Human V2A: A map of the peripheral visual hemifield with functional connections to scene-selective cortex.

Humans can recognize a scene in the blink of an eye. This gist-based visual scene perception is thought to be underpinned by specialized visual processing emphasizing the visual periphery at a cortical locus relatively low in the visual processing hierarchy. Using wide-field retinotopic mapping and population receptive field (pRF) modeling, we identified a new visual hemifield map anterior of area V2d and inferior to area V6, which we propose to call area V2A. Based on its location relative to other visual areas, V2A may correspond to area 23V described in nonhuman primates. The pRF analysis revealed unique receptive field properties for V2A: a large (FWHM ∼23°) and constant receptive field size across the central ∼70° of the visual field. Resting-state fMRI connectivity analysis further suggests that V2A is ideally suited to quickly feed the scene-processing network with information that is not biased towards the center of the visual field. Our findings not only indicate a likely cortical locus for the initial stages of gist-based visual scene perception, but also suggest a reappraisal of the organization of human dorsomedial occipital cortex with a strip of separate hemifield representations anterior to the early visual areas (V1, V2d, and V3d).

Congruent movement training as a rehabilitation method to ameliorate symptoms of neglect-proof of concept.

Stroke patients with visuospatial neglect (VSN) have difficulties responding to visual information located in the contralesional hemifield, affecting many daily life activities (ADL) such as eating, reading and mobility. Visual Scanning Therapy (VST) is widely used in clinical practice to ameliorate symptoms of VSN. Yet, not all patients benefit from this training and many training sessions are needed in order to achieve stable results. One potentially promising improvement to the VST is based on the theory that different effectors of the motor systems (e.g., eyes, hands) independently allocate attention during the programming of the movement (i.e., Pre Motor Theory of Attention (PMT)). Here, we studied this direct implementation of the PMT and tested whether a congruent movement training (CMT: congruent -i.e., executed at the same time to the same location-eye and pointing movements) is more effective to attenuate symptoms of neglect compared to VST. This study can be seen as a proof of concept. Attenuation of neglect symptoms was found in the CMT group after just 5 h of training in the subacute phase of neglect. In contrast, no training effects were found in the VST group. These findings indicate the potential of CMT which is a minimal -yet crucial-upgrade of the standard VST protocol that can be easily implemented in the clinic.

Impaired pre-saccadic shifts of attention in neglect patients.

Every saccade is generally preceded by a mandatory shift of attention to the saccade endpoint, allowing us to process visual information more effectively. Whether this 'pre-saccadic shift of attention' is still intact in hemispatial neglect is unknown. Whereas neglect patients exhibit lateralized impairments of attention and often show impaired saccadic behaviour, it is not yet clear how the pre-saccadic shift of attention is affected during accurately executed eye movements. In this study, we used a gaze contingent visual discrimination task, in which neglect patients had to discriminate a probe presented before saccade onset. Results revealed an imbalance in discrimination performance between the two hemifields with poor performance to probes in the contralesional compared to the ipsilesional hemifield when accounting for saccadic impairments. These results suggest that attention and eye movements are both unique impairments of neglect patients. We hypothesize that the impaired pre-saccadic shift of attention could be one of the key problems of neglect and might underlie other spatial and non-spatial deficits often reported in neglect patients.

Functional connectivity of the Precuneus reflects effectiveness of visual restitution training in chronic hemianopia.

Visual field defects in chronic hemianopia can improve through visual restitution training, yet not all patients benefit equally from this long and exhaustive procedure. Here, we asked if resting-state functional connectivity prior to visual restitution could predict training success. In two training sessions of eight weeks each, 20 patients with chronic hemianopia performed a visual discrimination task by directing spatial selective attention towards stimuli presented in either hemifield, while suppressing eye movements. We examined two effects: a sensitivity change in the attended (trained) minus the unattended (control) hemifield (i.e., a training-specific improvement), and an overall improvement (i.e., a total change in sensitivity after both sessions). We then identified five visual resting-state networks and evaluated their functional connectivity in relation to both training effects. We found that the functional connectivity strength between the anterior Precuneus and the Occipital Pole Network was positively related to the attention modulated (i.e., training-specific) improvement. No such relationship was found for the overall improvement or for the other visual networks of interest. Our finding suggests that the anterior Precuneus plays a role in attention-modulated visual field improvements. The resting-state functional connectivity between the anterior Precuneus and the Occipital Pole Network may thus serve as an imaging-based biomarker that quantifies a patient's potential capacity to direct spatial attention. This may help to identify hemianopia patients that are most likely to benefit from visual restitution training.

