Corticobulbar activity in healthy humans and Parkinson's disease: a study protocol for a novel biomarker of motivational arousal

Abstract

Background: The corticobulbar (CB) tract connects the primary motor cortex to oral and facial effectors and may contribute to affective-motivational processes through its interactions with dopaminergic circuits. Prior studies have shown that excitability in the tongue motor cortex (tM1), as well as surface electromyographic (sEMG) activity of submental muscles (SbM), is modulated by hedonic and aversive stimuli. These findings suggest a potential role for the CB system as a physiological interface between motivational states and motor expression.

Objectives: This protocol explores whether CB excitability can serve as an indirect marker of motivational arousal in both healthy individuals and patients with Parkinson's disease (PD), a condition marked by dopaminergic dysfunction.

Methods: Study 1 protocol consists in a virtual reality-based shopping task where healthy adults (n = 100) are asked to do different food shipping based on motivational-affective value, while their SbM EMG activity is recorded. Study 2 assesses CB excitability via SbM motor evoked potentials (MEPs) in PD patients (n = 15) before and after a 3-month period of dopaminergic therapy (levodopa), and across ON/OFF medication states. The study design includes a control group (n = 15) tested twice, after a 3-month period, without any drug or placebo administration. Behavioral and self-report measures related to motivation and reward sensitivity are also included in both studies.

Conclusion: This protocol combines advanced neurophysiological techniques with innovative experimental paradigms to investigate CB tract cortical excitability linkage with reward-related processing. By integrating neurophysiological, behavioral, and pharmacological measures, this protocol aims to clarify whether CB excitability reflects motivational and dopaminergic states. Findings may contribute to identifying non-invasive biomarkers of motivational functioning in both clinical and normative populations.

Keywords: Parkinson’s disease; TMS; corticobulbar excitability; methods and protocols; motivational arousal; submental EMG; virtual reality.

Figure 1

Experimental set-up and timeline Study 1. (A) Virtual Environment: Images of the virtual supermarket used, obtained from the Unity 3D store. (B) Technical Equipment: Oculus Quest 2 for virtual navigation and interaction, BIOPAC MP36 for electrophysiological recordings. (C) Timeline of experimental phases. (D) Table with instruction received by participants for each experimental condition.

Figure 2

Experimental Set-up and timeline Study 2. (A) An example of the experimental setup for recording MEPs from M1 cortex of the SBM. (B) Graphical representation of the target muscle (SbM) and the control muscle (ECR); (C) The timeline of the experimental session. The lower section illustrates the initial phases, which involve determining the resting motor threshold (RMT) for both the target muscle (SbM) and the control muscle (ECR). The upper section shows the subsequent stimulation blocks, during which TMS is applied to each muscle in a counterbalanced order across participants.