GABA and Glutamate in hMT+ Link to Individual Differences in Residual Visual Function After Occipital Stroke.

BACKGROUND: Damage to the primary visual cortex following an occipital stroke causes loss of conscious vision in the contralateral hemifield. Yet, some patients retain the ability to detect moving visual stimuli within their blind field. The present study asked whether such individual differences in blind field perception following loss of primary visual cortex could be explained by the concentration of neurotransmitters γ-aminobutyric acid (GABA) and glutamate or activity of the visual motion processing, human middle temporal complex (hMT+). METHODS: We used magnetic resonance imaging in 19 patients with chronic occipital stroke to measure the concentration of neurotransmitters GABA and glutamate (proton magnetic resonance spectroscopy) and functional activity in hMT+ (functional magnetic resonance imaging). We also tested each participant on a 2-interval forced choice detection task using high-contrast, moving Gabor patches. We then measured and assessed the strength of relationships between participants' residual vision in their blind field and in vivo neurotransmitter concentrations, as well as visually evoked functional magnetic resonance imaging activity in their hMT+. Levels of GABA and glutamate were also measured in a sensorimotor region, which served as a control. RESULTS: Magnetic resonance spectroscopy-derived GABA and glutamate concentrations in hMT+ (but not sensorimotor cortex) strongly predicted blind-field visual detection abilities. Performance was inversely related to levels of both inhibitory and excitatory neurotransmitters in hMT+ but, surprisingly, did not correlate with visually evoked blood oxygenation level-dependent signal change in this motion-sensitive region. CONCLUSIONS: Levels of GABA and glutamate in hMT+ appear to provide superior information about motion detection capabilities inside perimetrically defined blind fields compared to blood oxygenation level-dependent signal changes-in essence, serving as biomarkers for the quality of residual visual processing in the blind-field. Whether they also reflect a potential for successful rehabilitation of visual function remains to be determined.

Investigating the human binocular visual system using multi-modal magnetic resonance imaging.

Having two forward-facing eyes with slightly different viewpoints enables animals, including humans, to discriminate fine differences in depth (disparities), which can facilitate interaction with the world. The binocular visual system starts in the primary visual cortex because that is where information from the eyes is integrated for the first time. Magnetic resonance imaging (MRI) is an ideal tool to non-invasively investigate this system since it can provide a range of detailed measures about structure, function, neurochemistry and connectivity of the human brain. Since binocular disparity is used for both action and object recognition, the binocular visual system is a valuable model system in neuroscience for understanding how basic sensory cues are transformed into behaviourally relevant signals. In this review, we consider how MRI has contributed to the understanding of binocular vision and depth perception in the human brain. Firstly, MRI provides the ability to image the entire brain simultaneously to compare the contribution of specific visual areas to depth perception. A large body of work using functional MRI has led to an understanding of the extensive networks of brain areas involved in depth perception, but also the fine-scale macro-organisation for binocular processing within individual visual areas. Secondly, MRI can uncover mechanistic information underlying binocular combination with the use of MR spectroscopy. This method can quantify neurotransmitters including GABA and glutamate within restricted regions of the brain, and evaluate the role of these inhibitory and excitatory neurochemicals in binocular vision. Thirdly, it is possible to measure the nature and microstructure of pathways underlying depth perception using diffusion MRI. Understanding these pathways provides insight into the importance of the connections between areas implicated in depth perception. Finally, MRI can help to understand changes in the visual system resulting from amblyopia, a neural condition where binocular vision does not develop correctly in childhood.

Increased Visual Sensitivity and Occipital Activity in Patients With Hemianopia Following Vision Rehabilitation.

