Background and objectives: Focal epilepsies disrupt long-range networks with seizure recurrence driving both regional and global alterations in connectivity networks. While prior studies have focused on the interictal consequences, limited data exist on the direct aftermath of focal seizures. We hypothesize that mesial temporal lobe seizures lead to enduring cortical disorganization. The aim was to assess the effects of a mesial temporal lobe seizure on cortical activity and understand how the side of seizure onset influences these consequences. Methods: In this retrospective study, high-resolution EEG of patients with mesial temporal lobe epilepsy (mTLE) were analyzed. Groups of patients were identified based on the side of seizure onset. We compared relative powers in different frequency bands between interictal (prior to the seizure) and late postictal (one hour following the seizure) periods. Network-based statistics were employed to compare functional connectivity at source level between periods. Results: Twenty-three patients were included (13 left and 10 right mesial temporal lobe seizures). In patients with left mTLE, we observed a post-seizure increase in the relative spectral power in the delta band (p = 0.001) and a decrease in the relative spectral power in the alpha band (p = 0.013) over the left temporofrontal regions. We isolated a subnetwork that presented a decrease in connectivity strength in alpha band, primarily involving long-range left hemisphere connections (p = 0.042). We also identified a subnetwork that presented a decrease in connectivity strength in theta band, primarily involving interhemispheric connections (p = 0.039). No significant post-seizure changes were found in patients with right mTLE. Discussion: Left mesial temporal lobe seizures appear to be associated with lasting and widespread disorganization of cortical activity. We propose that the postictal state is associated with a prolonged functional deafferentation of the affected region in patients with left mTLE. This leads to a widespread disorganization of the functional networks, which may be associated with cognitive impairments and promote the progression of epilepsy. Further studies are required to fully understand the functional repercussions.

Les objectifs de cette étude était de tester les effets pharmacodynamiques du donépézil (inhibiteur de la cholinestérase) et de la mémantine (antagoniste des récepteurs NMDA) sur les troubles cognitifs induits par 24 heures de privation de sommeil (PS). Vingt-deux volontaires sains de sexe masculin ont participé à l’étude. Tous ont été soumis à l’ensemble conditions expérimentales. Le protocole incluait trois conditions expérimentales : 15 jours de traitement par donépézil (5 mg/jour) ou par mémantine (10 mg/jour) ou par placebo. Les volontaires étaient soumis à une batterie de tests évaluant l’attention et les fonctions exécutives. Un enregistrement EEG était également effectué pendant une tâche de oddball auditif induisant une P300. Puis les volontaires étaient privés de sommeil pendant 24 heures. À l’issue de la période de PS, une nouvelle session d’évaluation neuropsychologique et psychophysiologique était proposée. Les résultats montrent un impact de la PS sur les fonctions attentionnels et exécutives. Une modification des paramètres de la P300 a également été observée (diminution de l’amplitude de la P300, modification de la puissance spectrale des basses fréquences). Le donépézil et dans une moindre mesure la mémantine atténue ces modifications observées après la PS. Un traitement symptomatique ciblant le système cholinergique semble avoir une influence sur les troubles cognitifs induits par la PS. La PS semble être un bon modèle pharmacodynamique pour le développement de nouveaux médicaments de la cognition.

Cognitive deficits in Parkinson's disease are thought to be related to altered functional brain connectivity. To date, cognitive-related changes in Parkinson's disease have never been explored with dense-EEG with the aim of establishing a relationship between the degree of cognitive impairment, on the one hand, and alterations in the functional connectivity of brain networks, on the other hand. This study was aimed at identifying altered brain networks associated with cognitive phenotypes in Parkinson's disease using dense-EEG data recorded during rest with eyes closed. Three groups of Parkinson's disease patients (N = 124) with different cognitive phenotypes coming from a data-driven cluster analysis, were studied: G1) cognitively intact patients (63), G2) patients with mild cognitive deficits (46) and G3) patients with severe cognitive deficits (15). Functional brain networks were identified using a dense-EEG source connectivity method. Pairwise functional connectivity was computed for 68 brain regions in different EEG frequency bands. Network statistics were assessed at both global (network topology) and local (inter-regional connections) level. Results revealed progressive disruptions in functional connectivity between the three patient groups, typically in the alpha band. Differences between G1 and G2 (p < 0.001, corrected using permutation test) were mainly frontotemporal alterations. A statistically significant correlation (ρ = 0.49, p < 0.001) was also obtained between a proposed network-based index and the patients' cognitive score. Global properties of network topology in patients were relatively intact. These findings indicate that functional connectivity decreases with the worsening of cognitive performance and loss of frontotemporal connectivity may be a promising neuromarker of cognitive impairment in Parkinson's disease.

