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.

Syndrome of the trephined: clinical spectrum, risk factors, and impact of cranioplasty on neurologic recovery in a prospective cohort.

Syndrome of the trephined (SoT) is an underrecognized complication after decompressive craniectomy. We aimed to investigate SoT incidence, clinical spectrum, risk factors, and the impact of the cranioplasty on neurologic recovery. Patients undergoing a large craniectomy (> 80 cm2) and cranioplasty were prospectively evaluated using modified Rankin score (mRS), cognitive (attention/processing speed, executive function, language, visuospatial), motor (Motricity Index, Jamar dynamometer, postural score, gait assessment), and radiologic evaluation within four days before and after a cranioplasty. The primary outcome was SoT, diagnosed when a neurologic improvement was observed after the cranioplasty. The secondary outcome was a good neurologic outcome (mRS 0-3) 4 days and 90 days after the cranioplasty. Logistic regression models were used to evaluate the risk factors for SoT and the impact of cranioplasty timing on neurologic recovery. We enrolled 40 patients with a large craniectomy; 26 (65%) developed SoT and improved after the cranioplasty. Brain trauma, hemorrhagic lesions, and shifting of brain structures were associated with SoT. After cranioplasty, a shift towards a good outcome was observed within 4 days (p = 0.025) and persisted at 90 days (p = 0.005). Increasing delay to cranioplasty was associated with decreased odds of improvement when adjusting for age and baseline disability (odds ratio 0.96; 95% CI, 0.93-0.99, p = 0.012). In conclusion, SoT is frequent after craniectomy and interferes with neurologic recovery. High suspicion of SoT should be exercised in patients who fail to progress or have a previous trauma, hemorrhage, or shifting of brain structures. Performing the cranioplasty earlier was associated with improved and quantifiable neurologic recovery. Graphical abstract.

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.

Early signal from the hippocampus for memory encoding.

The mediotemporal lobe (MTL), including the hippocampus, is involved in all stages of episodic memory including memory encoding, consolidation, and retrieval. However, the exact timing of the hippocampus' involvement immediately after stimulus encounter remains unclear. In this study, we used high-density 156-channel electroencephalography to study the processing of entirely new stimuli, which had to be encoded, in comparison to highly overlearned stimuli. Sixteen healthy subjects performed a continuous recognition task with meaningful pictures repeated up to four consecutive times. Waveform and topographic cluster analyses of event-related potentials revealed that new items, in comparison to repetitions, were processed significantly differently at 220-300 ms. Source estimation localized activation for processing new stimuli in the right MTL. Our study demonstrates the occurrence of a transient signal from the MTL in response to new information already at 200-300 ms poststimulus onset, which presumably reflects encoding as an initial step toward memory consolidation.

[Lower urinary tract disorders in brain-damaged patients]. / Troubles des voies urinaires basses chez les patients cérébrolésés.

Bladder function is controlled by the autonomic and somatic nervous system in the spinal cord. It is coordinated in the brainstem. Different areas of the brain are involved in the voluntary control of this reflex functioning. Brain lesions often cause an overactive bladder syndrome with increased voiding frequency and urgency. Urinary incontinence, frequently present, may be linked to overactive bladder and associated motor and cognitive disorders. Urinary retention occurs in the acute phase of a hemispherical lesion and following brainstem lesions. The identification, evaluation and treatment of urinary disorders in brain-damaged patients require a global assessment and integrated management taking the other neurological consequences of brain damage into account.

Le fonctionnement vésical est commandé par les systèmes nerveux autonome et somatique situés dans la moelle épinière. Le tronc cérébral gère et coordonne leur action. Différentes zones du cerveau sont impliquées dans le contrôle volontaire du fonctionnement réflexe. Les lésions cérébrales provoquent souvent un syndrome d'hyperactivité vésicale (HAV) avec une augmentation de la fréquence mictionnelle et une urgenturie. L'incontinence urinaire, souvent présente, pourrait être liée à l'HAV et aux troubles moteurs et cognitifs associés. La rétention urinaire survient à la phase aiguë d'une lésion hémisphérique et suite aux lésions du tronc cérébral. L'identification, l'évaluation et le traitement des troubles urinaires chez les cérébrolésés nécessitent un bilan global et une gestion intégrée aux autres conséquences des lésions cérébrales.

