Longitudinal stability of individual brain plasticity patterns in blindness.

The primary visual cortex (V1) in blindness is engaged in a wide spectrum of tasks and sensory modalities, including audition, touch, language, and memory. This widespread involvement raises questions regarding the constancy of its role and whether it might exhibit flexibility in its function over time, connecting to diverse network functions specific to task demands. This would suggest that reorganized V1 assumes a role like multiple-demand system regions. Alternatively, varying patterns of plasticity in blind V1 may be attributed to individual factors, with different blind individuals recruiting V1 preferentially for different functions. In support of this, we recently showed that V1 functional connectivity (FC) varies greatly across blind individuals. But do these represent stable individual patterns of plasticity, or are they driven more by instantaneous changes, like a multiple-demand system now inhabiting V1? Here, we tested whether individual FC patterns from the V1 of blind individuals are stable over time. We show that over two years, FC from the V1 is unique and highly stable in a small sample of repeatedly sampled congenitally blind individuals. Further, using multivoxel pattern analysis, we demonstrate that the unique reorganization patterns of these individuals allow decoding of participant identity. Together with recent evidence for substantial individual differences in V1 connectivity, this indicates that there may be a consistent role for V1 in blindness, which may differ for each individual. Further, it suggests that the variability in visual reorganization in blindness across individuals could be used to seek stable neuromarkers for sight rehabilitation and assistive approaches.

The visual cortex in the blind but not the auditory cortex in the deaf becomes multiple-demand regions.

The fate of deprived sensory cortices (visual regions in the blind and auditory regions in the deaf) exemplifies the extent to which experience can change brain regions. These regions are frequently seen to activate during tasks involving other sensory modalities, leading many authors to infer that these regions have started to process sensory information of other modalities. However, such observations can also imply that these regions are now activating in response to any task event, regardless of the sensory modality. Activating in response to task events, irrespective of the sensory modality involved, is a feature of the multiple-demands (MD) network. This is a set of regions within the frontal and parietal cortices that activate in response to any kind of control demand. Thus, demands as diverse as attention, perceptual difficulty, rule-switching, updating working memory, inhibiting responses, decision-making and difficult arithmetic all activate the same set of regions that are thought to instantiate domain-general cognitive control and underpin fluid intelligence. We investigated whether deprived sensory cortices, or foci within them, become part of the MD network. We tested whether the same foci within the visual regions of the blind and auditory regions of the deaf activated in response to different control demands. We found that control demands related to updating auditory working memory, difficult tactile decisions, time-duration judgments and sensorimotor speed all activated the entire bilateral occipital regions in the blind but not in the sighted. These occipital regions in the blind were the only regions outside the canonical frontoparietal MD regions to show such activation in response to multiple control demands. Furthermore, compared with the sighted, these occipital regions in the blind had higher functional connectivity with frontoparietal MD regions. Early deaf, in contrast, did not activate their auditory regions in response to different control demands, showing that auditory regions do not become MD regions in the deaf. We suggest that visual regions in the blind do not take a new sensory role but become part of the MD network, and this is not a response of all deprived sensory cortices but a feature unique to the visual regions.

Visuospatial processing in early brain-based visual impairment is associated with differential recruitment of dorsal and ventral visual streams.

Visuospatial processing impairments are prevalent in individuals with cerebral visual impairment (CVI) and are typically ascribed to "dorsal stream dysfunction" (DSD). However, the contribution of other cortical regions, including early visual cortex (EVC), frontal cortex, or the ventral visual stream, to such impairments remains unknown. Thus, here, we examined fMRI activity in these regions, while individuals with CVI (and neurotypicals) performed a visual search task within a dynamic naturalistic scene. First, behavioral performance was measured with eye tracking. Participants were instructed to search and follow a walking human target. CVI participants took significantly longer to find the target, and their eye gaze patterns were less accurate and less precise. Second, we used the same task in the MRI scanner. Along the dorsal stream, activation was reduced in CVI participants, consistent with the proposed DSD in CVI. Intriguingly, however, visual areas along the ventral stream showed the complete opposite pattern, with greater activation in CVI participants. In contrast, we found no differences in either EVC or frontal cortex between groups. These results suggest that the impaired visuospatial processing abilities in CVI are associated with differential recruitment of the dorsal and ventral visual streams, likely resulting from impaired selective attention.

Atypical functional connectivity between the amygdala and visual, salience regions in infants with genetic liability for autism.

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.

Evaluation of potential alterations related to ADHD in the effective connectivity between the default mode network and cerebellum, hippocampus, thalamus, and primary visual cortex.

Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11 years disappeared after 14 years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.

Neural networks associated with eye movements in congenital blindness.

Recent studies have shown that during the typical resting-state, echo planar imaging (EPI) time series obtained from the eye orbit area correlate with brain regions associated with oculomotor control and lower-level visual cortex. Here, we asked whether congenitally blind (CB) shows similar patterns, suggesting a hard-wired constraint on connectivity. We find that orbital EPI signals in CB do correlate with activity in the motor cortex, but less so with activity in the visual cortex. However, the temporal patterns of this eye movement-related signal differed strongly between CB and sighted controls. Furthermore, in CB, a few participants showed uncoordinated orbital EPI signals between the two eyes, each correlated with activity in different brain networks. Our findings suggest a retained circuitry between motor cortex and eye movements in blind, but also a moderate reorganization due to the absence of visual input, and the inability of CB to control their eye movements or sense their positions.

Portable multi-focal visual evoked potential diagnostics for multiple sclerosis/optic neuritis patients.

PURPOSE: Multiple sclerosis (MS) is a neuro-inflammatory disease affecting the central nervous system (CNS), where the immune system targets and damages the protective myelin sheath surrounding nerve fibers, inhibiting axonal signal transmission. Demyelinating optic neuritis (ON), a common MS symptom, involves optic nerve damage. We've developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from the scalp using custom electroencephalography electrodes. METHODS: Subject vision is evaluated using a short 2.5-min full-field visual evoked potentials (ffVEP) test, followed by a 12.5-min multifocal VEP (mfVEP) test. The ffVEP evaluates the integrity of the visual pathway by analyzing the P100 component from each eye, while the mfVEP evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEPs. Key metrics from patients' ffVEP results were statistically evaluated against data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification. RESULTS: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging and Optical Coherence Tomography findings. CONCLUSION: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

Resting-State Functional Connectivity of the Primary Visual Cortex in Children with Anisometropia Amblyopia.

INTRODUCTION: This study aimed to explore the functional connectivity of the primary visual cortex (V1) in children with anisometropic amblyopia by using the resting-state functional connectivity analysis method and determine whether anisometropic amblyopia is associated with changes in brain function. METHODS: Functional magnetic resonance imaging (fMRI) data were obtained from 16 children with anisometropia amblyopia (CAA group) and 12 healthy children (HC group) during the resting state. The Brodmann area 17 (BA17) was used as the region of interest, and the functional connection (FC) of V1 was analyzed in both groups. A two-sample t test was used to analyze the FC value between the two groups. Pearson's correlation was used to analyze the correlation between the mean FC value in the brain function change area of the CAA group and the best corrected visual acuity (BCVA) of amblyopia. p < 0.05 was considered statistically significant. RESULTS: There were no significant differences in age and sex between the CAA and HC groups (p > 0.05). Compared to the HC group, the CAA group showed lower FC values in BA17 and the left medial frontal gyrus, as well as BA17 and the left triangle inferior frontal gyrus. Conversely, the CAA group showed higher FC values in BA17 and the left central posterior gyrus. Notably, BCVA in amblyopia did not correlate with the area of change in mean FC in the brain function of the CAA group. CONCLUSION: Resting-state fMRI-based functional connectivity analysis indicates a significant alteration in V1 of children with anisometropic amblyopia. These findings contribute additional insights into the neuropathological mechanisms underlying visual impairment in anisometropic amblyopia.

Rapid topographic reorganization in adult human primary visual cortex (V1) during noninvasive and reversible deprivation.

Can the primary visual cortex (V1), once wired up in development, change in adulthood? Although numerous studies have demonstrated topographic reorganization in adult V1 following the loss of bottom-up input, others have challenged such findings, offering alternative explanations. Here we use a noninvasive and reversible deprivation paradigm and converging neural and behavioral approaches to address these alternatives in the experimental test case of short-term topographic reorganization in adult human V1. Specifically, we patched one eye in typical adults, thereby depriving the cortical representation of the other eye's blind spot (BS), and immediately tested for topographic reorganization using functional magnetic resonance imaging and psychophysics. Strikingly, within just minutes of eye-patching, the BS representation in V1 began responding to stimuli presented outside of the BS, and these same stimuli were perceived as elongated toward the BS. Thus, we provide converging neural and behavioral evidence of rapid topographic reorganization in adult human V1, and the strongest evidence yet that visual deprivation produces bona fide cortical change.

Central neurogenetic signatures of the visuomotor integration system.

