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

People With Parkinson's Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles

OBJECTIVE: Freezing of gait is detrimental to patients with idiopathic Parkinson’s disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity. METHODS: We analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBS(only)) or the substantia nigra pars reticulate (SNr-DBS(only)), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in ‘regular gait’ and during the ‘freezing’ episodes. RESULTS: In stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing. CONCLUSION: We found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator