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Amid recent amendment of delineation of a mouse auditory cortical map, a caudal auditory field, originally defined as the primary auditory cortex (AI), was divided into the AI and dorsomedial field (DM), based on distinct high frequency areas. A low frequency area was not previously established in the DM because responses to low frequency tones were weak in this area. This may lead to the misconception that the DM is an atypical region that lacks a low frequency band. In the current study, we confirmed that the DM has a low frequency area that is completely independent from the AI. First, we conducted flavoprotein fluorescence imaging with improved signal to noise ratio and revealed the presence of two separated low frequency areas in the AI and DM. Next, we injected a retrograde neural tracer along the tonotopic axis of the AI or DM to reveal the thalamic origins in the ventral division of the medial geniculate body (MGv). We found that neurons projecting to low frequency areas of the AI and DM occupied different locations within the MGv and mutually independent topographic organizations consisting of thalamic neurons projecting to the AI or DM. These results indicate that the AI and DM have distinct low frequency areas with distinct thalamic projections from the MGv. Our findings reaffirm that the AI and DM should be regarded as independent regions in the mouse auditory cortex.

The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial-defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area-specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders.

International audience; Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.

The relationships between structural and functional measures of the human brain remain largely unknown. A majority of our limited knowledge regarding structure–function associations has been obtained through comparisons between specific groups of patients and healthy controls. Unfortunately, a direct and complete view of the associations across multiple structural and functional metrics in normal population is missing. We filled this gap by learning cross-individual co-variance among structural and functional measures using large-scale neuroimaging datasets. A discover-confirm scheme was applied to two independent samples (N = 184 and N = 340) of multi-modal neuroimaging datasets. A data mining tool, gRAICAR, was employed in the discover stage to generate quantitative and unbiased hypotheses of the co-variance among six functional and six structural imaging metrics. These hypotheses were validated using an independent dataset in the confirm stage. Fifteen multi-metric co-variance units, representing different co-variance relationships among the 12 metrics, were reliable across the two sets of neuroimaging datasets. The reliable co-variance units were summarized into a database, where users can select any location on the cortical map of any metric to examine the co-varying maps with the other 11 metrics. This database characterized the six functional metrics based on their co-variance with structural metrics, and provided a detailed reference to connect previous findings using different metrics and to predict maps of unexamined metrics. Gender, age, and handedness were associated to the co-variance units, and a sub-study of schizophrenia demonstrated the usefulness of the co-variance database. Electronic supplementary material The online version of this article (doi:10.1007/s00429-015-1177-6) contains supplementary material, which is available to authorized users.

Auditory spatial attention serves important functions in auditory source separation and selection. Although auditory spatial attention mechanisms have been generally investigated, the neural substrates encoding spatial information acted on by attention have not been identified in the human neocortex. We performed functional magnetic resonance imaging experiments to identify cortical regions that support auditory spatial attention and to test 2 hypotheses regarding the coding of auditory spatial attention: 1) auditory spatial attention might recruit the visuospatial maps of the intraparietal sulcus (IPS) to create multimodal spatial attention maps; 2) auditory spatial information might be encoded without explicit cortical maps. We mapped visuotopic IPS regions in individual subjects and measured auditory spatial attention effects within these regions of interest. Contrary to the multimodal map hypothesis, we observed that auditory spatial attentional modulations spared the visuotopic maps of IPS; the parietal regions activated by auditory attention lacked map structure. However, multivoxel pattern analysis revealed that the superior temporal gyrus and the supramarginal gyrus contained significant information about the direction of spatial attention. These findings support the hypothesis that auditory spatial information is coded without a cortical map representation. Our findings suggest that audiospatial and visuospatial attention utilize distinctly different spatial coding schemes.

Partial hearing loss often results in enlarged representations of the remaining hearing frequency range in primary auditory cortex (AI). Recent studies have implicated certain types of synaptic plasticity in AI map reorganization in response to transient and long-term hearing loss. How changes in neuronal excitability and morphology contribute to cortical map reorganization is less clear. In the present study, we exposed adult rats to a 4-kHz tone at 123 dB, which resulted in increased thresholds over their entire hearing range. The threshold shift gradually recovered in the lower-frequency, but not the higher-frequency, range. As reported previously, two distinct zones were observed 10 days after the noise exposure, an enlarged lower-characteristic frequency (CF) zone displaying normal threshold and enhanced cortical responses and a higher-CF zone showing higher threshold and a disorganized tonotopic map. Membrane excitability of layer II/III pyramidal neurons increased only in the higher-CF, but not the lower-CF, zone. In addition, dendritic morphology and spine density of the pyramidal neurons were altered in the higher-CF zone only. These results indicate that membrane excitability and neuronal morphology are altered by long-term, but not transient, threshold shift. They also suggest that these changes may contribute to tinnitus but are unlikely to be involved in map expansion in the lower-CF zone.

Phase-encoded designs advanced the early development of functional MRI, enabling the “killer app” of retinotopic mapping, which helped demonstrate fMRI's value to a skeptical scientific public. The design, also called “the traveling wave”, remains in wide use today, due to its ability to easily measure neural activity in a parameterized set of experimental conditions. In phase-encoded designs, stimuli defined by a numerical parameter, for example visual eccentricity, are presented continuously in the order specified by the parameter. The stimulus parameter that produces maximum response can be recovered from the timing of neural activity, i.e. its phase. From the outset, phase-encoded designs were used for two related, but complementary purposes: 1) to measure aggregate response properties of neurons in a voxel, for example the average visual field location of receptive fields, and 2) to segregate the set of voxels that corresponds to an organized cortical region, for example a retinotopically mapped visual area. This short review will cover the history and current uses of phase-encoded fMRI, while noting the ongoing tension in the field between the brain mapping and computational neuroimaging approaches.

