Consensus Paper: Cerebellum and Ageing.

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

An Appraisal of the Role of the Neocerebellum for Spatial Navigation in Healthy Aging.

Spatial navigation is an intricate ability, requiring multisensory and motor integration, that is particularly impacted in aging. The age-related decline in navigational capabilities is known to be associated with changes in brain regions such as the frontal, temporal, and cerebellar cortices. Age-related cerebellar differences in spatial navigation have generally been ascribed to motor impairments, omitting the central role of this structure in several cognitive processes. In the present voxel-based morphometric study, we investigated gray matter volume loss in older adults across cognitive and motor subregions of the cerebellum. Specifically, we hypothesized that age-related gray matter differences would occur mainly in cerebellar regions involved in cognitive processing. Our results showed a significant age-related atrophy in the left neocerebellum of healthy older adults that includes Crus I and lobule VI. The latter are important nodes in the network that subtends cognitive abilities such as object recognition and spatial cognition. This exploratory work sets the ground for future research to investigate the extent of the neocerebellum's contribution to spatial navigation deficits in aging.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Topography of Emotions in Cerebellum as Appraised by Functional Imaging.

Emotions induce complex patterns of cerebellar activity likely reflecting specific cerebellar modulation and multidimensional integration of the emotional experience, based on context-specific dynamic recruitment of limbic, cognitive, mnesic, and sensorimotor cortico-cerebellar loops. Meta-analyses have reported constant recruitment of lobules VI-VII during basic emotions. Activation of rostral lobules II-VI and lobule VIII may be preferentially in relation to motor responses, whereas rostral and caudal vermal activation may be linked to autonomic regulation and associative learning in conjunction with amygdala. Cognitive integration of emotion may rely, at least, on activation of limbic salience network (automatic bottom-up detection of salient stimulus), default-mode network (memory- and knowledge-based categorization), and central executive network (response selection and emotion regulation). As lobules VI-VII straddle all these intrinsically networks, it could be hypothesized that this part of the neocerebellum constitutes an integrator/modulator hub of the emotion-related limbic and cognitive system.

Selective neural coding of object, feature, and geometry spatial cues in humans.

Orienting in space requires the processing of visual spatial cues. The dominant hypothesis about the brain structures mediating the coding of spatial cues stipulates the existence of a hippocampal-dependent system for the representation of geometry and a striatal-dependent system for the representation of landmarks. However, this dual-system hypothesis is based on paradigms that presented spatial cues conveying either conflicting or ambiguous spatial information and that used the term landmark to refer to both discrete three-dimensional objects and wall features. Here, we test the hypothesis of complex activation patterns in the hippocampus and the striatum during visual coding. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation. We examined how the neural networks associated with geometry-, object-, and feature-based spatial navigation compared with a control condition in a two-choice behavioral paradigm using fMRI. We showed that the hippocampus was involved in all three types of cue-based navigation, whereas the striatum was more strongly recruited in the presence of geometric cues than object or feature cues. We also found that unique, specific neural signatures were associated with each spatial cue. Object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings extend the current view of a dual, juxtaposed hippocampal-striatal system for visual spatial coding in humans. They also provide novel insights into the neural networks mediating object versus feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Research Note: Functional Connectivity Between a Corticostriatal Network and the Cerebellum.

BACKGROUND: Basal ganglia and cerebellum are structurally and functionally connected in animals. In humans, tractography and seed-based functional connectivity have confirmed this cerebellar-striatal relation. Independent component analysis (ICA) showed that both cerebellum and basal ganglia take part in distinct intrinsic networks. METHODS: Probabilistic ICA analysis was applied to the brain images of 15 healthy volunteers during the resting state and using a 3 T MRI. RESULTS: A spatial map corresponding to dorsal and ventral basal ganglia circuits was also found to be in functional coherence with crus 2, especially with its vermal region. CONCLUSION: It is speculated that such cerebellar-basal ganglionic rsFC could reflect structural interconnections traced in animals and explain reward-based activity detected in the cerebellum.

