Reward-driven modulation of spatial attention in the human frontal eye-field.

Attentional selection and the decision of where to make an eye-movement are driven by various factors such as the representation of salience, task goal, and stimulus relevance, as well as expectations or predictions based on past experience. Brain systems implicated in these processes recruit cortico-subcortical areas including the Frontal Eye-Field (FEF), parietal cortex, or superior colliculus. How these areas interact to govern attention remains elusive. Priority maps of space have been observed in several brain regions, but the neural substrates where different sources of information are combined and integrated to guide attentional selection has not been elucidated. We investigated here the neural mechanisms subserving how reward cues influence the voluntary deployment of attention, in conditions where stimulus-driven capture and task-related goals compete for attention selection. Using fMRI in a visual search task in n = 23 participants, we found a selective modulation of FEF by the reward value of distractors during attentional shifts, particularly after high-predictive cueing to invalid locations. Reward information also modulated FEF connectivity to superior colliculus, striatum, and visual cortex. We conclude that FEF may occupy a central position within brain circuits integrating different sources of top-down biases for the generation of spatial saliency maps and guidance of selective attention.

Virtual prism adaptation for spatial neglect: A double-blind study.

ABSTRACTPrismatic adaptation (PA) with wedge prisms is a non-invasive technique used in the rehabilitation of patients suffering from spatial neglect. Unfortunately, as for many behavioural intervention techniques, it is nearly impossible to achieve adequate blinding using wedge prisms, and the potential benefit of PA in the rehabilitation of neglect remains controversial. In order to study an alternative to wedge prism, we examine whether virtual PA at different degrees of deviation may alleviate signs of neglect in a double-blind design. Fifteen neglect patients participated in three adaptation sessions, which differed by the degree of deviation (0°, 15°, or 30°). Performance in line bisection and item cancellation tasks was measured in virtual reality immediately before and after adaptation. Session allocation was concealed from patients and the examiner. Despite the presence of robust, dose-dependent effects of virtual PA on Open-Loop Pointing (OLP), no transfer to line bisection and item cancellation tests were observed. None of the patients were aware of differences between sessions. Virtual PA did not result in visuo-motor transfer effects despite inducing significant adaptation effects in OLP. Together with recent negative findings of randomized-controlled trials, these findings cast doubt on the general efficacy of PA as a rehabilitation method of spatial neglect.

Discrete Patterns of Cross-Hemispheric Functional Connectivity Underlie Impairments of Spatial Cognition after Stroke.

Despite intense research, the neural correlates of stroke-induced deficits of spatial cognition remain controversial. For example, several cortical regions and white-matter tracts have been designated as possible anatomic predictors of spatial neglect. However, many studies focused on local anatomy, an approach that does not harmonize with the notion that brain-behavior relationships are flexible and may involve interactions among distant regions. We studied in humans of either sex resting-state fMRI connectivity associated with performance in line bisection, reading and visual search, tasks commonly used for he clinical diagnosis of neglect. We defined left and right frontal, parietal, and temporal areas as seeds (or regions of interest, ROIs), and measured whole-brain seed-based functional connectivity (FC) and ROI-to-ROI connectivity in subacute right-hemisphere stroke patients. Performance on the line bisection task was associated with decreased FC between the right fusiform gyrus and left superior occipital cortex. Complementary increases and decreases of connectivity between both temporal and occipital lobes predicted reading errors. In addition, visual search deficits were associated with modifications of FC between left and right inferior parietal lobes and right insular cortex. These distinct connectivity patterns were substantiated by analyses of FC between left- and right-hemispheric ROIs, which revealed that decreased interhemispheric and right intrahemispheric FC was associated with higher levels of impairment. Together, these findings indicate that intrahemispheric and interhemispheric cooperation between brain regions lying outside the damaged area contributes to spatial deficits in a way that depends on the different cognitive components recruited during reading, spatial judgments, and visual exploration.SIGNIFICANCE STATEMENT Focal damage to the right cerebral hemisphere may result in a variety of deficits, often affecting the domain of spatial cognition. The neural correlates of these disorders have traditionally been studied with lesion-symptom mapping, but this method fails to capture the network dynamics that underlie cognitive performance. We studied functional connectivity in patients with right-hemisphere stroke and found a pattern of correlations between the left and right temporo-occipital, inferior parietal, and right insular cortex that were distinctively predictive of deficits in reading, spatial judgment, and visual exploration. This finding reveals the importance of interhemispheric interactions and network adaptations for the manifestation of spatial deficits after damage to the right hemisphere.