Although patients with mesial temporal lobe epilepsy (mTLE) are known to have theory of mind (ToM) impairments, the latter's neural functional bases have yet to be explored. We used functional magnetic resonance imaging (fMRI) to gain insights into the neural dysfunction associated with ToM impairments in patients with mTLE. Twenty-five patients (12 and 13 with right and left mTLE, respectively) and 25 healthy controls performed the "animated shapes" task during fMRI. This complex ToM task requires both explicit reasoning about mental states and implicit processing of information on biological motion and action. The animated shapes evoke both ToM and non-ToM interaction perception, and the corresponding neural activation patterns were compared. Behavioral performance (i.e. categorization of the interactions) was also recorded. Relative to healthy controls, both patients with right and left mTLE were impaired in categorizing ToM interactions. The fMRI results showed that both patients with right and left mTLE had less intense neural activation (relative to controls) in regions involved in the implicit component of ToM processes (i.e. the fusiform gyrus in patients with right mTLE and the supplementary motor area in patients with left mTLE). In patients with right mTLE, we also observed more intense activation (relative to controls) in regions involved in the explicit component of ToM processes (i.e. the dorsal medial prefrontal cortex); age at onset of epilepsy also mediated activation in regions involved in the explicit component (i.e. the ventral medial prefrontal cortex and the temporoparietal junction). Patients with left mTLE displayed greater activation of the contralateral mesial regions (relative to controls); we speculate that this may correspond to the deployment of a compensatory mechanism. This study provides insights into the disturbances of the implicit/explicit ToM neural network in patients with mTLE. These impairments in the ToM neural network depend on clinical characteristics, such as the laterality (right or left mTLE) and the age at onset of epilepsy.

Déterminer l’effet de l’introduction des traitements anti-parkinsoniens sur le sommeil, notamment les paramètres respiratoires et sur la somnolence diurne excessive dans la maladie de Parkinson (MP) débutante. Trente patients avec une MP ont été enregistrés en polysomnographie au moment du diagnostic (V0) puis après environ 15 mois de traitement (V1). Les paramètres respiratoires, de qualité de sommeil et la somnolence diurne objective (tests itératifs de latence d’endormissement, TILE) et subjective (échelle d’Epworth) ont été comparés entre V0 et V1. Des analyses de corrélations ont également été réalisées à V0 et V1 entre la sévérité des troubles moteurs (échelle UPDRS) et les paramètres respiratoires ; de même qu’entre les traitements anti-parkinsoniens (équivalent-dose dopa) et la latence aux TILE à V1. Le temps total de sommeil et le pourcentage de temps passé en sommeil paradoxal sont significativement inférieurs à V1 par rapport à V0. La saturation en oxygène moyenne et en sommeil paradoxal diminue significativement entre V1 et V0. La somnolence diurne objective et subjective est plus importante à V1. Une corrélation entre la dose de traitements dopaminergiques et la latence d’endormissement aux TILE est également mise en évidence. Aucune corrélation n’est retrouvée entre le score à l’UPDRS et les paramètres respiratoires à V0 et V1. L’introduction des traitements anti-parkinsoniens semble être associée à une baisse de la qualité de sommeil, une modification de la respiration et l’apparition d’une somnolence diurne excessive dans la MP débutante.