We explore the effects of gap junctions, direct neural transmission between adjacent cells, on activity-dependent network formation. It is found that endogenous neural activities and weak firing correlations via gap junctions can regulate elaborately both the topographic structure in vertical connections and the radial structure in horizontal connections. Provided that pre-establishment of the lateral connection structure is required for the postnatal cortical map organization and genetic factors cannot perform such detailed regulation of synaptic connections, neural interactions via gap junctions could play an indispensable role in the brain development.

To investigate motor cortical map patterns in children with diplegic and hemiplegic cerebral palsy (CP), and the relationships between motor cortical geometry and motor function in CP.Transcranial magnetic stimulation (TMS) was used to map motor cortical representations of the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles in 13 children with CP (age 9-16 years, 6 males.) The Gross Motor Function Measure (GMFM) and Melbourne upper extremity function were used to quantify motor ability.In the hemiplegic participants (N = 7), the affected (right) FDI cortical representation was mapped on the ipsilateral (N = 4), contralateral (N = 2), or bilateral (N = 1) cortex. Participants with diplegia (N = 6) showed either bilateral (N = 2) or contralateral (N = 4) cortical hand maps. The FDI and TA motor map center-of-gravity mediolateral location ranged from 2-8 cm and 3-6 cm from the midline, respectively. Among diplegics, more lateral FDI representation locations were associated with lower Melbourne scores, i.e. worse hand motor function (Spearman's rho = -0.841, p = 0.036).Abnormalities in TMS-derived motor maps cut across the clinical classifications of hemiplegic and diplegic CP. The lateralization of the upper and lower extremity motor representation demonstrates reorganization after insults to the affected hemispheres of both diplegic and hemiplegic children.The current study is a step towards defining the relationship between changes in motor maps and functional impairments in CP. These results suggest the need for further work to develop improved classification schemes that integrate clinical, radiologic, and neurophysiologic measures in CP.

The cytoarchitectonic map of the adult human cerebral cortex prepared by Korbinian Brodmann is probably the most widely used and reproduced cortical map. However, few people today realize that in the period between 1908 and 1914 (the first and last date of maps publication by Brodmann himself) that map was gradually developed, extended and subjected to some significant modifications. The aim of this article is to reproduce and briefly describe all versions of Brodmann’s map, trace its changes and highlight the importance of these changes — especially with respect to the speech and language related cortical regions of the left cerebral hemisphere.

Primary sensory cortical fields develop highly specific associative representational plasticity, notably enlarged area of representation of reinforced signal stimuli within their topographic maps. However, overtraining subjects after they have solved an instrumental task can reduce or eliminate the expansion while the successful behavior remains. As the development of this plasticity depends on the learning strategy used to solve a task, we asked whether the loss of expansion is due to the strategy used during overtraining. Adult male rats were trained in a three-tone auditory discrimination task to bar-press to the CS+ for water reward and refrain from doing so during the CS− tones and silent intertrial intervals; errors were punished by a flashing light and time-out penalty. Groups acquired this task to a criterion within seven training sessions by relying on a strategy that was “bar-press from tone-onset-to-error signal” (“TOTE”). Three groups then received different levels of overtraining: Group ST, none; Group RT, one week; Group OT, three weeks. Post-training mapping of their primary auditory fields (A1) showed that Groups ST and RT had developed significantly expanded representational areas, specifically restricted to the frequency band of the CS+ tone. In contrast, the A1 of Group OT was no different from naïve controls. Analysis of learning strategy revealed this group had shifted strategy to a refinement of TOTE in which they self-terminated bar-presses before making an error (“iTOTE”). Across all animals, the greater the use of iTOTE, the smaller was the representation of the CS+ in A1. Thus, the loss of cortical expansion is attributable to a shift or refinement in strategy. This reversal of expansion was considered in light of a novel theoretical framework (CONCERTO) highlighting four basic principles of brain function that resolve anomalous findings and explaining why even a minor change in strategy would involve concomitant shifts of involved brain sites, including reversal of cortical expansion.

2 Centre of Molecular Physiology of the Brain (CMPB) at University Medicine GDepartment of Neurology, GGermany Non-technical summary Optical imaging is widely used to map functional areas of the cerebral cortex. We present a method for fast fluorescence imaging of map-level cortical activity using a calciumindicatorprotein.Sensory-evokedneuronalactivitycanbeimagedrepeatedlyinthesame mouseover weeks, enablingnew opportunitiesforthe longitudinalstudyof corticalfunctionand dysfunction. We hope this method will be flexibly applied across different cortical areas and to a variety of newly developed genetically encoded calcium and voltage sensors. Abstract In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methodsforchronicrecordingarelimited.Herewepresentatechniqueforlong-terminvestigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals reportsensory-evokedactivityinanaesthetizedmousesomatosensorycortexwithhighsensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations.

Functional imaging studies, using blood oxygen level-dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging-navigated transcranial magnetic stimulation (TMS) to non-invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1-weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma-related anatomical changes and TMS parameters. SCI participants had increased AMTs (P = 0.01) and increased CSP duration (P = 0.01). The CoG of the EDC motor-evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (P = 0.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r 2 ‡ 0.26, P < 0.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI.

Sensory inputs triggered by external stimuli are projected into discrete arrays of neuronal modules in the primary sensory cortex. This whisker-to-barrel pathway has gained in popularity as a model system for studying the development of cortical circuits and sensory processing because its clear patterns facilitate the identification of genetically modified mice with whisker map deficits and make possible coordinated in vitro and in vivo electrophysiological studies. Numerous whisker map determinants have been identified in the past two decades. In this review, we summarize what have we learned from the detailed studies conducted in various mutant mice with cortical whisker map deficits. We will specifically focus on the anatomical and functional establishment of the somatosensory thalamocortical circuits.

