Cortico-thalamic disconnection in a patient with supernumerary phantom limb.

Supernumerary phantom limb (SPL) designates the experience of an illusory additional limb occurring after brain damage. Functional neuroimaging during SPL movements documented increased response in the ipsilesional supplementary motor area (SMA), premotor cortex (PMC), thalamus and caudate. This suggested that motor circuits are important for bodily related cognition, but anatomical evidence is sparse. Here, we tested this hypothesis by studying an extremely rare patient with chronic SPL, still present 3 years after a vascular stroke affecting cortical and subcortical right-hemisphere structures. Anatomical analysis included an advanced in vivo reconstruction of white matter tracts using diffusion-based spherical deconvolution. This reconstruction demonstrated a massive and relatively selective disconnection between anatomically preserved SMA/PMC and the thalamus. Our results provide strong anatomical support for the hypothesis that cortico-thalamic loops involving motor-related circuits are crucial to integrate sensorimotor processing with bodily self-awareness.

White matter lesional predictors of chronic visual neglect: a longitudinal study.

Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient's lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect.

When brain damage "improves" perception: neglect patients can localize motion-shifted probes better than controls.

When we look at bars flashed against a moving background, we see them displaced in the direction of the upcoming motion (flash-grab illusion). It is still debated whether these motion-induced position shifts are low-level, reflexive consequences of stimulus motion or high-level compensation engaged only when the stimulus is tracked with attention. To investigate whether attention is a causal factor for this striking illusory position shift, we evaluated the flash-grab illusion in six patients with damaged attentional networks in the right hemisphere and signs of left visual neglect and six age-matched controls. With stimuli in the top, right, and bottom visual fields, neglect patients experienced the same amount of illusion as controls. However, patients showed no significant shift when the test was presented in their left hemifield, despite having equally precise judgments. Thus, paradoxically, neglect patients perceived the position of the flash more veridically in their neglected hemifield. These results suggest that impaired attentional processes can reduce the interaction between a moving background and a superimposed stationary flash, and indicate that attention is a critical factor in generating the illusory motion-induced shifts of location.

Representational neglect in "invisible" drawing from memory.

We describe the case of a patient with right hemisphere damage and left unilateral neglect. The patient was asked to draw from memory common objects, either with or without visual feedback. In the conditions without visual feedback the patient was either blindfolded or he made "invisible" drawings using a pen with the cap on, the drawings being recorded with carbon paper underneath. Results showed more neglect without than with visual feedback, contrary to previously published cases. This patient's pattern of performance may result from the contribution of a deficit of spatial working memory. Alternatively or in addition, the patient, who was undergoing cognitive rehabilitation for neglect, may have found easier to compensate for his neglect with visual feedback, which allowed him to visually explore the left part of his drawings.

Anatomical predictors of successful prism adaptation in chronic visual neglect.

Visual neglect is a frequent and disabling consequence of right hemisphere damage. Previous work demonstrated a probable role of posterior callosal dysfunction in the chronic persistence of neglect signs. Prism adaptation is a non-invasive and convenient technique to rehabilitate chronic visual neglect, but it is not effective in all patients. Here we aimed to assess the hypothesis that prism adaptation improves left neglect by facilitating compensation through the contribution of the left, undamaged hemisphere. We assessed the relationship between prism adaptation effects, cortical thickness and white matter integrity in a group of 14 patients with unilateral right-hemisphere strokes and chronic visual neglect. Results showed that patients who benefitted from prism adaptation had thicker cortex in temporo-parietal, prefrontal and cingulate areas of the left, undamaged hemisphere. Additionally, these patients had a higher fractional anisotropy value in the body and genu of the corpus callosum. Results from normal controls show that these callosal regions connect temporo-parietal, sensorimotor and prefrontal areas. Finally, shorter time intervals from the stroke tended to improve patients' response to prism adaptation. We concluded that prism adaptation may improve left visual neglect by promoting the contribution of the left hemisphere to neglect compensation. These results support current hypotheses on the role of the healthy hemisphere in the compensation for stroke-induced, chronic neuropsychological deficits, and suggest that prism adaptation can foster this role by exploiting sensorimotor/prefrontal circuits, especially when applied at early stages post-stroke.

Seeing and imagining the "same" objects in unilateral neglect.