Hemianopia, loss of vision in half of the visual field, results from damage to the visual pathway posterior to the optic chiasm. Despite negative effects on quality of life, few rehabilitation options are currently available. Recently, several long-term training programs have been developed that show visual improvement within the blind field. Little is known of the underlying neural changes. Here, we have investigated functional and structural changes in the brain associated with visual rehabilitation. Seven human participants with occipital lobe damage enrolled in a visual training program to distinguish which of two intervals contained a drifting Gabor patch presented within the blind field. Participants performed ∼25 min of training each day for 3-6 months and undertook psychophysical tests and an magnetic resonance imaging scan before and after training. A control group undertook psychophysical tests before and after an equivalent period without training. Participants who were not at ceiling on baseline tests showed on average 9.6% improvement in Gabor detection, 8.3% in detection of moving dots, and 9.9% improvement in direction discrimination after training. Importantly, psychophysical improvement only correlated with improvement in Humphrey perimetry in the trained region of the visual field. Whole-brain analysis showed an increased neural response to moving stimuli in the blind visual field in motion area V5/hMT. Using a region-of-interest approach, training had a significant effect on the blood oxygenation level-dependent signal compared with baseline. Moreover, baseline V5/hMT activity was correlated to the amount of improvement in visual sensitivity using psychophysical and perimetry tests. This study, identifying a critical role for V5/hMT in boosting visual function, may allow us to identify which patients may benefit most from training and design adjunct intervention to increase training effects.SIGNIFICANCE STATEMENTHomonymous visual field loss is a common consequence of brain injury and is estimated to affect more than 230,000 people in the United Kingdom. Despite its high prevalence and well-described impact on quality of life, treatments to improve visual sensitivity remain experimental, and deficits are considered permanent after 6 months. Our study shows that behavioral changes following vision rehabilitation are associated with enhanced visual-evoked occipital activity to stimuli in the blind visual field. Unlike previous behavioral studies, we observe clinical changes that are specific to the trained region of vision. This lends significant weight to such training paradigms and offers a mechanism by which visual function can be improved despite damage to the primary visual pathway.

Optic Tract Shrinkage Limits Visual Restoration After Occipital Stroke.

Background and Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral visual hemifield, initiating a process of trans-synaptic retrograde degeneration. The present study examined functional implications of this process, asking if degeneration impacted the amount of visual recovery attainable from visual restoration training in chronic patients, and if restoration training impacted optic tract (OT) shrinkage. Methods: Magnetic resonance imaging was used to measure OT volumes bilaterally in 36 patients with unilateral occipital stroke. From OT volumes, we computed laterality indices (LI), estimating the stroke-induced OT shrinkage in each case. A subset of these chronic patients (n=14, 13±6 months poststroke) underwent an average of nearly 1 year of daily visual restoration training, which repeatedly stimulated vision in their blind field. The amount of visual field recovery was quantified using Humphrey perimetry, and post training magnetic resonance imaging was used to assess the impact of training on OT shrinkage. Results: OT LI was correlated with time since stroke: it was close to 0 (no measurable OT shrinkage) in subacute participants (<6 months poststroke) while chronic participants (>6 months poststroke) exhibited LI >0, but with significant variability. Visual training did not systematically alter LI, but chronic patients with baseline LI≈0 (no OT shrinkage) exhibited greater visual field recovery than those with LI>0. Conclusions: Unilateral OT shrinkage becomes detectable with magnetic resonance imaging by ≈7 months poststroke, albeit with significant interindividual variability. Although visual restoration training did not alter the amount of degeneration already sustained, OT shrinkage appeared to serve as a biomarker of the potential for training-induced visual recovery in chronic cortically blind patients.

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.

The Effect of Congenital and Acquired Bilateral Anophthalmia on Brain Structure.

The aim of this study was to compare the pattern of changes in brain structure resulting from congenital and acquired bilateral anophthalmia. Brain structure was investigated using 3T magnetic resonance imaging (MRI) in Oxford (congenital) or Manchester (acquired). T1-weighted structural and diffusion-weighted scans were acquired from people with anophthalmia and sighted control participants. Differences in grey matter between the groups were quantified using voxel-based morphometry and differences in white matter microstructure using tract-based spatial statistics. Quantification of optic nerve volume and cortical thickness in visual regions was also performed in all groups. The optic nerve was reduced in volume in both anophthalmic populations, but to a greater extent in the congenital group and anophthalmia acquired at an early age. A similar pattern was found for the white matter microstructure throughout the occipitotemporal regions of the brain, suggesting a greater reduction of integrity with increasing duration of anophthalmia. In contrast, grey matter volume changes differed between the two groups, with the acquired anophthalmia group showing a decrease in the calcarine sulcus, corresponding to the area that would have been peripheral primary visual cortex. In contrast, the acquired anophthalmia group showed a decrease in grey matter volume in the calcarine sulcus corresponding to the area that would have been peripheral primary visual cortex. There are both qualitative and quantitative differences in structural brain changes in congenital and acquired anophthalmia, indicating differential effects of development and degeneration.

Early Blindness Shapes Cortical Representations of Auditory Frequency within Auditory Cortex.

