Neuromodulation of Cerebellar Circuitry

Although diseases of the cerebellum can compromise quality of life, their treatment has received less research and clinical attention than diseases of other parts of the nervous system, such as the cerebral cortex and the spinal cord. The vision is a cerebellar prosthesis: a surgically implanted closed-loop neuromodulation system that can alleviate the symptoms of cerebellar dysfunction. Cerebellar disorders are varied, as are the opportunities for treatment. This study focuses on cerebellar disorders that impair arm and hand function as an entry point to study mechanisms of disability and treatment modalities. This first begins with exploring neuromodulation in the form of noninvasive transcranial stimulation.

Aim 1: Use noninvasive neuromodulation to improve upper-limb dysfunction associated with cerebellar disorders.

Deficits associated with cerebellar disorders can be subtle, yet persistent and frustrating for those who experience them. Motor adaptation is a well-established cerebellum-dependent process and remains an important entry point for broader effort to understand cerebellar dysfunction and develop treatment strategies. Upper-limb dysfunction in cerebellar disorders may also reflect impairments in sensory processing, motor control, and motor learning, as well as disruption of broader cerebello-cerebral networks, including posterior parietal cortical (PPC) regions involved in sensorimotor integration and movement updating. Working hypotheses: 1. Impaired sensorimotor performance, including deficits in motor learning during a fine-grained reaching task, will be observed in individuals with cerebellar disorders, 2. These impairments will be associated with damage to sensorimotor regions of the cerebellum that will serve as future targets for an NHP stroke model, and with disruption to a functionally connected network of cerebral sensorimotor regions including PPC, 3. Intermittent theta burst stimulation (iTBS) can modulate cerebro-cerebellar circuit-level function to healthier states, improving motor control and implicit adaptation during reaching tasks.

Aim 1 will (i) characterize impaired reaching in individuals with cerebellar disorders, (ii) identify neuroanatomical correlates of impaired reaching, and (iii) test whether iTBS can improve reaching abilities after cerebellar dysfunction. A rigorous behavioral battery of assessments are designed to assess sensory function, motor control, and motor learning during reaching-related tasks.