjects, increased DA D(2)r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with ROI data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex ROI (r = .94, p = .0001), which remained significant after correction for multiple comparisons (p < .03). Correlations of symptoms with parametric images of DA D(2)r levels revealed no significant clusters of correlations with negative symptoms but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. The results of this study demonstrate abnormal DA D(2)r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D(2)r mediate positive symptoms.

Spatially Directed Proteomics of the Human Lens Outer Cortex Reveals an Intermediate Filament Switch Associated With the Remodeling Zone

PubMed Central

Wenke, Jamie L.; McDonald, W. Hayes; Schey, Kevin L.

2016-01-01

Purpose To quantify protein changes in the morphologically distinct remodeling zone (RZ) and adjacent regions of the human lens outer cortex using spatially directed quantitative proteomics. Methods Lightly fixed human lens sections were deparaffinized and membranes labeled with fluorescent wheat germ agglutinin (WGA-TRITC). Morphology directed laser capture microdissection (LCM) was used to isolate tissue from four distinct regions of human lens outer cortex: differentiating zone (DF), RZ, transition zone (TZ), and inner cortex (IC). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of the plasma membrane fraction from three lenses (21-, 22-, and 27-year) revealed changes in major cytoskeletal proteins including vimentin, filensin, and phakinin. Peptides from proteins of interest were quantified using multiple reaction monitoring (MRM) mass spectrometry and isotopically-labeled internal peptide standards. Results Results revealed an intermediate filament switch from vimentin to beaded filament proteins filensin and phakinin that occurred at the RZ. Several other cytoskeletal proteins showed significant changes between regions, while most crystallins remained unchanged. Targeted proteomics provided accurate, absolute quantification of these proteins and confirmed vimentin, periplakin, and periaxin decrease from the DF to the IC, while filensin, phakinin, and brain acid soluble protein 1 (BASP1) increase significantly at the RZ. Conclusions Mass spectrometry-compatible fixation and morphology directed laser capture enabled proteomic analysis of narrow regions in the human lens outer cortex. Results reveal dramatic cytoskeletal protein changes associated with the RZ, suggesting that one role of these proteins is in membrane deformation and/or the establishment of ball and socket joints in the human RZ. PMID:27537260

Adrenocortical Carcinoma—Patient Version

Cancer.gov

Adrenocortical carcinoma is a rare cancer which forms in the cortex (outer layer) of an adrenal gland. There are two adrenal glands. One sits on top of each kidney. Start here to find information on adrenocortical carcinoma treatment and research.

The neural dynamics of updating person impressions

PubMed Central

Cai, Yang; Todorov, Alexander

2013-01-01

Person perception is a dynamic, evolving process. Because other people are an endless source of social information, people need to update their impressions of others based upon new information. We devised an fMRI study to identify brain regions involved in updating impressions. Participants saw faces paired with valenced behavioral information and were asked to form impressions of these individuals. Each face was seen five times in a row, each time with a different behavioral description. Critically, for half of the faces the behaviors were evaluatively consistent, while for the other half they were inconsistent. In line with prior work, dorsomedial prefrontal cortex (dmPFC) was associated with forming impressions of individuals based on behavioral information. More importantly, a whole-brain analysis revealed a network of other regions associated with updating impressions of individuals who exhibited evaluatively inconsistent behaviors, including rostrolateral PFC, superior temporal sulcus, right inferior parietal lobule and posterior cingulate cortex. PMID:22490923

When visual perception causes feeling: enhanced cross-modal processing in grapheme-color synesthesia.

PubMed

Weiss, Peter H; Zilles, Karl; Fink, Gereon R

2005-12-01

In synesthesia, stimulation of one sensory modality (e.g., hearing) triggers a percept in another, non-stimulated sensory modality (e.g., vision). Likewise, perception of a form (e.g., a letter) may induce a color percept (i.e., grapheme-color synesthesia). To date, the neural mechanisms underlying synesthesia remain to be elucidated. We disclosed by fMRI, while controlling for surface color processing, enhanced activity in the left intraparietal cortex during the experience of grapheme-color synesthesia (n = 9). In contrast, the perception of surface color per se activated the color centers in the fusiform gyrus bilaterally. The data support theoretical accounts that grapheme-color synesthesia may originate from enhanced cross-modal binding of form and color. A mismatch of surface color and grapheme induced synesthetically felt color additionally activated the left dorsolateral prefrontal cortex (DLPFC). This suggests that cognitive control processes become active to resolve the perceptual conflict resulting from synesthesia.

