23 research outputs found

    Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness

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    International audienceChronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and a minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals

    Intraoperative electrophysiology during deep brain surgeries in disorders of consciousness

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    International audienceThe efficacy on deep brain stimulation in disorders of consciousness (DC) is inconclusive. We investigated bilateral 30-Hz low-frequency stimulation designed to overdrive neuronal activity by dual pallido-thalamic targeting to promote conscious behavior in five patients. Five adult patients (mean age 38 years old) were included: one unresponsive-wakefulness-syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Pallido-thalamic electrode targeting were performed under sevoflurane general anesthesia with recording of extracellular muti-unit neuronal activity and local field potential (LFP). These data were compared with five GPi DBS implantations (three males) for Parkinson’s disease (n=4) or dystonia (59 years old) and three VIM DBS surgeries (two males) for Parkinson’s disease (n=1) or essential tremor (40 years old).The electrode implantation was realized after electrophysiological mapping using an intraoperative electrophysiological system for functional neurosurgery (MicroGuide Pro, Alpha Omega Eng., Israel). For each brain hemisphere, the mapping was performed using two exploration electrodes (Alpha Omega Eng.) steered by rigid guide tubes: one on the planned track and a second one on the parallel track located posteriorly at 2mm. The characteristics of our electrophysiological approach were as follow: systematic recordings of the spontaneous neuronal activity every 1 mm during 30 seconds along the distal 8.2 mm (min: 5; max: 13 mm) in the pallidum and the thalamus previously labelled and manually outlined on stereotactic MRI.Spikes were encountered for 50 out of 130 recordings in the pallidum (38.46%) and for 43 out of 185 (23.24%) in the thalamus of patients with disorders of consciousness. Concerning motor disease (MD) patients implanted under general anesthesia, spikes were found in 52 out of 150 recordings in the pallidum (34.66%) and for 54 out of 82 (65.85%) in the thalamus. Mean firing rate of neurons in the pallidum was 9.84 +/-8.71 Hz and 11.95 +/-10.31 Hz during surgery for patients with DC and MD respectively. Concerning Thalamus, mean firing rate was 3.78 +/-4.87 Hz versus 2.25 +/-2.15 Hz (DC vs MD).Percentage of raw power spectral density of LFP was similar in GPi for patients with DC and MD. Delta (47.8%), Theta (19.5%) and Alpha (17.0%) bands were preponderant for DC, while Delta (37.2%), Alpha (29.1%) and Beta (17.0%) range were powerful for MD patients.Pallidal neuronal activity is similar for patients under general anesthesia suffering from DC or MD. Differences were encountered for Thalamus: higher 7-30Hz frequency power was encountered for patients with MD and higher low (30Hz) band power was observed for DC. Thalamic neuronal activity differs between MD and DC patients. Few records have been obtained and published for patients with impaired consciousness. These results should be considered with caution given the small number of patients in the study.DBS-Post-coma study group and clinical research protocol are detailed here: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Facn3.648&file=acn3648-sup-0001-Suppinfo.doc

    Conscious Behaviors Following Bilateral Pallido-Thalamic Low Frequency Stimulation in Patients with Continuing Disorders of Consciousness

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    TalkInternational audienceIntroduction: Chronic electric deep brain stimulation (DBS) has been proposed to enable consciousness recovery, targeting mainly the central thalamus. Our aim was to study clinical effects of bilateral pallido-thalamic low frequency stimulation intended to overdrive neuronal activity in continuing disorders of consciousness. Methods: Five patients were included in a prospective, monocentric, 12-month clinical observational study, with blind crossover period (NCT01718249): P1 male, 32 y/o, 12 years after traumatic brain injury (TBI), vegetative status (VS); P2 female, 62 y/o, 14 months after intracerebral hemorrhage (ICH), minimally conscious state (MCS); P3 male, 24 y/o, 3 years after TBI, MCS; P4 female, 22 y/o, 4 years after TBI, MCS; P5 female, 47 y/o, 27 months after ICH, MCS. Four phases were individualized: (1) Baseline, at least 2 months; (2) DBS surgery and titration, 1 month; (3) blind, random, 3-month cross over (CO) period with 1.5month ON (CO-ON) and OFF (CO-OFF) conditions; (4) unblinded, at least 5 months, DBS period (DBS-ON). Electrodes (DBS 3389, Medtronic, USA) were placed within the right and left targets accounting for the lesions of patients. Two neuropacemakers (ACTIVA, Medtronic, USA) were implanted. Primary outcome was the analysis of scores of the Coma Recovery Scale Revised (CRS-R; 0-23): assessments 2 times per week; for the 5 patients, n=419, scores ranging from 1 to 18. Statistical analyses were conducted for a two-sided Type I error of 5% using random-effects models accounting between and within patient variability due to repeated measurements. Results: No mortality related to surgery and DBS. By individual we observed statistically significant improvement of CRS-R during DBS-ON versus baseline (P1, P3) and CO-On versus baseline (P3). For the 5 patients (group analysis) auditory, visual, motor, oromotor-verbal, communication subscores of CRS-R were significantly improved during DBS-ON versus baseline. Cross-over analysis did not show statistically significant improvement of CRS-R and subscores during CO-ON versus CO-OFF, except P2 and P3 motor sub scores. Conclusion: Bilateral low frequency DBS in severe continuing disorders of consciousness improved patients on the short term without irreversible adverse effects. Individual analysis seems preferable facing the complexity of clinical features and pathophysiology. Given the current state of knowledge, expectations of relatives, caregivers and physicians should be weighted

    Neural correlates of rehabilitation program with robot-assisted intensive therapy in one case of Holmes tremor

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    International audienceHolmes tremor (HT) is a rare movement disorder characterized by low-frequency tremor, inferior to 5 Hz, at rest and during postural and intentional conditions (1). It severely alters the functional abilities. The pathophysiology of tremor is unknown. However, dysfunctions of cortico-ponto-cerebello-thalamo-cortical loops were hypothesized by Bucy in 1944 and confirmed since notably in HT (2,3), involving contralateral sensorimotor and prefrontal cortices and the ipsilateral cerebellum. Treatments of HT include levodopa, dopamine agonists, anticholinergics, propranolol, primidone, levetiracetam, more recently botulinum toxin and deep brain stimulation, with variable and unpredictable responses (4). Hence we built a personalized rehabilitation program with intensive robotic rehabilitation, as proposed after stroke (5), associated to classical human-guided rehabilitation, in one case of HT. The lesions were scrutinized using structural magnetic resonance imaging (MRI). Both clinical effects and functional MRI (fMRI) activations were studied before and after rehabilitation, willing to explore underlying neural correlates
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