Temporal specificity of abnormal neural oscillations during phonatory events in laryngeal dystonia
Authors: Kothare Hardik , Schneider Sarah , Mizuiri Danielle , Hinkley Leighton , Bhutada Abhishek , Ranasinghe Kamalini , Honma Susanne , Garrett Coleman , Klein David , Naunheim Molly , Yung Katherine , Cheung Steven , Rosen Clark , Courey Mark , Nagarajan Srikantan , Houde John 
Published: February 2022

Abstract
Laryngeal dystonia is a debilitating disorder of voicing in which the laryngeal muscles are intermittently in spasm resulting in involuntary interruptions during speech. The central pathophysiology of laryngeal dystonia, underlying computational impairments in vocal motor control, remains poorly understood. Although prior imaging studies have found aberrant activity in the CNS during phonation in patients with laryngeal dystonia, it is not known at what timepoints during phonation these abnormalities emerge and what function may be impaired. To investigate this question, we recruited 22 adductor laryngeal dystonia patients (15 female, age range = 28.83–72.46 years) and 18 controls (eight female, age range = 27.40–71.34 years). We leveraged the fine temporal resolution of magnetoencephalography to monitor neural activity around glottal movement onset, subsequent voice onset and after the onset of pitch feedback perturbations. We examined event-related beta-band (12–30 Hz) and high-gamma-band (65–150 Hz) neural oscillations. Prior to glottal movement onset, we observed abnormal frontoparietal motor preparatory activity. After glottal movement onset, we observed abnormal activity in the somatosensory cortex persisting through voice onset. Prior to voice onset and continuing after, we also observed abnormal activity in the auditory cortex and the cerebellum. After pitch feedback perturbation onset, we observed no differences between controls and patients in their behavioural responses to the perturbation. But in patients, we did find abnormal activity in brain regions thought to be involved in the auditory feedback control of vocal pitch (premotor, motor, somatosensory and auditory cortices). Our study results confirm the abnormal processing of somatosensory feedback that has been seen in other studies. However, there were several remarkable findings in our study. First, patients have impaired vocal motor activity even before glottal movement onset, suggesting abnormal movement preparation. These results are significant because (i) they occur before movement onset, abnormalities in patients cannot be ascribed to deficits in vocal performance and (ii) they show that neural abnormalities in laryngeal dystonia are more than just abnormal responses to sensory feedback during phonation as has been hypothesized in some previous studies. Second, abnormal auditory cortical activity in patients begins even before voice onset, suggesting abnormalities in setting up auditory predictions before the arrival of auditory feedback at voice onset. Generally, activation abnormalities identified in key brain regions within the speech motor network around various phonation events not only provide temporal specificity to neuroimaging phenotypes in laryngeal dystonia but also may serve as potential therapeutic targets for neuromodulation.