We developed a technique of transcranial electrical stimulation (TES) to investigate cortico-cortical connections in mice. After the skull was shaved with the blade of a dental bar, a blunt tip of a needle was gently pushed onto the thinned skull. The skull was deformed by the force, and the subarachnoid space between the skull and the cortex was minimized around the needle tip. Under these conditions, stimulus currents applied to the needle directly flowed into the cortex through the thinned skull. Cortico-cortical functional connections stimulated by this method were visualized by transcranial flavoprotein fluorescence imaging. The cortical responses evoked by TES exhibited spatial and temporal activity patterns comparable to those elicited by a conventional method, in which an electrode is directly inserted into superficial cortical layers. A comparison of the two methods revealed that TES required a slightly stronger stimulus intensity and preferentially activated superficial layers of the cortex compared with the conventional method. Using the new method, we revealed the presence of reciprocal cortico-cortical functional connections between lateral and medial parts of higher visual cortices in mice. This new method combined with transcranial flavoprotein fluorescence imaging allowed us to activate cortico-cortical pathways arising from the primary sensory areas and investigate sensory information flow in the mouse cerebral cortex.

Sensory and motor representations embedded in topographic cortical maps are use-dependent, dynamically maintained, and self-organizing functional mosaics that constitute idiosyncratic entities involved in perceptual and motor learning abilities. Studies of cortical map plasticity have substantiated the view that local reorganization of sensory and motor areas has great significance in recovery of function following brain damage or spinal cord injury. In addition, the transfer of function to distributed cortical areas and subcortical structures represents an adaptive strategy for functional compensation. There is a growing consensus that subject-environment interactions, by continuously refining the canvas of synaptic connectivity and reshaping the anatomical and functional architecture of neural circuits, promote adaptive behavior throughout life. Taking advantage of use-dependent neural plasticity, early initiated rehabilitative procedures improve the potential for recovery.

A striking feature of cortical organization is that the encoding of many stimulus features, for example orientation or direction selectivity, is arranged into topographic maps. Functional imaging methods such as optical imaging of intrinsic signals, voltage sensitive dye imaging or functional magnetic resonance imaging are important tools for studying the structure of cortical maps. As functional imaging measurements are usually noisy, statistical processing of the data is necessary to extract maps from the imaging data. We here present a probabilistic model of functional imaging data based on Gaussian processes. In comparison to conventional approaches, our model yields superior estimates of cortical maps from smaller amounts of data. In addition, we obtain quantitative uncertainty estimates, i.e. error bars on properties of the estimated map. We use our probabilistic model to study the coding properties of the map and the role of noise-correlations by decoding the stimulus from single trials of an imaging experiment.

The aim of this study is to evaluate whether tDCS applied on the primary motor cortex (M1) in company with hand movements could enhance cortical activation, using functional MRI (fMRI). Twelve right-handed normal subjects were recruited. Real tDCS and sham tDCS with hand movements were applied during fMRI scanning. Subjects performed grasp-release hand movements at a metronome-guided frequency of 1 Hz, while direct current with 1.0 mA was delivered to the primary motor cortex. The averaged cortical map and the intensity index were compared between real tDCS with hand movements and sham tDCS with hand movements. Our result showed that cortical activation on the primary sensorimotor cortex was observed under both of two conditions; real tDCS with hand movements and sham tDCS with hand movements. Voxel count and peak intensity were 365.10 ± 227.23 and 5.66 ± 1.97, respectively, in the left primary sensorimotor cortex during real tDCS with right hand movements; in contrast, those were 182.20 ± 117.88 and 4.12 ± 0.88, respectively, during sham tDCS with right hand movements. Significant differences in voxel count and peak intensity were observed between real tDCS and sham tDCS (p < 0.05). We found that anodal tDCS application during motor task enhanced cortical activation on the underlying targeted motor cortex, compared with the same motor task without tDCS. Therefore, it seemed that tDCS induced more cortical activity and modulated brain function when concurrently applied with motor task.

SummaryCortical map plasticity is believed to be a key substrate of perceptual and skill learning. In the current study, we quantified changes in perceptual ability after pairing tones with stimulation of the cholinergic nucleus basalis to induce auditory cortex map plasticity outside of a behavioral context. Our results provide evidence that cortical map plasticity can enhance perceptual learning. However, auditory cortex map plasticity fades over weeks even though tone discrimination performance remains stable. This observation is consistent with recent reports that cortical map expansions associated with perceptual and motor learning are followed by a period of map renormalization without a decrement in performance. Our results indicate that cortical map plasticity enhances perceptual learning, but is not necessary to maintain improved discriminative ability.

The cholinergic basal forebrain projects throughout the neocortex, exerting a critical role in modulating plasticity associated with normal learning. Cholinergic modulation of cortical plasticity could arise from 3 distinct mechanisms by 1) ‘‘direct’’ modulation via cholinergic inputs to regions undergoing plasticity, 2) ‘‘indirect’’ modulation via cholinergic projections to anterior, prefrontal attentional systems, or 3) modulating more global aspects of processing via distributed inputs throughout the cortex. To segregate these potential mechanisms, we investigated cholinergic-dependent reorganization of cortical motor representations in rats undergoing skilled motor learning. Behavioral and electrophysiological consequences of depleting cholinergic inputs to either motor cortex, prefrontal cortex, or globally, were compared. We find that local depletion of cholinergic afferents to motor cortex significantly disrupts map plasticity and skilled motor behavior, whereas prefrontal cholinergic depletion has no effect on these measures. Global cholinergic depletion perturbs map plasticity comparable with motor cortex depletions but results in significantly greater impairments in skilled motor acquisition. These findings indicate that local cholinergic activation within motor cortex, as opposed to indirect regulation of prefrontal systems, modulate cortical map plasticity and motor learning. More globally acting cholinergic mechanisms provide additional support for the acquisition of skilled motor behaviors, beyond those associated with cortical map reorganization.