Dissociations between perceptual and imaginal neglect are typically investigated by using very different tasks (e.g. visual target cancellation vs. place descriptions). Here we report patients' performance on imaginal and perceptual tasks which shared identical stimuli and procedure, except for the modality of stimulus presentation. In different tasks, participants either saw towns/regions on a map of France or heard their names, and pressed one of two keys according to the stimulus location (left or right of Paris). Neglect patients as a group were less accurate for left-sided stimuli in both modalities, but on single-case analysis only one patient with perceptual neglect had asymmetrical imaginal accuracy. These results confirmed that imaginal neglect is relatively rare, and is usually associated with perceptual neglect. Perceptual neglect resulted more frequent and severe than imaginal neglect, also when assessed using strictly comparable tests, consistent with the exogenous orienting bias typically observed in these patients.

Common brain networks for distinct deficits in visual neglect. A combined structural and tractography MRI approach.

Visual neglect is a heterogeneous, multi-component syndrome resulting from right hemisphere damage. Neglect patients do not pay attention to events occurring on their left side, and have a poor functional outcome. The intra-hemispheric location of lesions producing neglect is debated, because studies using different methods reported different locations in the grey matter and in the white matter of the right hemisphere. These reported locations show various patterns of overlapping with the fronto-parietal attention networks demonstrated by functional neuroimaging. We explored the anatomical correlates of neglect patients' performance on distinct tests of neglect. For the first time in neglect anatomy studies, we individually assessed 25 patients with subacute strokes in the right hemisphere, by using a combined structural and diffusion tensor deterministic tractography approach, with separate analyses for each neglect test. The results revealed that lesions in nodes of the ventral attention network (angular and supramarginal gyri) were selectively associated with deficits in performance on all the tests used; damage to other structures correlated with impaired performance on specific tests, such as the bells test (middle and inferior frontal gyri), or the reading test (temporal regions). Importantly, however, white matter damage proved crucial in producing neglect-related deficits. Voxel-based lesion-symptom mapping (VLSM) and tractography consistently revealed that damage to the ventral branch of the superior longitudinal fasciculus (SLF III) and to the inferior fronto-occipital fasciculus (IFOF) predicted pathological scores on line bisection/drawing copy and on the bells test, respectively. Moreover, damage to distinct sectors of SLF III, or combined SLF/IFOF damage, gave rise to different performance profiles. Our results indicate that both grey and white matter lesion analysis must be taken into account to determine the neural correlates of neglect-related deficits. They also suggest that damage to distinct portions of white matter tracts may give rise to distinct clinical signs of neglect, presumably by inducing dysfunction of partly overlapping, but distinct networks.

Visualizing the blind brain: brain imaging of visual field defects from early recovery to rehabilitation techniques.

Visual field defects (VFDs) are one of the most common consequences observed after brain injury, especially after a stroke in the posterior cerebral artery territory. Less frequently, tumors, traumatic brain injury, brain surgery or demyelination can also determine various visual disabilities, from a decrease in visual acuity to cerebral blindness. Visual field defects is a factor of bad functional prognosis as it compromises many daily life activities (e.g., obstacle avoidance, driving, and reading) and therefore the patient's quality of life. Spontaneous recovery seems to be limited and restricted to the first 6 months, with the best chance of improvement at 1 month. The possible mechanisms at work could be partly due to cortical reorganization in the visual areas (plasticity) and/or partly to the use of intact alternative visual routes, first identified in animal studies and possibly underlying the phenomenon of blindsight. Despite processes of early recovery, which is rarely complete, and learning of compensatory strategies, the patient's autonomy may still be compromised at more chronic stages. Therefore, various rehabilitation therapies based on neuroanatomical knowledge have been developed to improve VFDs. These use eye-movement training techniques (e.g., visual search, saccadic eye movements), reading training, visual field restitution (the Vision Restoration Therapy, VRT), or perceptual learning. In this review, we will focus on studies of human adults with acquired VFDs, which have used different imaging techniques (Positron Emission Tomography, PET; Diffusion Tensor Imaging, DTI; functional Magnetic Resonance Imaging, fMRI; Magneto Encephalography, MEG) or neurostimulation techniques (Transcranial Magnetic Stimulation, TMS; transcranial Direct Current Stimulation, tDCS) to show brain activations in the course of spontaneous recovery or after specific rehabilitation techniques.

Educating the blind brain: a panorama of neural bases of vision and of training programs in organic neurovisual deficits.

