11. Excessive inhibitory visuomotor connections in Parkinson’s disease with freezing of gait

Abstract

Objectives Freezing of gait (FoG) is an invalidating symptom in patients with Parkinson’s disease (PD); it is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. The pathophysiology of this phenomenon remains obscure. Visual information are crucial for the initiation and control of movement, therefore an impairment of the visuomotor connections may underlie FoG. We used transcranial magnetic stimulation (TMS) to assess bilateral physiological connections (VMc) between primary visual (V1) and motor (M1) areas in PD with (PD + FoG) and without FoG (PD-FoG).We hypothesized that PD+FoG would show an abnormal response in M1. Methods Twelve PD+FoG were compared with 12 PD-FoG and 12 healthy subjects (HS) of similar age and sex. VMc was assessed bilaterally in resting participants by delivering a conditioning stimulus (CS) over the phosphene hotspot of V1 (intensity 90% phosphene threshold, PT) followed at two random interstimulus intervals (ISIs) (18 and 40 ms) by a test stimulus (TS) over left and right M1 to elicit a motor evoked potential (MEP) of ∼1 mV from the controlateral first dorsal interosseous (FDI). Results In HS, the VMc was reproducible with MEP suppression at ISI of 18 and 40 ms. Similar effects occurred in PD-FoG. PD+FoG behaved differently, since the inhibitory VMc was significantly enhanced in the right, non-dominant hemisphere. Conclusions PD+FoG had an excessive inhibitory response of the right M1 to inputs travelling from V1. Significance This may represent one core factor for the pathophysiology of FoG.