Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson’s disease: A potential biomarker for optimal electrode placement

Abstract

Background: Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson's Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. Objective: We explored whether recovery of the H-reflexdan easily measured electrophysiological analogue of the stretch reflex, known to be altered in PDdcould serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN-or GPi-DBS implantation. Methods: Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. Results: Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. Conclusion: H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

Anticipatory Postural Adjustments and Compensatory Postural Responses to Multidirectional Perturbations—Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease

“…This is supported by several other studies that found that STN-DBS alters postural alignment and consequently can effect postural reflex responses [ 71 , 76 , 105 ]. Studies investigating the latency of electrically induced so-called Hofmann (H) reflex, which is an analogue of the mechanically induced stretch reflex, also provide evidence that STN-DBS may change reflex timing [ 156 , 157 , 158 ]. Pötter-Nerger et al reported the facilitation effects of the H-reflex after STN-DBS was switched on [ 156 ].…”

The significance of the loss of presynaptic inhibition for step initiation in parkinsonian individuals with freezing of gait

“…On the other hand, the electrophysiological studies on PD patients undergoing deep brain stimulation (DBS) surgery showed significant improvement in PSI soon after the therapy (Pierantozzi et al 2008;Andrews et al 2020). Combining these study results (Morita et al 2000;Pierantozzi et al 2008;Silva-Batista et al 2017;Andrews et al 2020;Lira et al 2020), the significance of PSI in the motor output in PD is demonstrated. However, it is unclear whether this mechanism plays a role as a primary target, or represents, rather, a contributory mechanism to the disturbance in the cortical motor pathways, or represents an insufficient compensatory process to normalize the abnormal motor symptoms.…”

“…In another study (Silva-Batista et al 2017), improvement in the spinal inhibitory mechanisms including PSI was found to be positively associated with the postural instability and quality of life scores in PD subjects and improvement in this function was achieved after resistance training for 12 weeks (Silva-Batista et al 2017). On the other hand, the electrophysiological studies on PD patients undergoing deep brain stimulation (DBS) surgery showed significant improvement in PSI soon after the therapy (Pierantozzi et al 2008;Andrews et al 2020). Combining these study results (Morita et al 2000;Pierantozzi et al 2008;Silva-Batista et al 2017;Andrews et al 2020;Lira et al 2020), the significance of PSI in the motor output in PD is demonstrated.…”

“…2017; Andrews et al . 2020; Lira et al . 2020), the significance of PSI in the motor output in PD is demonstrated.…”

Deep brain–machine interfaces: sensing and modulating the human deep brain

“…A recent study illustrated cortical response features evoked by DBS that are closely related to the hyperdirect pathway through which STN receives input signals from cortical regions [ 101 ]. Another study used intraoperative H-reflex measurement as a potential biomarker for optimal electrode positioning [ 102 ]. Some closed-loop systems could also take multi-modal signals such as acceleration and heart rate as biomarkers [ 103 ].…”