The brainstem in multiple sclerosis: MR identification of tracts and nuclei damage.

OBJECTIVE: To evaluate the 3D Fast Gray Acquisition T1 Inversion Recovery (FGATIR) sequence for MRI identification of brainstem tracts and nuclei damage in multiple sclerosis (MS) patients. METHODS: From april to december 2020, 10 healthy volunteers and 50 patients with remitted-relapsing MS (58% female, mean age 36) underwent MR imaging in the Neuro-imaging department of the C.H.N.O. des Quinze-Vingts, Paris, France. MRI was achieved on a 3 T system (MAGNETOM Skyra) using a 64-channel coil. 3D FGATIR sequence was first performed on healthy volunteers to classify macroscopically identifiable brainstem structures. Then, FGATIR was assessed in MS patients to locate brainstem lesions detected with Proton Density/T2w (PD/T2w) sequence. RESULTS: In healthy volunteers, FGATIR allowed a precise visualization of tracts and nuclei according to their myelin density. Including FGATIR in MR follow-up of MS patients helped to identify structures frequently involved in the inflammatory process. Most damaged tracts were the superior cerebellar peduncle and the transverse fibers of the pons. Most frequently affected nuclei were the vestibular nuclei, the trigeminal tract, the facial nerve and the solitary tract. CONCLUSION: Combination of FGATIR and PD/T2w sequences opened prospects to define MS elective injury in brainstem tracts and nuclei, with particular lesion features suggesting variations of the inflammatory process within brainstem structures. In a further study, hypersignal quantification and microstructure information should be evaluated using relaxometry and diffusion tractography. Technical improvements would bring novel parameters to train an artificial neural network for accurate automated labeling of MS lesions within the brainstem.

Functional Connectivity of the Cognitive Cerebellum.

Anatomical tracing, human clinical data, and stimulation functional imaging have firmly established the major role of the (neo-)cerebellum in cognition and emotion. Telencephalization characterized by the great expansion of associative cortices, especially the prefrontal one, has been associated with parallel expansion of the neocerebellar cortex, especially the lobule VII, and by an increased number of interconnections between these two cortical structures. These anatomical modifications underlie the implication of the neocerebellum in cognitive control of complex motor and non-motor tasks. In humans, resting state functional connectivity has been used to determine a thorough anatomo-functional parcellation of the neocerebellum. This technique has identified central networks involving the neocerebellum and subserving its cognitive function. Neocerebellum participates in all intrinsic connected networks such as central executive, default mode, salience, dorsal and ventral attentional, and language-dedicated networks. The central executive network constitutes the main circuit represented within the neocerebellar cortex. Cerebellar zones devoted to these intrinsic networks appear multiple, interdigitated, and spatially ordered in three gradients. Such complex neocerebellar organization enables the neocerebellum to monitor and synchronize the main networks involved in cognition and emotion, likely by computing internal models.

Investigating efficient CNN architecture for multiple sclerosis lesion segmentation.

Purpose: The automatic segmentation of multiple sclerosis lesions in magnetic resonance imaging has the potential to reduce radiologists' efforts on a daily time-consuming task and to bring more reproducibility. Almost all new segmentation techniques make use of convolutional neural networks with their own different architecture. Architectural choices are rarely explained. We aimed at presenting the relevance of a U-net-like architecture for our specific task and at building an efficient and simple model. Approach: An experimental study was performed by observing the impact of applying different mutations and deletions to a simple U-net-like architecture. Results: The power of the U-net architecture is explained by the joint benefits of using an encoder-decoder architecture and by linking them with long skip connections. Augmenting the number of convolutional layers and decreasing the number of feature maps allowed us to build an exceptionally light and competitive architecture, the minimally parameterized U-net (MPU-net), with only ∼ 30,000 parameters. Conclusion: The empirical study of the U-net has led to a better understanding of its architecture. It has guided the building of the MPU-net, a model far less parameterized than others (at least by a factor of seven). This neural network achieves a human-level segmentation of multiple sclerosis lesions on fluid-attenuated inversion recovery images only. It shows that this segmentation task does not necessitate overly complicated models to be achieved. This gives the opportunity to build more explainable models that can help such methods to be adopted in a clinical environment.

