Optimizing Functional Accuracy of TMS in Cognitive Studies: A Comparison of Methods

TLDR

Transcranial magnetic stimulation (TMS) is a noninvasive tool used to transiently disrupt neural activity, and its application has broadened to study causal structure–function relationships across cognitive functions, making accurate target site determination increasingly critical. The study systematically compares four common TMS coil positioning approaches by applying them to a single cognitive task. Using a number‑comparison task, the authors applied right‑parietal TMS localized by (i) individual fMRI‑guided neuronavigation, (ii) individual MRI‑guided neuronavigation, (iii) group Talairach coordinates, or (iv) the 10–20 EEG position P4, then quantified behavioral effects, calculated effect sizes, and performed power analyses. Results showed that fMRI‑guided neuronavigation produced the largest effect size, requiring only five participants for significance, whereas P4 required 47 participants, with MRI‑guided and Talairach approaches needing nine and thirteen participants, respectively, highlighting graded effect size differences driven by interindividual target variability.

Abstract

Abstract Transcranial magnetic stimulation (TMS) is a tool for inducing transient disruptions of neural activity noninvasively in conscious human volunteers. In recent years, the investigative domain of TMS has expanded and now encompasses causal structure–function relationships across the whole gamut of cognitive functions and associated cortical brain regions. Consequently, the importance of how to determine the target stimulation site has increased and a number of alternative methods have emerged. Comparison across studies is precluded because different studies necessarily use different tasks, sites, TMS conditions, and have different goals. Here, therefore, we systematically compare four commonly used TMS coil positioning approaches by using them to induce behavioral change in a single cognitive study. Specifically, we investigated the behavioral impact of right parietal TMS during a number comparison task, while basing TMS localization either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI-guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv) 10–20 EEG position P4. We quantified the exact behavioral effects induced by TMS using each approach, calculated the standardized experimental effect sizes, and conducted a statistical power analysis in order to calculate the optimal sample size required to reveal statistical significance. Our findings revealed a systematic difference between the four approaches, with the individual fMRI-guided TMS neuronavigation yielding the strongest and the P4 stimulation approach yielding the smallest behavioral effect size. Accordingly, power analyses revealed that although in the fMRI-guided neuronavigation approach five participants were sufficient to reveal a significant behavioral effect, the number of necessary participants increased to n = 9 when employing MRI-guided neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates, and to n = 47 when applying TMS over P4. We discuss these graded effect size differences in light of the revealed interindividual variances in the actual target stimulation site within and between approaches.