Functional Brain Network Changes in Patients Undergoing Deep Brain Stimulation for Essential Tremor
- Conditions
- Essential Tremor
- Interventions
- Registration Number
- NCT06293638
- Lead Sponsor
- The Cleveland Clinic
- Brief Summary
The purpose of this study is to collect electrophysiological data related to functional brain network changes in patients undergoing deep brain stimulation for the treatment of essential tremor. Participants will either 1) have electroencephalography (EEG) scalp electrodes placed, or 2) remain seated with their head inside of a magnetoencephalography (MEG) recording system, as resting-state and task-related data are acquired. Spontaneous electrophysiological activity will be recorded in both the eyes open and eyes closed conditions with the participant seated comfortably. These recordings will be repeated in the DBS OFF and DBS ON states, with the ON state involving specific settings identified as optimal, sub-optimal, or ineffective at achieving tremor control. They will also be repeated following the optional administration non-DBS tremor mitigation techniques, which may include one or more of the following: 1) cooling the limb, 2) oral administration of alprazolam, 3) oral consumption of ethanol (alcohol), or 4) peripheral nerve stimulation.
- Detailed Description
Electrophysiological data from participants will be collected during electroencephalography (EEG) or magnetoencephalography (MEG) procedures. The EEG or MEG experiments will also include recordings from the DBS system that may be synchronized to externally recorded signals (e.g., MEG, EEG, EMG, accelerometry) via gentle tap-induced motion artifacts, and/or by applying a small, barely perceptible electrical current at the skin over the DBS system with use of a transcutaneous electrical nerve stimulation (TENS) unit.
It is hypothesized that the chronic, electrical stimulation of the target region has both local and circuit-wide effects, the net effect of which is to disrupt the pathophysiological neural activity present across both cortical and subcortical brain regions that and thought to underlie disease manifestation (i.e., tremor). By systemically characterizing the pathways involved in propagating tremor-related activity as well as mediating treatment-related benefits, the investigators hope to identify potential new therapeutic targets or treatment paradigms to further optimize tremor control in this population.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 55
- Between 30 and 80 years of age;
- Ability to provide informed consent;
- Clinical diagnosis of ET by a movement disorders neurologist with a disease duration of at least 3 years and being treated with a DBS; OR
- Clinical diagnosis of ET by a movement disorders neurologist with a disease duration of at least 3 years and not being treated with a DBS; OR
- No known neurological disease or disorder.
- The individual has a condition that, in the opinion of the investigator, would significantly increase the risk for interference with study compliance, safety, or outcome;
- Presence of active psychiatric symptoms meeting Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) criteria for Axis-I disorder on formal psychiatric evaluation other than depression or anxiety;
- History of cognitive impairment meeting Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) criteria for dementia on formal neuropsychological evaluation, as documented in chart;
- Lack of English-language fluency which would interfere with the ability to understand the study consenting process and potential study risks;
- Hearing or visual impairment precluding testing;
- Motor impairment impacting test responses (i.e., orthopedic injury or disease);
- Anyone currently taking medications with Antabuse-like effects (e.g. Flagyl, Bactrim, Tindamax) will be excluded from any alcohol administration.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Essential Tremor with DBS Alcohol 1. 30-80 years of age 2. Diagnosis of ET 3. Previously implanted with a DBS system for disease management per standard of care Essential Tremor with DBS Alprazolam 1. 30-80 years of age 2. Diagnosis of ET 3. Previously implanted with a DBS system for disease management per standard of care Essential Tremor with DBS Cold Therapy 1. 30-80 years of age 2. Diagnosis of ET 3. Previously implanted with a DBS system for disease management per standard of care Essential Tremor with DBS Peripheral Nerve Stimulation 1. 30-80 years of age 2. Diagnosis of ET 3. Previously implanted with a DBS system for disease management per standard of care Essential Tremor without DBS Alcohol 1. 30-80 years of age 2. Diagnosis of ET 3. Has not been previously implanted with a DBS system for disease management per standard of care No Known Neurological Disease or Disorder Peripheral Nerve Stimulation 1. 30-80 years of age 2. No known neurological disease or disorder Essential Tremor without DBS Alprazolam 1. 30-80 years of age 2. Diagnosis of ET 3. Has not been previously implanted with a DBS system for disease management per standard of care Essential Tremor without DBS Cold Therapy 1. 30-80 years of age 2. Diagnosis of ET 3. Has not been previously implanted with a DBS system for disease management per standard of care Essential Tremor without DBS Peripheral Nerve Stimulation 1. 30-80 years of age 2. Diagnosis of ET 3. Has not been previously implanted with a DBS system for disease management per standard of care No Known Neurological Disease or Disorder Alcohol 1. 30-80 years of age 2. No known neurological disease or disorder No Known Neurological Disease or Disorder Alprazolam 1. 30-80 years of age 2. No known neurological disease or disorder No Known Neurological Disease or Disorder Cold Therapy 1. 30-80 years of age 2. No known neurological disease or disorder
- Primary Outcome Measures
Name Time Method CTCM Coherence up to 8 hours in-lab during experiment Coherence, a unitless measure of correlation between signals, calculated across the cerebellothalmocorticomuscular (CTCM) circuit, will be computed from neurophysiological recordings including electroencephalography (EEG), electromyography (EMG), magnetoencephalography (MEG), and/or local field potential (LFP), using data collected at rest, during tremor-eliciting tasks, with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol).
Power of oscillatory activity across the CTCM network in response to tremor interventions up to 8 hours in-lab during experiment Power of tremor-related oscillatory activity, in the form of mean power in the 4-12Hz frequency band with units in mV\^2, will be computed from neurophysiological recordings including electroencephalography (EEG), electromyography (EMG), magnetoencephalography (MEG), and/or local field potential (LFP), using data collected at rest, during tremor-eliciting tasks, with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol).
- Secondary Outcome Measures
Name Time Method Essential tremor severity: Limb acceleration up to 8 hours in-lab during experiment Accelerometers placed on the limb will measure tremor energy in the 4-12Hz band, in units of mG\^2/Hz. Data is collected at rest, during tremor-eliciting tasks, with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol).
Essential tremor severity: Tremor Research Group Essential Tremor Rating Scale (TETRAS) up to 8 hours in-lab during experiment Numerical clinical tremor assessment scale correlated with severity of tremor. Data is collected with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol). Items are scored 0-4 with "0" being normal and "4" being severely abnormal.
Essential tremor severity: Grip force up to 8 hours in-lab during experiment A hand-held force sensor will measure grip force (Newtons). Data is collected at rest, during tremor-eliciting tasks, with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol).
Trial Locations
- Locations (1)
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States