DEEP PHENOTYPING AND FURTHER INSIGHTS INTO ITM2B-RELATED RETINAL DYSTROPHY.

PURPOSE: To reappraise the presentation and the course of ITM2B-related retinal dystrophy and give further insights into ITM2B expression in the retina. METHODS: The clinical data of nine subjects with ITM2B-related retinal dystrophy were retrospectively reviewed. The genetic mutation was assessed for its influence on splicing in cultured fibroblasts. The cellular expression of ITM2B within the inner retina was investigated in wild-type mice through mRNA in situ hybridization. RESULTS: All patients complained of decreased vision and mild photophobia around their twenties-thirties. The peculiar feature was the hyperreflective material on optical coherence tomography within the inner retina and the central outer nuclear layer with thinning of the retinal nerve fiber layer. Although retinal imaging revealed very mild or no changes over the years, the visual acuity slowly decreased with about one Early Treatment Diabetic Retinopathy Study letter per year. Finally, full-field electroretinography showed a mildly progressive inner retinal and cone dysfunction. ITM2B mRNA is expressed in all cellular types of the inner retina. Disease mechanism most likely involves mutant protein misfolding and/or modified protein interaction rather than misplicing. CONCLUSION: ITM2B-related retinal dystrophy is a peculiar, rare, slowly progressive retinal degeneration. Functional examinations (full-field electroretinography and visual acuity) seem more accurate in monitoring the progression in these patients because imaging tends to be stable over the years.

Postural Control While Walking Interferes With Spatial Learning in Older Adults Navigating in a Real Environment.

Cognitive demands for postural control increase with aging and cognitive-motor interference (CMI) exists for a number of walking situations, especially with visuo-spatial cognitive tasks. Such interference also influences spatial learning abilities among older adults; however, this is rarely considered in research on aging in spatial navigation. We posited that visually and physically exploring an unknown environment may be subject to CMI for older adults. We investigated potential indicators of postural control interfering with spatial learning. Given known associations between age-related alterations in gait and brain structure, we also examined potential neuroanatomical correlates of this interference. Fourteen young and 14 older adults had to find an invisible goal in an unfamiliar, real, ecological environment. We measured walking speed, trajectory efficiency (direct route over taken route) and goal fixations (proportion of visual fixations toward the goal area). We calculated the change in walking speed between the first and last trials and adaptation indices for all three variables to quantify their modulation across learning trials. All participants were screened with a battery of visuo-cognitive tests. Eighteen of our participants (10 young, 8 older) also underwent a magnetic resonance imaging (MRI) examination. Older adults reduced their walking speed considerably on the first, compared to the last trial. The adaptation index of walking speed correlated positively with those of trajectory efficiency and goal fixations, indicating a reduction in resource sharing between walking and encoding the environment. The change in walking speed correlated negatively with gray matter volume in superior parietal and occipital regions and the precuneus. We interpret older adults' change in walking speed as indicative of CMI, similar to dual task costs. This is supported by the correlations between the adaptation indices and between the change in walking speed and gray matter volume in brain regions that are important for navigation, given that they are involved in visual attention, sensory integration and encoding of space. These findings under ecological conditions in a natural spatial learning task question what constitutes dual tasking in older adults and they can lead future research to reconsider the actual cognitive burden of postural control in aging navigation research.

Differential Brain Activity in Regions Linked to Visuospatial Processing During Landmark-Based Navigation in Young and Healthy Older Adults.

