Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Abstract

Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency and amplitude of the ERNA decreased before reaching a steady state after ~70 s. Maximal ERNA amplitudes diminished over repeated stimulation blocks. Upon DBS cessation, the ERNA was revealed as an under-damped oscillation, and was more marked and lasted longer after short duration stimulation blocks. In contrast, activity in the beta band suppressed within 0.5 s of continuous DBS onset and drifted less over time. Spontaneous activity was also suppressed in the low gamma band, suggesting that the effects of high frequency stimulation on spontaneous oscillations may not be selective for pathological beta activity. High frequency oscillations were present in only six STN recordings before stimulation onset and their frequency was depressed by stimulation. The different dynamics of the ERNA and beta activity with stimulation imply different DBS mechanisms and may impact how these activities may be used in adaptive feedback.

Subthalamic deep brain stimulation induces finely-tuned gamma oscillations in the absence of levodopa

“…In 4 of 5 patients that displayed any FTG we observed an additional broad low-gamma rebound after stimulation was stopped ( Fig. 1 D), as seen in an earlier study ( Wiest et al, 2020 ). This activity spanned from 40 to 70 Hz.…”

“…In summary, the evidence argues against entrainment of the FTG by DBS off medication and is more in favour of the inducing of FTG as stimulation reconfigures networks to support this oscillation, perhaps paralleling how levodopa reconfigures networks to induce FTG ( Jenkinson et al, 2013 ). Interestingly, the duration over which FTG outlasted stimulation is similar to the time beta oscillations take to return to pre-stimulation levels ( Wiest et al, 2020 ), and corresponds to the delayed recovery of bradykinesia after cessation of DBS ( Kühn et al, 2009 ).…”

“…One explanation might be that the FTG was obscured by a broadband power suppression during DBS in many patients. However, this is unlikely given that power suppression is only significant in the beta and low-gamma range ( Wiest et al, 2020 ). Another explanation might be that patients without FTG were under-stimulated.…”

“…Clinical details are summarised in Table 1 . Data from patients 1 to 9 and patients 11 and 12 were previously published ( Wiest et al, 2020 ).…”

“…During the experiments, patients were comfortably seated in an armchair. Note that recordings were performed using different experimental protocols (some already published, see Wiest et al, 2020 ). Only a few patients were tested at different stimulation frequencies (patients 3, 4, 8 and 9) and durations (patients 4, 5, 6 and 9).…”