CE19 - Technologies pour la santé

Electro-molecular signature of the subthalamic nucleus-related functional territories for an accurate electrode implantation and directional stimulation – CuSTIMprint

Submission summary

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has now become a mainstay of functional neurosurgery in Parkinson’s disease (PD). The interest of its indication in obsessive-compulsive disorders (OCD) is currently assessed in several clinical trials since some groups have demonstrated spectacular cognitive improvements in OCD-related patients. This possibility to modulate both motor and cognitive symptoms through STN stimulation probably results from the functional heterogeneity of this nucleus.

Therefore, due to its boundaries with other nuclei and the existence, within the STN, of both motor and cognitive portions, the STN can be considered as complex nucleus to target. Although pre-operative imaging and per-operative electrophysiology enable distinction of STN from other nuclei, these approaches have revealed several limits and the delineation of this nucleus is still sometime difficult and more again, within the STN, the segregation of cognitive and motor parts. According to the motor (in PD) or cognitive (in OCD) feature of the disease, efficiency of neurostimulation is strongly related to the appropriate location of the electrode into the STN. And, an inaccurate electrode implantation may induce several motor, cognitive or neuropsychological side effects.

The emergence of directional stimulation through the development of new electrode system confirms a clinically-expressed medical need for more focused stimulation, which would enable to regulate, on demand, the motor and/or cognitive part of the behavior. Further processing of ‘motor’ information seems to involve the dorso-lateral part of the basal ganglia (BG). Reciprocally the cognitive modalities of behavior would instead involve the ventro-medial part of the BG. But today confirmative and complementary works are mandatory to finely distinguish the STN from others surrounding brain regions and the different parts of STN.

In this goal, the brain tissue imprints (BTIs) seems to be a promising concept. Recently, we have demonstrated for the first time that STN-related BTIs may be safely collected during DBS surgery in PD and OCD patients, opening the way to in vivo and per-operative molecular exploration of this nucleus in different diseases. In parallel, we have validated an innovative medical device allowing spatial tissue imprint of brain regions on mesoporous silicon surface and compatible with extensive molecular investigation of the so called samples.

The present proposal aims to identify molecular patterns specifically correlated to the STN and its functional subdivisions. In a non human primate model, BTIs will be performed in the different parts of the STN and analyzed by MALDI Imaging looking for associated molecular patterns. Then, stimulation/recording electrodes will be implanted at the same location. In healthy and then rendered parkinsonian animals, we will study BG's electrophysiology in order to identify electrical signatures of the STN subdivision, and will assess the potential benefit of a custom-oriented DBS on the improvement of motor and cognitive skills. For the first time, we propose to correlate molecular and electrophysiological data obtained in the explored brain regions.

Altogether, those data will pave the way to a clinical use of BTIs during DBS. Thanks to a peroperative molecular analysis, this approach could help in the delineation of the STN and its subdivisions for an accurate electrode implantation and a focused stimulation, thus responding to the clinical need.

Project coordination

Ali Bouamrani (Medimprint / Recherche et developpement)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

MEDIMPRINT Medimprint / Recherche et developpement
GIN Brigitte Piallat

Help of the ANR 482,492 euros
Beginning and duration of the scientific project: - 36 Months

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