[Feedback on post COVID-19 rehabilitation]. / Réadaptation post-COVID-19†: retour d'expérience.

The outbreak of Coronavirus Disease 19 (COVID-19) following the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) viral infection has placed particular pressure on occidental health systems, especially in terms of acute care resources and critical care skills. A number of affected patients subsequently required a rehabilitation process, due to multiple functional limitations, either as a result of an extended stay in intensive care or the consequences of the infection itself. The aim of this article is to report on the Geneva experience in post COVID19 rehabilitation, through 2 clinical vignettes, illustrating the heterogeneity of symptoms and deficits that may be encountered following this disease.

L'épidémie de la maladie Coronavirus Disease 19 (COVID-19), consécutive à l'infection virale du Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) a particulièrement mis sous pression les systèmes de santé occidentaux, notamment en termes de ressources de soins aigus et de compétences en soins intensifs. Un certain nombre de patients atteints ont nécessité par la suite une phase de réadaptation, en raison de limitations fonctionnelles multiples, consécutives, soit à un séjour prolongé aux soins intensifs, soit aux conséquences de l'infection elle-même. Le but de cet article est de rapporter l'expérience genevoise en réadaptation post-COVID-19, à travers 2 vignettes cliniques, illustrant l'hétérogénéité des symptômes et déficits qui peuvent se rencontrer suite à cette maladie.

[Emotional and behavior disorders after brain lesion]. / Troubles émotionnels et comportementaux après lésion cérébrale.

After a brain lesion, emotional and behavioral disorders affect the quality of life of the patients and their relatives. This article aims to give some cues to manage three problems chosen for their high frequency: apathy, aggression and depression. It will be reviewed how to recognize, to evaluate and to treat them.

Les lésions cérébrales sont fréquemment suivies de troubles émotionnels et comportementaux qui altèrent la qualité de vie du patient et de ses proches. Trois de ces troubles, particulièrement fréquents, sont discutés dans cet article : l'apathie, l'agressivité et la dépression. Une attention particulière sera prêtée à ces symptômes, à leur gravité, ainsi qu'à leur prise en charge, leur traitement médicamenteux ou psychothérapeutique.

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.

Resting-state connectivity predicts visuo-motor skill learning.

Spontaneous brain activity at rest is highly organized even when the brain is not explicitly engaged in a task. Functional connectivity (FC) in the alpha frequency band (α, 8-12 Hz) during rest is associated with improved performance on various cognitive and motor tasks. In this study we explored how FC is associated with visuo-motor skill learning and offline consolidation. We tested two hypotheses by which resting-state FC might achieve its impact on behavior: preparing the brain for an upcoming task or consolidating training gains. Twenty-four healthy participants were assigned to one of two groups: The experimental group (n = 12) performed a computerized mirror-drawing task. The control group (n = 12) performed a similar task but with concordant cursor direction. High-density 156-channel resting-state EEG was recorded before and after learning. Subjects were tested for offline consolidation 24h later. The Experimental group improved during training and showed offline consolidation. Increased α-FC between the left superior parietal cortex and the rest of the brain before training and decreased α-FC in the same region after training predicted learning. Resting-state FC following training did not predict offline consolidation and none of these effects were present in controls. These findings indicate that resting-state alpha-band FC is primarily implicated in providing optimal neural resources for upcoming tasks.

Comparison of Neuroplastic Responses to Cathodal Transcranial Direct Current Stimulation and Continuous Theta Burst Stimulation in Subacute Stroke.