Representation of Non-Spatial and Spatial Information in the Lateral Entorhinal Cortex

PubMed Central

Deshmukh, Sachin S.; Knierim, James J.

2011-01-01

Some theories of memory propose that the hippocampus integrates the individual items and events of experience within a contextual or spatial framework. The hippocampus receives cortical input from two major pathways: the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). During exploration in an open field, the firing fields of MEC grid cells form a periodically repeating, triangular array. In contrast, LEC neurons show little spatial selectivity, and it has been proposed that the LEC may provide non-spatial input to the hippocampus. Here, we recorded MEC and LEC neurons while rats explored an open field that contained discrete objects. LEC cells fired selectively at locations relative to the objects, whereas MEC cells were weakly influenced by the objects. These results provide the first direct demonstration of a double dissociation between LEC and MEC inputs to the hippocampus under conditions of exploration typically used to study hippocampal place cells. PMID:22065409

Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease

PubMed Central

Fu, Hongjun; Rodriguez, Gustavo A.; Herman, Mathieu; Emrani, Sheina; Nahmani, Eden; Barrett, Geoffrey; Figueroa, Helen Y.; Goldberg, Eliana

2017-01-01

Summary The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation system. Here we show in a transgenic mouse model expressing mutant human tau predominantly in the EC that the formation of mature tangles in old mice was associated with excitatory cell loss and deficits in grid cell function, including destabilized grid fields and reduced firing rates, as well as altered network activity. Overt tau pathology in the aged mice was accompanied by spatial memory deficits. Therefore, tau pathology initiated in the entorhinal cortex could lead to deficits in grid cell firing and underlie the deterioration of spatial cognition seen in human AD. PMID:28111080

Electron microscope study of the vitelline body of some spider oocytes.

PubMed

SOTELO, J R; TRUJILLO-CENOZ, O

1957-03-25

THE STRUCTURE OF THE VITELLINE NUCLEI OF LYCOSIDAE AND THOMISIDAE WAS DESCRIBED AS FOLLOWS: Vitelline nuclei are constituted of two parts: (a) a peripheral layer (vitelline body cortex), and (b) a central core. The vitelline body cortex is demonstrated to be formed by many cisternae of the endoplasmic reticulum among which mitochondria and Golgi elements are intermingled. The central core is made up mainly of a special type of body described under the name of "capsulated body." Capsulated bodies comprise a capsular layer, limited by a membrane, and two central masses called "geminated masses," each one limited by a double membrane. Irregular masses of closely packed vesicles are found in some cases among the capsulated bodies and free vesicles are present in large numbers. The optical properties of the vitelline body cortex compared with the electron microscope findings lead us to the concept that this layer is a "composite body" according to Weiner's theory.

Suppression of phase synchronisation in network based on cat's brain.

PubMed

Lameu, Ewandson L; Borges, Fernando S; Borges, Rafael R; Iarosz, Kelly C; Caldas, Iberê L; Batista, Antonio M; Viana, Ricardo L; Kurths, Jürgen

2016-04-01

We have studied the effects of perturbations on the cat's cerebral cortex. According to the literature, this cortex structure can be described by a clustered network. This way, we construct a clustered network with the same number of areas as in the cat matrix, where each area is described as a sub-network with a small-world property. We focus on the suppression of neuronal phase synchronisation considering different kinds of perturbations. Among the various controlling interventions, we choose three methods: delayed feedback control, external time-periodic driving, and activation of selected neurons. We simulate these interventions to provide a procedure to suppress undesired and pathological abnormal rhythms that can be associated with many forms of synchronisation. In our simulations, we have verified that the efficiency of synchronisation suppression by delayed feedback control is higher than external time-periodic driving and activation of selected neurons of the cat's cerebral cortex with the same coupling strengths.