Idiopathic rapid-eye-movement sleep behavior disorder (iRBD) is becoming widely considered a prodromal symptom of Parkinson's disease (PD). Visuoperceptual deficits have been described in iRBD with still conflicting results. Since this cognitive domain is often impaired in PD, it appears of great interest to better describe visuoperceptual deficits in iRBD patients. Secondly, defining the neurophysiological correlates of these deficits would bring important data on the pathophysiology of iRBD. This study aimed to study the visual object processing in iRBD patients. High-density electroencephalograms were used to record event-related potential in fourteen iRBD patients and fourteen matched healthy volunteers during a fragmented images categorization task. The task consisted in categorizing “recognizable” images as real objects, and “unrecognizable” images as non-objects. The Ncl component (negativity associated with closure) was recorded and used as a marker of incomplete objects recognition processing. Behavioral results revealed no significant differences between the 2 groups in number of correct categorization and response time. The ERPs in the control group had significantly smaller amplitude for “recognizable” compared to “unrecognizable” images from 240 to 640 ms in the left posterior scalp regions. This relative negativity (Ncl) was absent in the iRBD patients group. This study provides neurophysiological data suggesting changes in the fragmented images processing in iRBD patients.

The pathophysiology of visual hallucinations in Parkinson’s disease has yet to be characterized. Although stimulus-driven (“bottom-up”) processes are known to be impaired, the role of “top-down” processes remains to be determined. Distinguishing between conscious and non-conscious detections (i.e. access to consciousness) may be a valuable way of monitoring top-down processes. Conscious access to visual inputs was investigated to identify the neural substrates underlying susceptibility to hallucinations in Parkinson’s disease. Seventeen healthy controls, 18 Parkinson’s disease patients with minor visual hallucinations and 16 without were enrolled in the study. During functional magnetic resonance imaging, the participants performed a visual detection task. The detection threshold was significantly higher in each patient group than in healthy controls while the two groups of patients did not differ significantly. Compared with hallucination-free patients, patients with minor hallucinations displayed hyperactivation of prefrontal and right occipital cortices, and hypoactivation of the left cingulate, temporal and occipital cortices. During conscious access to visual inputs, the functional network in patients with visual hallucinations differed from that seen in patients without visual hallucinations. This suggests that the supremacy of top-down processes in visual information processing may enhance susceptibility to hallucinations in Parkinson’s disease.

Un nombre croissant d’arguments mène à considérer les troubles du comportement en sommeil paradoxal dits idiopathiques (TCSPi) comme un symptôme « pré-moteur » de la maladie de Parkinson (MP). Des troubles visuo-perceptifs ont été décrits dans les TCSPi avec toutefois des résultats divergents. Ce domaine cognitif étant spécifiquement touché dans la MP, il semble intéressant de pouvoir décrire plus précisément ces troubles chez les patients avec TCSPi. Par ailleurs, l’étude des corrélats électrophysiologiques de ces troubles apporterait des données importantes sur la physiopathologie des TCSPi. L’objectif de cette étude était d’analyser le traitement perceptif de l’information visuelle chez les patients avec TCSPi. Des enregistrements électroencéphalographiques haute résolution ont été réalisés chez 14 patients avec TCSPi et 14 sujets contrôles afin d’analyser les potentiels évoqués cognitifs (PEc) engendrés par une tâche de catégorisation d’images fragmentées. La tâche consistait à catégoriser des images « reconnaissables » comme des objets réels et des images « non reconnaissables » comme des dessins aléatoires. La composante « Ncl » pour negativity associated with closure était analysée et utilisée comme un marqueur des processus de perception d’objets incomplets. Les résultats comportementaux n’ont mis en évidence aucune différence entre les deux groupes concernant le nombre de catégorisation correcte et le temps de réponse. Dans le groupe contrôle, le PEc avait une amplitude moyenne significativement plus faible pour les images « reconnaissables » que pour les images « non reconnaissables » dans la fenêtre de temps 240-640 ms. Cette différence concernait les régions postérieures gauches du scalp. Cette relative négativité (Ncl) était absente chez les patients avec TCSPi. Ces résultats vont dans le sens d’une modification des processus de traitement visuo-perceptif associée aux TCSPi. Les sources corticales de la Ncl ayant été décrites dans des régions de la voie ventrale de reconnaissance visuelle, nos résultats pourraient suggérer une atteinte corticale postérieure dans les TCSPi.

Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment-naive patients with early-stage PD has not been extensively investigated. Moreover, whether apathy is related to other non-motor symptoms in early-stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment-naive patients with early-stage PD. Ninety-five treatmentnaive patients with early-stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non-apathetic patients. When considering non-motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non-apathetic patients. In treatment-naive patients with early-stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anhedonia. (C) 2014 International Parkinson and Movement Disorder Society

OBJECTIVE:Patients with idiopathic REM sleep behavior disorder (iRBD) often develop synucleinopathies (Parkinson's disease [PD], in particular). Cognitive disorders affecting different domains have been reported in patients with iRBD. Dysexecutive disorders seem to predominate, but there is no consensus on the nature of visuospatial disorders in iRBD. The objective is to identify and characterize visuospatial disorders in patients with REM sleep behavior disorder (RBD - either idiopathic or associated with PD).METHODS:Fifteen patients with iRBD, 30 patients with PD (15 of whom had RBD), and 20 healthy control subjects underwent an extensive assessment of visuospatial functions. Two computerized tasks were used: a Biederman task (to assess the 3 levels of visuoperceptive processing) and a Posner paradigm (to assess visual attention).RESULTS:The visual priming effects classically described for the Biederman task in healthy controls were not found in iRBD patients. Patients with iRBD were no quicker in naming objects with the same general structure as previously presented objects but did have a normal priming effect for strictly identical objects. Parkinson's disease patients with RBD had poorer visuoperceptive performance levels than PD patients without RBD. There were no significant differences between the 4 groups in the Posner attentional task.CONCLUSIONS:First, this study confirms the presence of visuoperceptive dysfunction in iRBD patients and revealed a selective defect in intermediate visuoperceptive processing (i.e., general object representation). Second, RBD in PD appeared to be associated with poorer visuoperceptive abilities. Third, this visuoperceptive dysfunction in RBD patients was not associated with impaired attention.

Les troubles du comportement en sommeil paradoxal (TCSP) ont ete individualises comme un type de parasomnie par Carlos Schenck en 1986. Il s’agit d’une parasomnie caracterisee par l’absence d’atonie musculaire pendant le sommeil paradoxal associee a l’apparition de mouvements anormaux allant de simples secousses a des comportements elabores souvent violents. Ces comportements dependent de l’activite onirique et sont decrits comme une « mise en acte des reves ». Les TCSP sont frequents dans la maladie de Parkinson. Les patients parkinsoniens ayant des TCSP ont des troubles cognitifs plus importants et ont un risque de demence plus important que les autres patients. Les TCSP peuvent egalement se presenter de maniere isolee, sans aucune cause pathologique apparente. Ils sont alors consideres comme « idiopathiques » (TCSPi). Ce terme « idiopathique » a neanmoins ete remis en cause du fait de la presence de nombreux signes evocateurs d’une synucleinopathie chez ces patients (affaiblissement des performances cognitives, anomalies cerebrales structurales et fonctionnelles). De nombreux patients ayant des TCSP initialement consideres comme idiopathiques, vont developper un syndrome parkinsonien et/ou une demence apres plusieurs annees d’evolution. Une etude recente rapporte que cela concerne 81 % des patients apres 16 ans de suivi. Ces donnees ont conduit a l’hypothese selon laquelle les TCSP seraient un symptome revelant les stades precoces « non-moteurs » de la MP. Les agregats pathologiques d’alpha-synucleine touchant les structures du tronc cerebral seraient a l’origine de l’apparition de TCSP avant meme le syndrome parkinsonien. Cette chronologie dans les stades d’evolution de la MP (pre-clinique, pre-moteur, moteur, demence) ne semble neanmoins pas etre retrouvee chez tous les patients parkinsoniens. Elle revelerait plutot un certain sous-type de MP, caracterisee par de nombreux symptomes non-moteurs precedant le syndrome parkinsonien et par un risque accru de demence precoce. Parmi ces symptomes non moteurs, les troubles cognitifs seraient importants et toucheraient notamment le fonctionnement visuo-perceptif. Ce travail a eu pour objectif d’etudier le lien entre les TCSP, les troubles visuo-perceptifs et la maladie de Parkinson. Dans une premiere etude, des evaluations specifiques des fonctions visuo-spatiales ont permis de mettre en evidence des troubles visuo-perceptifs chez les patients ayant des TCSPi. Les patients parkinsoniens ayant des TCSP avaient des troubles visuo-perceptifs plus marques que ceux n’ayant pas de TCSP. Les resultats ont egalement permis d’identifier la nature des troubles visuo-perceptifs. Les processus intermediaires de traitement de l’information visuelle semblent specifiquement touches dans ces groupes de patients.La deuxieme partie de notre travail a ete consacree a l’exploration des correlats neurophysiologiques de cette atteinte perceptive chez les patients ayant des TCSPi. Cette etude etait basee sur l’analyse d’un potentiel evoque cognitif : la Ncl (negativity associated with closure) decrite comme un marqueur de notre capacite a reconnaitre des objets partiellement occultes ; autrement dit, une composante generee par la mise en jeu des processus intermediaires de traitement de l’information visuelle. L’absence de Ncl observee chez les patients ayant des TCSPi est compatible avec l’hypothese d’un dysfonctionnement des regions du Lateral occipital complex (LOC) situees sur la voie ventrale de traitement de l’information visuelle. [...]

Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for dementia in Parkinson disease (PD) patients. The objectives of our study were to prospectively evaluate the frequency of RBD in a sample of treatment-naive, newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups.Methods: Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center. All patients underwent two overnight polysomnography (PSG) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders, Second Revision criteria. Daytime sleepiness was measured in a multiple sleep latency test (MSLT). Cognition was assessed in a standard neuropsychologic examination.Results: Seventeen PD patients (30%) met the criteria for RBD. The RBD patients and non-RBD patients did not significantly differ in mean age, gender ratio, disease duration, motor symptom subtype and severity, total sleep time, percentage of REM sleep, apnea-hypopnea index, mean oxygen saturation, and importantly cognitive performance. However, non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients (15 vs 18 min, respectively; P = .014).Conclusion: A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients. At this stage in the disease, RBD was not found to be associated with other sleep disorders or cognitive decline. Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD. (C) 2013 Elsevier B. V. All rights reserved.

High-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) has been shown to reduce akinesia in Parkinsons disease (PD). Given that the processing of sensory afferents is deficient in PD and might be involved in akinesia, we sought to determine whether or not the application of very HF rTMS [intermittent theta-burst stimulation (iTBS) protocol] over the M1 affected sensorimotor integration (SMI) and akinesia. The experiments were carried out in: (i) 11 patients taking their usual dopaminergic treatment (on-drug); (ii) eight of the latter patients after withdrawal of dopaminergic treatment (off-drug); and (iii) 10 de novo (drug-naive) patients. Sham stimulation was applied in 11 other patients in the on-drug condition. SMI was investigated by conditioning a supra-threshold transcranial magnetic stimulation pulse in the motor region controlling the abductor pollicis brevis with a nerve shock over the median nerve at time intervals corresponding to short- and long-latency afferent inhibition (SAI and LAI) and afferent-induced facilitation (AIF). Akinesia was assessed with a pointing test. In on-drug, off-drug and de novo patients, akinesia in the contralateral arm was lower after iTBS. Sham stimulation had no effect. In on-drug patients (but not other groups), SMI was also influenced by iTBS, with an increase in AIF. No changes in SAI and LAI were observed. Our data suggest that iTBS might improve both akinesia and sensory processing in patients with PD taking levodopa.