The disengagement deficit after right-hemisphere damage: Distinct roles of lateral frontal and parietal damage.

An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention.

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.

Electrophysiological analysis of signal detection outcomes emphasizes the role of decisional factors in recognition memory.

Introduction: Event-related potential (ERP) studies have identified two time windows associated with recognition memory and interpreted them as reflecting two processes: familiarity and recollection. However, using relatively simple stimuli and achieving high recognition rates, most studies focused on hits and correct rejections. This leaves out some information (misses and false alarms) that according to Signal Detection Theory (SDT) is necessary to understand signal processing. Methods: We used a difficult visual recognition task with colored pictures of different categories to obtain enough of the four possible SDT outcomes and analyzed them with modern ERP methods. Results: Non-parametric analysis of these outcomes identified a single time window (470 to 670 ms) which reflected activity within fronto-central and posterior-left clusters of electrodes, indicating differential processing. The posterior-left cluster significantly distinguished all STD outcomes. The fronto-central cluster only distinguished ERPs according to the subject's response: yes vs. no. Additionally, only electrophysiological activity within the posterior-left cluster correlated with the discrimination index (d'). Discussion: We show that when all SDT outcomes are examined, ERPs of recognition memory reflect a single-time window that may reveal a bottom-up factor discriminating the history of items (i.e. memory strength), as well as a top-down factor indicating participants' decision.

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.

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.

Anatomical predictors of mental rotation with bodily and non-bodily stimuli: A lesion-symptom study.

Mental rotation (MR) is widely regarded as a quintessential example of an embodied cognitive process. This viewpoint stems from the functional parallels between MR and the physical rotation of tangible objects, as well as participants' inclination to employ motor-based strategies when tackling MR tasks involving bodily stimuli. These commonalities imply that MR may depend on brain regions crucial for the planning and execution of motor programs. However, there is disagreement regarding the anatomy of MR between findings from functional imaging and lesion studies involving brain-injured patients. The former indicate the involvement of the right-hemispheric parietal cortex, while the latter underscore the significance of posterior areas in the left hemisphere. In this study, we aimed to discern the neural underpinnings of MR using lesion-symptom mapping (LSM) for both bodily (hands) and non-bodily (letters) stimuli. Behavioral results from the two MR tasks revealed impaired MR of bodily stimuli in patients with left hemisphere damage. LSM results pinpointed the left primary motor and somatosensory cortices, along with the superior parietal lobule, as the anatomical substrates of MR for both bodily and non-bodily stimuli. Furthermore, damage to the left angular gyrus, supramarginal gyrus, supplementary motor area, and retrosplenial cortex was associated with MR of non-bodily stimuli. These findings support the causal involvement of the left hemisphere in MR and underscore the existence of a common anatomical substrate in brain regions pertinent to motor planning and execution.

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.

Anatomical and functional predictors of disorientation after first-ever brain damage.

BACKGROUND AND OBJECTIVES: Disorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated. Impaired memory as its commonly assumed mechanism predicts that disorientation is associated with medial temporal damage. The alternative is that disorientation reflects defective orbitofrontal reality filtering (ORFi) - a specific failure to identify whether thoughts or memories refer to present reality or not. The latter is a function of the posterior orbitofrontal cortex and connected structures. This study examined the mechanisms and anatomical basis of disorientation in an unselected group of patients with first-ever subacute brain injury. METHODS: Participants hospitalized for neurorehabilitation were asked to participate in this observational cohort study if they had first-ever organic hemispheric brain dysfunction as evident in a localizable brain lesion or verbal amnesia (often without localizable brain damage). Orientation to time, place, situation and person was tested with a 20-items questionnaire. To identify the mechanisms of disorientation, we determined its correlations with executive tasks, verbal episodic memory, and ORFi in all patients. ORFi was examined with a continuous recognition task, which measures learning and item recognition in the first run, and ORFi as reflected in the increase of false positive responses in the second run (temporal context confusion). Lesions of patients having localizable brain damage were manually delineated and normalized before entering multivariate lesion-symptom-mapping (LSM) to determine anatomical predictors of orientation. RESULTS: Eighty-four patients (61.1 ± 14.4 years, 29 women) were included. Among measures of memory and executive functioning, a step-wise regression retained temporal context confusion (R = -0.71, p < 0.0001), item recognition (R = 0.67, p < 0.0001) and delayed free recall (R = 0.63, p < 0.0001) as significant predictors of orientation. LSM was possible in 67 participants; it revealed an association of disorientation with damage of the right OFC and the bilateral head of the caudate nucleus. CONCLUSION: Disorientation in non-confused, non-demented patients with first-ever brain damage is associated with impaired orbitofrontal reality filtering and memory dysfunction, but not with executive dysfunction. Its main anatomical determinant is damage to the orbitofrontal cortex and its subcortical relay, the head of the caudate.