Distinct hippocampal functional networks revealed by tractography-based parcellation.

PubMed

Adnan, Areeba; Barnett, Alexander; Moayedi, Massieh; McCormick, Cornelia; Cohn, Melanie; McAndrews, Mary Pat

2016-07-01

Recent research suggests the anterior and posterior hippocampus form part of two distinct functional neural networks. Here we investigate the structural underpinnings of this functional connectivity difference using diffusion-weighted imaging-based parcellation. Using this technique, we substantiated that the hippocampus can be parcellated into distinct anterior and posterior segments. These structurally defined segments did indeed show different patterns of resting state functional connectivity, in that the anterior segment showed greater connectivity with temporal and orbitofrontal cortex, whereas the posterior segment was more highly connected to medial and lateral parietal cortex. Furthermore, we showed that the posterior hippocampal connectivity to memory processing regions, including the dorsolateral prefrontal cortex, parahippocampal, inferior temporal and fusiform gyri and the precuneus, predicted interindividual relational memory performance. These findings provide important support for the integration of structural and functional connectivity in understanding the brain networks underlying episodic memory.

Critical period plasticity is disrupted in the barrel cortex of Fmr1 knockout mice

PubMed Central

Harlow, Emily G.; Till, Sally M.; Russell, Theron A.; Wijetunge, Lasani S.; Kind, Peter; Contractor, Anis

2010-01-01

Summary Alterations in sensory processing constitute prominent symptoms of Fragile X syndrome; however, little is known about how disrupted synaptic and circuit development in sensory cortex contributes to these deficits. To investigate how the loss of fragile X mental retardation protein (FMRP) impacts the development of cortical synapses, we examined excitatory thalamocortical synapses in somatosensory cortex during the perinatal critical period in Fmr1 knockout mice. FMRP ablation resulted in dysregulation of glutamatergic signaling maturation. The fraction of silent synapses persisting to later developmental times was increased, there was a temporal delay in the window for synaptic plasticity, while other forms of developmental plasticity were not altered in Fmr1 knockout mice. Our results indicate that FMRP is required for the normal developmental progression of synaptic maturation, and loss of this important RNA binding protein impacts the timing of the critical period for layer IV synaptic plasticity. PMID:20159451

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

PubMed Central

Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

2018-01-01

Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely to form the anatomical basis for the impaired functioning of this brain area. Indeed, impaired functioning of the prefrontal cortex, such as cognitive deficits are common in stressed individuals as well as in depressed patients. PMID:29440995

Saturation in Phosphene Size with Increasing Current Levels Delivered to Human Visual Cortex.

PubMed

Bosking, William H; Sun, Ping; Ozker, Muge; Pei, Xiaomei; Foster, Brett L; Beauchamp, Michael S; Yoshor, Daniel

2017-07-26

Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. SIGNIFICANCE STATEMENT Understanding the neural basis for phosphenes, the visual percepts created by electrical stimulation of visual cortex, is fundamental to the development of a visual cortical prosthetic. Our experiments in human subjects implanted with electrodes over visual cortex show that it is the activity of a large population of cells spread out across several millimeters of tissue that supports the perception of a phosphene. In addition, we describe an important feature of the production of phosphenes by electrical stimulation: phosphene size saturates at a relatively low current level. This finding implies that, with current methods, visual prosthetics will have a limited dynamic range available to control the production of spatial forms and that more advanced stimulation methods may be required. Copyright © 2017 the authors 0270-6474/17/377188-10$15.00/0.

Decoding "us" and "them": Neural representations of generalized group concepts.

