Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease

Abstract

Strong synchronization of neuronal activity occurs in the 8-35 Hz band in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is evident as oscillatory local field potential (LFP) activity. To test whether such synchronization may contribute to bradykinesia and rigidity, we sought correlations between the suppression of synchronization at 8-35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep-brain stimulation electrodes in nine PD patients. LFP power was calculated over the frequencies of the most prominent spectral peak within the 8-35 Hz frequency band on each of 17 sides (off medication), and over the frequencies of any peak in the 60-90 Hz band, if present (seven sides, on medication). Levodopa-induced reduction of LFP power over these two frequency ranges was then correlated with improvement in motor impairment as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak activity in the 8-35 Hz band with levodopa positively correlated with the improvement in the contralateral hemibody motor UPDRS score with levodopa (r = 0.811, P < 0.001) as well as with hemibody subscores of akinesia-rigidity (r = 0.835, P < 0.001), but not tremor. A trend for negative correlations was found between peak 60-90 Hz LFP power and UPDRS hemibody score, suggesting that positive correlations were relatively frequency-specific. Our results support a link between levodopa-induced improvements in bradykinesia and rigidity and reductions in population synchrony at frequencies < 35 Hz in the region of the STN in patients with PD.

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

“…Using conventionally defined frequency bands, we find SChI stimulation increased alpha oscillations (8-15 Hz) in striatum but not in M1. Interestingly, the PD motor symptoms of bradykinesia and rigidity are correlated with elevated beta oscillations in basal ganglia that can extend down to 8 Hz and, thus, includes the alpha frequency range (4,28).…”

“…Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4,5). Beta oscillations are also found in the CBT circuits of patients with other movement-related disorders, such as epilepsy and dystonia (6,7), and in normal, nonhuman primates (8,9) and normal rodents (10,11).…”

“…striatum | optogenetics | beta oscillations | coherence | cholinergic interneurons E xaggerated beta oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1)(2)(3)(4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4,5).…”

Thalamic Deep Brain Stimulation for Parkinson’s Disease

“…STN LFPs in PD patients show synchronized activity with the basal ganglia; these oscillations occur mainly in the range (15-30 Hz) (Kühn et al, 2004;Hammond et al, 2007). Both STN-DBS and Ldopa administration either ameliorate this -range oscillation or shift it to a higher ( range) frequency (Brown et al, 2001;Kühn et al, 2006). The -range STN stimulation causes further impairment of movement in PD patients (Brown et al, 2001;Fogelson et al, 2005;Chen et al, 2007;Eusebio et al, 2008).…”

Non-invasive brain stimulation for Parkinson’s disease: Current concepts and outlook 2015

“…In PD patients in the off-condition, pathological oscillatory activity in the beta-frequency range (10-30 Hz) predominates (Brown, 2007). This beta-activity decreases in response to dopamine (Kuhn, Kupsch, Schneider, & Brown, 2006) and high-frequency (130 Hz) DBS (Kuhn et al, 2008), while gamma activity (>30 Hz) emerges along with clinical improvement (Brown et al, 2001). Further support comes from beta-frequency (20 Hz) stimulation of the subthalamic nucleus which enhances bradykinesia (C. C. Chen et al, 2007) indicating a potential contribution of beta-activity to bradykinesia and rigidity in PD (Brown, 2007).…”