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.

Does mental rotation emulate motor processes? An electrophysiological study of objects and body parts.

Several arguments suggest that motor planning may share embodied neural mechanisms with mental rotation (MR). However, it is not well established whether this overlap occurs regardless of the type of stimulus that is manipulated, in particular manipulable or non-manipulable objects and body parts. We here used high-density electroencephalography (EEG) to examine the cognitive similarity between MR of objects that do not afford specific hand actions (chairs) and bodily stimuli (hands). Participants had identical response options for both types of stimuli, and they gave responses orally in order to prevent possible interference with motor imagery. MR of hands and chairs generated very similar behavioral responses, time-courses and neural sources of evoked-response potentials (ERPs). ERP segmentation analysis revealed distinct time windows during which differential effects of stimulus type and angular disparity were observed. An early period (90-160 ms) differentiated only between stimulus types, and was associated with occipito-temporal activity. A later period (290-330 ms) revealed strong effects of angular disparity, associated with electrical sources in the right angular gyrus and primary motor/somatosensory cortex. These data suggest that spatial transformation processes and motor planning are recruited simultaneously, supporting the involvement of motor emulation processes in MR.

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.

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.

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.

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.

Rapid Sequential Implication of the Human Medial Temporal Lobe in Memory Encoding and Recognition.

The medial temporal lobe (MTL) is crucial for memory encoding and recognition. The time course of these processes is unknown. The present study juxtaposed encoding and recognition in a single paradigm. Twenty healthy subjects performed a continuous recognition task as brain activity was monitored with a high-density electroencephalography. The task presented New pictures thought to evoke encoding. The stimuli were then repeated up to 4 consecutive times to produce over-familiarity. These repeated stimuli served as "baseline" for comparison with the other stimuli. Stimuli later reappeared after 9-15 intervening items, presumably associated with new encoding and recognition. Encoding-related differences in evoked response potential amplitudes and in spatiotemporal analysis were observed at 145-300 ms, whereby source estimation indicated MTL and orbitofrontal activity from 145 to 205 ms. Recognition-related activity evoked by late repetitions occurred at 405-470 ms, implicating the MTL and neocortical structures. These findings indicate that encoding of information is initiated before it is recognized. The result helps to explain modifications of memories over time, including false memories, confabulation, and consolidation.

Distinct outcome processing in deterministic and probabilistic reversal learning.

Anticipations that fail to happen are important drivers of behavioral adaptation. Their processing appears to depend on the context. In a deterministic environment, where a stimulus unequivocally predicts the outcome, processing of absent outcomes involves the posterior orbitofrontal cortex (OFC). Failure has been linked to reality confusion with confabulations and disorientation. In a probabilistic environment, absent outcomes appear to be processed by the anterior cingulate cortex (ACC) rather than the OFC. Failure has been associated with poor decision making and schizophrenia. These data suggest different mechanisms depending on the context. Here, healthy human subjects made two formally similar reversal learning tasks, but one with deterministic, the other with probabilistic instructions. Brain activity was monitored using high-density electroencephalography. We found that in the deterministic task, negative outcomes, which unequivocally call for a behavioral switch, induced a distinct frontal potential at 200-300 msec. Computational modeling indicated a strong association of evoked potentials with prediction error, surprise, and behavioral adaptation. In the probabilistic task, where behavioral adaptation follows the cumulated processing of outcomes, negative outcomes evoked potentials that were associated with prediction error and surprise, but had a weak link with subsequent behavior. Outcome processing in the probabilistic task induced stronger activation than the deterministic task of an extended network including the ACC, OFC and striatum at 300-400 msec. In both tasks, negative outcomes were processed differently from positive outcomes at 400-600 msec, possibly reflecting updating of the outcome record. We conclude that the brain disposes of at least two distinct systems processing outcomes with unequivocal or ambiguous behavioral significance. These systems differ along behavioral, clinical, electrophysiological and anatomical dimensions.

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.