Early loss of vision is classically linked to large-scale cross-modal plasticity within occipital cortex. Much less is known about the effects of early blindness on auditory cortex. Here, we examine the effects of early blindness on the cortical representation of auditory frequency within human primary and secondary auditory areas using fMRI. We observe that 4 individuals with early blindness (2 females), and a group of 5 individuals with anophthalmia (1 female), a condition in which both eyes fail to develop, have lower response amplitudes and narrower voxelwise tuning bandwidths compared with a group of typically sighted individuals. These results provide some of the first evidence in human participants for compensatory plasticity within nondeprived sensory areas as a result of sensory loss.SIGNIFICANCE STATEMENT Early blindness has been linked to enhanced perception of the auditory world, including auditory localization and pitch perception. Here we used fMRI to compare neural responses with auditory stimuli within auditory cortex across sighted, early blind, and anophthalmic individuals, in whom both eyes fail to develop. We find more refined frequency tuning in blind subjects, providing some of the first evidence in human subjects for compensation within nondeprived primary sensory areas as a result of blindness early in life.

Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex.

We investigated the relationship between neurochemical and hemodynamic responses as a function of image contrast in the human primary visual cortex (V1). Simultaneously acquired BOLD-fMRI and single voxel proton MR spectroscopy signals were measured in V1 of 24 healthy human participants of either sex at 7 tesla field strength, in response to presentations (64 s blocks) of different levels of image contrast (3%, 12.5%, 50%, 100%). Our results suggest that complementary measures of neurotransmission and energy metabolism are in partial agreement: BOLD and glutamate signals were linear with image contrast; however, a significant increase in glutamate concentration was evident only at the highest intensity level. In contrast, GABA signals were steady across all intensity levels. These results suggest that neurochemical concentrations are maintained at lower ranges of contrast levels, which match the statistics of natural vision, and that high stimulus intensity may be critical to increase sensitivity to visually modulated glutamate signals in the early visual cortex using MR spectroscopy.SIGNIFICANCE STATEMENT Glutamate and GABA are the major excitatory and inhibitory neurotransmitters of the brain. To better understand the relationship between MRS-visible neurochemicals, the BOLD signal change, and stimulus intensity, we measured combined neurochemical and BOLD signals (combined fMRI-MRS) to different image contrasts in human V1 at 7 tesla. While a linear change to contrast was present for both signals, the increase in glutamate was significant only at the highest stimulus intensity. These results suggest that hemodynamic and neurochemical signals reflect common metabolic markers of neural activity, whereas the mismatch at lower contrast levels may indicate a sensitivity threshold for detecting neurochemical changes during visual processing. Our results highlight the challenge and importance of reconciling cellular and metabolic measures of neural activity in the human brain.

Normative cerebral cortical thickness for human visual areas.

Studies of changes in cerebral neocortical thickness often rely on small control samples for comparison with specific populations with abnormal visual systems. We present a normative dataset for FreeSurfer-derived cortical thickness across 25 human visual areas derived from 960 participants in the Human Connectome Project. Cortical thickness varies systematically across visual areas, in broad agreement with canonical visual system hierarchies in the dorsal and ventral pathways. In addition, cortical thickness estimates show consistent within-subject variability and reliability. Importantly, cortical thickness estimates in visual areas are well described by a normal distribution, making them amenable to direct statistical comparison.

The elephant in the room: understanding the pathogenesis of Charles Bonnet syndrome.

PURPOSE: Charles Bonnet syndrome (CBS) is a syndrome characterised by complex visual hallucinations in individuals who are cognitively normal, though often elderly and visually impaired. Although first described over 250 years ago, the condition remains poorly understood and difficult to treat. RECENT FINDINGS: Our understanding of CBS pathogenesis has advanced little since it was first described, and much of the recent literature consists of case studies strikingly similar to the first published account of CBS. However, imaging studies have provided some indication as to the cortical areas implicated in the genesis of complex visual hallucinations, and the existence of similar hallucinatory syndromes in other sensory modalities suggests a common underlying mechanism. SUMMARY: This review begins by describing what is currently known about CBS, focusing on epidemiology, clinical presentation and diagnosis. It then explores potential starting points for better understanding the pathogenesis of CBS, namely the existence of similar conditions in other sensory modalities and the reproduction of complex visual hallucinations in sensory deprivation scenarios. Finally, it discusses how CBS should be approached in clinical practice.

Increase in MST activity correlates with visual motion learning: A functional MRI study of perceptual learning.

