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

Abstract

Background and objectivesCortical excitability (CE) is commonly assessed by recording motor evoked potentials (MEPs) in response to single-pulse transcranial magnetic stimulation (sp-TMS). While the motor threshold (MT) remains the most widely used measure of CE, it provides a one-dimensional, criterion-based assessment. In contrast, the recruitment curve (RC) offers a more comprehensive characterization of the full dynamics of cortical recruitment. Yet, only a few preclinical studies involving translationally relevant non-human primates were conducted, and most were under anaesthesia. Hence, we aimed to characterise CE in awake rhesus macaques by recording traditionally defined MT and RCs. MethodsTraditional MT with a 100 {micro}V MEP criterion ( tradMT) was measured in 8 awake adult male rhesus macaques using C-B65 coil and MagVenture stimulator. RCs were recorded at nine relative intensity levels (0.5 - 1.5 x tradMT) in 4 macaques. A sigmoid function was fitted to obtain key CE parameters: the inflection point, lower ankle point, and plateau. ResultsTradMT values were stable and replicable, and aligned most closely with the inflection point of the RC. The lower ankle points were found around at 0.9 x tradMT, marking the transition from a constant to a logarithmic phase, representing a physiologically relevant threshold. Plateau MEP amplitudes were substantially smaller compared to those reported in humans. ConclusionFitted RC parameters revealed a distinction between tradMT and the physiologically relevant threshold. The overall RC shape was consistent with human data, suggesting similar recruitment processes, leading to high translational validity. However, the marked difference in maximal MEP magnitude emphasises the importance of species-specific adaptations.