Short-interval interhemispheric inhibition does not originate from the motor hotspot

• Published in: Brain stimulation Vol. 18; no. 4; pp. 1074 - 1081
• Main Authors: Vetter, David Emanuel, Jooß, Andreas, Mutanen, Tuomas P., Kozák, Gábor, Ziemann, Ulf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2025; Elsevier
• Subjects: Adult; Association algorithm; Brain Mapping - methods; Corpus Callosum - physiology; E-field; Electromyography; EMG; Evoked Potentials, Motor - physiology; Female; Functional Laterality - physiology; Hand - physiology; Humans; Male; Motor Cortex - physiology; Motor mapping; Muscle, Skeletal - physiology; Neural Inhibition - physiology; Primary motor cortex; Short-interval interhemispheric inhibition; TMS; Transcranial Magnetic Stimulation - methods; Young Adult; Motor mapping; Primary motor cortex; Association algorithm; E-field; TMS; Short-interval interhemispheric inhibition; EMG
• ISSN: 1935-861X; 1876-4754; 1876-4754
• DOI: 10.1016/j.brs.2025.05.115

Paired-coil TMS can delineate causal connections between cortical areas. Short-interval interhemispheric inhibition (SIHI) is a rapid inhibitory process, in which one primary motor cortex (M1) inhibits the other through the corpus callosum. Previous work suggests that both SIHI and motor evoked potentials (MEPs) originate in the motor hotspot. However, SIHI and MEPs are mediated by different neuronal populations. Here we used a recently published TMS-based association-method (Weise et al., 2023, Nat Protoc 18:293–318) to test if the neuronal populations mediating SIHI and MEPs can be spatially discriminated. s: We mapped the origin of SIHI and MEPs of hand muscles in each hemisphere, using the novel association-method to perform a ‘source space’ mapping on 18 healthy volunteers. The origin of SIHI (the ‘coldspot’) was identifiable in the majority of subjects near the motor hotspot, at the hand-knob and around the central sulcus. It was displaced posterolaterally from the motor hotspot by about 6 mm. Post-hoc analyses revealed that precisely targeting the coldspot elicited significantly stronger SIHI compared to targeting the motor hotspot. Findings demonstrate that the TMS-based association-method for source-space mapping enables physiological investigation of the distinct neuronal populations that give rise to interhemispheric inhibition of the contralateral motor cortex versus motor evoked potentials in contralateral hand muscles. SIHI can be more effectively elicited by targeting the coldspot rather than the hotspot, a potentially relevant distinction when aiming to modify interhemispheric neural communication, e.g., in stroke rehabilitation. •Regression-based TMS mapping of short-interval interhemispheric inhibition (SIHI).•Neural origin of SIHI shifted posterolaterally from the motor hotspot by around 6 mm.•Potential for increase of SIHI by around 15 percentage points.