Neural mechanisms underlying improved new-word learning with high-density transcranial direct current stimulation.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

How embodied is cognition? fMRI and behavioral evidence for common neural resources underlying motor planning and mental rotation of bodily stimuli.

Functional neuroimaging shows that dorsal frontoparietal regions exhibit conjoint activity during various motor and cognitive tasks. However, it is unclear whether these regions serve several, computationally independent functions, or underlie a motor "core process" that is reused to serve higher-order functions. We hypothesized that mental rotation capacity relies on a phylogenetically older motor process that is rooted within these areas. This hypothesis entails that neural and cognitive resources recruited during motor planning predict performance in seemingly unrelated mental rotation tasks. To test this hypothesis, we first identified brain regions associated with motor planning by measuring functional activations to internally-triggered vs externally-triggered finger presses in 30 healthy participants. Internally-triggered finger presses yielded significant activations in parietal, premotor, and occipitotemporal regions. We then asked participants to perform two mental rotation tasks outside the scanner, consisting of hands or letters as stimuli. Parietal and premotor activations were significant predictors of individual reaction times when mental rotation involved hands. We found no association between motor planning and performance in mental rotation of letters. Our results indicate that neural resources in parietal and premotor cortex recruited during motor planning also contribute to mental rotation of bodily stimuli, suggesting a common core component underlying both capacities.

Rehabilitation of hemianopia and visuospatial hemineglect with a mixed intervention including adapted boxing therapy: An exploratory case study.

Visual field loss and visuospatial neglect are frequent consequences of cerebral stroke. They often have a strong impact on independence in many daily activities. Rehabilitation aiming to decrease these disabilities is therefore important, and several techniques have been proposed to foster awareness, compensation, or restitution of the impaired visual field. We here describe a rehabilitation intervention using adapted boxing therapy that was part of a pluridisciplinary intervention tailored for a particular case. A 58-year-old man with left homonymous hemianopia (HH) and mild visuospatial hemineglect participated in 36 sessions of boxing therapy six months after a right temporo-occipital stroke. Repeated stimulation of his blind and neglected hemifield, and training to compensate for his deficits through improved use of his healthy hemifield were performed through boxing exercises. The patient showed a stable HH before the beginning of the training. After six months of boxing therapy, he reported improved awareness of his visual environment. Critically, his HH had evolved to a left superior quadrantanopia and spatial attention for left-sided stimuli had improved. Several cognitive functions and his mood also showed improvement. We conclude that boxing therapy has the potential to improve the compensation of visuospatial impairments in individual patients with visual field loss.

Task-based functional connectivity identifies two segregated networks underlying intentional action.

While much of motor behavior is automatic, intentional action is necessary for the selection and initiation of controlled motor acts and is thus an essential part of goal-directed behavior. Neuroimaging studies have shown that self-generated action implicates several dorsal and ventral frontoparietal areas. However, knowledge of the functional coupling between these brain regions during intentional action remains limited. We here studied brain activations and functional connectivity (FC) of thirty right-handed healthy participants performing a finger pressing task instructed to use a specific finger (externally-triggered action) or to select one of four fingers randomly (internally-generated action). Participants performed the task in alternating order either with their dominant right hand or the left hand. Consistent with previous studies, we observed stronger involvement of posterior parietal cortex and premotor regions when contrasting internally-generated with externally-triggered action. Interestingly, this contrast also revealed significant engagement of medial occipitotemporal regions including the left lingual and right fusiform gyrus. Task-based FC analysis identified increased functional coupling among frontoparietal regions as well as increased and decreased coupling between occipitotemporal regions, thus differentiating between two segregated networks. When comparing results of the dominant and nondominant hand we found less activation, but stronger connectivity for the former, suggesting increased neural efficiency when participants use their dominant hand. Taken together, our results reveal that two segregated networks that encompass the frontoparietal and occipitotemporal cortex contribute independently to intentional action.

Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

Deficient Novelty Detection and Encoding in Early Alzheimer's Disease: An ERP Study.

