The Motor Network in Essential Tremor: Mechanisms of Therapy

Summary

Essential tremor (ET) is among the most common movement disorders, and is the most prevalent tremor disorder. It is a progressive, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US (2.2% of the population) and estimates from population studies worldwide range from 0.4% to 6.3%. ET is directly linked to progressive functional impairment, social embarrassment, and even depression. Intention (kinetic) tremor of the arms occurs in approximately half of ET patients, and is typically a slow tremor (\~5-10Hz) that occurs at the end of a purposeful movement, and is insidiously progressive over many years. Based on direct and indirect neurophysiological studies, it has been suggested that a pathological synchronous oscillation in a neuronal network involving the ventral intermediate nucleus (Vim) of the thalamus, the premotor (PM), primary motor (M1) cortices, and the cerebellum, may result in the production of ET. In spite of the numerous therapeutic modalities available, 65% of those suffering from upper limb tremor report serious difficulties during their daily lives. Deep brain stimulation (DBS) has emerged as an effective treatment option for those suffering from medically refractory ET. The accepted target for ET DBS therapy is the Vim thalamus. Vim projects to PM, M1, and supplementary motor areas (SMA) and receives afferents from the ipsilateral cerebellum. Moreover, electrophysiological recordings from Vim during stereotactic surgery have identified "tremor cells" that synchronously discharge with oscillatory muscle activity during tremor. Clinical and computational findings indicate that DBS suppresses tremor by masking these "burst driver" inputs to the thalamus. The overall goal is to investigate the neural signatures of tremor generation in the thalamocortical network by recording data during DBS implantation surgery. Investigators will record data from the macroelectrode implanted in the Vim for DBS therapy, and through an additional 6-contact subdural cortical strip that will be placed on the hand motor cortical area temporarily through the same burr hole opened for the implantation of the DBS electrode.

Conditions

• Essential Tremor
• Parkinson's Disease

Interventions

PROCEDURE

Deep brain stimulation implantation surgery

Deep brain stimulation is a neuromodulatory therapy in which electrodes are implanted in deep brain structures. Electrical pulses are delivered through these electrodes to suppress pathological activity that are causing the symptoms of essential tremor or Parkinson's disease.

DEVICE

Ad-Tech Medical Instrumentation Corp. electrodes/subdural strips

Ad-Tech Medical Instrumentation Corp. electrodes are intraoperative monitoring subdural strips will be placed on the surface of the cortex (non-penetrating).

DEVICE

FHC Guideline 4000+ system and/or Medtronic RC+S

Brain signals will be recorded using the clinical Participants in this group with Parkinson's disease will be undergoing deep brain stimulation implantation surgery as part of the standard of care. In addition, the Ad-Tech Medical Instrumentation Corp. device will be used to test responses with wireless sensors placed on the participant's arms, which can record EMG activity. Brain signals will be recorded using the clinical FHC Guideline 4000+ system and/or Medtronic RC+S devices, which are capable of recording during stimulation.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• Medtronic

  collaborator INDUSTRY

• University of Florida

  lead OTHER

Principal Investigators

• Aysegul Gunduz, PhD · University of Florida

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-03-15

Primary Completion

2025-10-13

Completion

2025-10-13

Countries

• United States

Study Locations