Investigating the Role of the Primary Motor Cortex (M1) in Upper Limb Freezing (ULF)

Abstract

We used phase-locked single-pulse transcranial magnetic stimulation (sTMS) to examine primary motor cortex (M1) excitability in 11 patients with Parkinson’s disease (PD) during self-paced finger tapping and episodes of upper limb freezing (ULF). During regular finger tapping, cortical excitability fluctuated throughout the tapping cycle, showing increased excitability during the downward tapping phase and decreased excitability during relaxation. ULF was associated with M1 hypoactivity - however, the lowest excitability levels were not seen during ULF itself but occurred a few taps earlier in the relaxation phase of the transition period when motor output was still intact. This observation suggests that M1 hypoactivity alone may not necessarily result in freezing. Instead, the overall decrease in excitability during the transition phase — prior to any visible changes in the kinematic signal — supports the notion of a gradual accumulation of motor deficits, potentially reflecting a loss of excitatory input from premotor and other frontal cortical areas prior to freezing. Thus, M1 appears to play an important role in the pathophysiology of ULF and could represent a potential target for future adaptive brain stimulation approaches.