Vision is a complex function, which is achieved by movements of the eyes to properly foveate targets at any location in 3D space and to continuously refresh neural information in the different visual pathways. The visual system involves five main routes originating in the retinas but varying in their destination within the brain: the occipital cortex, but also the superior colliculus (SC), the pretectum, the supra-chiasmatic nucleus, the nucleus of the optic tract and terminal dorsal, medial and lateral nuclei. Visual pathway architecture obeys systematization in sagittal and transversal planes so that visual information from left/right and upper/lower hemi-retinas, corresponding respectively to right/left and lower/upper visual fields, is processed ipsilaterally and ipsialtitudinally to hemi-retinas in left/right hemispheres and upper/lower fibers. Organic neurovisual deficits may occur at any level of this circuitry from the optic nerve to subcortical and cortical destinations, resulting in low or high-level visual deficits. In this didactic review article, we provide a panorama of the neural bases of eye movements and visual systems, and of related neurovisual deficits. Additionally, we briefly review the different schools of rehabilitation of organic neurovisual deficits, and show that whatever the emphasis is put on action or perception, benefits may be observed at both motor and perceptual levels. Given the extent of its neural bases in the brain, vision in its motor and perceptual aspects is also a useful tool to assess and modulate central nervous system (CNS) in general.

Dual-tasking postural control in patients with right brain damage.

The control of dual-tasking effects is a daily challenge in stroke neurorehabilitation. It maybe one of the reasons why there is poor functional prognosis after a stroke in the right hemisphere, which plays a dominant role in posture control. The purpose of this study was to explore cognitive motor interference in right brain-lesioned and healthy subjects maintaining a standing position while performing three different tasks: a control task, a simple attentional task and a complex attentional task. We measured the sway area of the subjects on a force platform, including the center of pressure and its displacements. Results showed that stroke patients presented a reduced postural sway compared to healthy subjects, who were able to maintain their posture while performing a concomitant attentional task in the same dual-tasking conditions. Moreover, in both groups, the postural sway decreased with the increase in attentional load from cognitive tasks. We also noticed that the stability of stroke patients in dual-tasking conditions increased together with the weight-bearing rightward deviation, especially when the attentional load of the cognitive tasks and lower limb motor impairments were high. These results suggest that stroke patients and healthy subjects adopt a similar postural regulation pattern aimed at maintaining stability in dual-tasking conditions involving a static standing position and different attention-related cognitive tasks. Our results indicate that attention processes might facilitate static postural control.

Visual mental imagery: what the head's eye tells the mind's eye.

The demonstration of an implication of attentional/eye gaze systems in visual mental imagery might help to understand why some patients with visual neglect, who suffer from severe attentional deficits, also show neglect for mental images. When normal participants generate mental images of previously explored visual scenes, their oculomotor behavior resembles that used during visual exploration. However, this could be a case of encoding specificity, whereby the probability of retrieving an event increases if some information encoded with the event (in this case its spatial location) is present at retrieval. In the present study, normal participants were invited to conjure up a mental image of the map of France and to say whether auditorily presented towns or regions were situated left or right of Paris. A perceptual version of the task was administered after the imaginal condition. Thus, in the imaginal condition participants had to retrieve information from long-term memory. Vocal response times and, unbeknownst to participants, also eye movements were recorded. Participants tended to produce similar eye movements on the imaginal and on the perceptual conditions of the task. We concluded that some mechanisms involved in spontaneous oculomotor behavior may be shared in exploration of visuospatial mental images. Deficits of these common processes participating in the oculomotor exploration might contribute to imaginal neglect.

Vocal response times to real and imagined stimuli in spatial neglect: A group study and single-case report.

The relationships between spatial neglect for perceptual objects and representational for imagined items are difficult to explore because of several methodological problems, including the dearth of comparable tests for real and imagined scenes. We asked 19 patients with right brain damage and 12 healthy controls to say whether an auditorily presented French geographical location was left or right of Paris, and recorded their vocal response times. Afterwards, participants performed a similar test with visually presented items. Although several patients had asymmetries of performance on the perceptual version of the test, only one patient was more accurate for right-sided than for left-sided imagined stimuli, thus showing evidence for imaginal neglect. However, this patient performed normally on place description and on mental number line bisection, perhaps as a consequence of different strategies he employed for these tasks. Overall, our results confirm previous evidence showing that imaginal neglect is less frequent than, and often occurs in association with, perceptual neglect. Imaginal neglect may result from the contribution of deficits partly distinct from those implicated in perceptual neglect, such as impaired endogenous orienting of attention or deficits of spatial working memory.