Pallidal stimulation suppresses pathological dysrhythmia in the parkinsonian motor cortex

Abstract

McCairn KW, Turner RS. Pallidal stimulation suppresses pathological dysrhythmia in the parkinsonian motor cortex. J Neurophysiol 113: 2537-2548, 2015. First published February 4, 2015 doi:10.1152/jn.00701.2014.-Although there is general consensus that deep brain stimulation (DBS) yields substantial clinical benefit in patients with Parkinson's disease (PD), the therapeutic mechanism of DBS remains a matter of debate. Recent studies demonstrate that DBS targeting the globus pallidus internus (GPi-DBS) suppresses pathological oscillations in firing rate and between-cell spike synchrony in the vicinity of the electrode but has negligible effects on populationlevel firing rate or the prevalence of burst firing. The present investigation examines the downstream consequences of GPi-DBS at the level of the primary motor cortex (M1). Multielectrode, single cell recordings were conducted in the M1 of two parkinsonian nonhuman primates (Macaca fasicularis). GPi-DBS that induced significant reductions in muscular rigidity also reduced the prevalence of both beta (12-30 Hz) oscillations in single unit firing rates and of coherent spiking between pairs of M1 neurons. In individual neurons, GPi-DBS-induced increases in mean firing rate were three times more common than decreases; however, averaged across the population of M1 neurons, GPi-DBS induced no net change in mean firing rate. The population-level prevalence of burst firing was also not affected by GPi-DBS. The results are consistent with the hypothesis that suppression of both pathological, beta oscillations and synchronous activity throughout the cortico-basal ganglia network is a major therapeutic mechanism of GPi-DBS. deep brain stimulation; MPTP; nonhuman primate; Parkinson's disease; primary motor cortex; globus pallidus

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…For instance, STN DBS in patients with PD suppresses beta-band oscillations in the basal ganglia and reduces the aforementioned pathological coupling between beta-band phase and gamma-band amplitudes in MC [307][308][309][310]. GPi DBS also reduces beta-band oscillations in GPi and MC [297,311]. These findings suggest that DBS may exert some of its effects by disrupting abnormal cortical synchronization.…”

“…Thus, it has been found in the MPTP-treated monkey that therapeutically effective STN DBS alters the pattern and power of oscillatory activity of neuronal activity in the motor thalamus, resulting in more regular firing patterns and significant changes in bursting activities [295]. Other recent studies in such animals have shown that clinically effective levels of GPi DBS also affected the firing rates and rhythmicity of cortical neurons [296,297].…”

“…While antidromic stimulation of cortex has also been shown in nonhuman primates and in patients, based on short-latency cortical-evoked potentials [298,301,[303][304][305], it is not clear what role they play in the overall behavioral response to STN DBS in patients with movement disorders. Antidromic effects are not likely to play a prominent role in the case of GPi DBS [297,298], which achieves the same motor result as STN DBS. Finally, a recent rodent study of STN DBS showed that STN DBS may also engage cerebellar activity to improve parkinsonian motor symptoms [306].…”

“…The finding of increased cross-correlation of single-cell discharge in many basal ganglia regions in animal models and patients with PD and increased LFP amplitudes in specific power spectral ranges indicates that the normal level of independence of discharge is substantially reduced in the parkinsonian state [44,322,323,325,326]. Effective antiparkinsonian therapies, including levodopa replacement and DBS reduce the LFP amplitudes to more normal levels, and reduce the abnormal synchrony of neurons in at least some brain regions [see, e.g., 152,297,327].…”

Modulation of Neuronal Activity in the Motor Thalamus during GPi-DBS in the MPTP Nonhuman Primate Model of Parkinson's Disease

“…Multiple other studies, however, have reported increased cGMP levels in the GPi [28] [29] [30] and in the SNr [30] during STN DBS suggesting increased levels of synaptic/metabolic activity consistent with activation of output from the stimulated structure. Regardless of whether one supports the inhibition or activation hypothesis, the far-reaching effect of DBS on other structures in the circuit is supported by a number of studies demonstrating alterations in cortical activity with STN [31] [32] or GPi DBS [33] as well as previous modeling [34,35] and animal studies recording from multiple structures in the circuit [9,24] [36–38]. Changes in extracellular concentrations of striatal GABA and glutamate during STN stimulation lend further support to the varied and complex changes that occur during DBS [39,40].…”