Repeated practice of a specific task can improve visual performance, but the neural mechanisms underlying this improvement in performance are not yet well understood. Here we trained healthy participants on a visual motion task daily for 5 days in one visual hemifield. Before and after training, we used functional magnetic resonance imaging (fMRI) to measure the change in neural activity. We also imaged a control group of participants on two occasions who did not receive any task training. While in the MRI scanner, all participants completed the motion task in the trained and untrained visual hemifields separately. Following training, participants improved their ability to discriminate motion direction in the trained hemifield and, to a lesser extent, in the untrained hemifield. The amount of task learning correlated positively with the change in activity in the medial superior temporal (MST) area. MST is the anterior portion of the human motion complex (hMT+). MST changes were localized to the hemisphere contralateral to the region of the visual field, where perceptual training was delivered. Visual areas V2 and V3a showed an increase in activity between the first and second scan in the training group, but this was not correlated with performance. The contralateral anterior hippocampus and bilateral dorsolateral prefrontal cortex (DLPFC) and frontal pole showed changes in neural activity that also correlated with the amount of task learning. These findings emphasize the importance of MST in perceptual learning of a visual motion task. Hum Brain Mapp 39:145-156, 2018. © 2017 Wiley Periodicals, Inc.

Visual training in hemianopia alters neural activity in the absence of behavioural improvement: a pilot study.

BACKGROUND: Damage to the primary visual cortex (V1) due to stroke often results in permanent loss of sight affecting one side of the visual field (homonymous hemianopia). Some rehabilitation approaches have shown improvement in visual performance in the blind region, but require a significant time investment. METHODS: Seven patients with cortical damage performed 400 trials of a motion direction discrimination task daily for 5 days. Three patients received anodal transcranial direct current stimulation (tDCS) during training, three received sham stimulation and one had no stimulation. Each patient had an assessment of visual performance and a functional magnetic resonance imaging (fMRI) scan before and after training to measure changes in visual performance and cortical activity. RESULTS: No patients showed improvement in visual function due to the training protocol, and application of tDCS had no effect on visual performance. However, following training, the neural response in motion area hMT+ to a moving stimulus was altered. When the stimulus was presented to the sighted hemifield, activity decreased in hMT+ of the damaged hemisphere. There was no change in hMT+ response when the stimulus was presented to the impaired hemifield. There was a decrease in activity in the inferior precuneus after training when the stimulus was presented to either the impaired or sighted hemifield. Preliminary analysis of tDCS data suggested that anodal tDCS interacted with the delivered training, modulating the neural response in hMT+ in the healthy side of the brain. CONCLUSION: Training can affect the neural responses in hMT+ even in the absence of change in visual performance.

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain.

Combined fMRI-MRS is a novel method to non-invasively investigate functional activation in the human brain using simultaneous acquisition of hemodynamic and neurochemical measures. The aim of the current study was to quantify neural activity using combined fMRI-MRS at 7T. BOLD-fMRI and semi-LASER localization MRS data were acquired from the visual cortex of 13 participants during short blocks (64s) of flickering checkerboards. We demonstrate a correlation between glutamate and BOLD-fMRI time courses (R=0.381, p=0.031). In addition, we show increases in BOLD-fMRI (1.43±0.17%) and glutamate concentrations (0.15±0.05 I.U., ~2%) during visual stimulation. In contrast, we observed no change in glutamate concentrations in resting state MRS data during sham stimulation periods. Spectral line width changes generated by the BOLD-response were corrected using line broadening. In summary, our results establish the feasibility of concurrent measurements of BOLD-fMRI and neurochemicals using a novel combined fMRI-MRS sequence. Our findings strengthen the link between glutamate and functional activity in the human brain by demonstrating a significant correlation of BOLD-fMRI and glutamate over time, and by showing ~2% glutamate increases during 64s of visual stimulation. Our tool may become useful for studies characterizing functional dynamics between neurochemicals and hemodynamics in health and disease.

Altered functional brain connectivity in children and young people with opsoclonus-myoclonus syndrome.

AIM: Opsoclonus-myoclonus syndrome (OMS) is a rare, poorly understood condition that can result in long-term cognitive, behavioural, and motor sequelae. Several studies have investigated structural brain changes associated with this condition, but little is known about changes in function. This study aimed to investigate changes in brain functional connectivity in patients with OMS. METHOD: Seven patients with OMS and 10 age-matched comparison participants underwent 3T magnetic resonance imaging (MRI) to acquire resting-state functional MRI data (whole-brain echo-planar images; 2mm isotropic voxels; multiband factor ×2) for a cross-sectional study. A seed-based analysis identified brain regions in which signal changes over time correlated with the cerebellum. Model-free analysis was used to determine brain networks showing altered connectivity. RESULTS: In patients with OMS, the motor cortex showed significantly reduced connectivity, and the occipito-parietal region significantly increased connectivity with the cerebellum relative to the comparison group. A model-free analysis also showed extensive connectivity within a visual network, including the cerebellum and basal ganglia, not present in the comparison group. No other networks showed any differences between groups. INTERPRETATION: Patients with OMS showed reduced connectivity between the cerebellum and motor cortex, but increased connectivity with occipito-parietal regions. This pattern of change supports widespread brain involvement in OMS.

