Effect of deep brain stimulation on vocal motor control mechanisms in Parkinson's disease

Abstract

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for limb motor symptoms in Parkinson's disease (PD); however, its effect on vocal motor function has yielded conflicted and highly variable results. The present study investigated the effects of STN-DBS on the mechanisms of vocal production and motor control.

Methods: A total of 10 PD subjects with bilateral STN-DBS implantation were tested with DBS ON and OFF while they performed steady vowel vocalizations and received randomized upward or downward pitch-shift stimuli (±100 cents) in their voice auditory feedback.

Results: Data showed that the magnitude of vocal compensation responses to pitch-shift stimuli was significantly attenuated during DBS ON vs. OFF (p = 0.012). This effect was direction-specific and was only observed when subjects raised their voice fundamental frequency (F0) in the opposite direction to downward stimuli (p = 0.019). In addition, we found that voice F0 perturbation (i.e. jitter) was significantly reduced during DBS ON vs. OFF (p = 0.022), and this DBS-induced modulation was positively correlated with the attenuation of vocal compensation responses to downward pitch-shift stimuli (r = +0.57, p = 0.028).

Conclusions: These findings provide the first data supporting the role of STN in vocal F0 motor control in response to altered auditory feedback. The DBS-induced attenuation of vocal compensation responses may result from increased inhibitory effects of the subcortical hyperdirect (fronto-subthalamic) pathways on the vocal motor cortex, which can help stabilize voice F0 and ameliorate vocal motor symptoms by impeding PD subjects' abnormal (i.e. overshooting) vocal responses to alterations in the auditory feedback.

Keywords: Auditory feedback; Deep brain stimulation; Parkinson's disease; Subthalamic nucleus; Voice motor control.

Fig. 1.

Panels A–C: the mean of vocalization F0, intensity, and HNR across all trials overlaid for DBS ON vs. DBS OFF in one representative subject (shaded areas show the standard deviation; time 0 denotes onset of vocalization). Panels D–H: bar plot representations of the mean (and standard error of the mean: SE_M) for the grand-average (n = 10 subjects) measures of vocalization F0, intensity, HNR, jitter, and shimmer for DBS ON vs. DBS OFF.

Fig. 2.

Panels A–C: Vocal compensation responses to upward pitch-shift stimuli (+100 cents). Panel A: profiles of grand-average mean voice F0 responses overlaid for DBS ON vs. OFF (time 0 notes onset of pitch-shift stimuli). Panel B: bar plot representation of the grand-average response means within a 200 ms window centered on the peak. Panel C: correlation plots of vocal compensation vs. jitter modulation during DBS ON vs. DBS OFF. Panels D–F Results for vocal compensations to downward pitch-shift stimuli (−100 cents). All error bars represent the standard error of the mean (SE_M).

Fig. 3.

The sensorimotor integration model of vocal control. In this model, the auditory-motor interface transforms efference copies of motor plans into forward predictions and compares them with auditory feedback to detect and correct for errors through generating compensatory vocal motor responses. In Parkinson's disease, dysfunctions in cortico-basal ganglia network results in reduced inhibitory input to cortical motor areas. This reduced inhibition contributes to increased corrective efforts in the feedforward motor system leading to abnormal (overshooting) vocal compensation responses to alterations in the auditory feedback (AAF). In addition, reduced inhibition of the vocal motor cortex increases its top-down effect on enhancing auditory neural sensitivity to feedback alterations. This increased neural sensitivity results in elevated sensory gain for generating larger error signals, and subsequently, larger compensatory vocal responses to alterations in the auditory feedback. vPMC: ventral pre-motor cortex; IFG: inferior frontal gyrus; M1: primary motor cortex; HG: Heschl's gyrus; STG: superior temporal gyrus; STS: superior temporal sulcus; Spt: Sylvian parietal temporal; PT; planum temporale.