Spasmodic dysphonia (SD) is a debilitating disorder of voicing where the laryngeal muscles are intermittently in spasm. This prevents the vocal folds from vibrating efficiently and results in involuntary interruptions during speech. Treatment options for SD are limited, with only temporary symptom relief provided by Botulinum toxin (Botox) injections. SD is thought to be a dysfunction originating in the central nervous system (CNS), and may involve abnormal cortical processing of sensory feedback during phonation. However, the underlying causes of SD remain ambiguous and largely unknown. Several neuroimaging studies have examined phonation in patients with SD and have found aberrant activations in a number of cortical and subcortical regions. However, because these studies were based on fMRI and PET, which have poor temporal resolution, they do not resolve when these aberrant activations occurred in relation to the phonation act. As a result, critical clues about what causes SD have likely been missed. Our lab has done extensive work modeling the dynamics of speech production. From our model, we conclude that inferring functional impairments in SD from aberrant CNS activity requires knowing more than where in the CNS the aberrant activity occurs. It also requires knowing when in the act of phonation (e.g., initial glottal movement, voice onset, and sustained phonation) it is occurring. Here we propose to address this issue using magnetoencephalographic imaging (MEGI) - a functional imaging method our lab has developed based on MEG, which can reconstruct cortical activity with millisecond accuracy and sub-centimeter resolution.
In Specific Aim 1, we will reconstruct cortical activity using MEGI while subjects (patients with SD and neurotypical controls) repeatedly produce a steady-state phonation and we monitor their glottal movement with electromyography (EMG). Abnormal pre/motor cortical activity in patients (compared to controls) prior to glottal movement would suggest impairments in feed forward motor preparation. Abnormal activity immediately after glottal movement onset but prior to phonation would suggest selective deficits in somatosensory feedback processing, whereas abnormal activity following phonation would suggest deficits in somatosensory and/or auditory feedback processing. To isolate whether SD specifically involves deficits in auditory feedback processing, in Specific Aim 2 we will use MEGI to monitor cortical activity as subjects phonate when we briefly perturb the pitch they hear in the audio feedback of their ongoing phonation. Abnormal cortical responses to the perturbation seen in patients prior to compensation would suggest deficits in auditory feedback processing, while those seen after onset of compensation would suggest abnormal motor responses to auditory feedback. Results from proposed studies will help us to isolate where and when the deficits related to SD arise in the cortical pathways controlling phonation. This will help us to devise novel, and perhaps more effective, treatments for SD and also help us to better understand how existing treatments work or can be improved.
Spasmodic dysphonia (SD) is a debilitating disorder of voicing where the glottal muscles are in spasm, preventing proper phonation. Treatment options for SD are severely limited, mostly to Botox injections that temporarily relieve symptoms. SD is thought to be a dysfunction originating in the central nervous system (CNS), but beyond this, little is known about the cause of SD. Here, we propose to use magnetoencephalography (MEG), which has high time resolution, to examine the neural events associated with utterance production in SD. The results of the proposed studies will give us a clearer understanding of the causes of SD, which will likely lead to greatly improved treatments for this disorder.
| Sekihara, Kensuke; Adachi, Yoshiaki; Kubota, Hiroshi K et al. (2018) Beamspace dual signal space projection (bDSSP): a method for selective detection of deep sources in MEG measurements. J Neural Eng 15:036026 |
| Ranasinghe, Kamalini G; Gill, Jeevit S; Kothare, Hardik et al. (2017) Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease. Neurobiol Aging 52:71-80 |
| Sekihara, Kensuke; Nagarajan, Srikantan S (2017) Subspace-based interference removal methods for a multichannel biomagnetic sensor array. J Neural Eng 14:051001 |
| Houde, John F; Chang, Edward F (2015) The cortical computations underlying feedback control in vocal production. Curr Opin Neurobiol 33:174-81 |
