A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis).

Artificial brain-machine interfaces (BMIs) represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis) and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and three the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1-8 V, 1-10 Hz, 500 ms, biphasic waves), we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being <1 ms and interblock intervals of 1.5-4 s) have been analyzed. We found 150-250 ms delayed cortical responses from fast finger touches, often spread to nearby motor stations. We also evaluated the grid electrical stimulus interference with somatotopic natural tactile sensory processing showing no suppressing interference with sensory stimulus detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses.

A micro-silicon chip for in vivo cerebral imprint in monkey.

Access to cerebral tissue is essential to better understand the molecular mechanisms associated with neurodegenerative diseases. In this study, we present, for the first time, a new tool designed to obtain molecular and cellular cerebral imprints in the striatum of anesthetized monkeys. The imprint is obtained during a spatially controlled interaction of a chemically modified micro-silicon chip with the brain tissue. Scanning electron and immunofluorescence microscopies showed homogeneous capture of cerebral tissue. Nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis of proteins harvested on the chip allowed the identification of 1158 different species of proteins. The gene expression profiles of mRNA extracted from the imprint tool showed great similarity to those obtained via the gold standard approach, which is based on post-mortem sections of the same nucleus. Functional analysis of the harvested molecules confirmed the spatially controlled capture of striatal proteins implicated in dopaminergic regulation. Finally, the behavioral monitoring and histological results establish the safety of obtaining repeated cerebral imprints in striatal regions. These results demonstrate the ability of our imprint tool to explore the molecular content of deep brain regions in vivo. They open the way to the molecular exploration of brain in animal models of neurological diseases and will provide complementary information to current data mainly restricted to post-mortem samples.

Subthalamic neuronal firing in obsessive-compulsive disorder and Parkinson disease.

OBJECTIVE: Although electrophysiologic dysfunction of the subthalamic nucleus is putative, deep brain stimulation of this structure has recently been reported to improve obsessions and compulsions. In Parkinson disease, sensorimotor subthalamic neurons display high-frequency burst firing, which is considered as an electrophysiologic signature of motor loop dysfunction. We addressed whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops involved in patients with obsessive-compulsive disorder. METHODS: We compared the neuronal activity of the subthalamic nucleus recorded in 9 patients with obsessive-compulsive disorder with that of 11 patients with Parkinson disease measured during intraoperative exploration for deep brain stimulation. RESULTS: The mean subthalamic neuron discharge rate was statistically lower in patients with obsessive-compulsive disorder than in patients with Parkinson disease (20.5 ± 11.0 Hz, n = 100 and 30.8 ± 15.6 Hz, n = 93, respectively, p < 0.001). The relative proportion of burst neurons did not differ significantly between the 2 diseases (75% vs 73%). Interestingly, burst neurons were predominantly left-sided in obsessive-compulsive disorder. INTERPRETATION: The recording of burst neurons within the nonmotor subthalamic nucleus in patients with obsessive-compulsive disorder is a novel finding that suggests the existence of deregulation of the nonmotor basal ganglia loop, possibly left-sided. Potentially, burst activity might interfere with normal processes occurring within nonmotor loops.

Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease.

We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group.

Stereoelectroencephalography in the presurgical evaluation of focal epilepsy: a retrospective analysis of 215 procedures.

OBJECTIVE: To report on indications, surgical technique, results, and morbidity of stereoelectroencephalography (SEEG) in the presurgical evaluation of patients with drug-resistant focal epilepsy. METHODS: Two-hundred fifteen stereotactic implantations of multilead intracerebral electrodes were performed in 211 patients (4 patients were explored twice), who showed variable patterns of localizing incoherence among electrical (interictal/ictal scalp electroencephalography), clinical (ictal semeiology), and anatomic (magnetic resonance imaging [MRI]) investigations. MRI scanning showed a lesion in 134 patients (63%; associated with mesial temporal sclerosis in 7) and no lesion in 77 patients (37%; with mesial temporal sclerosis in 14 patients). A total of 2666 electrodes (mean, 12.4 per patient) were implanted (unilaterally in 175 procedures and bilaterally in 40). For electrode targeting, stereotactic stereoscopic cerebral angiograms were used in all patients, coupled with a coregistered three-dimensional MRI scan in 108 patients. RESULTS: One hundred eighty-three patients (87%) were scheduled for resective surgery after SEEG recording, and 174 have undergone surgery thus far. Resections sites were temporal in 47 patients (27%), frontal in 55 patients (31.6%), parietal in 14 patients (8%), occipital in one patient (0.6%), rolandic in one patient (0.6%), and multilobar in 56 patients (32.2%). Outcome on seizures (Engel's classification) in 165 patients with a follow-up period of more than 12 months was: Class I, 56.4%; Class II, 15.1%; Class III, 10.9%; and Class IV, 17.6%. Outcome was significantly associated with the results of MRI scanning (P = 0.0001) and with completeness of lesion removal (P = 0.038). Morbidity related to electrode implantation occurred in 12 procedures (5.6%), with severe permanent deficits from intracerebral hemorrhage in 2 (1%) patients. CONCLUSION: SEEG is a useful and relatively safe tool in the evaluation of surgical candidates when noninvasive investigations fail to localize the epileptogenic zone. SEEG-based resective surgery may provide excellent results in particularly complex drug-resistant epilepsies.

Mechanisms of deep brain stimulation.

The mechanism of action of high frequency deep brain stimulation is still unknown. However, in all circumstances and in all target nuclei so far stimulated, the effects mimic those of lesions previously made during thalamotomies, pallidotomies or even subthalamotomies, suggesting an inhibition of at least the neuronal network containing the target, if not of the target itself. On the contrary, fiber bundles are consistently activated at low or high frequencies. The hypothetical mechanisms envisioned should therefore be compatible and even produce these observed effects, to be acceptable as hypotheses. The mechanism could be either one or a combination of several causes: jamming of a feedback loop, activation of inhibitory structures included in a more complex network, blockade of membrane ion channels, deplorisation blockade, synaptic exhaustion, induction of early genes, changes in local blood flow, neuroplasticity, etc. It is probable that some are more involved in the acute effects and others in the long term changes, close to neuroplasticity. It is clear that the understanding of this strange and powerful phenomenon will profit from both clinical observation and well designed animal experiments.