Utility of Obtaining TMS Metrics of Cortical Excitation and Inhibition from Proximal Muscles of Patients with Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD)
Abstract number :
3.144
Submission category :
3. Neurophysiology / 3E. Brain Stimulation
Year :
2023
Submission ID :
1187
Source :
www.aesnet.org
Presentation date :
12/4/2023 12:00:00 AM
Published date :
Authors :
First Author: Paul MacMullin, MS – Boston Children's Hospital
Presenting Author: Melissa Tsuboyama, MD – Boston Children's Hospital
Melissa Tsuboyama, MD – Attending, Epilepsy, Boston Children's Hospital; Deniz Aygun, BA – Research Assistant, Epilepsy, Boston Children's Hospital; Melissa DiBacco, MD – Clinical Research Manager, Epilepsy, Boston Children's Hospital; Philip Pearl, MD – Director, Epilepsy, Boston Children's Hospital; alexander Rotenberg, MD,PhD – Attending, Epilepsy, Boston Children's Hospital
Rationale:
Transcranial magnetic stimulation (TMS) is a method for noninvasive brain stimulation. When applied over the motor cortex (M1), TMS can be used to obtain metrics reflecting cortical excitability and inhibitory tone (i.e., resting motor threshold (rMT), cortical silent period (CSP) and long interval cortical inhibition (LICI)). TMS is typically delivered to the hand M1 region, and the above metrics are derived from contralateral intrinsic hand muscle motor evoked potentials (MEPs). Young children and patients with developmental delay or behavioral dysregulation may not tolerate surface EMG electrodes on the hands. Proximal muscle (e.g., deltoid) EMG may be better tolerated, but feasibility of obtaining TMS metrics from proximal muscle groups has not yet been studied systematically. We therefore tested whether rMT, CSP, and LICI can be reliably recorded from the deltoid muscle in participants with SSADHD and whether the profile is similar to that obtained from intrinsic hand muscles.
Methods:
In this single-center observational study, 21 people with SSADHD and 15 healthy controls underwent TMS. rMT (n=21) and LICI (n=10) were measured from the right deltoid muscle EMG. rMT is the minimum machine output required to elicit an MEP ≥ 50 μV from the target muscle at rest in >50% of trials of stimulation over the designated hotspot. To measure CSP (n=10), a suprathreshold stimulus of 120% rMT was delivered over the M1 hotspot, with the muscle in a pre-activated state. CSP was calculated as the duration from the time of stimulation to return of spontaneous EMG activity. To elicit LICI, two stimulations at 120% rMT 100 milliseconds apart were delivered to the M1 hotspot: a conditioning stimulus (CS) followed by a test stimulus (TS). LICI was expressed as a log10 transformation of the ratio of peak-to-peak MEP amplitudes resultant from each TS and CS.
Results:
rMT is higher in people with SSADHD (p=0.0196, t test) and deltoid CSP is shorter in those with SSADHD (p=0.0311, t test), both compared to age-matched controls. Less inhibition in the deltoid (LICI) is seen in participants with SSADHD compared to healthy controls, at times even demonstrating a facilitation response (p=0.0100, t test). Notably, these findings are consistent with those seen when comparing these TMS metrics from intrinsic hand muscles of these study participants. (MacMullin et al., 2022 AES abstract).
Conclusions:
Motor cortex TMS coupled with deltoid EMG is a viable option in patient populations in whom achieving a resting state of the hands or cooperation to perform voluntary contractions of hand muscles is not possible or surface EMG electrodes on the hands is not tolerated. Similar neurophysiologic characteristics are also seen from both the intrinsic hand muscles and deltoid muscles, providing another potential biomarker of target engagement that can be used in disease-specific drug development.
Funding:
National Institutes of Health (1R01HD091142; Gibson), the SSADH Association (grant to Gibson), the Office Of The Director of the NIH (Award # S10OD025111), and the Harvard Catalyst Clinical and Translational Research Center (NCATS #8UL1TR000170).
Neurophysiology