Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson’s disease: a meta-analysis of controlled trials

Abstract

This study aims to investigate how the frequency settings of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) influence the motor symptoms of Parkinson’s disease (PD). Stimulation with frequencies less than 100 Hz (mostly 60 or 80 Hz) is considered low-frequency stimulation (LFS) and with frequencies greater than 100 Hz (mostly 130 or 150 Hz) is considered high-frequency stimulation (HFS). We conducted a comprehensive literature review and meta-analysis with a random-effect model. Ten studies with 132 patients were included in our analysis. The pooled results showed no significant difference in the total Unified Parkinson Disease Rating Scale part III (UPDRS-III) scores (mean effect, −1.50; p = 0.19) or the rigidity subscore between HFS and LFS. Compared to LFS, HFS induced greater reduction in the tremor subscore within the medication-off condition (mean effect, 1.01; p = 0.002), while no significance was shown within the medication-on condition (mean effect, 0.01; p = 0.92). LFS induced greater reduction in akinesia subscore (mean effect, −1.68, p = 0.003), the time to complete the stand-walk-sit (SWS) test (mean effect, −4.84; p < 0.00001), and the number of freezing of gait (FOG) (mean effect, −1.71; p = 0.03). These results suggest that two types of frequency settings may have different effects, that is, HFS induces better responses for tremor and LFS induces greater response for akinesia, gait, and FOG, respectively, which are worthwhile to be confirmed in future study, and will ultimately inform the clinical practice in the management of PD using STN-DBS.

Systematic Evaluation of DBS Parameters in the Hemi-Parkinsonian Rat Model

“…A range of stimulation frequencies ( f ), amplitudes ( Amp. ), pulse-widths ( PW ) and pulse shapes have been investigated over the years ( Moro et al, 2002 ; Spieles-Engemann et al, 2010 ; Gimsa et al, 2011 ; So et al, 2012 ; Kang and Lowery, 2014 ; Khoo et al, 2014 ; Vallabhajosula et al, 2015 ; Picillo et al, 2016 ; Su et al, 2018 ). However, testing alternative DBS parameters in PD patients can be challenging for ethical, certification and technical reasons, demanding a more versatile platform to study the biological outcomes of DBS parameters.…”

Noise-Induced Synchronization and Antiresonance in Interacting Excitable Systems: Applications to Deep Brain Stimulation in Parkinson’s Disease

“…Clinically, the impact of DBS strongly depends on stimulation amplitude and frequency [81]: too-high stimulation frequencies (>180 Hz) were reported to be therapeutically ineffective [50,82], while too low stimulation frequencies have a still debated impact. Indeed, some studies showed that low-frequency stimulation could worsen some parkinsonian symptoms such as tremors and rigidity [83], possibly by imposing another oscillatory rhythm onto the basal ganglia network, while others showed a beneficial impact of lowfrequency stimulation for gait control and cognitive functions [84]. A comparable dependence on amplitude was reported in patients [85], with too-low stimulations abolishing the improvement of symptoms, sometimes with sudden, thresholdlike loss of efficiency [86].…”

A Framework for Adapting Deep Brain Stimulation Using Parkinsonian State Estimates

“…Generally, studies show that the frequency settings of DBS of the STN influence the motor symptoms of PD. For example, the study in Su et al (2018), observed that frequency-specific effects can ultimately inform the frequency programming of STN-DBS in the clinical use. From the studies, what is clear is that DBS has a multimodal and modulating effect on neuronal activities at the stimulation site (Hell et al, 2019).…”

“…More research has focused on stimulation frequency alone (Birdno and Grill, 2008;Baker et al, 2011;Brocker et al, 2013). Varying the stimulation frequency is essential for the therapeutic effects of STN-DBS on motor symptoms in PD (Su et al, 2018). Nevertheless, the major considerations in selecting stimulation parameters are patient responses to stimulation patterns and power consumption to conserve battery life (Kuncel and Grill, 2004).…”

“…Because of the limited availability of PD data incorporating the effects of stimulation, stimulation was modeled only by varying stimulation frequencies. This was chosen because stimulation frequency has proven to be more beneficial and reliable than other stimulation parameters (Birdno and Grill, 2008;Baker et al, 2011;Brocker et al, 2013;Su et al, 2018).…”