The Motor Network in Essential Tremor: Mechanisms of Therapy
| Status: | Recruiting |
|---|---|
| Conditions: | Parkinsons Disease |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 21 - Any |
| Updated: | 2/3/2019 |
| Start Date: | March 2016 |
| End Date: | March 2021 |
| Contact: | Aysegul Gunduz, PhD |
| Email: | agunduz@ufl.edu |
| Phone: | 3522736877 |
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.
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.
The research study goal is to advance the understanding of the mechanisms for essential
tremor through brain recordings. The investigators will collect brain signals in persons with
essential tremor undergoing neurosurgical treatment (deep brain stimulation implantation). By
recording from the implanted electrodes for deep brain stimulation along with two other
non-invasive intraoperative monitoring electrodes, the origins of tremor will be studied in
the human motor network. Moreover, by performing recordings during deep brain stimulation
delivery, the mechanisms in which deep brain stimulation modulates this network to suppress
tremor will be investigated.
During the standard of care DBS procedure neural recordings are performed as the participant
is in a reclined position on the operating table. In addition to neural recordings it is
standard to ask the patient to move their arms and legs during the procedure. An additional
intraoperative monitoring subdural electrode strip, used in epilepsy and tumor surgeries to
perform functional mapping, will be placed by the neurosurgeon after the DBS electrode is
placed per the clinical need of the patient. 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, which is capable of recording during stimulation. This additional
testing will add approximately 30-45 minutes to the surgical time.
tremor through brain recordings. The investigators will collect brain signals in persons with
essential tremor undergoing neurosurgical treatment (deep brain stimulation implantation). By
recording from the implanted electrodes for deep brain stimulation along with two other
non-invasive intraoperative monitoring electrodes, the origins of tremor will be studied in
the human motor network. Moreover, by performing recordings during deep brain stimulation
delivery, the mechanisms in which deep brain stimulation modulates this network to suppress
tremor will be investigated.
During the standard of care DBS procedure neural recordings are performed as the participant
is in a reclined position on the operating table. In addition to neural recordings it is
standard to ask the patient to move their arms and legs during the procedure. An additional
intraoperative monitoring subdural electrode strip, used in epilepsy and tumor surgeries to
perform functional mapping, will be placed by the neurosurgeon after the DBS electrode is
placed per the clinical need of the patient. 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, which is capable of recording during stimulation. This additional
testing will add approximately 30-45 minutes to the surgical time.
Inclusion Criteria:
- Neurosurgical patient populations with essential tremor (main cohort) and Parkinson's
disease (control cohort)
Exclusion Criteria:
- Non surgical candidates
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