The neural correlates of intermanual transfer.

Intermanual transfer of motor learning is a form of learning generalization that leads to behavioral advantages in various tasks of daily life. It might also be useful for rehabilitation of patients with unilateral motor deficits. Little is known about neural structures and cognitive processes that mediate intermanual transfer. Previous studies have suggested a role for primary motor cortex (M1) and the supplementary motor area (SMA). Here, we investigated the functional neuroanatomy of intermanual transfer with a special emphasis on functional connectivity within the motor network and between motor regions and attentional networks, including the fronto-parietal executive control network and visual attention networks. We designed a finger tapping task, in which young, heathy subjects trained the non-dominant left hand in the MRI scanner. Behaviorally, transfer of sequence learning was observed in most cases, independently of the trained hand's performance. Pre- and post-training functional connectivity patterns of cortical motor seeds were investigated using generalized psychophysiological interaction analyses. Transfer was correlated with the strength of connectivity between the left premotor cortex and structures within the dorsal attention network (superior parietal cortex, left middle temporal gyrus) and executive control network (right prefrontal regions) during pre-training, relative to post-training. Changes in connectivity within the motor network, and more particularly between trained and untrained M1, as well as between the SMA and untrained M1, correlated with transfer after training. Together, these results suggest that the interplay between attentional, executive and motor networks may support processes leading to transfer, whereas, following training, transfer translates into increased connectivity within the motor network.

Does the insula contribute to emotion-related distortion of time? A neuropsychological approach.

The literature points to a large distributed brain network involved in the estimation of time. Among these regions, the role of the insular cortex is still poorly understood. At the confluence of emotional, interoceptive, and environmental signals, this brain structure has been proposed to underlie awareness of the passage of time and emotion related time dilation. Yet, this assumption has not been tested so far. This study aimed at exploring how a lesion of the insula affects subjective duration, either in an emotional context or in a non-emotional context. Twenty-one patients with a stroke affecting the insula, either left or right, were studied for their perception of sub and supra second durations. A verbal estimation task and a temporal bisection task were used with either pure tones or neutral and emotional sounds lasting between 300 and 1500 ms and presented monaurally. Results revealed that patients with a right insular lesion, showed less temporal sensitivity than both control participants and patients with a left insular lesion. Unexpectedly, emotional effects were similar in patients and control participants. Altogether, these results suggest a specific role of the right insula in the discrimination of durations, but not in emotion related temporal distortion. In addition, an ear × emotion interaction in control participants suggests that temporal processing of positive and negative sounds may be lateralized in the brain.

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.

How does reward compete with goal-directed and stimulus-driven shifts of attention?

In order to behave adaptively, attention can be directed in space either voluntarily (i.e. endogenously) according to strategic goals, or involuntarily (i.e. exogenously) through reflexive capture by salient or novel events. The emotional or motivational values of stimuli can also influence attentional orienting. However, little is known about how reward-related effects compete or interact with endogenous and exogenous attention mechanisms. Here we designed a visual search paradigm in which goal-driven and stimulus-driven shifts of attention were manipulated by classic spatial cueing procedures, while an irrelevant, but previously rewarded stimulus also appeared as a distractor and hence competed with both types of spatial attention during search. Our results demonstrated that stimuli previously associated with a high monetary reward received higher attentional priority in the subsequent visual search task, even though these stimuli and reward were no longer task-relevant, mitigating the attentional orienting induced by both endogenous and exogenous cues.

Disengagement of attention with spatial neglect: A systematic review of behavioral and anatomical findings.