Patients with early Alzheimer's disease (AD) have difficulty in learning new information and in detecting novel stimuli. The underlying physiological mechanisms are not well known. We investigated the electrophysiological correlates of the early (< 400 ms), automatic phase of novelty detection and encoding in AD. We used high-density EEG Queryin patients with early AD and healthy age-matched controls who performed a continuous recognition task (CRT) involving new stimuli (New), thought to provoke novelty detection and encoding, which were then repeated up to 4 consecutive times to produce over-familiarity with the stimuli. Stimuli then reappeared after 9-15 intervening items (N-back) to be re-encoded. AD patients had substantial difficulty in detecting novel stimuli and recognizing repeated ones. Main evoked potential differences between repeated and new stimuli emerged at 180-260 ms: neural source estimations in controls revealed more extended MTL activation for N-back stimuli and anterior temporal lobe activations for New stimuli compared to highly familiar repetitions. In contrast, AD patients exhibited no activation differences between the three stimulus types. In direct comparison, healthy subjects had significantly stronger MTL activation in response to New and N-back stimuli than AD patients. These results point to abnormally weak early MTL activity as a correlate of deficient novelty detection and encoding in early AD.

Insular Cortex Mediates Attentional Capture by Behaviorally Relevant Stimuli after Damage to the Right Temporoparietal Junction.

The right temporoparietal junction (rTPJ) and insula both play a key role for the processing of relevant stimuli. However, while both have been conceived as neural "switches" that detect salient events and redirect the focus of attention, it remains unclear how these brain regions interact to achieve this behavioral goal. Here, we tested human participants with focal left-hemispheric or right-hemispheric lesions in a spatial cuing task that requires participants to react to lateralized stimuli preceded by a distracter that shares or does not share a relevant feature with the target. Using machine learning to identify significant lesion-behavior relationships, we found that rTPJ damage produces distinctive, pathologically increased attentional capture, but only by relevant distracters. Functional connectivity analyses revealed that the degree of capture is positively associated with a functional connection between insula and rTPJ, together with functional isolation of the rTPJ from right dorsal prefrontal cortex (dPFC). These findings suggest a mechanistic model where the insula-rTPJ connection constitutes a crucial functional unit that breaks attentional focus upon detection of behaviorally relevant events, while the dPFC appears to attune this activity.

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.

Adaptation to virtual prisms and its relevance for neglect rehabilitation: a single-blind dose-response study with healthy participants.

Prism adaptation (PA) has been applied with mixed success as a rehabilitation method of spatial neglect. Results from many single-case and multiple case studies as well as randomised controlled trials do not produce a clear picture of the efficacy of PA. We here tested a new method of PA, by inducing adaptation effects in the virtual reality. Healthy participants were attributed to one of four groups: no deviation, 10-, 20-, or 30-degrees rightward deviation. In contrast to classical wedge prisms, we induced the visual shift progressively. Participants performed two variants of the bisection and the landmark task to measure cognitive transfer of adaptation effects. Pointing error was directly related to the degree of optical deviation, and was greatest immediately following adaptation. Transfer was only observed in the bisection tasks, and only in the 30-degrees group. Due to the gradual induction of the spatial deviation the majority of participants were unaware of the adaptation effects. These findings show that large rightward deviation may affect sensorimotor performance in healthy participants similarly to neglect patients. Moreover, the finding that only participants adapted to 30-degrees showed biased bisection performance suggests that a critical threshold must be reached in order to induce significant visuomotor transfer.

Absence of an early hippocampal encoding signal after medial temporal lesions: No consequence for the spacing effect.

Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200-300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements, and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE)-the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL-mediated signal but not the spacing effect. We conclude that the SE does not depend on MTL integrity. We suggest that the early frontal signal at 200-300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's.

Functional connectivity and the failure to retrieve meaning from shape in visual object agnosia.

The neural mechanisms underlying the access to object knowledge from early representations of shape are little known. Functional imaging studies support the view that representations of visual properties are distributed across occipito-temporal cortex of both cerebral hemispheres. By contrast, brain lesion studies show that focal occipito-temporal damage may lead to object agnosia - a specific impairment of object recognition. How does distributed processing fit with functional specialization implied by the existence of stimulus-specific agnosias? Using fMRI we studied functional connectivity (FC) in a patient with object agnosia following left lateral occipital damage. Despite intact global and local processing of 2D and 3D object structure, the patient made consistent object identification errors. Seven experiments testing naming, visual matching or object priming showed that his errors mainly reflected the global shape similarity between objects. Compared to controls the patient exhibited strongly reduced FC between the damaged left and the intact right medial/lateral occipital cortex. In addition, controls showed stronger connectivity between the right occipital cortex and the left and right inferior and anterior temporal cortices. Interestingly, the patient also showed compensatory increases of FC between dorsal occipital and medial parietal cortex. These findings show that focal damage to the lateral occipital cortex may have global effects on representations of objects in bilateral occipito-temporal cortex, thus supporting the view that bilaterally distributed coding is necessary for the retrieval of associative knowledge from shape.