OBJECTIVE: To investigate the effects of cathodal transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural network connectivity and motor recovery in individuals with subacute stroke. DESIGN: Double-blinded, randomized, placebo-controlled study. SETTING: University hospital rehabilitation unit. PARTICIPANTS: Inpatients with stroke (N=41; mean age, 65y; range, 28-85y; mean weeks poststroke, 5; range, 2-10) with resultant paresis in the upper extremity (mean Fugl-Meyer score, 14; range, 3-48). INTERVENTIONS: Subjects with stroke were randomly assigned to neuronavigated cTBS (n=14), cathodal tDCS (n=14), or sham transcranial magnetic stimulation/sham tDCS (n=13) over the contralesional primary motor cortex (M1). Each subject completed 9 stimulation sessions over 3 weeks, combined with physical therapy. MAIN OUTCOME MEASURES: Brain function was assessed with directed and nondirected functional connectivity based on high-density electroencephalography before and after stimulation sessions. Primary clinical end point was the change in slope of the multifaceted motor score composed of the upper extremity Fugl-Meyer Assessment score, Box and Block test score, 9-Hole Peg Test score, and Jamar dynamometer results between the baseline period and the treatment time. RESULTS: Neither stimulation treatment enhanced clinical motor gains. Cathodal tDCS and cTBS induced different neural effects. Only cTBS was able to reduce transcallosal influences from the contralesional to the ipsilesional M1 during rest. Conversely, tDCS enhanced perilesional beta-band oscillation coherence compared with cTBS and sham groups. Correlation analyses indicated that the modulation of interhemispheric driving and perilesional beta-band connectivity were not independent mediators for functional recovery across all patients. However, exploratory subgroup analyses suggest that the enhancement of perilesional beta-band connectivity through tDCS might have more robust clinical gains if started within the first 4 weeks after stroke. CONCLUSIONS: The inhibition of the contralesional M1 or the reduction of interhemispheric interactions was not clinically useful in the heterogeneous group of subjects with subacute stroke. An early modulation of perilesional oscillation coherence seems to be a more promising strategy for brain stimulation interventions.

[Neurological consequences and complications of alcohol consumption]. / Conséquences et complications neurologiques de la consommation d'alcool.

In Switzerland, alcohol consumption is often trivialized and widely accepted as normal behavior. However, even in small quantities, repeated alcohol intake can cause injury to both the central nervous system and the peripheral one. Various mechanisms are involved : direct neurotoxicity, metabolic disorders, vitamin deficiencies, systemic injuries (hepatic, cardiovascular, immune), and accidents. This article describes potential neurological complications and their mechanisms, emphasizing the importance of early screenings for abusive consumption.

En Suisse, la consommation d'alcool est une pratique bien ancrée dans les mœurs, considérée comme normale. Cependant, même pris en petites quantités, l'alcool peut provoquer une atteinte du système nerveux, tant central que périphérique. Les mécanismes impliqués sont divers : neurotoxicité directe, désordres métaboliques, carences vitaminiques, atteintes systémiques (en particulier du système hépatique, cardiovasculaire et immunitaire) ou accidents en tous genres. Cet article décrit les complications neurologiques possibles et évoque leurs mécanismes dans l'intention de souligner l'importance d'un dépistage précoce d'une consommation à risque.

Rapid memory stabilization by transient theta coherence in the human medial temporal lobe.

Presenting stimuli again after presentation of intervening stimuli improves their retention, an effect known as the spacing effect. However, using event-related potentials (ERPs), we had observed that immediate, in comparison to spaced, repetition of pictures induced a positive frontal potential at 200-300 ms. This potential appeared to emanate from the left medial temporal lobe (MTL), a structure critical for memory consolidation. In this study, we tested the behavioral relevance of this signal and explored functional connectivity changes during picture repetition. We obtained high-density electroencephalographic recordings from 14 healthy subjects performing a continuous recognition task where pictures were either repeated immediately or after 9 intervening items. Conventional ERP analysis replicated the positive frontal potential emanating from the left MTL at 250-350 ms in response to immediately repeated stimuli. Connectivity analysis showed that this ERP was associated with increased coherence in the MTL region--left more that right--in the theta-band (3.5-7 Hz) 200-400 ms following immediate, but not spaced, repetition. This increase was stronger in subjects who better recognized immediately repeated stimuli after 30 min. These findings indicate that transient theta-band synchronization between the MTL and the rest of the brain at 200-400 ms reflects a memory stabilizing signal.

Differential processing of immediately repeated verbal and non-verbal stimuli: an evoked-potential study.

Stimuli are better retained in memory if they are repeated after a delay than if they are immediately repeated. This effect is called the spacing effect (SE). Recent electroencephalographic (EEG) studies showed that delayed repetition of meaningful designs in a continuous recognition task induces an evoked response very similar to new presentations. In contrast, immediately repeated designs induced circumscribed, stronger activation of the left medio-temporal lobe (MTL) at 200-300 ms. In amnesic subjects, this signal was missing, indicating that it has a memory-protective effect. Here, high-density EEG was used in humans to explore whether meaningless verbal (non-words) and non-verbal (geometric designs) stimuli also have a SE associated with such lateralized, temporally limited activation of the left MTL upon immediate repetition. The results revealed a SE for both materials. Timing and localization of brain activity differed as a function of stimulus material. Specific responses to immediate repetitions occurred at 200-285 ms for non-verbal stimuli and at 285-380 ms for verbal material. Source estimations revealed increased activity in right inferior frontal areas for immediate non-verbal repetitions and in left fronto-parietal areas for immediate verbal repetition in comparison to new presentations. These findings show that, while the SE is a ubiquitous phenomenon, the neural processes underlying it vary according to stimulus material.