Recovery of motor function in brain and spinal cord disorders is an area of active research that seeks to maximize improvement after an episode of neuronal death or dysfunction. Recovery likely results from changes in structure and function of undamaged neurons, and this plasticity is a target for rehabilitative strategies. Sensory and motor function are mapped onto brain regions somatotopically, and these maps have been demonstrated to change in response to experience, particularly in development, but also in adults after injury. The map concept, while appealing, is limited, as the fine structure of the motor representation is not well-ordered somatotopically. But after stroke, the spared areas of the main cortical map for movement appears to participate in representing affected body parts, expanding representation in an experience dependent manner. This occurs in both animal models, and in human clinical trials, although one must be cautious in comparing the results of invasive electrophysiological techniques with non-invasive ones such as transcranial magnetic stimulation. Developmental brain disorders, such as cerebral palsy, and embryonic abnormalities, such as dysmelia, demonstrate the potential of the human brain to remap the motor system. Future therapies may be able to use that potential to maximize recovery.

Functional maps are observed in various areas in the brain of many species and are considered as key features that reveal the working mechanism of neural circuits. One particular example is the orientation preference map in the primary visual cortex (V1) in higher mammals, in which neurons respond selectively to the orientations of spatial components in visual stimuli. This cortical map has been studied extensively for years because it is thought important to understand how sensory information is encoded and decoded in the cortical neural network. An important question raised is how this map structure is created during early development, which has not been clearly answered for the past decades. Here I introduce the latest model views on this issue to discuss the developmental mechanism of the orientation preference maps, and more generally, how the development of the functional structure in the nervous system can be understood in mathematical model.

In many species, adjacent topographic maps in sensory neocortex are found to be oriented as roughly mirror-image copies of one another. Here we use a computational model to show for the first time that, in principle, adjacent cortical topographic maps that are mirror-image symmetric along two dimensions can arise from activity-dependent changes if the distribution radius of afferents sufficiently exceeds that of horizontal intracortical interactions. We also find that infrequently, other types of intermap symmetry and previously unexpected map relationships (such as interlocking rotation, in which two adjacent maps become intertwined) can occur. These results support the hypothesis that activity-dependent synaptic changes play a more important role in forming the orientations of adjacent cortical maps than is currently recognized.

Sensorimotor activity has been shown to play a key role in functional recovery after partial spinal cord injury (SCI). Most studies in rodents have focused on the rehabilitation of hindlimb locomotor functions after thoracic or lumbar SCI, whereas forelimb motor and somatosensory abilities after cervical SCI remain largely uninvestigated, despite the high incidence of such injuries in humans. Moreover, little is known about the neurophysiological substrates of training-induced recovery in supraspinal structures. This study was aimed at evaluating the effects of a training procedure combining both motor and sensory stimulation on behavioral performance and somatosensory cortical map remodeling after cervical (C4-C5) spinal hemisection in rats. This SCI severely impaired both sensory and motor capacities in the ipsilateral limbs. Without training, post-lesion motor capacities gradually improved, whereas forepaw tactile abilities remained impaired. Consistently, no stimulus-evoked responses were recorded within the forepaw representational zone in the primary somatosensory (S1) cortex at 2 months after the SCI. However, our data reveal that with training started from the 7th day post-lesion, a nearly complete recovery (characterized by an early and rapid improvement of motor functions) was associated with a gradual compensation of tactile deficits. Furthermore, the recovery of tactile abilities was correlated with the areal extent of reactivation of S1 cortex forepaw representations. Rehabilitative training promoted post-lesion adaptive plasticity, probably by enhancing endogenous activity within spared spinal and supraspinal circuits and pathways sustaining sensory and motor functions. This study highlights the beneficial effect of sensorimotor training in motor improvement and its critical influence on tactile recovery after SCI.

Development of the cortical map is experience dependent, with different critical periods in different cortical layers. Previous work in rodent barrel cortex indicates that sensory deprivation leads to changes in synaptic transmission and plasticity in layer 2/3 and 4. Here, we studied the impact of sensory deprivation on the intrinsic properties of layer 5 pyramidal neurons located in rat barrel cortex using simultaneous somatic and dendritic recording. Sensory deprivation was achieved by clipping all the whiskers on one side of the snout. Loss of sensory input did not change somatic active and resting membrane properties, and did not influence dendritic action potential (AP) backpropagation. In contrast, sensory deprivation led to an increase in the percentage of layer 5 pyramidal neurons showing burst firing. This was associated with a reduction in the threshold for generation of dendritic calcium spikes during high-frequency AP trains. Cell-attached recordings were used to assess changes in the properties and expression of dendritic HCN channels. These experiments indicated that sensory deprivation caused a decrease in HCN channel density in distal regions of the apical dendrite. To assess the contribution of HCN down-regulation on the observed increase in dendritic excitability following sensory deprivation, we investigated the impact of blocking HCN channels. Block of HCN channels removed differences in dendritic calcium electrogenesis between control and deprived neurons. In conclusion, these observations indicate that sensory loss leads to increased dendritic excitability of cortical layer 5 pyramidal neurons. Furthermore, they suggest that increased dendritic calcium electrogenesis following sensory deprivation is mediated in part via down-regulation of dendritic HCN channels.

Recent research suggests that changes in cortical structures can contribute to the pathophysiology of Complex Regional Pain Syndrome (CRPS). This review provides an overview of studies showing cortical involvement in CRPS, including mislocalizations of tactile stimuli, changes in size and organization of the somatosensory map, changes in motor cortex representation and body perception disturbances. In addition, we review experimental treatment approaches, such as mirror therapy and motor imagery programs, aimed at restoring the integrity of neural processing in the sensory-motor cortex in individuals with CRPS. The intervention effects are promising and can be theoretically motivated on the basis of established principles of neural organization, although important questions concerning the precise neural mechanisms of action remain unanswered. © 2008 European Federation of International Association for the Study of Pain Chapters.

