Objective: To study the dynamics of corticospinal development​

What are​

• The molecular scenarios?​
• The links between molecular defects, corticospinal development, and motor dysfunction?​

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How: Translational approach in patients and mouse models to study​

• The genome-wide genetics and epigenetics in our cohort​
• The molecular roles of CMM genes in the corticospinal tract (in vitro/in vivo)​
• The consequence of the defect on motor function (mice/patients)​

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Expected results​

• Identify new genetic and epigenetic causes of CMM​
• Understand the molecular mechanism of corticospinal tract defects​
• Modifications of cognitive processes associated with motor control​

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Objective: Ultrasonic neuromodulation​

To investigate the ultrasonic neuromodulation parameters of TUS on the neuronal responses (activation inhibition)​.

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Combination of ultrasound imaging and neuromodulation​

Combine single unit recordings with FUSi and TUS to better understand the role of each parameter of ultrasonic neuromodulation.​

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Combination of ultrasound and pharmacological neuromodulation ​

Combine BBB opening and GABA systemic injections in awake animals to evoke transient deficits and/or attenuate neuromelanin-linked Parkinson’s disease pathology​.

Improve targeting techniques using ultrasounds and innovative MRI sequences in patients.​

Objective: What is the role of the cerebello-striato-cortical interactions?​

• In reward-based motor learning (short-time scale)?​
• In the recall of motor programs (across sessions time scale)?​‍

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Methods​

• In patients with ADCY5 mutations: Striatal dysfunction​
• In patients with PRRT2 and SGCE mutations: Cerebellar dysfunction​
• In healthy volunteers: Neuromodulation (TMS) of the cerebellum​
• + In animal model of dystonia:  Mice with ADCY5/SGCE mutation​

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Expected results​

• Cerebello-striatal loops play a role in immediate reward-based motor learning​
• Striato-cerebellar loops play a role in recall of motor programs ​

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