PubMed

Cikara, Mina; Van Bavel, Jay J; Ingbretsen, Zachary A; Lau, Tatiana

2017-05-01

Humans form social coalitions in every society on earth, yet we know very little about how the general concepts us and them are represented in the brain. Evolutionary psychologists have argued that the human capacity for group affiliation is a byproduct of adaptations that evolved for tracking coalitions in general. These theories suggest that humans possess a common neural code for the concepts in-group and out-group, regardless of the category by which group boundaries are instantiated. The authors used multivoxel pattern analysis to identify the neural substrates of generalized group concept representations. They trained a classifier to encode how people represented the most basic instantiation of a specific social group (i.e., arbitrary teams created in the lab with no history of interaction or associated stereotypes) and tested how well the neural data decoded membership along an objectively orthogonal, real-world category (i.e., political parties). The dorsal anterior cingulate cortex/middle cingulate cortex and anterior insula were associated with representing groups across multiple social categories. Restricting the analyses to these regions in a separate sample of participants performing an explicit categorization task, the authors replicated cross-categorization classification in anterior insula. Classification accuracy across categories was driven predominantly by the correct categorization of in-group targets, consistent with theories indicating in-group preference is more central than out-group derogation to group perception and cognition. These findings highlight the extent to which social group concepts rely on domain-general circuitry associated with encoding stimuli's functional significance. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Hand and mouth: Cortical correlates of lexical processing in British Sign Language and speechreading English

PubMed Central

Capek, Cheryl M.; Waters, Dafydd; Woll, Bencie; MacSweeney, Mairéad; Brammer, Michael J.; McGuire, Philip K.; David, Anthony S.; Campbell, Ruth

2012-01-01

Spoken languages use one set of articulators – the vocal tract, whereas signed languages use multiple articulators, including both manual and facial actions. How sensitive are the cortical circuits for language processing to the particular articulators that are observed? This question can only be addressed with participants who use both speech and a signed language. In this study, we used fMRI to compare the processing of speechreading and sign processing in deaf native signers of British Sign Language (BSL) who were also proficient speechreaders. The following questions were addressed: To what extent do these different language types rely on a common brain network? To what extent do the patterns of activation differ? How are these networks affected by the articulators that languages use? Common perisylvian regions were activated both for speechreading English words and for BSL signs. Distinctive activation was also observed reflecting the language form. Speechreading elicited greater activation in the left mid-superior temporal cortex than BSL, whereas BSL processing generated greater activation at the parieto-occipito-temporal junction in both hemispheres. We probed this distinction further within BSL, where manual signs can be accompanied by different sorts of mouth action. BSL signs with speech-like mouth actions showed greater superior temporal activation, while signs made with non-speech-like mouth actions showed more activation in posterior and inferior temporal regions. Distinct regions within the temporal cortex are not only differentially sensitive to perception of the distinctive articulators for speech and for sign, but also show sensitivity to the different articulators within the (signed) language. PMID:18284353

Brain mechanisms of recovery from pure alexia: A single case study with multiple longitudinal scans.

PubMed

Cohen, Laurent; Dehaene, Stanislas; McCormick, Samantha; Durant, Szonya; Zanker, Johannes M

2016-10-01

Pure alexia is an acquired reading disorder, typically due to a left occipito-temporal lesion affecting the Visual Word Form Area (VWFA). It is unclear whether the VWFA acts as a unique bottleneck for reading, or whether alternative routes are available for recovery. Here, we address this issue through the single-case longitudinal study of a neuroscientist who experienced pure alexia and participated in 17 behavioral, 9 anatomical, and 9 fMRI assessment sessions over a period of two years. The origin of the impairment was assigned to a small left fusiform lesion, accompanied by a loss of VWFA responsivity and by the degeneracy of the associated white matter pathways. fMRI experiments allowed us to image longitudinally the visual perception of words, as compared to other classes of stimuli, as well as the mechanisms of letter-by-letter reading. The progressive improvement of reading was not associated with the re-emergence of a new area selective to words, but with increasing responses in spared occipital cortex posterior to the lesion and in contralateral right occipital cortex. Those regions showed a non-specific increase of activations over time and an increase in functional correlation with distant language areas. Those results confirm the existence of an alternative occipital route for reading, bypassing the VWFA, but they also point to its key limitation: the patient remained a slow letter-by-letter reader, thus supporting the critical importance of the VWFA for the efficient parallel recognition of written words. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability

PubMed Central

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-01-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1–3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal–parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID. PMID:27457812

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

PubMed

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-11-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

The impact of multiple memory formation on dendritic complexity in the hippocampus and anterior cingulate cortex assessed at recent and remote time points

PubMed Central

Wartman, Brianne C.; Holahan, Matthew R.