Functional mapping of eloquent cortex is often necessary prior to invasive brain surgery, but current techniques that derive this mapping have important limitations. In this article, we demonstrate the first comprehensive evaluation of a rapid, robust, and practical mapping system that uses passive recordings of electrocorticographic signals. This mapping procedure is based on the BCI2000 and SIGFRIED technologies that we have been developing over the past several years. In our study, we evaluated 10 patients with epilepsy from four different institutions and compared the results of our procedure with the results derived using electrical cortical stimulation (ECS) mapping. The results show that our procedure derives a functional motor cortical map in only a few minutes. They also show a substantial concurrence with the results derived using ECS mapping. Specifically, compared with ECS maps, a next-neighbor evaluation showed no false negatives, and only 0.46 and 1.10% false positives for hand and tongue maps, respectively. In summary, we demonstrate the first comprehensive evaluation of a practical and robust mapping procedure that could become a new tool for planning of invasive brain surgeries.

The processing deficit in amblyopia is not restricted to just high spatial frequencies but also involves low‐medium spatial frequency processing, for suprathreshold stimuli with a broad orientational bandwidth. This is the case in all three forms of amblyopia; strabismic, anisometropic, and deprivation. Here we use both a random block design and a phase‐encoded design to ascertain (1) the extent to which fMRI activation is reduced at low‐mid spatial frequencies in different visual areas, (2) how accurately spatial frequency is mapped across the amblyopic cortex. We report a loss of function to suprathreshold low‐medium spatial frequency stimuli that involves more than just area V1, suggesting a diffuse loss in spatial frequency processing in a number of different cortical areas. An analysis of the fidelity of the spatial frequency cortical map reveals that many voxels lose their spatial frequency preference when driven by the amblyopic eye, suggesting a broader tuning for spatial frequency for neurons driven by the amblyopic eye within this low‐mid spatial frequency range. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

The primary somatosensory cortex (SI) retains its capability for cortical reorganization after injury or differential use into adulthood. The plastic response of SI cells to peripheral stimulation is characterized by extension of cortical representations accompanied by changes of the receptive field size of neurons. We used intracortical microstimulation that is known to enforce local, intracortical synchronous activity, to induce cortical reorganization and applied immunohistochemical methods in the same individual animals to investigate how plasticity in the cortical topographic maps is linked to changes in the spatial layout of the inhibitory and excitatory neurotransmitter systems. The results reveal a differential spatiotemporal pattern of upregulation and downregulation of specific factors for an excitatory (glutamatergic) and an inhibitory (GABAergic) system, associated with changes of receptive field size and reorganization of the somatotopic map in the rat SI. Predominantly local mechanisms are the specific reduction of the calcium-binding protein parvalbumin in inhibitory neurons and the low expression of the activity marker c-Fos. Reorganization in the hindpaw representation and in the adjacent SI cortical areas (motor cortex and parietal cortex) is accompanied by a major increase of the excitatory transmitter glutamate and c-Fos. The spatial extent of the reorganization appears to be limited by an increase of glutamic acid decarboxylase and the inhibitory transmitter GABA. The local and medium-range net effects are excitatory and can facilitate receptive field enlargements and cortical map expansion. The longer-range increase of inhibition appears suited to limit these effects and to prevent neurons from pathological hyperexcitability.

Over the past 30 years, extensive research has been conducted in the field of cortical plasticity, under the impetus of seminal studies showing that the mature brain retains a capacity to reorganize the morphological and functional architecture of its neural circuits in order to adapt to environmental changes and mediate functional recovery following injury. Much effort has been focused on determining how idiosyncratic experience translates into molecular, structural and physiological changes in the sensory and motor representations embedded within cortical networks. The wealth of data generated by a broad spectrum of experimental manipulations has allowed unprecedented progress in our understanding of the physiological processes and neuroplasticity mechanisms underlying cortical representational remodeling. The objective of the present review is to put various facets of cortical map plasticity into perspective so as to examine possible links between changes occurring at multiple scales of the neural organization of the mature brain. The main focus is on neural substrates that mediate the instructive influence of experience and behavioral context on cortical reorganization, and perceptual correlates of representational remodeling.

Sensory experiences contribute to the development and specialization of signal processing capacities in the mammalian auditory system during a "critical period" of postnatal development. Earlier studies have shown that passive exposure to tonal stimuli during this postnatal epoch induces a large-scale expansion of the representations of those stimuli within the primary auditory cortex (A1) [Zhang LI, Bao S, Merzenich MM (2001) Persistent and specific influences of early acoustic environments on primary auditory cortex. Nat Neurosci 4:1123-1130]. Here, we show that exposing rat pups through the normal critical period epoch and beyond to continuous, un-modulated, moderate-level tones induces no such representational distortion, and in fact disrupts the normal development of frequency response selectivity and tonotopicity all across area A1. The area of cortex responding selectively to continuously exposed sound frequencies was actually reduced, when compared with rats reared in normal environments. Strong exposure-driven plasticity characteristic of the critical period could be induced well beyond the normal end of the critical period, by simply modulating the tonal stimulus. Thus, continuous tone exposure, like continuous noise exposure [Chang EF, Merzenich MM (2003) Environmental noise retards auditory cortical development. Science 300:498-502], ineffectively induces critical period plasticity, and indefinitely blocks the closure of a normally-brief critical period window. These findings again demonstrate the crucial role of temporally structured inputs for inducing the progressive cortical maturational changes that result in the closure of the critical period window.