The present review examined the consequences of focal brain injury on spatial attention studied with cueing paradigms, with a particular focus on the disengagement deficit, which refers to the abnormal slowing of reactions following an ipsilesional cue. Our review supports the established notion that the disengagement deficit is a functional marker of spatial neglect and is particularly pronounced when elicited by peripheral cues. Recent research has revealed that this deficit critically depends on cues that have task-relevant characteristics or are associated with negative reinforcement. Attentional capture by task-relevant cues is contingent on damage to the right temporo-parietal junction (TPJ) and is modulated by functional connections between the TPJ and the right insular cortex. Furthermore, damage to the dorsal premotor or prefrontal cortex (dPMC/dPFC) reduces the effect of task-relevant cues. These findings support an interactive model of the disengagement deficit, involving the right TPJ, the insula, and the dPMC/dPFC. These interconnected regions play a crucial role in regulating and adapting spatial attention to changing intrinsic values of stimuli in the environment.

Intracortical recordings reveal vision-to-action cortical gradients driving human exogenous attention.

Exogenous attention, the process that makes external salient stimuli pop-out of a visual scene, is essential for survival. How attention-capturing events modulate human brain processing remains unclear. Here we show how the psychological construct of exogenous attention gradually emerges over large-scale gradients in the human cortex, by analyzing activity from 1,403 intracortical contacts implanted in 28 individuals, while they performed an exogenous attention task. The timing, location and task-relevance of attentional events defined a spatiotemporal gradient of three neural clusters, which mapped onto cortical gradients and presented a hierarchy of timescales. Visual attributes modulated neural activity at one end of the gradient, while at the other end it reflected the upcoming response timing, with attentional effects occurring at the intersection of visual and response signals. These findings challenge multi-step models of attention, and suggest that frontoparietal networks, which process sequential stimuli as separate events sharing the same location, drive exogenous attention phenomena such as inhibition of return.

Fronto-parietal networks shape human conscious report through attention gain and reorienting.

How do attention and consciousness interact in the human brain? Rival theories of consciousness disagree on the role of fronto-parietal attentional networks in conscious perception. We recorded neural activity from 727 intracerebral contacts in 13 epileptic patients, while they detected near-threshold targets preceded by attentional cues. Clustering revealed three neural patterns: first, attention-enhanced conscious report accompanied sustained right-hemisphere fronto-temporal activity in networks connected by the superior longitudinal fasciculus (SLF) II-III, and late accumulation of activity (>300 ms post-target) in bilateral dorso-prefrontal and right-hemisphere orbitofrontal cortex (SLF I-III). Second, attentional reorienting affected conscious report through early, sustained activity in a right-hemisphere network (SLF III). Third, conscious report accompanied left-hemisphere dorsolateral-prefrontal activity. Task modeling with recurrent neural networks revealed multiple clusters matching the identified brain clusters, elucidating the causal relationship between clusters in conscious perception of near-threshold targets. Thus, distinct, hemisphere-asymmetric fronto-parietal networks support attentional gain and reorienting in shaping human conscious experience.

Task relevance and negative reward modulate the disengagement deficit of patients with spatial neglect.

Though motivational value is a recognized trigger of approach and avoidance behavior, less is known about the potential of reward to capture attention. We here explored whether positive or negative reward modulates the characteristic deficit of patients with left spatial neglect to disengage attention from an ipsilesional distracter. We built our study on recent observations showing that the disengagement deficit is exaggerated for distracters with target-defining features, indicating that task-relevance captures attention. Patients with left neglect and matched healthy controls were asked to react to lateralized, colored targets preceded by a peripheral cue. Crucially, the cue either possessed the color of the target and was thus task-relevant, or was followed by a positive, negative, or neutral symbolic reward. Neglect patients only exhibited a disengagement deficit when cues were task-relevant or were followed by a negative reward. This finding indicates that attentional selection is driven by task-relevance and negative reward, possibly through interactions between limbic and attention networks.

Machine learning algorithms on eye tracking trajectories to classify patients with spatial neglect.

