High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson's disease

Abstract

Parkinson's disease (PD) is marked by excessive synchronous activity in the beta (8–35 Hz) band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS) within the subthalamic nucleus (STN) region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and is of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI) to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway (HDP) between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05). Cortical signals over the estimated origin of the HDP also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially-specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.

Network effects of deep brain stimulation

“…In addition, these authors proposed that broadband cortical gamma activity might maintain this abnormal coupling by feedback via the hyperdirect pathway from cortex to STN. Separately, Whitmer and colleagues (Whitmer et al 2012). However, the findings of Whitmer and colleagues were not reproducible across a larger patient sample, and in more extensive work de Hemptinne and colleagues showed that DBS reversibly reduced an exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity in motor cortex (de Hemptinne et al 2015).…”

Neuroscience: Tuning the brain

“…There is some evidence 2 that as Parkinson's destroys neurons in the basal ganglia, the activity of groups of cells in the STN and across this sensorimotor network becomes abnormally synchronized, locking at certain frequencies. DBS seems to release them from these activity patterns, as do some of the drugs that relieve Parkinson's symptoms 3,4 .…”

Neuromagnetic investigations of mechanisms and effects of STN-DBS and medication in Parkinson's disease

“…While Whitmer et al (2012)s showed that DBS in STN suppresses motor cortical beta band power, others showed no effect of DBS on beta (13-30 Hz) or broadband gamma (50-200 Hz) oscillations (de Hemptinne et al, 2013;Rowland et al, 2015). The only two available studies using MEG and testing PD patients ON and OFF DBS in resting state also showed no effect of beta power at rest, though gamma power (34-38 Hz) was affected by DBS (Cao et al, 2015(Cao et al, , 2017.…”

“…Functionally, beta oscillations are thought to signal status quo while gamma activity is thought to underlie active processing in the underlying neuronal population (Fries, 2009;Manning et al, 2009;Engel and Fries, 2010). For instance, the enhanced beta-band oscillations in STN and motor cortex are accompanied by motor symptoms in PD (Pollok et al, 2012;Whitmer et al, 2012). Dopaminergic treatment and DBS suppress beta-activity and boost Background 32 Background gamma-activity in the STN and this is shown to correlate with better motor symptoms (Kühn et al, 2006.…”

“…High-frequency DBS in the STN (and slightly dorsal to it) reduced the resting state beta power in cortex (Whitmer et al, 2012), a phenomenon observed in the STN, as well, and the reduction is known to correlate with improved motor performance (Kühn et al, 2006. ECoG studies with sophisticated metrics like phase-amplitude coupling (PAC) have shown that the pathological exaggerated PAC between beta-phase and gamma amplitude in the motor cortex is suppressed with DBS (de Hemptinne et al, 2013.…”