In classical sensory cortical map plasticity, the representation of deprived or underused inputs contracts within cortical sensory maps, whereas spared inputs expand. Expansion of spared inputs occurs preferentially into nearby cortical columns representing temporally correlated spared inputs, suggesting that expansion involves correlation-based learning rules at cross-columnar synapses. It is unknown whether deprived representations contract in a similar anisotropic manner, which would implicate similar learning rules and sites of plasticity. We briefly deprived D-row whiskers in 20-day-old rats, so that each deprived whisker had deprived (D-row) and spared (C- and E-row) neighbors. Intrinsic signal optical imaging revealed that D-row deprivation weakened and contracted the functional representation of deprived D-row whiskers in L2/3 of somatosensory (S1) cortex. Spared whisker representations did not strengthen or expand, indicating that D-row deprivation selectively engages the depression component of map plasticity. Contraction of deprived whisker representations was spatially uniform, with equal withdrawal from spared and deprived neighbors. Single-unit electrophysiological recordings confirmed these results, and showed substantial weakening of responses to deprived whiskers in layer 2/3 of S1, and modest weakening in L4. The observed isotropic contraction of deprived whisker representations during D-row deprivation is consistent with plasticity at intracolumnar, rather than cross-columnar, synapses.

Neuroimaging research over the past decade has revealed a detailed picture of the functional organization of the human brain. Here we focus on two fundamental questions that are raised by the detailed mapping of sensory and cognitive functions and illustrate these questions with findings from the object-vision pathway. First, are functionally specific regions that are located close together best understood as distinct cortical modules or as parts of a larger-scale cortical map? Second, what functional properties define each cortical map or module? We propose a model in which overlapping continuous maps of simple features give rise to discrete modules that are selective for complex stimuli.

Functional maps arise in developing visual cortex as response selectivities become organized into columnar patterns of population activity. Recent studies of developing orientation and direction maps indicate that both are sensitive to visual experience, but not to the same degree or duration. Direction maps have a greater dependence on early vision, while orientation maps remain sensitive to experience for a longer period of cortical maturation. There is also a darker side to experience: abnormal vision through closed lids produces severe impairments in neuronal selectivity, rendering these maps nearly undetectable. Thus, the rules that govern their formation and the construction of the underlying neural circuits are modulated-for better or worse-by early vision. Direction maps, and possibly maps of other properties that are dependent upon precise conjunctions of spatial and temporal signals, are most susceptible to the potential benefits and maladaptive consequences of early sensory experience.

In the adult visual cortex, multiple feature maps exist and have characteristic spatial relationships with one another. The relationships can be reproduced by “dimension-reduction” computational models, suggesting that the principles of continuity and coverage may underlie cortical map organization. However, the mechanisms responsible for establishing these relationships are unknown. We explored whether removing one feature map during development causes a coordinated reorganization of the remaining maps or whether the remaining maps are unaffected. We removed the ocular dominance map by monocular enucleation in newborn ferrets, so that single eye stimulation drove the cortex in a more spatially uniform manner in adult monocular animals compared with normal animals. Maps of orientation, spatial frequency, and retinotopy formed in monocular ferrets, but their structures and spatial relationships differed from those in normal ferrets. The wavelength of the orientation map increased, so that the average orientation gradient across the cortex decreased. The decrease in the orientation gradient in monocular animals was most prominent in the high gradient regions of the spatial frequency map, indicating a coordinated reorganization between these two maps. In monocular animals, the orthogonal relationship between the orientation and spatial frequency maps was preserved, and the orthogonal relationship between the orientation and retinotopic maps became more pronounced. These results were consistent with detailed predictions of a dimension-reduction model of cortical organization. Thus, the number of feature maps in a cortical area influences the relationships between them, and inputs to the cortex have a significant role in generating these relationships.

The primary somatosensory cortex contains a topographic map of the body surface, with two notable discontinuities-the representation of the face is next to that of the hands, and that of the feet is next to the genitals. Farah [Why does the somatosensory homunculus have hands next to face and feet next to genitals? a hypothesis. Neural Computation 10(8) (1998) 1983-1985] has suggested that these discontinuities are due to the mechanisms of self-organisation which underlie cortical map development. The typical position of the foetus in the womb means that these two pairs of body parts will often touch and hence their representations will be simultaneously co-active, even though they are distal in terms of the body surface. We use the Kohonen self-organising map algorithm to provide an existence proof of the plausibility of Farah's hypotheses. We then use the model to test the viability of other possible causes of the known map structure and to explore the limitations of self-organisation for explaining the features of the somatosensory map. The model shows that (a) the Kohonen algorithm requires high frequencies of co-activation to introduce a selective discontinuity into the map, and (b) that higher frequency of separate activation of the critical patterns alone is not sufficient to generate the selective discontinuity and (c) the consistency of near-optimal map formation, and in particular the medial-lateral ordering, cannot be reliably generated by a simple Kohonen algorithm.

Removal of retinal input from a restricted region of adult cat visual cortex leads to a substantial reorganization of the retinotopy within the sensory-deprived cortical lesion projection zone (LPZ). Still little is known about the molecular mechanisms underlying this cortical map reorganization. We chose two members of the collapsin response mediator protein (CRMP) family, CRMP2 and CRMP4, because of their involvement in neurite growth, and compared gene and protein expression levels between normal control and reorganizing visual cortex upon induction of central retinal lesions. Parallel analysis of Dynamin I (Dyn I) and Synaptotagmin I (Syt I), two molecules implicated in the exocytosis-endocytosis cycle, was performed because changes in neurotransmitter release have been implicated in cortical plasticity. Western blotting and real-time polymerase chain reaction revealed a clear time-dependent effect of retinal lesioning on CRMP2 and CRMP4 expression, with maximal impact 2 weeks post-lesion. Altered CRMP levels were not a direct consequence of decreased visual activity in the LPZ as complete surgical removal of retinal input to one hemisphere had no effect on CRMP2 or CRMP4 expression. Thus, CRMP expression is correlated to cortical reorganization following partial deafferentation of adult visual cortex. In contrast, Dyn I and Syt I were not influenced and thereby do not promote exocytosis-endocytosis cycle modifications in adult cat cortical plasticity.