Older adults have difficulties in navigating unfamiliar environments and updating their wayfinding behavior when faced with blocked routes. This decline in navigational capabilities has traditionally been ascribed to memory impairments and dysexecutive function, whereas the impact of visual aging has often been overlooked. The ability to perceive visuospatial information such as salient landmarks is essential to navigating efficiently. To date, the functional and neurobiological factors underpinning landmark processing in aging remain insufficiently characterized. To address this issue, functional magnetic resonance imaging (fMRI) was used to investigate the brain activity associated with landmark-based navigation in young and healthy older participants. The performances of 25 young adults (µ = 25.4 years, σ = 2.7; seven females) and 17 older adults (µ = 73.0 years, σ = 3.9; 10 females) were assessed in a virtual-navigation task in which they had to orient using salient landmarks. The underlying whole-brain patterns of activity as well as the functional roles of specific cerebral regions involved in landmark processing, namely the parahippocampal place area (PPA), the occipital place area (OPA), and the retrosplenial cortex (RSC), were analyzed. Older adults' navigational abilities were overall diminished compared to young adults. Also, the two age groups relied on distinct navigational strategies to solve the task. Better performances during landmark-based navigation were associated with increased neural activity in an extended neural network comprising several cortical and cerebellar regions. Direct comparisons between age groups revealed that young participants had greater anterior temporal activity. Also, only young adults showed significant activity in occipital areas corresponding to the cortical projection of the central visual field during landmark-based navigation. The region-of-interest analysis revealed an increased OPA activation in older adult participants during the landmark condition. There were no significant between-group differences in PPA and RSC activations. These preliminary results hint at the possibility that aging diminishes fine-grained information processing in occipital and temporal regions, thus hindering the capacity to use landmarks adequately for navigation. Keeping sight of its exploratory nature, this work helps towards a better comprehension of the neural dynamics subtending landmark-based navigation and it provides new insights on the impact of age-related visuospatial processing differences on navigation capabilities.

Glaucoma: A Degenerative Optic Neuropathy Related to Neuroinflammation?

Glaucoma is one of the leading causes of irreversible blindness in the world and remains a major public health problem. To date, incomplete knowledge of this disease's pathophysiology has resulted in current therapies (pharmaceutical or surgical) unfortunately having only a slowing effect on disease progression. Recent research suggests that glaucomatous optic neuropathy is a disease that shares common neuroinflammatory mechanisms with "classical" neurodegenerative pathologies. In addition to the death of retinal ganglion cells (RGCs), neuroinflammation appears to be a key element in the progression and spread of this disease. Indeed, early reactivity of glial cells has been observed in the retina, but also in the central visual pathways of glaucoma patients and in preclinical models of ocular hypertension. Moreover, neuronal lesions are not limited to retinal structure, but also occur in central visual pathways. This review summarizes and puts into perspective the experimental and clinical data obtained to date to highlight the need to develop neuroprotective and immunomodulatory therapies to prevent blindness in glaucoma patients.

Does the Cerebellum Implement or Select Geometries? A Speculative Note.

During evolution, living systems, actively interacting with their environment, developed the ability, through sensorimotor contingencies, to construct functional spaces shaping their perception and their movements. These geometries were modularly embedded in specific functional neuro-architectures. In particular, human movements were shown to obey several empirical laws, such as the 2/3 power law, isochrony, or jerk minimization principles, which constrain and adapt motor planning and execution. Outstandingly, such laws can be deduced from a combination of Euclidean, affine, and equi-affine geometries, whose neural correlates have been partly detected in several brain areas including the cerebellum and the basal ganglia. Reviving Pellionisz and Llinas general hypothesis regarding the cerebrum and the cerebellum as geometric machines, we speculate that the cerebellum should be involved in implementing and/or selecting task-specific geometries for motor and cognitive skills. More precisely, the cerebellum is assumed to compute forward internal models to help specific cortical and subcortical regions to select appropriate geometries among, at least, Euclidean and affine geometries. We emphasize that the geometrical role of the cerebellum deserves a renewal of interest, which may provide a better understanding of its specific contributions to motor and associative (cognitive) functions.

