Alim-Louis Benabid

Monophasic but not biphasic pulses induce brain tissue damage during monopolar high-frequency deep brain stimulation.

OBJECTIVEElectrical high-frequency stimulation (HFS) of deep brain structures has been successfully used as a treatment for patients with movement disorders. The mechanisms of HFS allowing therapeutic clinical effects remain unclear, which justifies experimental studies to address these questions. These experiments require an external stimulator, which may offer the possibility to deliver a current with monophasic or biphasic pulses. The aim of the present study was to quantify the evolution of a potentially deleterious effect of HFS according to the duration and/or intensity in monophasic and biphasic conditions. METHODSIn all rats, HFS was performed with monophasic pulses in deep brain structures of 1 hemisphere and with biphasic pulses symmetrically in the other hemisphere. The effect of HFS was tested, first for various durations of HFS at a constant intensity (100 μA) and, second, for measuring the effect of various current intensities of HFS at constant duration (10 minutes). At the end of each stimulation test, the volume of lesion was determined and analyzed. RESULTSIn all hemispheres in which stimulation using biphasic pulses was delivered, we never found any relevant lesions. Conversely, monophasic electrical stimulation always created a lesion: at 100μA, a minimal duration of HFS of 5 minutes induced a tissue damage volume of 0.0055 ± 0.0015 mm3. For 10 minutes of HFS, a minimal intensity of 100 μA induced a tissue damage volume of 0.0062 ± 0.0017 mm3. Regression analysis showed that the extent of lesion increased linearly with the intensity and duration. CONCLUSIONIn conclusion, this study proved that HFS using monophasic pulses systematically created tissue damage after 5 minutes of stimulation at 100 μA. HFS is safe when biphasic pulses are used for intensities as high as 2 mA and durations as long as 120 minutes. Monophasic pulses can be safely used only during short stimulation and at low intensities.

Deep brain stimulation: BCI at large, where are we going to?

UNLABELLEDnBrain-computer interfaces (BCIs) include stimulators, infusion devices, and neuroprostheses. They all belong to functional neurosurgery. Deep brain stimulators (DBS) are widely used for therapy and are in need of innovative evolutions. Robotized exoskeletons require BCIs able to drive up to 26 degrees of freedom (DoF). We report the nanomicrotechnology development of prototypes for new 3D DBS and for motor neuroprostheses. For this complex project, all compounds have been designed and are being tested. Experiments were performed in rats and primates for proof of concepts and development of the electroencephalogram (EEG) recognition algorithm.nnnMETHODSnVarious devices have been designed. (A) In human, a programmable multiplexer connecting five tetrapolar (20 contacts) electrodes to one DBS channel has been designed and implanted bilaterally into STN in two Parkinsonian patients. (B) A 50-mm diameter titanium implant, telepowered, including a radioset, emitting ECoG data recorded by a 64-electrode array using an application-specific integrated circuit, is being designed to be implanted in a 50-mm trephine opening. Data received by the radioreceiver are processed through an original wavelet-based Iterative N-way Partial Least Square algorithm (INPLS, CEA patent). Animals, implanted with ECoG recording electrodes, had to press a lever to obtain a reward. The brain signature associated to the lever press (LP) was detected online by ECoG processing using INPLS. This detection allowed triggering the food dispenser.nnnRESULTSn(A) The 3D multiplexer allowed tailoring the electrical field to the STN. The multiplication of the contacts affected the battery life and suggested different implantation schemes. (B) The components of the human implantable cortical BCI are being tested for reliability and toxicology to meet criteria for chronicle implantation in 2012

Control of neuronal network organization by chemical surface functionalization of multi-walled carbon nanotube arrays

Carbon nanotube substrates are promising candidates for biological applications and devices. Interfacing of these carbon nanotubes with neurons can be controlled by chemical modifications. In this study, we investigated how chemical surface functionalization of multi-walled carbon nanotube arrays (MWNT-A) influences neuronal adhesion and network organization. Functionalization of MWNT-A dramatically modifies the length of neurite fascicles, cluster inter-connection success rate, and the percentage of neurites that escape from the clusters. We propose that chemical functionalization represents a method of choice for developing applications in which neuronal patterning on MWNT-A substrates is required.