Evolution of brain gray matter loss in Huntington's disease: a meta-analysis.

International audienceHuntington's disease is characterized by neuronal loss throughout the disease course. Voxel-based morphometry studies have reported reductions in gray matter concentration (GMC) in many brain regions in patients with Huntington. The description of the time course of gray matter loss may help to identify some evolution markers. Here, we conducted a meta-analysis of voxel-based morphometry studies of Huntington's disease to describe the evolution of brain gray matter loss. A systematic search led to the inclusion of 11 articles on Huntington's disease (297 patients and 205 controls). We extracted data from patients with preclinical Huntington, patients with clinical Huntington, and controls. Finally, anatomical likelihood estimation analyses were conducted to identify GMC changes between preclinical patients and controls, between clinical patients and controls, and between preclinical and clinical patients. Preclinical patients exhibited gray matter loss in the left basal ganglia and the prefrontal cortex. Clinical patients had bilateral gray matter loss in the basal ganglia, the prefrontal cortex, and the insula. The left striatum was smaller in clinical patients than in preclinical patients. Neurodegenerative processes associated with Huntington's disease, as assessed by GMC reduction, begin in the left hemisphere and extend to the contralateral hemisphere throughout the inexorable course of the disease. Changes in gray matter, especially the volumetric side ratio of the striatum, could represent a relevant biomarker for characterizing the different progression stages of the disease

Visual Information Routes in the Posterior Dorsal and Ventral Face Network Studied with Intracranial Neurophysiology and White Matter Tract Endpoints

International audienceOccipitotemporal regions within the face network process perceptual and socioemotional information, but the dynamics and information f low between different nodes of this network are still debated. Here, we analyzed intracerebral EEG from 11 epileptic patients viewing a stimulus sequence beginning with a neutral face with direct gaze. The gaze could avert or remain direct, while the emotion changed to fearful or happy. N200 field potential peak latencies indicated that face processing begins in inferior occipital cortex and proceeds anteroventrally to fusiform and inferior temporal cortices, in parallel. The superior temporal sulcus responded preferentially to gaze changes with augmented field potential amplitudes for averted versus direct gaze, and large effect sizes relative to other network regions. An overlap analysis of posterior white matter tractography endpoints (from 1066 healthy brains) relative to active intracerebral electrodes in the 11 patients showed likely involvement of both dorsal and ventral posterior white matter pathways. Overall, our data provide new insight into the timing of face and social cue processing in the occipitotemporal brain and anchor the superior temporal cortex in dynamic gaze processing

Differential role of visuospatial working memory in the propensity toward uncertainty in patients with obsessive-compulsive disorder and in healthy subjects.

International audienceObsessive-compulsive disorder (OCD) is associated with visuospatial working memory deficits. Intolerance of uncertainty is thought to be a core component of OCD symptoms. Recent findings argue for a possible relationship between abilities in visuospatial memory and uncertainty. However, this relationship remains unclear in both OCD patients and healthy subjects. To address this issue, we measured performance in visuospatial working memory and the propensity to express uncertainty during decision making. We assessed their relationship and the temporal direction of this relationship in both OCD patients and healthy subjects. Baseline abilities in visuospatial working memory were measured with the Corsi block-tapping test. A delayed matching-to-sample task was used to identify explicit situations of certainty, uncertainty and ignorance and to assess continuous performance in visuospatial working memory. Behavioural variables were recorded over 360 consecutive trials in both groups. Baseline scores of visuospatial working memory did not predict the number of uncertain situations in OCD patients whereas they did in healthy subjects. Uncertain trials led to reduced abilities in visuospatial working memory to 65% of usual performance in OCD patients whereas they remained stable in healthy subjects. The present findings show an opposite temporal direction in the relationship between abilities in working memory and uncertainty in OCD patients and healthy subjects. Poor working memory performance contributes to the propensity to feel uncertainty in healthy subjects whereas uncertainty contributes to decreased continuous performance in working memory in OCD patients

Lesions in the associative striatum improve obsessive-compulsive disorder.

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The associative and limbic thalamus in the pathophysiology of obsessive-compulsive disorder: an experimental study in the monkey.

International audienceObsessive-compulsive disorder (OCD) is a frequent psychiatric disorder characterized by repetitive intrusive thoughts and severe anxiety, leading to compulsive behaviors. Although medical treatment is effective in most cases, resistance is observed in about 30% of patients. In this context, deep brain stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed with encouraging results. However, some patients were unimproved or exhibited awkward side effects. Therefore, exploration of new targets for DBS remains critical in OCD. In the latter, functional imaging studies revealed overactivity in the limbic and associative cortico-subcortical loops encompassing the thalamus. However, the role of the thalamus in the genesis of repetitive behaviors and related anxiety is unknown. Here, we tested the hypothesis that pharmacological-induced overactivity of the medial thalamus could give rise to abnormal behaviors close to that observed in OCD. We modulated the ventral anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline (GABA(A) antagonist) microinjections in subhuman primates and assessed their pharmacological-induced behavior. Bicuculline injections within the VA caused significant repetitive and time-consuming motor acts whereas those performed within the MD induced symptoms of dysautonomic dysregulation along with abnormal vocalizations and marked motor hypoactivity. These findings suggest that overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like behaviors and neurovegetative manifestations usually associated with the feeling of anxiety in OCD patients. In further research, this translational approach should allow us to test the effectiveness and side effects of these thalamic nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this technique to severely disabled OCD patients

Multiple system atrophy: current and future approaches to management

Multiple system atrophy (MSA) is a rare neurodegenerative disorder without any effective treatment in slowing or stopping disease progression. It is characterized by poor levodopa responsive Parkinsonism, cerebellar ataxia, pyramidal signs and autonomic failure in any combination. Current therapeutic strategies are primarily based on dopamine replacement and improvement of autonomic failure. However, symptomatic management remains disappointing and no curative treatment is yet available. Recent experimental evidence has confirmed the key role of alpha-synuclein aggregation in the pathogenesis of MSA. Referring to this hypothesis, transgenic and toxic animal models have been developed to assess candidate drugs for MSA. The standardization of diagnosis criteria and assessment procedures will allow large multicentre clinical trials to be conducted. In this article we review the available symptomatic treatment, recent results of studies investigating potential neuroprotective drugs, and future approaches for the management in MSA

Epilepsie liée à une lipofuscinose neuronale focale : localisation extra-frontale, signatures EEG et implication du GABA

International audienceFocal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue