Motor evoked potentials as a side effect biomarker for deep brain stimulation.

To determine if motor evoked potentials (mEP) - stimulation-induced muscle activation measured using electromyography - can serve as a biomarker of corticobulbar (CBT) and corticospinal (CST) tract activation for deep brain stimulation (DBS) programming. In 12 patients with Parkinson's disease and subthalamic or pallidal DBS, contact mapping determined clinical motor side effect thresholds. For equivalent stimulation parameters, EMG was recorded from cranial and arm muscles to determine the presence, peak amplitudes and latencies of mEP. Clinical and mEP thresholds were compared and accuracy metrics calculated to assess similarity between mEP and reported side effects. The mEP amplitudes increased with stimulation intensity. Latencies were shorter for cranial muscles, which were more likely to generate an mEP. Clinical and mEP thresholds were significantly correlated (R 2 = 0.31; p=0.0006), although most mEP thresholds were lower than clinical side effect thresholds. The mEP accuracy in predicting side effects was 0.72, with a sensitivity of 0.68 and a specificity of 0.73. EMG-recorded mEP correlated well with clinical side effects, and mEP often indicated subclinical CBT and CST activations. This study characterizes motor potentials evoked by DBS and demonstrates their utility as an objective biomarker for motor side effect threshold detection during DBS programming. Deep brain stimulation can activate corticospinal/bulbar tract and evoke motor potentials in muscles measurable by surface EMGMotor evoked potential thresholds correlate significantly with clinical side effect thresholds but occur at lower stimulation intensitiesMotor evoked potentials may be a useful side effect biomarker for deep brain stimulation programming.

Introduction: The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using intraoperative motor-evoked potentials (MEPs) through direct lead stimulation and determining their correlation to the thresholds of postoperative stimulation-induced side effects. Methods: This study included 22 consecutive patients with advanced Parkinson’s disease who underwent surgery in our institution between January 2021 and September 2023. All patients underwent bilateral implantation in the STN (44 leads) under general anesthesia without microelectrode recordings (MERs) by using MEPs with electrostimulation directly through the DBS lead. No cortical stimulation was performed during this process. Intraoperative fluoroscopic guidance and immediate postoperative computed tomography were used to verify the electrode’s position. The lowest MEP thresholds were recorded and were correlated to the postoperative stimulation-induced side-effect threshold. The predictive values of the MEPs were analyzed. Five DBS leads were repositioned intraoperatively due to the MEP results. Results: A moderately strong positive correlation was found between the MEP threshold and the capsular side-effect threshold (RS = 0.425, 95% CI, 0.17–0.67, p = 0.004). The highest sensitivity and specificity for predicting a side-effect threshold of 5 mA were found to be at 2.4 mA MEP threshold (sensitivity 97%, specificity 87.5%, positive predictive value 97%, and negative predictive value 87.5%). We also found high sensitivity and specificity (100%) at 1.15 mA MEP threshold and 3 mA side-effect threshold. Out of the total 44 leads, 5 (11.3%) leads were repositioned intraoperatively due to MEP thresholds lower than 1 mA (4 leads) or higher than 5 mA (1 lead). The mean accuracy on postoperative CT was 1.05 mm, and there were no postoperative side-effects under 2.8 mA. Conclusion: Intraoperative MEPs with electrostimulation directly through the contacts of the DBS lead correlate with the stimulation-induced capsular side effects. The lead reposition based on intraoperative MEP may enlarge the therapeutic window of DBS stimulation.

EP 62. Motor evoked potentials mapping improves detection of capsular side effects during deep brain stimulation

Corticomyographic motor evoked potentials (MEP) activated by transcranial magnetic stimulation of the motor cortex provide clinicians with an opportunity to evaluate corticospinal motor systems quantitatively and noninvasively. Threshold, amplitude, and latency of the corticomyographic MEP, however, are variable between subjects mainly because current directions and intensities induced by magnetic stimulation cannot be determined precisely due to anatomical variations of subjects. The variability of corticomyographic MEPs has limited the use of corticomyographic MEP for evaluating mild changes in corticospinal motor function. In the present study, we used an internal standard to assess hemiplegia, expressing relative amplitude, latency, and threshold of responses on the paretic side as a function of responses elicited from the intact side (%MEP). Neurological function of paretic muscles, as determined by a muscle maneuver test (MMT), clearly correlated to %MEP threshold, amplitude, and latency. Since corticomyographic MEP are similar when recorded from symmetrical sites on two extremities of normal subjects, %MEP provided a sensitive measure of mild hemiparesis. The %MEP approach revealed abnormal MMT scores of 3 or 4 more frequently than did standard MEP approaches. %MEP amplitude was more sensitive to mild hemiparesis than %MEP latency or %MEP threshold. Since magnetic stimulation with a safe intensity range cannot reliably produce corticomyographic MEP in severely paretic muscles with MMT scores of 2 or less, the MEP appears to be most useful for evaluating mild hemiparesis. This technique should expand significantly the clinical usefulness of corticomyographic MEP in neurosurgical practice.

In deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD), there is debate concerning the use of neuroimaging alone to confirm correct anatomic placement of the DBS lead into the STN, versus the use of microelectrode recording (MER) to confirm functional placement. We performed a retrospective study of a contemporaneous cohort of 45 consecutive patients who underwent either interventional-MRI (iMRI) or MER-guided DBS lead implantation. We compared radial lead error, motor and sensory side effect, and clinical benefit programming thresholds, and pre- and post-operative unified PD rating scale scores, and levodopa equivalent dosages. MER-guided surgery was associated with greater radial error compared to the intended target. In general, side effect thresholds during initial programming were slightly lower in the MER group, but clinical benefit thresholds were similar. No significant difference in the reduction of clinical symptoms or medication dosage was observed. In summary, iMRI lead implantation occurred with greater anatomic accuracy, in locations demonstrated to be the appropriate functional region of the STN, based on the observation of similar programming side effect and benefit thresholds obtained with MER. The production of equivalent clinical outcomes suggests that surgeon and patient preference can be used to guide the decision of whether to recommend iMRI or MER-guided DBS lead implantation to appropriate patients with PD.

Voluntary motor function in patients with chronic fatigue syndrome

Motor evoked potentials versus Macrostimulation in predicting the postoperative motor threshold in STN Deep brain stimulation

Motor Evoked Potentials Improve Targeting in Deep Brain Stimulation Surgery

Segmented deep brain stimulation (DBS) leads, which are capable of steering current in the direction of any 1 of 3 segments, can result in a wider therapeutic window by directing current away from unintended structures, particularly, the corticospinal tract (CST). It is unclear whether the use of motor evoked potentials (MEPs) is feasible during DBS surgery via stimulation of individual contacts/segments in order to quantify CST activation thresholds and optimal contacts/segments intraoperatively. To assess the feasibility of using MEP to identify CST thresholds for ring and individual segments of the DBS lead under general anesthesia. MEP testing was performed during pulse generator implantation under general anesthesia on subjects who underwent DBS lead implantation into the subthalamic nucleus (STN). Stimulation of each ring and segmented contacts of the directional DBS lead was performed until CST threshold was reached. Stereotactic coordinates and thresholds for each contact/segment were recorded along with the initially activated muscle group. A total of 34 hemispheres were included for analysis. MEP thresholds were recorded from 268 total contacts/segments. For segmented contacts (2 and 3, respectively), the mean highest CST thresholds were 2.33 and 2.62 mA, while the mean lowest CST thresholds were 1.7 and 1.89 mA, suggesting differential thresholds in relation to CST. First dorsal interosseous and abductor pollicis brevis (34% each) were the most commonly activated muscle groups. MEP threshold recording from segmented DBS leads is feasible. MEP recordings can identify segments with highest CST thresholds and may identify segment orientation in relation to CST.

Intraoperative DBS targeting of the globus pallidus internus by using motor evoked potentials

Pulse width modulation-based TMS: Primary motor cortex responses compared to conventional monophasic stimuli

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to study human neurophysiology. A single TMS pulse delivered to the primary motor cortex can elicit a motor evoked potential (MEP) in a target muscle. MEP amplitude is a measure of corticospinal excitability and MEP latency is a measure of the time taken for intracortical processing, corticofugal conduction, spinal processing, and neuromuscular transmission. Although MEP amplitude is known to vary across trials with constant stimulus intensity, little is known about MEP latency variation. To investigate MEP amplitude and latency variation at the individual level, we scored single-pulse MEP amplitude and latency in a resting hand muscle from two datasets. MEP latency varied from trial to trial in individual participants with a median range of 3.9 ms. Shorter MEP latencies were associated with larger MEP amplitudes for most individuals (median r = − 0.47), showing that latency and amplitude are jointly determined by the excitability of the corticospinal system when TMS is delivered. TMS delivered during heightened excitability could discharge a greater number of cortico-cortical and corticospinal cells, increasing the amplitude and, by recurrent activation of corticospinal cells, the number of descending indirect waves. An increase in the amplitude and number of indirect waves would progressively recruit larger spinal motor neurons with large-diameter fast-conducting fibers, which would shorten MEP onset latency and increase MEP amplitude. In addition to MEP amplitude variability, understanding MEP latency variability is important given that these parameters are used to help characterize pathophysiology of movement disorders.

