Functional properties of dorsolateral prefrontal cortex to primary motor cortex connectivity: a dual-site TMS study

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in cognitive-motor integration through its top-down regulation of the primary motor cortex (M1). However, the functional lateralization of the left and right DLPFC and the differences between intra-hemispheric and inter-hemispheric regulation of M1, particularly in populations with brain injury, remain controversial and insufficiently studied.

This study aimed to systematically achieve the following four objectives using a dual-site paired-pulse transcranial magnetic stimulation (TMS) technique: (1) to evaluate the integrated regulatory effects of bilateral DLPFC on M1; (2) to compare the differences in regulatory effects between ipsilateral and contralateral DLPFC; (3) to analyze the impact of functional lateralization of the left and right DLPFC on their regulation of M1; (4) to investigate the effects of brain injury on the DLPFC-M1 regulatory pathway by comparing healthy participants and stroke patients.

A total of 30 right-handed participants were enrolled, including 20 stroke patients in the recovery phase (divided into left and right lesion groups) and 10 healthy volunteers. These three participant groups were tested under conditions that varied the targeted motor cortex (M1) side, yielding four key experimental conditions for analysis. Accordingly, a paired-pulse TMS paradigm was employed. Following a conditioning stimulus (CS) applied to the left or right DLPFC, a test stimulus (TS) was delivered to the ipsilateral or contralateral M1 after an inter-stimulus interval of 20 ms. The amplitude of the motor evoked potential (MEP) was recorded.

In experiments targeting the left M1, both the healthy group (Experiment 1) and the patient group (Experiment 3) exhibited significant regulatory effects (χ ² = 12.2, p = 0.002; χ ² = 9.6, p = 0.008). Post-hoc analysis revealed that, compared to baseline, both ipsilateral DLPFC (p = 0.011; p = 0.022) and contralateral DLPFC (p = 0.005; p = 0.022) significantly enhanced M1 excitability, with no significant difference between the two (p = 1.000). However, in experiments targeting the right M1 across all groups (Experiments 2 and 4), no significant regulatory effect of DLPFC was observed (χ ² = 0.2, p = 0.905).

This study confirms that, at rest, the bilateral DLPFC exerts a stable and non-specific facilitatory regulation on the left M1. This effect persists in the affected M1 of stroke patients, suggesting plasticity in the relevant pathways after injury. The negative findings for the right M1 reveal a lateralization characteristic in DLPFC-M1 regulation. These results provide an important basis for elucidating the physiological mechanisms of cognitive-motor circuits and for developing targeted neurorehabilitation strategies.