Is congruent movement training more effective than standard visual scanning therapy to ameliorate symptoms of visuospatial neglect? Study protocol of a randomised control trial.

INTRODUCTION: Approximately 30% of all patients with stroke show visuospatial neglect (VSN). Currently, visual scanning therapy (VST) is applied in clinical settings to attenuate neglect symptoms. VST builds on the premise that eye movements to the affected hemifield lead to a concurrent shift of visual attention. Congruent movements with different effectors of the motor system, for example, eye and hand, can produce an even larger boost of attention compared with a single effector. This congruency principle may produce a powerful bias in the motor system, which may counteract the pathological biases in the attentional system of neglect patients. Therefore, an intervention with congruent eye and hand movements may result in greater attenuation of neglect compared with an intervention with single eye movements as applied in standard VST. The current randomised controlled trial will investigate the beneficial effects of this updated version of VST by comparing changes in performance on standard neuropsychological neglect tasks and severity of neglect in activities of daily living. METHODS AND ANALYSIS: Thirty VSN patients in the subacute phase poststroke onset will be randomly assigned to one of two groups: congruent eye and hand movement training (experimental group) versus standard VST (control group). Each patient will receive 10 sessions of training, 30 min each, within 2 weeks. Performance on standard neuropsychological neglect tasks, a visual discrimination task, severity of neglect in ADL and eye movement characteristics before and after intervention will be compared for and between both groups. ETHICS AND DISSEMINATION: This study has been approved by the ethical committee of the University Medical Centre Utrecht. All subjects will participate voluntarily and will give written informed consent. Results of this study will be published in peer-reviewed scientific journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NTR7005.

Improvement in activities of daily living after visual training in patients with homonymous visual field defects using Goal Attainment Scaling.

BACKGROUND: Stroke is the most common cause of homonymous visual field defects (HVFDs). Yet, there is no standard protocol for composing a rehabilitation program. OBJECTIVE: In this study we assess ADL gain of visual training for vision restoration in HVFD patients by means of Goal Attainment Scaling. METHODS: Thirty-five patients trained two predefined regions of the visual field successively at home. In each region we compared the effects of both training rounds, one of which was thus 'directed' and the other 'undirected'. Visual fields were measured with Humphrey and Goldmann perimetry. QoL was assessed with three stroke-related questionnaires and ADL with Goal Attainment Scaling (GAS). RESULTS: Visual training improved the visual field for both Goldmann (ECSG = 5.82±0.94 mm; p = <0.001; n = 31) and Humphrey (0.79±0.20 dB; p = <0.001; n = 28) perimetry. All standardized stroke questionnaires were significantly improved after training (p < 0.039; n = 29), but showed no significant relation with either type of field improvement (p > 0.359). About 75% of the patients improved on their (personalized) GAS score. Interestingly, after both training rounds the GAS score increased in proportion to the extent of visual field improvement, for Goldmann border shift (p = 0.042; r = 0.38; n = 29) but not for Humphrey sensitivity increase (p = 0.337; r = 0.192; n = 28). Multiple regression revealed that GAS score was linearly related to the directed training component for Humphrey perimetry, but not for undirected training. CONCLUSION: Together these data suggest that (1) visual training aimed at vision restoration leads to visual field improvement and (2) the extent of visual field improvement is linearly related to the improvement of personal activities of daily living as evaluated by means of GAS. In conclusion, a personalized evaluation to assess treatment success showed the clinical significance of a visual training for vision restoration.

Segregation of Spontaneous and Training Induced Recovery from Visual Field Defects in Subacute Stroke Patients.