Visuomotor impairments characterize numerous neurological disorders and neurogenetic syndromes, such as autism spectrum disorder (ASD) and Dravet, Fragile X, Prader-Willi, Turner, and Williams syndromes. Despite recent advances in systems neuroscience, the biological basis underlying visuomotor functional impairments associated with these clinical conditions is poorly understood. In this study, we used neuroimaging connectomic approaches to map the visuomotor integration (VMI) system in the human brain and investigated the topology approximation of the VMI network to the Allen Human Brain Atlas, a whole-brain transcriptome-wide atlas of cortical genetic expression. We found the genetic expression of four genes-TBR1, SCN1A, MAGEL2, and CACNB4-to be prominently associated with visuomotor integrators in the human cortex. TBR1 gene transcripts, an ASD gene whose expression is related to neural development of the cortex and the hippocampus, showed a central spatial allocation within the VMI system. Our findings delineate gene expression traits underlying the VMI system in the human cortex, where specific genes, such as TBR1, are likely to play a central role in its neuronal organization, as well as on specific phenotypes of neurogenetic syndromes.

Excitatory Contribution to Binocular Interactions in Human Visual Cortex Is Reduced in Strabismic Amblyopia.

Binocular summation in strabismic amblyopia is typically reported as being absent or greatly reduced in behavioral studies and is thought to be because of a preferential loss of excitatory interactions between the eyes. Here, we studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with strabismic and anisometropic amblyopia in both sexes, using source-imaged steady-state visual evoked potentials (SSVEP) over a wide range of relative contrast between the two eyes. Dichoptic parallel grating stimuli modulated at unique temporal frequencies in each eye allowed us to quantify spectral response components associated with monocular inputs (self-terms) and the response components because of interaction of the inputs of the two eyes [intermodulation (IM) terms]. Although anisometropic amblyopes revealed a similar pattern of responses to normal-vision observers, strabismic amblyopes exhibited substantially reduced IM responses across cortical regions of interest (V1, V3a, hV4, hMT+ and lateral occipital cortex), indicating reduced interocular interactions in visual cortex. A contrast gain control model that simultaneously fits self- and IM-term responses within each cortical area revealed different patterns of binocular interactions between individuals with normal and disrupted binocularity. Our model fits show that in strabismic amblyopia, the excitatory contribution to binocular interactions is significantly reduced in both V1 and extra-striate cortex, whereas suppressive contributions remain intact. Our results provide robust electrophysiological evidence supporting the view that disruption of binocular interactions in strabismus or amblyopia is because of preferential loss of excitatory interactions between the eyes.SIGNIFICANCE STATEMENT We studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with normal and amblyopic vision, using source-imaged SSVEP and frequency-domain analysis of dichoptic stimuli over a wide range of relative contrast between the two eyes. A dichoptic contrast gain control model was used to characterize these interactions in amblyopia and provided a quantitative comparison to normal vision. Our model fits revealed different patterns of binocular interactions between normal and amblyopic vision. Strabismic amblyopia significantly reduced excitatory contributions to binocular interactions, whereas suppressive contributions remained intact. Our results provide robust evidence supporting the view that the preferential loss of excitatory interactions disrupts binocular interactions in strabismic amblyopia.

Cortical Visual Mapping following Ocular Gene Augmentation Therapy for Achromatopsia.

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3-achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3-achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception.SIGNIFICANCE STATEMENT The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital CNGA3-achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input.

Diminished Cortical Excitation and Elevated Inhibition During Perceptual Impairments in a Mouse Model of Autism.

Sensory impairments are a core feature of autism spectrum disorder (ASD). These impairments affect visual perception and have been hypothesized to arise from imbalances in cortical excitatory and inhibitory activity. There is conflicting evidence for this hypothesis from several recent studies of transgenic mouse models of ASD; crucially, none have measured activity from identified excitatory and inhibitory neurons during simultaneous impairments of sensory perception. Here, we directly recorded putative excitatory and inhibitory population spiking in primary visual cortex (V1) while simultaneously measuring visual perceptual behavior in CNTNAP2-/- knockout (KO) mice. We observed quantitative impairments in the speed, accuracy, and contrast sensitivity of visual perception in KO mice. During these perceptual impairments, stimuli evoked more firing of inhibitory neurons and less firing of excitatory neurons, with reduced neural sensitivity to contrast. In addition, pervasive 3-10 Hz oscillations in superficial cortical layers 2/3 (L2/3) of KO mice degraded predictions of behavioral performance from neural activity. Our findings show that perceptual deficits relevant to ASD may be associated with elevated cortical inhibitory activity along with diminished and aberrant excitatory population activity in L2/3, a major source of feedforward projections to higher cortical regions.