Background and Purpose Deficits in upper-extremity function in individuals with tetraplegia are primarily due to the loss of motor pathways. Detrimental cortical reorganization, however, may create further loss of function. The purpose of this case report is to describe the cortical changes associated with a combination intervention using bimanual massed practice training with somatosensory stimulation. Case Description “BR” was a 22-year-old man with C6 tetraplegia and hand impairment who participated in this training intervention for 3 weeks. Outcomes BR demonstrated improvements in sensory function, strength (the force-generating capacity of muscle), and performance of functional hand skills. Following the training, the cortical motor map of the biceps brachii muscle shifted anteriorly and increased in area and volume. Discussion This is the first documented case in which changes in the size and location of the cortical map were associated with an intervention and improvement in function in an individual with tetraplegia. This case suggests that an intensive training intervention may induce both functional and neurophysiological changes.

Tinnitus, the phenomenon of ringing or buzzing in the ears without an external sound source is one of the most commonly reported symptoms in otorhinolaryngology and affects 10 – 15% of the general population. Models have been developed to account for neural basis of tinnitus, its pathogenesis and its consequences on mental health (deRidder et al., 2013). In most cases tinnitus onset follows a partial hearing impairment. Peripheral sensory deprivation due to cochlear damages may prompt increased neuronal activity in the central auditory system in order to adapt the neural sensitivity to the reduced sensory inputs. This central gain could over amplify the “neural noise” and thus trigger a homeostatic down-regulation of inhibitory synapses in the auditory cortical map leading to specific reorganization of the cortical representation of the tinnitus percept. Dysfunctional feedback connections from limbic regions to auditory brain areas, interacting at the thalamic level, may account for the psychological impairment.

The occipital face area (OFA) and fusiform face area (FFA) are brain regions thought to be specialized for face perception. However, their intrinsic functional organization and status as cortical areas with well-defined boundaries remains unclear. Here we test these regions for ?faciotopy?, a particular hypothesis about their intrinsic functional organisation. A faciotopic area would contain a face-feature map on the cortical surface, where cortical patches represent face features and neighbouring patches represent features that are physically neighbouring in a face. The faciotopy hypothesis is motivated by the idea that face regions might develop from a retinotopic protomap and acquire their selectivity for face features through natural visual experience. Faces have a prototypical configuration of features, are usually perceived in a canonical upright orientation, and are frequently fixated in particular locations. To test the faciotopy hypothesis, we presented images of isolated face features at fixation to subjects during functional magnetic resonance imaging. The responses in V1 were best explained by low-level image properties of the stimuli. OFA, and to a lesser degree FFA, showed evidence for faciotopic organization. When a single patch of cortex was estimated for each face feature, the cortical distances between the feature patches reflected the physical distance between the features in a face. Faciotopy would be the first example, to our knowledge, of a cortical map reflecting the topology, not of a part of the organism itself (its retina in retinotopy, its body in somatotopy), but of an external object of particular perceptual significance.

The bidirectional flow of perceptual and motor information has recently proven useful as rehabilitative tool for re-building motor memories. We analyzed how the visual-motor approach has been successfully applied in neurorehabilitation, leading to surprisingly rapid and effective improvements in action execution. We proposed that the contribution of multiple sensory channels during treatment enables individuals to predict and optimize motor behavior, having a greater effect than visual input alone. We explored how the state-of-the-art neuroscience techniques show direct evidence that employment of visual-motor approach leads to increased motor cortex excitability and synaptic and cortical map plasticity. This super-additive response to multimodal stimulation may maximize neural plasticity, potentiating the effect of conventional treatment, and will be a valuable approach when it comes to advances in innovative methodologies.

Background Pairing sensory or motor events with vagus nerve stimulation (VNS) can reorganize sensory or motor cortex. Repeatedly pairing a tone with a brief period of VNS increases the proportion of primary auditory cortex (A1) responding to the frequency of the paired tone. However, the relationship between VNS intensity and cortical map plasticity is not known. Objective/hypothesis The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity. Methods The rats were exposed to a 9 kHz tone paired with VNS at intensities of 0.4, 0.8, 1.2, or 1.6 mA. Results In rats that received moderate (0.4–0.8 mA) intensity VNS, 75% more cortical neurons were tuned to frequencies near the paired tone frequency. A two-fold effective range is broader than expected based on previous VNS studies. Rats that received high (1.2–1.6 mA) intensity VNS had significantly fewer neurons tuned to the same frequency range compared to the moderate intensity group. Conclusion This result is consistent with previous results documenting that VNS is memory enhancing as a non-monotonic relationship of VNS intensity.

Visual cortical neurons are sensitive to visual stimulus contrast and most cells adapt their sensitivity to the prevailing visual environment. Specifically, they match the steepest region of their contrast response function to the prevailing contrast (contrast gain control), and reduce spike rates to limit saturation (response gain control). Most neurons are also tuned for stimulus orientation, and neurons with similar orientation preference are clustered together into iso-orientation zones arranged around pinwheels, i.e. points where all orientations are represented. Here we investigated the relationship between the contrast adaptation properties of neurons and their location relative to pinwheels in the orientation preference map. We measured orientation preference maps in cat cortex using optical intrinsic signal imaging. We then characterized the contrast adaptation properties of single neurons located close to pinwheels, in iso-orientation zones, and at regions in between. We found little evidence of differential contrast sensitivity of neurons adapted to zero contrast. However, after adaptation to their preferred orientation at high contrast, changes in both contrast and response gain were greater for neurons near pinwheels compared with other map regions. Therefore, in the adapted state, which is probably typical during natural viewing, there is a spatial map of contrast sensitivity that is associated with the orientation preference map. This differential adaptation revealed a new dimension of cortical functional organization, linking the contrast adaptation of cells with the orientation preference of their nearest neighbours.