Age-Related Differences in Functional and Structural Connectivity in the Spatial Navigation Brain Network.

Spatial navigation involves multiple cognitive processes including multisensory integration, visuospatial coding, memory, and decision-making. These functions are mediated by the interplay of cerebral structures that can be broadly separated into a posterior network (subserving visual and spatial processing) and an anterior network (dedicated to memory and navigation planning). Within these networks, areas such as the hippocampus (HC) are known to be affected by aging and to be associated with cognitive decline and navigation impairments. However, age-related changes in brain connectivity within the spatial navigation network remain to be investigated. For this purpose, we performed a neuroimaging study combining functional and structural connectivity analyses between cerebral regions involved in spatial navigation. Nineteen young (µ = 27 years, σ = 4.3; 10 F) and 22 older (µ = 73 years, σ = 4.1; 10 F) participants were examined in this study. Our analyses focused on the parahippocampal place area (PPA), the retrosplenial cortex (RSC), the occipital place area (OPA), and the projections into the visual cortex of central and peripheral visual fields, delineated from independent functional localizers. In addition, we segmented the HC and the medial prefrontal cortex (mPFC) from anatomical images. Our results show an age-related decrease in functional connectivity between low-visual areas and the HC, associated with an increase in functional connectivity between OPA and PPA in older participants compared to young subjects. Concerning the structural connectivity, we found age-related differences in white matter integrity within the navigation brain network, with the exception of the OPA. The OPA is known to be involved in egocentric navigation, as opposed to allocentric strategies which are more related to the hippocampal region. The increase in functional connectivity between the OPA and PPA may thus reflect a compensatory mechanism for the age-related alterations around the HC, favoring the use of the preserved structural network mediating egocentric navigation. Overall, these findings on age-related differences of functional and structural connectivity may help to elucidate the cerebral bases of spatial navigation deficits in healthy and pathological aging.

The Cerebellar Thalamus.

The thalamus is a neural processor and integrator for the activities of the forebrain. Surprisingly, little is known about the roles of the "cerebellar" thalamus despite the anatomical observation that all the cortico-cerebello-cortical loops make relay in the main subnuclei of the thalamus. The thalamus displays a broad range of electrophysiological responses, such as neuronal spiking, bursting, or oscillatory rhythms, which contribute to precisely shape and to synchronize activities of cortical areas. We emphasize that the cerebellar thalamus deserves a renewal of interest to better understand its specific contributions to the cerebellar motor and associative functions, especially at a time where the anatomy between cerebellum and basal ganglia is being rewritten.

The development of white matter structural changes during the process of deterioration of the visual field.

Emerging evidence suggests that white matter plasticity in the adult brain is preserved after sensory and behavioral modifications. However, little is known about the progression of structural changes during the process of decline in visual input. Here we studied two groups of patients suffering from advanced retinitis pigmentosa with specific deterioration of the visual field: patients who had lost their peripheral visual field, retaining only central ("tunnel") vision, and blind patients with complete visual field loss. Testing of these homogeneous groups made it possible to assess the extent to which the white matter is affected by loss of partial visual input and whether partially preserved visual input suffices to sustain stability in tracts beyond the primary visual system. Our results showed gradual changes in diffusivity that are indicative of degenerative processes in the primary visual pathway comprising the optic tract and the optic radiation. Interestingly, changes were also found in tracts of the ventral stream and the corticospinal fasciculus, depicting a gradual reorganisation of these tracts consequentially to the gradual loss of visual field coverage (from intact perception to partial vision to complete blindness). This reorganisation may point to microstructural plasticity underlying adaptive behavior and cross-modal integration after partial visual deprivation.