What role for prism adaptation in the rehabilitation of pure neglect dyslexia?

Prism adaptation (PA) has been successfully applied in the rehabilitation of spatial neglect, with significant transfer to classic neglect tests and activities of daily living. However, well-controlled studies were unable to replicate these findings, and recent reports suggest that PA may affect selectively visuo-motor symptoms. Here, a patient with pure left neglect dyslexia was tested before, immediately after, and 24 h after PA. Despite a significant adaptation aftereffect adaptation had no effect omissions, substitutions and letter-based errors. PA does not affect pure neglect dyslexia and should therefore be reserved for the rehabilitation of motor-intentional, rather than visual-attentional symptoms.

Emotion Regulation After Traumatic Brain Injury: Distinct Patterns of Sympathetic Activity During Anger Expression and Recognition.

OBJECTIVE: To assess psychological and psychophysiological correlates of emotion recognition and anger experience in participants with traumatic brain injury (TBI). PARTICIPANTS: Twenty participants with TBI presenting with anger problems and 22 healthy controls. PROCEDURES: Participants were administered tasks assessing emotion recognition (The French Evaluation Task) and anger expression (Anger regulation task). The latter, designed to elicit and modulate anger feelings through verbal recall of a self-experienced event, involved 4 recall conditions that followed a resting period: neutral, uninstructed anger recall, anger rumination, and anger reappraisal. MEASURES: Skin conductance levels during recall and a self-report anger questionnaire between each condition. RESULTS: In the TBI and control groups, self-reported anger was similarly modulated across emotion regulation conditions. However, only in the TBI group did skin conductance levels significantly increase between neutral and uninstructed anger recall conditions. CONCLUSIONS: Impaired emotion regulation in TBI participants could be related to increased levels of autonomic system activity during emotional experience. However, anger feelings in these participants can also be modulated with the use of emotion regulation strategies, including adaptive strategies such as reappraisal. Thus, promoting awareness and management of physiological activation and encouraging cognitive restructuring can be recommended as a component of interventions targeting emotion regulation in TBI patients.

Effects of group psychotherapy on anger management following acquired brain injury.

OBJECTIVE: To assess the effects of an anger management group programme for patients with acquired brain injury (ABI) on self-reported anger and to identify specific effects of intervention components at different time-points. PARTICIPANTS: Twenty-six participants with ABI were randomized, 24 started the programme and 19 completed it. DESIGN: A paired-randomization was held following the first baseline (T0) and a second baseline (T1) was held several weeks later. One group (n = 8) started with an 8-week anger management programme followed by a 4-week intervention focusing on the psychosocial impact of brain injury. This order was reversed in the other group (n = 11). Assessment was carried-out every 4 weeks (T1-T4) during the 12-week intervention period. MAIN OUTCOME MEASURES: The Aggression Questionnaire-12, The State-Trait Anger and Expression Inventory-2 and The Multidimensional Anger Reaction Scale. RESULTS: Anger levels did not significantly change between T0 and T1, but decreased significantly at T4. Adaptive anger coping strategies also increased following intervention. Inwardly expressed anger decreased following the anger management programme compared to the psychosocial adjustment programme. CONCLUSIONS: Group psychotherapy may improve parameters of anger management in patients with ABI. However, specific effects of different components of the anger management programme merit further investigation.

Two intrinsic coupling types for resting-state integration in the human brain.

