Subthalamic nucleus stimulation restores the efferent cortical drive to muscle in parallel to functional motor improvement.
ABSTRACT Pathological synchronization in large-scale motor networks constitutes a pathophysiological hallmark of Parkinson's disease (PD). Corticomuscular synchronization in PD is pronounced in lower frequency bands (< 10 Hz), whereas efficient cortical motor integration in healthy persons is driven in the beta frequency range. Electroencephalogram and electromyogram recordings at rest and during an isometric precision grip task were performed in four perioperative sessions in 10 patients with PD undergoing subthalamic nucleus deep-brain stimulation: (i) 1 day before (D0); (ii) 1 day after (D1); (iii) 8 days after implantation of macroelectrodes with stimulation off (D8StimOff); and (iv) on (D8StimOn). Analyses of coherence and phase delays were performed in order to challenge the effects of microlesion and stimulation on corticomuscular coherence (CMC). Additionally, local field potentials recorded from the subthalamic nucleus on D1 allowed comprehensive mapping of motor-related synchronization in subthalamocortical and cerebromuscular networks. Motor performance improved at D8StimOn compared with D0 and D8StimOff paralleled by a reduction of muscular activity and CMC in the theta band (3.9-7.8 Hz) and by an increase of CMC in the low-beta band (13.7-19.5 Hz). Efferent motor cortical drives to muscle presented mainly below 10 Hz on D8StimOff that were suppressed on D8StimOn and occurred on higher frequencies from 13 to 45 Hz. On D1, coherence of the high-beta band (20.5-30.2 Hz) increased during movement compared with rest in subthalamomuscular and corticomuscular projections, whereas it was attenuated in subcorticocortical projections. The present findings lend further support to the concept of pathological network synchronization in PD that is beneficially modulated by stimulation.
- SourceAvailable from: PubMed Central[show abstract] [hide abstract]
ABSTRACT: Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson's Disease Rating Scale score (Scale II items 13-15, Scale III items 27-31) at '3-week follow-up'. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the '3-week follow-up'. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.Brain 06/2013; 136(Pt 7):2098-2108. · 9.92 Impact Factor