Driving motor cortex oscillations modulates bradykinesia in Parkinson’s disease

• Published in: Brain (London, England : 1878) Vol. 145; no. 1; pp. 224 - 236
• Main Authors: Guerra, Andrea, Colella, Donato, Giangrosso, Margherita, Cannavacciuolo, Antonio, Paparella, Giulia, Fabbrini, Giovanni, Suppa, Antonio, Berardelli, Alfredo, Bologna, Matteo
• Format: Journal Article
• Language: English
• Published: England 29.03.2022
• Subjects: Evoked Potentials, Motor - physiology; Gamma Rhythm - physiology; Humans; Hypokinesia - etiology; Motor Cortex; Parkinson Disease - complications; Transcranial Direct Current Stimulation - methods; motor cortex; bradykinesia; oscillations; GABA-A; Parkinson’s disease
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awab257

In patients with Parkinson’s disease, beta (β) and gamma (γ) oscillations are altered in the basal ganglia, and this abnormality contributes to the pathophysiology of bradykinesia. However, it is unclear whether β and γ rhythms at the primary motor cortex (M1) level influence bradykinesia. Transcranial alternating current stimulation (tACS) can modulate cortical rhythms by entraining endogenous oscillations. We tested whether β- and γ-tACS on M1 modulate bradykinesia in patients with Parkinson’s disease by analysing the kinematic features of repetitive finger tapping, including movement amplitude, velocity and sequence effect, recorded during β-, γ- and sham tACS. We also verified whether possible tACS-induced bradykinesia changes depended on modifications in specific M1 circuits, as assessed by short-interval intracortical inhibition and short-latency afferent inhibition. Patients were studied OFF and ON dopaminergic therapy. Results were compared to those obtained in a group of healthy subjects. In patients, movement velocity significantly worsened during β-tACS and movement amplitude improved during γ-tACS, while the sequence effect did not change. In addition, short-latency afferent inhibition decreased (reduced inhibition) during β-tACS and short-interval intracortical inhibition decreased during both γ- and β-tACS in Parkinson’s disease. The effects of tACS were comparable between OFF and ON sessions. In patients OFF therapy, the degree of short-interval intracortical inhibition modulation during β- and γ-tACS correlated with movement velocity and amplitude changes. Moreover, there was a positive correlation between the effect of γ-tACS on movement amplitude and motor symptoms severity. Our results show that cortical β and γ oscillations are relevant in the pathophysiology of bradykinesia in Parkinson’s disease and that changes in inhibitory GABA-A-ergic interneuronal activity may reflect compensatory M1 mechanisms to counteract bradykinesia. In conclusion, abnormal oscillations at the M1 level of the basal ganglia-thalamo-cortical network play a relevant role in the pathophysiology of bradykinesia in Parkinson’s disease.