2014-01-01

Consolidation processes, involving synaptic and systems level changes, are suggested to stabilize memories once they are formed. At the synaptic level, dendritic structural changes are associated with long-term memory storage. At the systems level, memory storage dynamics between the hippocampus and anterior cingulate cortex (ACC) may be influenced by the number of sequentially encoded memories. The present experiment utilized Golgi-Cox staining and neuron reconstruction to examine recent and remote structural changes in the hippocampus and ACC following training on three different behavioral procedures. Rats were trained on one hippocampal-dependent task only (a water maze task), two hippocampal-dependent tasks (a water maze task followed by a radial arm maze task), or one hippocampal-dependent and one non-hippocampal-dependent task (a water maze task followed by an operant conditioning task). Rats were euthanized recently or remotely. Brains underwent Golgi-Cox processing and neurons were reconstructed using Neurolucida software (MicroBrightField, Williston, VT, USA). Rats trained on two hippocampal-dependent tasks displayed increased dendritic complexity compared to control rats, in neurons examined in both the ACC and hippocampus at recent and remote time points. Importantly, this behavioral group showed consistent, significant structural differences in the ACC compared to the control group at the recent time point. These findings suggest that taxing the demand placed upon the hippocampus, by training rats on two hippocampal-dependent tasks, engages synaptic and systems consolidation processes in the ACC at an accelerated rate for recent and remote storage of spatial memories. PMID:24795581

Conflict adaptation in prefrontal cortex: now you see it, now you don't.

PubMed

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2014-01-01

Daily life requires people to monitor and resolve conflict arising from distracting information irrelevant to current goals. The highly influential conflict monitoring theory (CMT) holds that the anterior cingulate cortex (ACC) detects conflict and subsequently triggers the dorsolateral prefrontal cortex (DLPFC) to regulate that conflict. Multiple lines of evidence have provided support for CMT. For example, performance is faster on incongruent trials that follow other incongruent trials (iI), and is accompanied by reduced ACC and increased DLPFC activation (the conflict adaptation effect). In this fMRI study, we explored whether ACC-DLPFC conflict signaling can result in behavioral adjustments beyond on-line contexts. Participants completed a modified version of the Stroop conflict adaptation paradigm which tested for conflict adaptation effects on the current (N) trial associated with not only the immediately preceding (N - 1) trial, but also 2-back (N - 2) trials. Results demonstrated evidence for direct relationships between ACC activity on N - 2 trials and both N trial DLPFC activity and behavioral adjustment when intervening trials were congruent (i.e., icI). In contrast, when N - 1 trials were incongruent (i.e., iiI), ACC-DLPFC signaling failed and conflict adaptation was absent. These results provide new evidence demonstrating that the conflict monitor-controller maintains previously experienced conflict in the service of subsequent behavioral adjustment. However, the processing of multiple, temporally proximal conflict signals takes a toll on the working memory (WM) system, which appears to require resetting in order to adapt our behavior to frequently changing environmental demands. Copyright © 2013 Elsevier Ltd. All rights reserved.

Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

PubMed Central

Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

2011-01-01

The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

White and gray matter damage in primary progressive MS

PubMed Central

Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-01

Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

White and gray matter damage in primary progressive MS: The chicken or the egg?

PubMed

Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-12

The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

Brain Regions Involved in the Learning and Application of Reward Rules in a Two-Deck Gambling Task

ERIC Educational Resources Information Center

Hartstra, E.; Oldenburg, J. F. E.; Van Leijenhorst, L.; Rombouts, S. A. R. B.; Crone, E. A.

2010-01-01

Decision-making involves the ability to choose between competing actions that are associated with uncertain benefits and penalties. The Iowa Gambling Task (IGT), which mimics real-life decision-making, involves learning a reward-punishment rule over multiple trials. Patients with damage to ventromedial prefrontal cortex (VMPFC) show deficits…

'What' and 'where' in the human brain.

PubMed

Ungerleider, L G; Haxby, J V

1994-04-01

Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms.