Brief Communication External globus pallidus stimulation modulates brain connectivity in Huntington's disease

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington's disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.

International audienceIn humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry

Deep brain stimulation of the subthalamic nucleus in obsessive–compulsives disorders: long-term follow-up of an open, prospective, observational cohort

International audienceBackground: Obsessive-compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD.Method: We analysed, in a prospective, observational, monocentric, open label cohort, the effect of chronic non-motor STN-DBS in 19 patients with treatment-resistant OCD consecutively operated in a single centre. Severity of OCD was evaluated using the Yale and Brown Obsessive-Compulsive Scale (YBOCS). YBOCS scores at 6, 12 and 24 months postoperatively were compared with baseline. Responders were defined by >35% improvement of YBOCS scores. Global Assessment Functioning (GAF) scale was used to evaluate the impact of improvement.Results: At a 24-month follow-up, the mean YBOCS score improved by 53.4% from 33.3±3.5 to 15.8±9.1 (95% CI 11.2-20.4; p<0.0001). Fourteen out of 19 patients were considered as responders, 5 out of 19 being improved over 75% and 10 out of 19 over 50%. GAF scale improved by 92% from 34.1±3.9 to 66.4±18.8 (95% CI 56.7-76.1; p=0.0003). The most frequent adverse events consisted of transient DBS-induced hypomania and anxiety.Conclusion: Chronic DBS of the non-motor STN is an effective and relatively safe procedure to treat severe OCD resistant to conventional management

Distinct striatal targets in treating obsessive-compulsive disorder and major depression.

International audienceThe ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). However, the respective roles of these structures in the pathophysiology of OCD and MD remain to be clarified. To address this issue, DBS of the ventral striatum was tested in 2 patients with severely distressing and intractable forms of OCD and MD. Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. These findings suggest that the caudate nucleus and nucleus accumbens participate differently in the pathogenesis of both of these psychiatric conditions

Electromagnetic articulography assessment of tongue function in non-dysarthric speakers with Parkinson’s disease

Objective: To compare the levels of lipid peroxidation products between Parkinson’s disease (PD) and study controls, and the relationship of these products in relation to clinical progression in PD. Background: Oxidative stress may be important in the pathogenesis of Parkinson’s disease (PD). The extent of oxidative stress damage was assessed using markers of lipid peroxidation in a cohort of PD patients and study controls. Methods: A total of 62 PD patients and 86 age-gender matched study controls (25 ischemic stroke and 61 community-based healthy controls) participated in this study. Their demographic and clinical characteristics were obtained using a standardized questionnaire. In PD patients, the clinical severity of their disease was assessed using the Hoehn-Yahr scale and the Unified Parkinson’s Disease Rating scales (UPDRS), and their cumulative exposure to levodopa calculated. Markers of lipid peroxidation (F2-isoprostanes, F2-IsoPs; hydroxyeicosatetraenoic acid, HETEs; and cholesterol oxidation products, COPs), were assessed in the plasma and urine samples using the gas chromatography-mass spectrometry method. Results: The mean (standard deviation) age was 64 (8) years and there were no differences in the gender, ethnicity and medical history in the PD and study control groups (p>0.05). Higher levels of plasma esterified F2-IsoPs, plasma free HETEs and COPs were observed in PD patients as compared to stroke and healthy controls (p<0.05, t-test). No significant correlation was observed between F2- IsoPs, HETEs and COPs in relation to the cumulative dosage of levodopa (r5 -0.15 to 0.21). A significant decrease in plasma free F2-IsoPs was observed with clinical progression of PD, according to the Hoehn-Yahr (p-trend<0.05) and UPDRS severity scales (r5 -0.372, p50.004). After adjusting for age, gender and cumulative levodopa dosage, lower plasma levels of free F2-IsoPs independently predicted UPDRS scores (OR -292, 95% CI -527 to -56). Conclusions: We identified certain markers of lipid peroxidation and COPs to be elevated in PD and suggested the use of plasma free F2-IsoPs as a potential marker of clinical progression

Decreased neuronal activity in the sensori-motor network induced by bilateral GPe stimulation in Huntington Disease

info:eu-repo/semantics/nonPublishe

External globus pallidus stimulation modulates brain connectivity in Huntington's disease.

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington's disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dysfunction of Basal Ganglia Circuitry in Patients with Obsessive-Compulsive Disorders: Subthalamic Neuronal Activity Correlates with Symptom Severity

International audienceObjective: to characterize subthalamic neuronal activity in obsessive compulsive disorder (OCD) patients, in comparison to patients with Parkinson's disease (PD), and its relationship to the severity of obsessions and compulsions.Background: modifications in the function and connectivity of the brain's corticostriatal systems have been reported in patients with OCD. However changes in the basal ganglia neuronal activity in the relation of severity of OCD have never been adequately elucidated.Design/Methods: twelve patients with OCD and 12 patients with PD operated for subthalamic stimulation were included. Resting-state subthalamic single unit neuronal activity was recorded during surgery. Recorded neurons were located with precision and mapped according to the motor, associative and limbic subdivisions of the subthalamic nucleus. Discharge frequency, pattern, bursting and oscillatory activities were characterized for each recorded neuron and compared between OCD and PD patients. Correlations with the severity of symptoms in OCD patients were explored.Results: one hundred and thirty-seven subthalamic neurons were isolated and recorded in OCD patients and 173 subthalamic neurons in PD patients. Between groups, OCD patients had lower STN neuronal discharge frequency, with a similar fraction of subthalamic neurons exhibiting burst-type activity. Significant oscillatory activity was present in 46% and 68% of neurons in OCD and PD patients, respectively; predominantly in the low frequency band (1-8 Hz). In the OCD patients, abnormal neuronal activity was mainly observed in the associative-limbic part of the subthalamic nucleus. Additionally, OCD patients with more severe symptoms exhibited oscillatory activity. Conclusions: heightened burst and low frequency oscillatory activities in the associative limbic subthalamic subdivision demonstrate its involvement in the pathophysiology of OCD

Optimal target localization for subthalamic stimulation in patients with Parkinson disease

To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD). Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts. Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms. In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location