Motor cortex excitability is reduced during freezing of upper limb movement in Parkinson's disease

Whilst involvement of the motor cortex in the phenomenon of freezing in Parkinson's disease has been previously suggested, few empiric studies have been conducted to date. We investigated motor cortex (M1) excitability in eleven right-handed Parkinson's disease patients (aged 69.7 ± 9.6 years, disease duration 11.2 ± 3.9 years, akinesia-rigidity type) with verified gait freezing using a single-pulse transcranial magnetic stimulation (TMS) repetitive finger tapping paradigm. We delivered single TMS pulses at 120% of the active motor threshold at the 'ascending (contraction)' and 'descending (relaxation)' slope of the tap cycle during i) regular tapping, ii) the transition period of the three taps prior to a freeze and iii) during freezing of upper limb movement. M1 excitability was modulated along the tap cycle with greater motor evoked potentials (MEPs) during 'ascending' than 'descending'. Furthermore, MEPs during the 'ascending' phase of regular tapping, but not during the transition period, were greater compared to the MEPs recorded throughout a freeze. Neither force nor EMG activity 10-110 s before the stimulus predicted MEP size. This piloting study suggests that M1 excitability is reduced during freezing and the transition period preceding a freeze. This supports that M1 excitability is critical to freezing in Parkinson's disease.