Disruption of Critical Period Plasticity in a Mouse Model of Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a common monogenic neurodevelopmental disorder associated with physical and cognitive problems. The cognitive issues are thought to arise from increased release of the neurotransmitter GABA. Modulating the signaling pathways causing increased GABA release in a mouse model of NF1 reverts deficits in hippocampal learning. However, clinical trials based on these approaches have so far been unsuccessful. We therefore used a combination of slice electrophysiology, in vivo two-photon calcium imaging, and optical imaging of intrinsic signal in a mouse model of NF1 to investigate whether cortical development is affected in NF1, possibly causing lifelong consequences that cannot be rescued by reducing inhibition later in life. We find that, in NF1 mice of both sexes, inhibition increases strongly during the development of the visual cortex and remains high. While this increase in cortical inhibition does not affect spontaneous cortical activity patterns during early cortical development, the critical period for ocular dominance plasticity is shortened in NF1 mice due to its early closure but unaltered onset. Notably, after environmental enrichment, differences in inhibitory innervation and ocular dominance plasticity between NF1 mice and WT littermates disappear. These results provide the first evidence for critical period dysregulation in NF1 and suggest that treatments aimed at normalizing levels of inhibition will need to start at early stages of development.SIGNIFICANCE STATEMENT Neurofibromatosis type 1 is associated with cognitive problems for which no treatment is currently available. This study shows that, in a mouse model of neurofibromatosis type 1, cortical inhibition is increased during development and critical period regulation is disturbed. Rearing the mice in an environment that stimulates cognitive function overcomes these deficits. These results uncover critical period dysregulation as a novel mechanism in the pathogenesis of neurofibromatosis type 1. This suggests that targeting the affected signaling pathways in neurofibromatosis type 1 for the treatment of cognitive disabilities may have to start at a much younger age than has so far been tested in clinical trials.

Beyond imagination: Hypnotic visual hallucination induces greater lateralised brain activity than visual mental imagery.

Hypnotic suggestions can produce a broad range of perceptual experiences, including hallucinations. Visual hypnotic hallucinations differ in many ways from regular mental images. For example, they are usually experienced as automatic, vivid, and real images, typically compromising the sense of reality. While both hypnotic hallucination and mental imagery are believed to mainly rely on the activation of the visual cortex via top-down mechanisms, it is unknown how they differ in the neural processes they engage. Here we used an adaptation paradigm to test and compare top-down processing between hypnotic hallucination, mental imagery, and visual perception in very highly hypnotisable individuals whose ability to hallucinate was assessed. By measuring the N170/VPP event-related complex and using multivariate decoding analysis, we found that hypnotic hallucination of faces involves greater top-down activation of sensory processing through lateralised neural mechanisms in the right hemisphere compared to mental imagery. Our findings suggest that the neural signatures that distinguish hypnotically hallucinated faces from imagined faces lie in the right brain hemisphere.

Site-specific abnormalities in the visual system of a mouse model of CDKL5 deficiency disorder.

CDKL5 deficiency disorder (CDD) is a neurodevelopmental disorder characterized by a severe global developmental delay and early-onset seizures. Notably, patients show distinctive visual abnormalities often clinically diagnosed as cortical visual impairment. However, the involvement of cerebral cortical dysfunctions in the origin of the symptoms is poorly understood. CDD mouse models also display visual deficits, and cortical visual responses can be used as a robust biomarker in CDKL5 mutant mice. A deeper understanding of the circuits underlying the described visual deficits is essential for directing preclinical research and translational approaches. Here, we addressed this question in two ways: first, we performed an in-depth morphological analysis of the visual pathway, from the retina to the primary visual cortex (V1), of CDKL5 null mice. We found that the lack of CDKL5 produced no alteration in the organization of retinal circuits. Conversely, CDKL5 mutants showed reduced density and altered morphology of spines and decreased excitatory synapse marker PSD95 in the dorsal lateral geniculate nucleus and in V1. An increase in the inhibitory marker VGAT was selectively present in V1. Second, using a conditional CDKL5 knockout model, we showed that selective cortical deletion of CDKL5 from excitatory cells is sufficient to produce abnormalities of visual cortical responses, demonstrating that the normal function of cortical circuits is dependent on CDKL5. Intriguingly, these deficits were associated with morphological alterations of V1 excitatory and inhibitory synaptic contacts. In summary, this work proposes cortical circuit structure and function as a critically important target for studying CDD.

Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients.