Recent findings indicate that synchronous neural activity at rest influences human performance in subsequent tasks. Synchronization can occur in form of phase coupling or amplitude correlation. It is unknown whether these coupling types have differing behavioral significance at rest. To address this, we performed resting-state electroencephalography (EEG) and source connectivity analysis in several populations of healthy subjects and patients with brain lesions. We systematically compared different types and frequencies of neural synchronization and investigated their association with behavioral performance in verbal and spatial attention tasks. Behavioral performance could be consistently predicted by two distinct resting-state coupling patterns: (1) amplitude envelope correlation of beta activity between homologous areas of both hemispheres, (2) lagged phase synchronization in EEG alpha activity between a brain area and the entire cortex. A disruption of these coupling patterns was also associated with neurological deficits in patients with stroke lesions. This suggests the existence of two distinct network systems responsible for resting-state integration. Lagged phase synchronization in the alpha band is associated with global interaction across networks while amplitude envelope correlation seems to be behaviorally relevant for interactions within networks and between hemispheres. These two coupling types may therefore provide complementary insights on brain physiology and pathology.

Neural Correlate of Anterograde Amnesia in Wernicke-Korsakoff Syndrome.

The neural correlate of anterograde amnesia in Wernicke-Korsakoff syndrome (WKS) is still debated. While the capacity to learn new information has been associated with integrity of the medial temporal lobe (MTL), previous studies indicated that the WKS is associated with diencephalic lesions, mainly in the mammillary bodies and anterior or dorsomedial thalamic nuclei. The present study tested the hypothesis that amnesia in WKS is associated with a disrupted neural circuit between diencephalic and hippocampal structures. High-density evoked potentials were recorded in four severely amnesic patients with chronic WKS, in five patients with chronic alcoholism without WKS, and in ten age matched controls. Participants performed a continuous recognition task of pictures previously shown to induce a left medial temporal lobe dependent positive potential between 250 and 350 ms. In addition, the integrity of the fornix was assessed using diffusion tensor imaging (DTI). WKS, but not alcoholic patients without WKS, showed absence of the early, left MTL dependent positive potential following immediate picture repetitions. DTI indicated disruption of the fornix, which connects diencephalic and hippocampal structures. The findings support an interpretation of anterograde amnesia in WKS as a consequence of a disconnection between diencephalic and MTL structures with deficient contribution of the MTL to rapid consolidation.

Task relevance effects in electrophysiological brain activity: early, but not first.

A current controversy surrounds the question whether high-level features of a stimulus such as its relevance to the current task may affect early attentional processes. According to one view abruptly appearing stimuli gain priority during an initial feedforward processing stage and therefore capture attention even if they are irrelevant to the task. Alternatively, only stimuli that share a relevant property with the target may capture attention of the observer. Here, we used high-density EEG to test whether task relevance may modulate early feedforward brain activity, or whether it only becomes effective once the physical characteristics of the stimulus have been processed. We manipulated task relevance and visual saliency of distracters presented left or right of an upcoming central target. We found that only the relevance of distracters had an effect on manual reaction times to the target. However, the analysis of electrocortical activity revealed three discrete processing stages during which pure effects of distracter saliency (~80-160 ms), followed by an interaction between saliency and relevance (~130-240 ms) and finally pure effects of relevance (~230-370 ms) were observed. Electrical sources of early saliency effects and later relevance effects were localized in the posterior parietal cortex, predominantly over the right hemisphere. These findings support the view that during the initial feedforward stage only physical (bottom-up) factors determine cortical responses to visual stimuli, while top-down effects interfere at later processing stages.

Exploring the world with Bálint syndrome: biased bottom-up guidance of gaze by local saliency differences.

Bálint syndrome is a combination of severe deficits affecting spatial attention, visuo-motor control and oculomotor function. While the severe restriction of attention (simultanagnosia) and impairments of visually guided reaching have been extensively studied, oculomotor apraxia has received comparatively little attention. The main explanatory hypothesis of oculomotor apraxia is that it is a direct consequence of the severe restriction of attention. Here, we examined in a patient with Bálint syndrome to what extent local image features such as luminance and contrast predict whether a region will be fixated or not. During the viewing of natural photographs, the patient made saccades of very small amplitude, but showed strongly increased fixation duration. In addition, the horizontal and vertical range of fixations was severely restrained compared to control subjects. When analysing the local feature content at fixation, we found that central fixations of the patient contained less local luminance and contrast than fixations of controls while he made fixations to peripheral image regions with disproportionately high luminance and contrast. These findings suggest that while our patient gazes at central regions irrespective of their local feature content, he only looks to the periphery when his gaze is captured by particularly conspicuous features. We propose that oculomotor apraxia in Bálint syndrome reflects a combination of biased representations within a parietal priority map and increased fixational activity due to biased interactions within the oculomotor network.

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.