Sensory-specific Peripheral Stimulation for Tremor Management

Sensory-specific Peripheral Stimulation for Tremor Management

The purpose of this study is to understand the neurophysiological mechanisms of peripheral electrical stimulation (PES) in modulating supraspinal tremorogenic input to motoneurons. For this purpose, the investigators will use transcutaneous PES, high-density electromyography (HD-EMG), transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and neuromusculoskeletal modelling. This study will be carried out in both healthy participants and patients with essential tremor (ET) and Parkinson's disease (PD).

In Experiment A, the investigators will recruit healthy participants without motor disorders and medications influencing brain function (n = 25). The investigators will characterize inhibition of wrist flexors/wrist extensors and first dorsal interossei (FDI) and abductor pollicis brevis (APB) muscles with PES, and also use TMS to stimulate the corresponding areas in the brain and see if the movement can be reduced through PES. HD-EMG will be used to collect data and identify associated motor unit spike trains. Motor-evoked potentials (MEPs) will be recorded with EMG when TMS is targeted to the primary motor cortex. Resting state functional magnetic imaging resonance (rs-fMRI) and high-angular resolution diffusion imaging (HARDI) tractography of the brain will be recorded.

In Experiment B, the investigators will recruit patients with essential tremor (ET) and/or Parkinson's disease (PD) (n = 25 for each pathology). The investigators will repeat the same characterization of inhibition of wrist flexors/wrist extensors and PDI/APB with PES and also use TMS to stimulate corresponding areas in the brain. Additionally, the investigators will test PES conditions as a tremor reduction strategy at the wrist level. The investigators will also test PES conditions at the elbow and shoulder joints as a tremor reduction strategy. Finally, the investigators will observe and characterize the long-term effects (lasting 24h, 48h, and 7 days post stimulation) of PES via coherence between HD-EMG and EEG at the tremor frequency.

Inclusion Criteria for Healthy Participants:

• Age from 18 to 80 years
• No history of a brain and/or skull lesion
• Normal hearing and (corrected) vision
• Able to understand and give informed consent
• No neurological disorders, no tremor
• Absence of pathology that could cause abnormal movements of extremities (e.g., epilepsy, stroke, marked arthritis)
• Able to understand and speak English

Inclusion Criteria for Patients:

• Age from 18 to 80 years
• No prior history of skull lesions or craniotomy
• Normal hearing and (corrected) vision
• Able to understand and give informed consent
• Diagnosis of ET (Tremor Research investigation Group criteria) or diagnosis of PD (UK PD Society Brain bank diagnostic criteria) by a physician
• Tremor in at least an upper limb with pure flexion-extension wrist tremor with posture (ET) and rest (PD).
• Tremor at least moderate-severe by clinician judgment and tremor scales (Fahn Tolosa Marin Tremor Rating Scale (TETRAS), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS))
• Absence of pathology that could cause abnormal movements of extremities (e.g., epilepsy, stroke, marked arthritis, moderate to severe dyskinesias in PD)
• Stable medication doses for at least 30 days prior to study enrollment
• Able to understand and speak English

Exclusion Criteria for Healthy Participants:

• Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
• Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
• Surgical clips in the head or previous neurosurgery
• Any magnetic particles in the body
• Cochlear implants
• Prosthetic heart valves
• Epilepsy or any other type of seizure history
• Any neurological diagnoses or medications influencing brain function
• History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae)
• Known structural brain lesion
• Significant other disease (heart disease, malignant tumors, mental disorders)
• Significant claustrophobia; Ménière's disease
• Pregnancy (ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible), breast feeding
• Non prescribed drug use
• History of current substance abuse (exception: current nicotine use is allowed)
• Recreational marijuana
• Tremor, parkinsonism; neurological diseases; medical (cardiological, renal, hepatic, oncological) or psychiatric disease that would interfere with study procedures for asES, HD-EMG, TMS, or EEG
• Dementia; severe depression; or prior neurosurgical procedures
• Failure to perform the behavioral tasks or neuropsychological evaluation tests
• Prisoners

Exclusion Criteria for Patients:

• Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
• Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
• Surgical clips or shunts in the head
• Any magnetic particles in the body
• Cochlear implants
• Prosthetic heart valves
• Epilepsy or any other type of seizure history
• Significant claustrophobia; Ménière's disease
• Pregnancy, breast feeding
• Medications increasing risk for seizures
• History of current substance abuse (exception: current nicotine use is allowed)
• Failure to perform tasks (e.g., follow instructions to stay still in the scanner) or fill in safety screening forms
• Prisoners
• Atypical or secondary parkinsonism
• Co-existence of other neurological diseases
• Mixed or complex tremors
• Inability or unwillingness to discontinue medications for tremor on the day of study assessments
• Medical (cardiological, renal, hepatic, oncological) or psychiatric disease that would interfere with study procedures for asES, HD-EMG, TMS, or EEG; dementia; severe depression; prior neurosurgical procedures