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.

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.

Panic Attack, Severe Hypophosphatemia and Rhabdomyolysis in the Setting of a Motor Functional Neurological Disorder.

(1) Background: panic attack is often regarded as a benign disorder with variable physical and psychological symptoms. (2) Case Presentation: We here report the case of a 22-year-old patient known for an episode of motor functional neurological disorder a year earlier who presented a panic attack with hyperventilation causing severe hypophosphatemia and rhabdomyolysis, as well as mild tetraparesis. Electrolyte disturbances quickly resolved after phosphate substitution and rehydration. However, clinical signs suggesting a relapse of a motor functional neurological disorder appeared (improved walking with dual tasks). Diagnostic workup, including brain and spinal magnetic resonance imaging, as well as electroneuromyography and genetic testing for hypokalemic periodic paralysis, was unremarkable. Tetraparesis, lack of endurance, and fatigue eventually improved after several months. (3) Conclusions: the present case report highlights the intertwined relationship between a psychiatric disorder, leading to hyperventilation and acute metabolic disturbances, and functional neurological manifestations.

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.

Intensive Multi-Disciplinary Outpatient Rehabilitation for Facilitating Return-to-Work after Acquired Brain Injury: A Case-Control Study.

OBJECTIVE: Return-to-work is often the most important objective of working-age patients with acquired brain injury, but is often difficult to achieve. There is a lack of evidence for effective treatment. This study aimed to assess the benefit of a multidisciplinary neurorehabilitation in a daytime hospital on return-to-work after an acquired brain injury. DESIGN: Retrospective case-control study. PATIENTS: Acquired brain injury patients between 18 and 65 years of age. METHODS: Two periods, before (n = 82 patients) and after (n = 89 patients) the implementation of a daytime hospital in our neuro-rehabilitation unit were compared. Patients followed in the daytime hospital received intensive, interdisciplinary, coordinated, individual and group-level physical, cognitive, and vocational rehabilitation. During the control period, patients received outpatient neurorehabilitation with less intensive treatment without interdisciplinary coordination. The main outcome was the proportion of patients returning to > 50% of their premorbid work activity. RESULTS: Fifty-five percent of patients were able to resume more than 50% of their premorbid work level in the daytime hospital period vs 41% in the control period (p = 0.076). CONCLUSION: Intensive and coordinated outpatient neurorehabilitation may facilitate return-to-work after an acquired brain injury.

Flexible adjustment of anticipations in human outcome processing.

To sense whether thoughts refer to current reality or not, a capacity called orbitofrontal reality filtering, depends on an orbitofrontal signal when anticipated outcomes fail to occur. Here, we explored the flexibility and precision of outcome processing in a deterministic reversal learning task. Healthy subjects decided which one of two colored squares hid a target stimulus. Brain activity was measured with high-density electroencephalography. Stimuli resembling, but not identical with, the target stimuli were initially processed like different stimuli from 210 to 250 ms, irrespective of behavioral relevance. From 250 ms on, they were processed according to behavioral relevance: If they required a subsequent switch, they were processed like different stimuli; if they had been declared potential targets, they were treated like true targets. Stimuli requiring a behavioral switch induced strong theta activity in orbitofrontal, ventromedial, and medial temporal regions. The study indicates flexible adaptation of anticipations but precise processing of outcomes, mainly determined by behavioral relevance.

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.

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.

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.

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.

Altered orbitofrontal activation in preterm-born young adolescents during performance of a reality filtering task.

Preterm birth is one of the main causes for neurodevelopmental problems, and has been associated with a wide range of impairments in cognitive functions including executive functions and memory. One of the factors contributing to these adverse outcomes is the intrinsic vulnerability of the premature brain. Neuroimaging studies have highlighted structural and functional alterations in several brain regions in preterm individuals across lifetime. The orbitofrontal cortex (OFC) is crucial for a multitude of complex and adaptive behaviours, and its structure is particularly affected by premature birth. Nevertheless, studies on the functional impact of prematurity on the OFC are still missing. Orbitofrontal Reality filtering (ORFi) refers to the ability to distinguish if a thought is relevant to present reality or not. It can be tested using a continuous recognition task and is mediated by the OFC in adults and typically developing young adolescents. Therefore, the ORFi task was used to investigate whether OFC functioning is affected by prematurity. We compared the neural correlates of ORFi in 35 young adolescents born preterm (below 32 weeks of gestation) and aged 10 to 14 years with 25 full term-born controls. Our findings indicate that OFC activation was required only in the full-term group, whereas preterm young adolescents did not involve OFC in processing the ORFi task, despite being able to correctly perform it.

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.

[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.

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.

[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.

[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.

Get real: Orbitofrontal cortex mediates the ability to sense reality in early adolescents.

INTRODUCTION: Orbitofrontal reality filtering (ORFi) is a memory mechanism that distinguishes whether a thought is relevant to present reality or not. In adults, it is mediated by the orbitofrontal cortex (OFC). This region is still not fully developed in preteenagers, but ORFi is already active from age 7. Here, we probe the neural correlates of ORFi in early adolescents, hypothesizing that OFC mediates the sense of reality in this population. METHODS: Functional magnetic resonance images (fMRI) were acquired in 22 early adolescents during a task composed of two runs: run 1 measuring recognition capacity; run 2 measuring ORFi; each containing two types of images (conditions): distractors (D: images seen for the first time in the current run) and targets (T: images seen for the second time in the current run). Group region of interest (ROI) analysis was performed in a flexible factorial design with two factors (run and condition) using SPM12. RESULTS: We found significant main effects for the experimental run and condition. The bilateral OFC activation was higher during ORFi than during the first run. Additionally, the OFC was more active while processing distractors than targets. CONCLUSION: These results confirm, for the first time, the role of OFC in reality filtering in early adolescents.

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.