Abstract

The reliability of transcranial magnetic stimulation (TMS) measures in healthy older adults and stroke patients has been insufficiently characterized. We determined whether common TMS measures could reliably evaluate change in individuals and in groups using the smallest detectable change (SDC), or could tell subjects apart using the intraclass correlation coefficient (ICC). We used a single-rater test-retest design in older healthy, subacute stroke, and chronic stroke subjects. At twice daily sessions on two consecutive days, we recorded resting motor threshold, test stimulus intensity, recruitment curves, short-interval intracortical inhibition, and facilitation, and long-interval intracortical inhibition. Using variances estimated from a random effects model, we calculated the SDC and ICC for each TMS measure. For all TMS measures in all groups, SDCs for single subjects were large; only with modest group sizes did the SDCs become low. Thus, while these TMS measures cannot be reliably used as a biomarker to detect individual change, they can reliably detect change exceeding measurement noise in moderate-sized groups. For several of the TMS measures, ICCs were universally high, suggesting that they can reliably discriminate between subjects. TMS measures should be used based on their reliability in particular contexts. More work establishing their validity, responsiveness, and clinical relevance is still needed.

Highlights

  • Over the past three decades, increasing numbers of studies have used transcranial magnetic stimulation (TMS) to examine neurophysiology in pathology and health

  • The paretic first dorsal interosseous (FDI) of subacute and chronic stroke subjects was significantly weaker than right FDI of healthy older subjects on the Medical Research Council (MRC) scale but not by maximal voluntary contractions (MVC)

  • We found that smallest detectable change (SDC) for individuals were universally large across all TMS measures, precluding reasonable single-subject evaluative use; these TMS measures should not be used as biomarkers for assessing individual change

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Summary

Introduction

Over the past three decades, increasing numbers of studies have used transcranial magnetic stimulation (TMS) to examine neurophysiology in pathology and health. It is generally assumed that change in the average motor evoked potential (MEP) amplitude, resulting from the same stimulation intensities, reflects true biological change in the corticospinal. TMS has great potential for establishing physiological biomarkers, a rigorous appraisal of the quality of TMS as a measurement instrument has never been sufficiently undertaken. The instrument of TMS encapsulates the stimulation and recording setup and the operator. We have not established the degree to which TMS measurements are precise, accurate, or clinically relevant. Without this foundational knowledge, we risk ascribing meaningful neurophysiological mechanisms to meaningless TMS changes

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