Sensory Block + Brain Imaging for Spasmodic Dysphonia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Massachusetts Eye and Ear Infirmary
Must not be taking: CNS drugs
Disqualifiers: Neurological, Psychiatric, Laryngeal, others
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
The researchers will examine functional neural correlates that differentiate between laryngeal dystonia and voice tremor and contribute to disorder-specific pathophysiology using a cross-disciplinary approach of multimodal brain imaging.
Will I have to stop taking my current medications?
If you are taking medications that affect the central nervous system, you will not be able to participate in the trial. The protocol does not specify other medication restrictions, but you will be asked about all medications during the initial screening.
What data supports the effectiveness of the treatment for spasmodic dysphonia?
The research suggests that treatments like botulinum toxin injections can improve brain processing and reduce symptoms in spasmodic dysphonia by enhancing the brain's ability to control voice-related movements. This indicates that brain imaging and sensory block treatments might also help by targeting similar brain areas involved in voice control.12345
Is the sensory block and brain imaging treatment for spasmodic dysphonia safe for humans?
How does the treatment of brain imaging differ from other treatments for spasmodic dysphonia?
Brain imaging for spasmodic dysphonia is unique because it focuses on identifying specific brain activity patterns and abnormalities associated with the condition, rather than directly treating the symptoms. This approach helps in understanding the underlying brain mechanisms and could lead to more targeted therapies in the future.36789
Eligibility Criteria
This trial is for native English-speaking, right-handed adults aged 18-80 who are healthy or have laryngeal dystonia or voice tremor. Excluded are those with other neurological issues, psychiatric disorders, certain laryngeal conditions, history of brain/laryngeal surgery affecting anatomy/function, tattoos/objects unsafe for MRI, and use of central nervous system drugs.Inclusion Criteria
I belong to a diverse racial or ethnic background.
You primarily use your right hand.
I am between 18 and 80 years old.
See 4 more
Exclusion Criteria
I am not taking any medications that affect the brain.
I experience muscle contractions without moving or have mirror dystonia.
You have tattoos or metal objects inside your body that can't be taken out for MRI scans.
See 6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants undergo sensorimotor modulations and auditory feedback processing using bupivacaine, placebo, and MEG imaging to assess CNS pathophysiology
5 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Brain Imaging (Other)
- Topical Bupivacaine (Local Anesthetic)
Trial OverviewThe study aims to understand the differences in brain function between laryngeal dystonia and voice tremor using a sensory block with bupivacaine and advanced brain imaging techniques to identify disorder-specific neural activity patterns.
Participant Groups
5Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Spatial and temporal CNS pathophysiology of laryngeal dystonia and voice tremorExperimental Treatment1 Intervention
Simultaneous fMRI with EEG and MEG imaging will be used to examine neural dynamics during phonation.
Group II: Motor learning and CNS pathophysiology of laryngeal dystonia and voice tremorExperimental Treatment1 Intervention
Implicit learning of the production of motor sequences will be examined during simultaneous fMRI/EEG and MEG imaging.
Sensorimotor adaptation of speech production during MEG imaging will be examined during perturbing pitch or formants of auditory feedback consistently during speech production and examining the behavioral and neural correlates of the resulting across-trial adaptation responses.
Group III: Auditory feedback processing in laryngeal dystonia and voice tremorExperimental Treatment1 Intervention
The role of auditory feedback processing on task-induced speech sensorimotor activity will be examined using MEG imaging during perturbing pitch or formants of auditory feedback, unpredictably during speech production, and examining the behavioral and neural correlates of the resulting within-trial compensation responses.
Group IV: Sensorimotor modulations of laryngeal dystonia and voice tremor with bupivacaineActive Control1 Intervention
Topical laryngeal block (1 ml of 0.75% bupivacaine solution) will be used to modulate somatosensory feedback from the laryngeal mucosa during speech production and examine associated changes in brain activity.
Group V: Placebo effects in laryngeal dystonia and voice tremorPlacebo Group1 Intervention
1 ml of saline placebo matching to 1 ml of 0.75% bupivacaine solution will be used for a comparison with the topical laryngeal block to modulate somatosensory feedback from the laryngeal mucosa during speech production and examine associated changes in brain activity.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts Eye and Ear and University of California San FranciscoBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts Eye and Ear InfirmaryLead Sponsor
University of California, San FranciscoCollaborator
References
Spasmodic dysphonia subsequent to head trauma. [2019]Spasmodic dysphonia (SD) is a low-incidence voice disorder of unknown origin. A subgroup of seven patients with SD from our larger pool of 70 report vocal symptoms subsequent to head injury. This article is a case report of the neurodiagnostic findings, including computed tomography, magnetic resonance imaging, auditory brain-stem response, brain electrical activity mapping, and single photon emission computed tomography for three such patients. For each patient, two or more tests revealed positive neurologic findings. Each test, except computed tomography, demonstrated abnormalities in one or more patients. Two principles of clinical management are derived: (1) information regarding head trauma sustained before SD symptom onset is significant; (2) the absence of neuropathology on a single measure of central nervous system function should not be considered conclusive evidence that no neurologic lesions exist.
Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: an H215O PET study. [2019]Speech-related changes in regional cerebral blood flow (rCBF) were measured using H(2)(15)O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest and during production of continuous narrative speech and whispered speech. Speech was recorded during scan acquisition for offline quantification of voice breaks, pitch breaks, and percentage aperiodicity to assess correlations between treatment-related changes in rCBF and clinical improvement. Results demonstrated that speech-related responses in heteromodal sensory areas were significantly reduced in persons with ADSD, compared with volunteers, before the administration of BTX. Three to 4 weeks after BTX injection, speech-related responses were significantly augmented in these regions and in left hemisphere motor areas commonly associated with oral-laryngeal motor control. This pattern of responses was most strongly correlated with the objective measures of clinical improvement (decreases in the frequency of voice breaks, pitch breaks, and percentage aperiodicity). These data suggest a pathophysiological model for ADSD in which BTX treatment results in more efficient cortical processing of sensory information, making this information available to motor areas that use it to more effectively regulate laryngeal movements.
Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. [2021]Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 spasmodic dysphonia patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus and cerebellar white and grey matter in the patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions, containing calcium, phosphorus and iron, in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus and cerebellum in the postmortem brain tissue from one patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization, limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of spasmodic dysphonia (r = 0.509, P = 0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of this disorder.
Magnetic resonance imaging findings and correlations in spasmodic dysphonia patients. [2017]A sample of 19 spasmodic dysphonia (SD) patients was selected from a larger population of such patients to undergo magnetic resonance imaging (MRI), auditory brain stem response (ABR) testing, speech analysis, and extensive physical examination. Six patients had abnormal spin-echo MRI findings, ranging from infarcts within the basal ganglia to demyelinating lesions within the supralateral angles of the lateral ventricles. A weakly positive correlation was noted between the abnormal MRI findings and an abnormal ABR. The lack of a significant correlation between the MRI findings and other predictors of brain stem and midbrain disease, and the current spatial resolution limitations of MRI, suggest that we are visualizing the associated lesions rather than the actual foci of SD. The range of MRI findings is consistent with the concept that SD is a voice disorder in a heterogeneous patient population.
Type II thyroplasty changes cortical activation in patients with spasmodic dysphonia. [2016]Spasmodic dysphonia (SD) is a complex neurological communication disorder characterized by a choked, strain-strangled vocal quality with voice stoppages in phonation. Its symptoms are exacerbated by situations where communication failures are anticipated, and reduced when talking with animals or small children. Symptoms are also reduced following selected forms of treatment. It is reasonable to assume that surgical alteration reducing symptoms would also alter brain activity, though demonstration of such a phenomenon has not been documented. The objective of this study is to reveal brain activity of SD patients before and after surgical treatment.
Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. [2021]Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.
Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia. [2021]Spasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.
Central auditory evaluation of patients with spasmodic dysphonia. [2010]Spasmodic dysphonia is a focal laryngeal dystonia characterized by inappropriate contractions of the intrinsic laryngeal musculature. The prevalence of associated neurological findings has led to detailed investigation of the central nervous system. Previous research revealed latency abnormalities in patients' auditory brainstem responses. The present study further investigated central auditory findings in patients with spasmodic dysphonia, including brainstem and cortical function. Fourteen normal-hearing patients with spasmodic dysphonia were tested using the auditory brainstem response (ABR) and SCAN-A test of central auditory processing. The ABR estimated brainstem transmission time and evaluated auditory pathway integrity at a high stimulus rate. SCAN-A assessed the auditory cerebral cortex. Implications of these findings are discussed. We found no ABR abnormalities in subjects with spasmodic dysphonia. Positive SCAN-A findings were negligible. The ABR findings contradict previous reports.
Altered sensory system activity and connectivity patterns in adductor spasmodic dysphonia. [2021]Adductor-type spasmodic dysphonia (ADSD) manifests in effortful speech temporarily relievable by botulinum neurotoxin type A (BoNT-A). Previously, abnormal structure, phonation-related and resting-state sensorimotor abnormalities as well as peripheral tactile thresholds in ADSD were described. This study aimed at assessing abnormal central tactile processing patterns, their spatial relation with dysfunctional resting-state connectivity, and their BoNT-A responsiveness. Functional MRI in 14/12 ADSD patients before/under BoNT-A effect and 15 controls was performed (i) during automatized tactile stimulus application to face/hand, and (ii) at rest. Between-group differential stimulation-induced activation and resting-state connectivity (regional homogeneity, connectivity strength within selected sensory(motor) networks), as well as within-patient BoNT-A effects on these differences were investigated. Contralateral-to-stimulation overactivity in ADSD before BoNT-A involved primary and secondary somatosensory representations, along with abnormalities in higher-order parietal, insular, temporal or premotor cortices. Dysphonic impairment in ADSD positively associated with left-hemispheric temporal activity. Connectivity was increased within right premotor (sensorimotor network), left primary auditory cortex (auditory network), and regionally reduced at the temporoparietal junction. Activation/connectivity before/after BoNT-A within-patients did not significantly differ. Abnormal ADSD central somatosensory processing supports its significance as common pathophysiologic focal dystonia trait. Abnormal temporal cortex tactile processing and resting-state connectivity might hint at abnormal cross-modal sensory interactions.