BACKGROUND AND OBJECTIVE: Eye-movement trajectories are rich behavioral data, providing a window on how the brain processes information. We address the challenge of characterizing signs of visuo-spatial neglect from saccadic eye trajectories recorded in brain-damaged patients with spatial neglect as well as in healthy controls during a visual search task. METHODS: We establish a standardized pre-processing pipeline adaptable to other task-based eye-tracker measurements. We use traditional machine learning algorithms together with deep convolutional networks (both 1D and 2D) to automatically analyze eye trajectories. RESULTS: Our top-performing machine learning models classified neglect patients vs. healthy individuals with an Area Under the ROC curve (AUC) ranging from 0.83 to 0.86. Moreover, the 1D convolutional neural network scores correlated with the degree of severity of neglect behavior as estimated with standardized paper-and-pencil tests and with the integrity of white matter tracts measured from Diffusion Tensor Imaging (DTI). Interestingly, the latter showed a clear correlation with the third branch of the superior longitudinal fasciculus (SLF), especially damaged in neglect. CONCLUSIONS: The study introduces new methods for both the pre-processing and the classification of eye-movement trajectories in patients with neglect syndrome. The proposed methods can likely be applied to other types of neurological diseases opening the possibility of new computer-aided, precise, sensitive and non-invasive diagnostic tools.

From Action to Cognition: Neural Reuse, Network Theory and the Emergence of Higher Cognitive Functions.

The aim of this article is to discuss the logic and assumptions behind the concept of neural reuse, to explore its biological advantages and to discuss the implications for the cognition of a brain that reuses existing circuits and resources. We first address the requirements that must be fulfilled for neural reuse to be a biologically plausible mechanism. Neural reuse theories generally take a developmental approach and model the brain as a dynamic system composed of highly flexible neural networks. They often argue against domain-specificity and for a distributed, embodied representation of knowledge, which sets them apart from modular theories of mental processes. We provide an example of reuse by proposing how a phylogenetically more modern mental capacity (mental rotation) may appear through the reuse and recombination of existing resources from an older capacity (motor planning). We conclude by putting arguments into context regarding functional modularity, embodied representation, and the current ontology of mental processes.

Visual but Not Auditory-Verbal Feedback Induces Aftereffects Following Adaptation to Virtual Prisms.

Visuo-motor adaptation with optical prisms that displace the visual scene (prism adaptation, PA) has been widely used to study visuo-motor plasticity in healthy individuals and to decrease the lateralized bias of brain-damaged patients suffering from spatial neglect. Several factors may influence PA aftereffects, such as the degree of optical deviation (generally measured in dioptres of wedge prisms) or the direction of the prismatic shift (leftward vs. rightward). However, the mechanisms through which aftereffects of adaptation in healthy individuals and in neglect affect performance in tasks probing spatial cognition remain controversial. For example, some studies have reported positive effects of PA on auditory neglect, while other studies failed to obtain any changes of performance even in the visual modality. We here tested a new adaptation method in virtual reality to evaluate how sensory parameters influence PA aftereffects. Visual vs. auditory-verbal feedback of optical deviations were contrasted to assess whether rightward deviations influence manual and perceptual judgments in healthy individuals. Our results revealed that altered visual, but not altered auditory-verbal feedback induces aftereffects following adaptation to virtual prisms after 30-degrees of deviation. These findings refine current models of the mechanisms underlying the cognitive effects of virtual PA in emphasizing the importance of visual vs. auditory-verbal feedback during the adaptation phase on visuospatial judgments. Our study also specifies parameters which influence virtual PA and its aftereffect, such as the sensory modality used for the feedback.

Periinfarct rewiring supports recovery after primary motor cortex stroke.

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies.

Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders.

Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.

Pulvino-cortical interaction: An integrative role in the control of attention.

Selective attention is a fundamental cognitive function that guides behavior by selecting and prioritizing salient or relevant sensory information of our environment. Despite early evidence and theoretical proposal pointing to an implication of thalamic control in attention, most studies in the past two decades focused on cortical substrates, largely ignoring the contribution of subcortical regions as well as cortico-subcortical interactions. Here, we suggest a key role of the pulvinar in the selection of salient and relevant information via its involvement in priority maps. Prioritization may be achieved through a pulvinar-mediated generation of alpha oscillations, which may then modulate neuronal gain in thalamo-cortical circuits. Such mechanism might orchestrate the synchrony of cortico-cortical interaction, by rendering neural communication more effective, precise and selective. We propose that this theoretical framework will support a timely shift from the prevailing cortico-centric view of cognition to a more integrative perspective of thalamic contributions to attention and executive control processes.

Impaired visual search with paradoxically increased facilitation by emotional features after unilateral pulvinar damage.

