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.

Cortical mechanisms of movement recovery after freezing in Parkinson's disease.

Involuntary interruptions of upper limb movements, referred to as "upper limb freezing" (ULF) belong to the most disabling symptoms of Parkinson's disease (PD). Our study aimed to explore the cortical neuronal mechanisms underlying the reinstation of regular movement after a freezing episode and to control them by voluntary stops. We hypothesized that this movement recovery after a freeze would be accompanied by a decrease of beta power (13-30 Hz) over the primary sensorimotor cortex (electrode "C3"). We recorded a 62-channel surface EEG in 14 PD patients during a repetitive finger tapping task. After performing time-frequency analysis of the EEG data we segmented it to i) regular finger taps, ii) ULF episodes, and iii) voluntary movement stops (VS). We analysed cortical activity during each movement modality and later focused on the last 500 ms of ULF and VS and the first half of the following regular tap. At the beginning of regular finger taps we found decreased alpha power (6-12 Hz) over C3 (P = 0.01). During ULF, there was no significant activity modulation in the alpha and beta frequency bands, whereas beta power increased over C3 during VS (P = 0.0038). When tapping was reinstated after a freeze, we found that 100 ms before movement onset beta power decreased first present over C3, followed by fronto-central electrodes and then reaching the ipsilateral right fronto-temporal electrodes when reinstating regular tapping (P = 0.0256). Initiating movement after a VS showed a different pattern with a decrease of parieto-occipital beta activity 200 ms prior to the first tap (P = 0.044). Our findings suggest that PD freezers make use of different cortical pathways when re-initiating movement after ULF or VS. This includes either fronto-central or parieto-occipital pathways. These findings may help to customize novel neuromodulation strategies to counteract freezing behaviour.

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-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), 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.