OBJECTIVE: The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. METHODS: De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. RESULTS: In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. INTERPRETATION: Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.

Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar.

When the primary visual cortex (V1) is damaged, the principal visual pathway is lost, causing a loss of vision in the opposite visual field. While conscious vision is impaired, patients can still respond to certain images; this is known as 'blindsight'. Recently, a direct anatomical connection between the lateral geniculate nucleus (LGN) and human motion area hMT+ has been implicated in blindsight. However, a functional connection between these structures has not been demonstrated. We quantified functional MRI responses to motion in 14 patients with unilateral V1 damage (with and without blindsight). Patients with blindsight showed significant activity and a preserved sensitivity to speed in motion area hMT+, which was absent in patients without blindsight. We then compared functional connectivity between motion area hMT+ and a number of structures implicated in blindsight, including the ventral pulvinar. Only patients with blindsight showed an intact functional connection with the LGN but not the other structures, supporting a specific functional role for the LGN in blindsight.

Mapping migraine to a common brain network.

Inconsistent findings from migraine neuroimaging studies have limited attempts to localize migraine symptomatology. Novel brain network mapping techniques offer a new approach for linking neuroimaging findings to a common neuroanatomical substrate and localizing therapeutic targets. In this study, we attempted to determine whether neuroanatomically heterogeneous neuroimaging findings of migraine localize to a common brain network. We used meta-analytic coordinates of decreased grey matter volume in migraineurs as seed regions to generate resting state functional connectivity network maps from a normative connectome (n = 1000). Network maps were overlapped to identify common regions of connectivity across all coordinates. Specificity of our findings was evaluated using a whole-brain Bayesian spatial generalized linear mixed model and a region of interest analysis with comparison groups of chronic pain and a neurologic control (Alzheimer's disease). We found that all migraine coordinates (11/11, 100%) were negatively connected (t ≥ ±7, P < 10-6 family-wise error corrected for multiple comparisons) to a single location in left extrastriate visual cortex overlying dorsal V3 and V3A subregions. More than 90% of coordinates (10/11) were also positively connected with bilateral insula and negatively connected with the hypothalamus. Bayesian spatial generalized linear mixed model whole-brain analysis identified left V3/V3A as the area with the most specific connectivity to migraine coordinates compared to control coordinates (voxel-wise probability of ≥90%). Post hoc region of interest analyses further supported the specificity of this finding (ANOVA P = 0.02; pairwise t-tests P = 0.03 and P = 0.003, respectively). In conclusion, using coordinate-based network mapping, we show that regions of grey matter volume loss in migraineurs localize to a common brain network defined by connectivity to visual cortex V3/V3A, a region previously implicated in mechanisms of cortical spreading depression in migraine. Our findings help unify migraine neuroimaging literature and offer a migraine-specific target for neuromodulatory treatment.

Functional preservation and enhanced capacity for visual restoration in subacute occipital stroke.

Stroke damage to the primary visual cortex (V1) causes a loss of vision known as hemianopia or cortically-induced blindness. While perimetric visual field improvements can occur spontaneously in the first few months post-stroke, by 6 months post-stroke, the deficit is considered chronic and permanent. Despite evidence from sensorimotor stroke showing that early injury responses heighten neuroplastic potential, to date, visual rehabilitation research has focused on patients with chronic cortically-induced blindness. Consequently, little is known about the functional properties of the post-stroke visual system in the subacute period, nor do we know if these properties can be harnessed to enhance visual recovery. Here, for the first time, we show that 'conscious' visual discrimination abilities are often preserved inside subacute, perimetrically-defined blind fields, but they disappear by ∼6 months post-stroke. Complementing this discovery, we now show that training initiated subacutely can recover global motion discrimination and integration, as well as luminance detection perimetry, just as it does in chronic cortically-induced blindness. However, subacute recovery was attained six times faster; it also generalized to deeper, untrained regions of the blind field, and to other (untrained) aspects of motion perception, preventing their degradation upon reaching the chronic period. In contrast, untrained subacutes exhibited spontaneous improvements in luminance detection perimetry, but spontaneous recovery of motion discriminations was never observed. Thus, in cortically-induced blindness, the early post-stroke period appears characterized by gradual-rather than sudden-loss of visual processing. Subacute training stops this degradation, and is far more efficient at eliciting recovery than identical training in the chronic period. Finally, spontaneous visual improvements in subacutes were restricted to luminance detection; discrimination abilities only recovered following deliberate training. Our findings suggest that after V1 damage, rather than waiting for vision to stabilize, early training interventions may be key to maximize the system's potential for recovery.