Posterior thalamic pulvinar nuclei have been implicated in different aspects of spatial attention, but their exact role in humans remain unclear. Most neuropsychological studies of attention deficits after pulvinar lesion have concerned single patients or small samples. Here we examined a group of 13 patients with focal damage to posterior thalamus on a visual search task with faces, allowing us to test several hypotheses concerning pulvinar function in controlling attention to visually salient or emotionally significant stimuli. Our results identified two subgroups of thalamic patients with distinct patterns of attentional responsiveness to emotional and colour features in face targets. One group with lesions located in anterior and ventral portions of thalamus showed intact performance, with a normal facilitation of visual search for faces with emotional (fearful or happy) expressions on both side of space, similar to healthy controls. By contrast, a second group showed a slower and poorer detection of face targets, most severe for neutral faces, but with a paradoxically enhanced facilitation by both colour and emotional features. This second group had lesions centred on the pulvinar, involving mainly the dorso-medial sectors in patients showing enhanced effects of colour features, but extending to more dorso-lateral sectors in those with enhanced effects of emotional features. These findings reveal that pulvinar nuclei are not critical for orienting attention to emotionally or visually salient features, but instead provide new evidence in support of previous hypotheses suggesting an important role in controlling attention in visual scenes with distracting information.

Value-driven attentional capture in neglect.

OBJECTIVE: Recent studies suggest that motivational cues such as rewards may be a powerful determinant of attentional selection, both in healthy subjects and in brain-damaged patients suffering from neglect. However, the exact brain mechanisms underlying these effects and their relation to other well-known attentional systems are still poorly known. METHODS: We designed a visual search paradigm to examine how value-based attentional priority could modulate spatial orienting in patients with pathological biases due to neglect after right hemispheric stroke. Targets were preceded by exogenous valid or invalid spatial cues, in the presence or absence of distractors that were associated with high reward values subsequent to an initial reinforcement training phase. RESULTS: We found that the learned reward value of distractors interfered with spatial reorienting toward the left (neglected) side when neglect patients were invalidly cued to the right side. Moreover, the presence of reward-associated distractors in the contralesional field interfered most with the detection of task-relevant targets on the same side, and this interference was exaggerated with more severe neglect. Voxelwise anatomical lesion analysis indicated that damage to the right angular gyrus, as well as lateral occipital and inferior temporal areas of the right hemisphere, were associated with stronger value-driven attentional effects. CONCLUSIONS: Visual stimuli previously associated with rewards receive higher attentional priority during visual search despite pathological spatial biases due to neglect, and thus interfere with orienting to contralesional targets, presumably by competing with top-down mechanisms controlling exogenous spatial attention. Reward signals may bias neural activity evoked by visual stimuli, independent of conscious control, through a common priority map integrating several different attentional influences. These results do not only provide novel insights to link spatial orienting and motivational signals within current models of attention, but also open new perspectives that may usefully be exploited for neurological rehabilitation strategies in patients suffering from attentional deficits and neglect.

Cross-modal integration during value-driven attentional capture.

A growing body of evidence suggests that reward may be a powerful determinant of attentional selection. To date, the study of value-based attentional capture has been mainly focused on the visual sensory modality. It is yet unknown how reward information is communicated and integrated across the different senses in order to resolve between competing choices during selective attention. Our study investigated the interference produced by an auditory reward-associated distractor when a semantically-related visual target was concurrently presented. We measured both manual and saccadic response times towards a target image (drum or trumpet), while an irrelevant sound (congruent or incongruent instrument) was heard. Each sound was previously associated with either a high or a low reward. We found that manual responses were slowed by a high-reward auditory distractor when sound and image were semantically congruent. A similar effect was observed for saccadic responses, but only for participants aware of the past reward contingencies. Auditory events associated with reward value were thus capable of involuntarily capturing attention in the visual modality. This reward effect can mitigate cross-modal semantic integration and appears to be differentially modulated by awareness for saccadic vs. manual responses. Together, our results extend previous work on value-driven attentional biases in perception by showing that these may operate across sensory modalities and override cross-modal integration for semantically-related stimuli. This study sheds new light on the potential implication of brain regions underlying value-driven attention across sensory modalities.