Sound categorization is essential for auditory behaviors like acoustic communication, but its genesis within the auditory pathway is not well understood—especially for learned natural categories like vocalizations, which often share overlapping acoustic features that must be distinguished (e.g., speech). We use electrophysiological mapping and single-unit recordings in mice to investigate how representations of natural vocal categories within core auditory cortex are modulated when one category acquires enhanced behavioral relevance. Taking advantage of a maternal mouse model of acoustic communication, we found no long-term auditory cortical map expansion to represent a behaviorally relevant pup vocalization category—contrary to expectations from the cortical plasticity literature on conditioning with pure tones. Instead, we observed plasticity that improved the separation between acoustically similar pup and adult vocalization categories among a physiologically defined subset of late-onset, putative pyramidal neurons, but not among putative interneurons. Additionally, a larger proportion of these putative pyramidal neurons in maternal animals compared with nonmaternal animals responded to the individual pup call exemplars having combinations of acoustic features most typical of that category. Together, these data suggest that higher-order representations of acoustic categories arise from a subset of core auditory cortical pyramidal neurons that become biased toward the combination of acoustic features statistically predictive of membership to a behaviorally relevant sound category.

The organization of the motor cortex has been studied and debated for more than 130 years. Although it contains a map of the body, the map is overlapping and fractured, and therefore, additional principles of organization may be needed to explain the topography. Recently, a growing body of evidence suggests one such principle. The motor cortex appears to be partly organized as a map of complex, behaviorally useful actions that compose the animal's movement repertoire. In the action map perspective, the statistical complexity of the movement repertoire leads to the complexity of the cortical map.

Here we propose that earlier-demonstrated details in the primate visual cortical map may account for an otherwise puzzling (and problematic) finding in the current human fMRI literature. Specifically, the well-known regions LO and MT(+) reportedly overlap in the human cortical visual map, when those two regions are localized using standard stimulus comparisons in conventional fMRI experiments. Here we describe evidence supporting the idea that the apparent functional overlap between LO and MT arises from a third area (the MT crescent: “MTc”), which is well known to surround posterior MT based on earlier histological, neuroanatomical, and electrophysiological studies in nonhuman primates. If we assume that MTc also exists in human visual cortex, and that it has a location and functional properties intermediate to those in LO and MT, simplistic modeling confirmed that this arrangement could produce apparent overlap between localizers for LO and MT in conventional fMRI maps in human visual cortex.

Several studies have already demonstrated that patients with steeply sloping hearing loss of cochlear origin exhibit an improvement in frequency discrimination performance at or around the cut-off frequency. This enhancement cannot be explained in terms of peripheral mechanisms and should rather be interpreted in terms of central reorganization: i.e., injury-induced cortical plasticity. However, the reversibility and time course of such reorganization has not yet been described. The main goal of the present study was therefore to investigate the occurrence of rehabilitation plasticity associated with hearing-aid fitting in human subjects. Nine subjects with steeply sloping hearing loss and who were candidates for auditory rehabilitation were tested. Discrimination-limen-for-frequency (DLF) enhancement was investigated at the frequency with the best DLF (bDLF) for each individual subject before and during auditory rehabilitation (at 1 month, 3 months and 6 months). From 1 month on, frequency discrimination performance decreased significantly at the bDLF frequency, while remaining stable at other frequencies. This normalization may reflect a new central reorganization reversing the initial injury-induced changes in the cortical map. A correlation between subject's age and alteration in DLF at 1 month was also found, suggesting that plasticity operates faster in younger patients.

We develop schematic, self-organizing, neural-network models to describe mechanisms associated with mental processes, by a neurocomputational substrate. These models are examples of real world complex networks with interesting general topological structures. Considering dopaminergic signal-to-noise neuronal modulation in the central nervous system, we propose neural network models to explain development of cortical map structure and dynamics of memory access, and unify different mental processes into a single neurocomputational substrate. Based on our neural network models, neurotic behavior may be understood as an associative memory process in the brain, and the linguistic, symbolic associative process involved in psychoanalytic working-through can be mapped onto a corresponding process of reconfiguration of the neural network. The models are illustrated through computer simulations, where we varied dopaminergic modulation and observed the self-organizing emergent patterns at the resulting semantic map, interpreting them as different manifestations of mental functioning, from psychotic through to normal and neurotic behavior, and creativity.

The mammalian visual system has been extensively studied since Hubel and Wiesel’s work on cortical feature maps in the 1960s. Feature maps representing the cortical neurons’ ocular dominance, orientation and direction preferences have been well explored experimentally and computationally. The predominant view has been that direction selectivity (DS) in particular, is a feature entirely dependent upon visual experience and as such does not exist prior to eye opening (EO). However, recent experimental work has shown that there is in fact a DS bias already present at EO. In the current work we use a computational model to reproduce the main results of this experimental work and show that the DS bias present at EO could arise purely from the cortical architecture without any explicit coding for DS and prior to any self-organising process facilitated by spontaneous activity or training. We explore how this latent DS (and its corresponding cortical map) is refined by training and that the time-course of development exhibits similar features to those seen in the experimental study. In particular we show that the specific cortical connectivity or ‘proto-architecture’ is required for DS to mature rapidly and correctly with visual experience.

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex—changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies Fil: Peng, Yu Hao. University of Southern California; Estados Unidos Fil: Heintz, Ryan. University of Southern California; Estados Unidos Fil: Wang, Zhuo. University of Southern California; Estados Unidos Fil: Guo,Yumei. University of Southern California; Estados Unidos Fil: Myers, Kalisa G.. University of Southern California; Estados Unidos Fil: Scremin, Oscar Umberto. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles; Estados Unidos. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Maarek, Jean Michel. University of Southern California; Estados Unidos Fil: Holschneider, Daniel P.. University of Southern California; Estados Unidos