EP 6. Chronic directional subthalamic nucleus deep brain stimulation in Parkinson’s disease – A pilot study

Event Abstract Back to Event Using Transcranial Magnetic Stimulation as a valid tool to evaluate sports concussion. A systematic review with preliminary results. Brendan P. Major1*, Mark Rogers1* and Alan Pearce1* 1 Deakin University, Australia This systematic review analysed cortical excitability and inhibition, via transcranial magnetic stimulation (TMS), following sports concussion. The following electronic databases were searched between January and March 2014: PsycINFO, MEDLINE Complete, Psycarticles, Pubmed, Sport Discus, Web of Science, Science Direct, and Cochrane Library using the following inclusion criteria; human, peer reviewed articles published between years 1995 to 2014 in English, age range of 18-60 years, sustained a mild to moderate sports concussion, single pulse TMS outcome measures of motor evoked potentials (MEPs) amplitude and latency, cortical silent period (cSP), short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition. Of the 667 search results 17 studies met the inclusion criteria. For short term (<12 days) 3 studies reported immediate increases in MEP threshold, amplitude and latency following concussion or mild traumatic brain injury. In one study, shortening of cSP was reported 10 days post concussion matched with one reporting and immediate increase following injury. These measures were associated with changes in cognitive performance. For long term investigations (>3 years) 3 studies reported MEP and cSP threshold changes, 4 studies reported lengthening in cSP duration, with one study reporting a reduction. Similarly, cognitive changes were associated with alterations in cSP duration. These results demonstrate the validity of TMS as an investigative tool in elucidating the neurophysiological consequences of a sports concussion and can be used alongside standardised cognitive testing batteries. Keywords: Motor Cortex, Transcranial Magnetic Stimulation, concussion, review, motor evoked potential, Silent Period Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Motor Behaviour Citation: Major BP, Rogers M and Pearce A (2015). Using Transcranial Magnetic Stimulation as a valid tool to evaluate sports concussion. A systematic review with preliminary results.. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00237 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Brendan P Major, Deakin University, Melbourne, Australia, Brendan.major@monash.edu Dr. Mark Rogers, Deakin University, Melbourne, Australia, mark.rogers@deakin.edu.au Dr. Alan Pearce, Deakin University, Melbourne, Australia, alan.pearce@latrobe.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Brendan P Major Mark Rogers Alan Pearce Google Brendan P Major Mark Rogers Alan Pearce Google Scholar Brendan P Major Mark Rogers Alan Pearce PubMed Brendan P Major Mark Rogers Alan Pearce Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Background: Assessment of concussion is primarily based on self-reported symptoms, neurological examination and neuropsychological testing. The neurophysiologic sequelae and the integrity of the corticomotor pathways could be obtained by evaluating motor evoked potentials (MEPs).Objectives: To compare MEPs obtained through transcranial magnetic stimulation (TMS) in acutely concussed and non-concussed collegiate athletes.Methods: Eighteen collegiate athletes (12 males, six females, aged 20.4 ± 1.3 years) including nine subjects with acute concussion (≤24 hours) matched to nine control subjects. TMS was applied over the motor cortex and MEP responses were recorded from the contralateral upper extremity. MEP thresholds (%), latencies (milliseconds per metre) and amplitudes were assessed. Central motor conduction time (CMCT) was calculated from MEP, M response and F wave latencies. Testing was performed on days 1, 3, 5 and 10 post-concussion.Results: Ulnar MEP amplitudes were significantly different between post-concussion days 3 and 5 (F3,48 = 3.13, p = 0.041) with smaller amplitudes recorded on day 3 (0.28 ± 0.10 ms m−1). Median MEP latencies were significantly longer (F3,48 = 4.53, p = 0.023) 10 days post-concussion (27.1 ± 1.4 ms m−1) compared to day 1 (25.7 ± 1.5 ms m−1). No significant differences for motor thresholds or CMCTs were observed (p > 0.05).Conclusion: MEP abnormalities among acutely concussed collegiate athletes provide direct electrophysiologic evidence for the immediate effects of concussion.