The visual white matter: The application of diffusion MRI and fiber tractography to vision science.

Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data.

Abnormal contrast responses in the extrastriate cortex of blindsight patients.

When the human primary visual cortex (V1) is damaged, the dominant geniculo-striate pathway can no longer convey visual information to the occipital cortex. However, many patients with such damage retain some residual visual function that must rely on an alternative pathway directly to extrastriate occipital regions. This residual vision is most robust for moving stimuli, suggesting a role for motion area hMT+. However, residual vision also requires high-contrast stimuli, which is inconsistent with hMT+ sensitivity to contrast in which even low-contrast levels elicit near-maximal neural activation. We sought to investigate this discrepancy by measuring behavioral and neural responses to increasing contrast in patients with V1 damage. Eight patients underwent behavioral testing and functional magnetic resonance imaging to record contrast sensitivity in hMT+ of their damaged hemisphere, using Gabor stimuli with a spatial frequency of 1 cycle/°. The responses from hMT+ of the blind hemisphere were compared with hMT+ and V1 responses in the sighted hemisphere of patients and a group of age-matched controls. Unlike hMT+, neural responses in V1 tend to increase linearly with increasing contrast, likely reflecting a dominant parvocellular channel input. Across all patients, the responses in hMT+ of the blind hemisphere no longer showed early saturation but increased linearly with contrast. Given the spatiotemporal parameters used in this study and the known direct subcortical projections from the koniocellular layers of the lateral geniculate nucleus to hMT+, we propose that this altered contrast sensitivity in hMT+ could be consistent with input from the koniocellular pathway.

Resting-State Retinotopic Organization in the Absence of Retinal Input and Visual Experience.

Early visual areas have neuronal receptive fields that form a sampling mosaic of visual space, resulting in a series of retinotopic maps in which the same region of space is represented in multiple visual areas. It is not clear to what extent the development and maintenance of this retinotopic organization in humans depend on retinal waves and/or visual experience. We examined the corticocortical receptive field organization of resting-state BOLD data in normally sighted, early blind, and anophthalmic (in which both eyes fail to develop) individuals and found that resting-state correlations between V1 and V2/V3 were retinotopically organized for all subject groups. These results show that the gross retinotopic pattern of resting-state connectivity across V1-V3 requires neither retinal waves nor visual experience to develop and persist into adulthood. Significance statement: Evidence from resting-state BOLD data suggests that the connections between early visual areas develop and are maintained even in the absence of retinal waves and visual experience.

Motion area V5/MT+ response to global motion in the absence of V1 resembles early visual cortex.

Motion area V5/MT+ shows a variety of characteristic visual responses, often linked to perception, which are heavily influenced by its rich connectivity with the primary visual cortex (V1). This human motion area also receives a number of inputs from other visual regions, including direct subcortical connections and callosal connections with the contralateral hemisphere. Little is currently known about such alternative inputs to V5/MT+ and how they may drive and influence its activity. Using functional magnetic resonance imaging, the response of human V5/MT+ to increasing the proportion of coherent motion was measured in seven patients with unilateral V1 damage acquired during adulthood, and a group of healthy age-matched controls. When V1 was damaged, the typical V5/MT+ response to increasing coherence was lost. Rather, V5/MT+ in patients showed a negative trend with coherence that was similar to coherence-related activity in V1 of healthy control subjects. This shift to a response-pattern more typical of early visual cortex suggests that in the absence of V1, V5/MT+ activity may be shaped by similar direct subcortical input. This is likely to reflect intact residual pathways rather than a change in connectivity, and has important implications for blindsight function. It also confirms predictions that V1 is critically involved in normal V5/MT+ global motion processing, consistent with a convergent model of V1 input to V5/MT+. Historically, most attempts to model cortical visual responses do not consider the contribution of direct subcortical inputs that may bypass striate cortex, such as input to V5/MT+. We have shown that the signal change driven by these non-striate pathways can be measured, and suggest that models of the intact visual system may benefit from considering their contribution.

Subcortical functional reorganization due to early blindness.

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

Neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral anophthalmia.

Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, (1)H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests that the lack of visual input from the eyes might have delayed or arrested the maturation of this cortical region. High levels of choline and glutamate/glutamine are consistent with enhanced excitatory circuits in the anophthalmic occipital cortex, which could reflect a shift toward enhanced plasticity or sensitivity that could in turn mediate or unmask cross-modal responses. Finally, it is possible that the change in function of the occipital cortex results in biochemical profiles that resemble those of auditory, language, or somatosensory cortex.