Assessment of cortical excitability in awake rhesus macaques with transcranial magnetic stimulation: Translational insights from recruitment curves

Abstract

Cortical excitability (CE) is commonly assessed via motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (sp-TMS). While the motor threshold (MT) remains the most widely used measure of CE, it provides a limited, one-dimensional measure based on a fixed MEP amplitude criterion. In contrast, the recruitment curve (RC) offers a more comprehensive characterization of corticospinal recruitment dynamics. To date, the few available preclinical TMS studies measuring RC in non-human primates have been conducted under anaesthesia with limited translational relevance. Hence, we characterised CE in 20 sessions of 4 awake rhesus macaques by recording RCs at nine stimulation intensity levels and parametrising them using exponentiated sigmoid functions. The traditional 100 µV MEP MT criterion level (SI_100µV) aligned most closely with the inflection point of the RC sigmoid fit and was consistent with relative frequency-based traditional MT (tradMT) measured in separate sessions. The onset of the logarithmic recruitment phase of the sigmoid (lower ankle point) was found at 0.9 × SI_100µV/tradMT. Well-formed MEPs were measured below the SI_100µV/tradMT, but not below the lower ankle point, which is a physiologically relevant response threshold. Thus, in rhesus macaques the 100-µV criterion may be suitable to approximate the RC inflection point, but not the physiological motor threshold. The overall RC shape was consistent with previous human data, however, plateau MEP amplitudes were substantially smaller than those reported in humans. These results lay the groundwork for the adaptation of TMS protocols and CE metrics to non-human primates that is necessary for translationally valid research.