Development of a peripheral neuroprosthesis to elicit fine hand movements in primates

Neurological disorders such as spinal cord lesion and stroke disturb sensorimotor pathways and result in severe motor deficits that can dreadfully impact the quality of life of affected individuals. Strategies aiming at restoring hand function after upper-limb paralysis have relied on functional electrical stimulation (FES) of the remnant muscles but have shown limited functional benefits. Other electrical stimulation approaches have employed peripheral nerve electrodes to engage multiple distal muscles from a single proximal location on the nerve. Interestingly, intrafascicular interfaces penetrating the nerve have shown impressive capabilities for the restoration of specific somatosensory percepts in humans following limb amputation. In this thesis, I developed a peripheral neuroprosthesis based on intrafascicular implants for the restoration of fine hand movements in the pre-clinical primate model. The first part of this work focuses on building an adaptable technological platform for the design of arm and hand sensorimotor tasks in monkeys. I demonstrated the significance of our platform for fundamental and translational studies by studying a rich collection of physiological signals during unconstrained reaching and grasping tasks. In the second part of this work, I mobilized this experimental framework for the functional evaluation of intrafascicular stimulation paradigms in monkeys. More specifically, I used complementary neuroanatomical and computational analyses to tailor an intrafascicular interface to the arm motor nerves of monkeys. I then demonstrated that intrafascicular stimulation promotes selective hand muscle activation, evokes a large diversity of functional hand movements, and generates sustained and controllable levels of force. Finally, I coupled intrafascicular stimulation to motor cortical signals to enable a temporarily paralyzed monkey to perform a functional grasping task. The last part of this thesis is dedicated to a pilot study investigating the use of low-dimensional cortical dynamics for the direct control of a neuroprosthetic device. It provides exploratory routes for the design of an adaptive brain-control paradigm to drive peripheral implants using robust, voluntary commands. This thesis brings evidence of the high selectivity and functionality of intraneural implants for motor applications and demonstrates their potential for eliciting precise hand movements. These findings open promising perspectives for the development of peripheral intraneural neuroprosthetic systems to restore functional and dexterous hand control after paralysis.