Whether rehabilitation after stroke profits from an early start is difficult to establish as the contributions of spontaneous recovery and treatment are difficult to tease apart. Here, we use a novel training design to dissociate these components for visual rehabilitation of subacute stroke patients with visual field defects such as hemianopia. Visual discrimination training was started within 6 weeks after stroke in 17 patients. Spontaneous and training-induced recoveries were distinguished by training one-half of the defect for 8 weeks, while monitoring spontaneous recovery in the other (control) half of the defect. Next, trained and control regions were swapped, and training continued for another 8 weeks. The same paradigm was also applied to seven chronic patients for whom spontaneous recovery can be excluded and changes in the control half of the defect point to a spillover effect of training. In both groups, field stability was assessed during a no-intervention period. Defect reduction was significantly greater in the trained part of the defect than in the simultaneously untrained part of the defect irrespective of training onset (p = 0.001). In subacute patients, training contributed about twice as much to their defect reduction as the spontaneous recovery. Goal Attainment Scores were significantly and positively correlated with the total defect reduction (p = 0.01), percentage increase reading speed was significantly and positively correlated with the defect reduction induced by training (epoch 1: p = 0.0044; epoch 2: p = 0.023). Visual training adds significantly to the spontaneous recovery of visual field defects, both during training in the early and the chronic stroke phase. However, field recovery as a result of training in this subacute phase was as large as in the chronic phase. This suggests that patients benefited primarily of early onset training by gaining access to a larger visual field sooner.

Visual Rehabilitation in Chronic Cerebral Blindness: A Randomized Controlled Crossover Study.

The treatment of patients suffering from cerebral blindness following stroke is a topic of much recent interest. Several types of treatment are under investigation, such as substitution with prisms and compensation training of saccades. A third approach, aimed at vision restitution is controversial, as a proper controlled study design is missing. In the current study, 27 chronic stroke patients with homonymous visual field defects were trained at home with a visual training device. We used a discrimination task for two types of stimuli: a static point stimulus and a new optic flow-discontinuity stimulus. Using a randomized controlled crossover design, each patient received two successive training rounds, one with high contrast stimuli in their affected hemifield (test) and one round with low-contrast stimuli in their intact hemifield (control). Goldmann and Humphrey perimetry were performed at the start of the study and following each training round. In addition, reading performance was measured. Goldmann perimetry revealed a statistically significant reduction of the visual field defect after the test training, but not after the control training or after no intervention. For both training rounds combined, Humphrey perimetry revealed that the effect of a directed training (sensitivity change in trained hemifield) exceeded that of an undirected training (sensitivity change in untrained hemifield). The interaction between trained and tested hemifield was just above the threshold of significance (p = 0.058). Interestingly, reduction of the field defect assessed by Goldmann perimetry increases with the difference between defect size as measured by Humphrey and Goldmann perimetry prior to training. Moreover, improvement of visual sensitivity measured by Humphrey perimetry increases with the fraction of non-responsive elements (i.e., more relative field loss) in Humphrey perimetry prior to training. Reading speed revealed a significant improvement after training. Our findings demonstrate that our training can result in reduction of the visual field. Improved reading performance after defect training further supports the significance of our training for improvement in daily life activities.

Dissociable effects of dopamine and serotonin on reversal learning.

Serotonin and dopamine are speculated to subserve motivationally opponent functions, but this hypothesis has not been directly tested. We studied the role of these neurotransmitters in probabilistic reversal learning in nearly 700 individuals as a function of two polymorphisms in the genes encoding the serotonin and dopamine transporters (SERT: 5HTTLPR plus rs25531; DAT1 3'UTR VNTR). A double dissociation was observed. The SERT polymorphism altered behavioral adaptation after losses, with increased lose-shift associated with L' homozygosity, while leaving unaffected perseveration after reversal. In contrast, the DAT1 genotype affected the influence of prior choices on perseveration, while leaving lose-shifting unaltered. A model of reinforcement learning captured the dose-dependent effect of DAT1 genotype, such that an increasing number of 9R-alleles resulted in a stronger reliance on previous experience and therefore reluctance to update learned associations. These data provide direct evidence for doubly dissociable effects of serotonin and dopamine systems.