Coherent neural oscillations predict future motor and language improvement after stroke.

Recent findings have demonstrated that stroke lesions affect neural communication in the entire brain. However, it is less clear whether network interactions are also relevant for plasticity and repair. This study investigated whether the coherence of neural oscillations at language or motor nodes is associated with future clinical improvement. Twenty-four stroke patients underwent high-density EEG recordings and standardized motor and language tests at 2-3 weeks (T0) and 3 months (T1) after stroke onset. In addition, EEG and motor assessments were obtained from a second population of 18 stroke patients. The graph theoretical measure of weighted node degree at language and motor areas was computed as the sum of absolute imaginary coherence with all other brain regions and compared to the amount of clinical improvement from T0 to T1. At T0, beta-band weighted node degree at the ipsilesional motor cortex was linearly correlated with better subsequent motor improvement, while beta-band weighted node degree at Broca's area was correlated with better language improvement. Clinical recovery was further associated with contralesional theta-band weighted node degree. These correlations were each specific to the corresponding brain area and independent of initial clinical severity, age, and lesion size. Findings were reproduced in the second stroke group. Conversely, later coherence increases occurring between T0 and T1 were associated with less clinical improvement. Improvement of language and motor functions after stroke is therefore associated with inter-regional synchronization of neural oscillations in the first weeks after stroke. A better understanding of network mechanisms of plasticity may lead to new prognostic biomarkers and therapeutic targets.See Ward (doi:10.1093/brain/awv265) for a scientific commentary on this article.

[Detection and management of the neurologic dysphagia]. / Détection et prise en charge d'un trouble de déglutition neurologique.

Neurologic dysphagia is frequent and has consequences which can be severe, such as, denutrition andpneumonia. In most cases, it can be detected with a clinical exam. The management includes some general measures, an adaptation of textures, specific rehabilitation, and nutritional assessment to judge whether complementary enteral nutrition is needed.

An electrophysiological dissociation between orbitofrontal reality filtering and context source monitoring.

Memory influences behavior in multiple ways. One important aspect is to remember in what precise context in the past a piece of information was acquired (context source monitoring). Another important aspect is to sense whether an upcoming thought, composed of fragments of memories, refers to present reality and can be acted upon (orbitofrontal reality filtering). Whether these memory control processes share common underlying mechanisms is unknown. Failures of both have been held accountable for false memories, including confabulation. Electrophysiological and imaging studies suggest a dissociation but used very different paradigms. In this study, we juxtaposed the requirements of context source monitoring and reality filtering within a unique continuous recognition task, which healthy participants performed while high-resolution evoked potentials were recorded. The mechanisms dissociated both behaviorally and electrophysiologically: Reality filtering induced a frontal positivity, absence of a specific electrocortical configuration, and posterior medial orbitofrontal activity at 200-300 msec. Context source monitoring had no electrophysiological expression in this early period. It was slower and less accurate than reality filtering and induced a prolonged positive potential over frontal leads starting at 400 msec. The study demonstrates a hitherto unrecognized separation between orbitofrontal reality filtering and source monitoring. Whereas deficient orbitofrontal reality filtering is associated with reality confusion in thinking, the behavioral correlates of deficient source monitoring should be verified with controlled experimental exploration.

Impairment of semantic memory after basal forebrain and fornix lesion.

Semantic memory impairment is classically associated with lesion of the anterior temporal lobe. We report the case of a patient with severe semantic knowledge impairment and anterograde amnesia after bilateral ischemic lesion of the fornix and of the basal forebrain following surgical clipping of an aneurysm of the anterior communicating artery. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed a temporal hypometabolism. Severe semantic impairment is a rare complication after rupture of an anterior communicating artery aneurysm and may result from disconnection of the temporal lobe.

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.