Clinical Trial: Role of Neurotransmission and Functional CNS Networks in Spasmodic Dysphonia
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Role of Neurotransmission and Functional CNS Networks in Spasmodic Dysphonia and Other Focal Dystonias
Brief Summary:
This study will examine how the brain controls speech in patients with spasmodic dysphonia, a voice disorder that involves involuntary spasms of muscles in the larynx (voice box), causing breaks in speech. Although the causes of spasmodic dysphonia are unknown, recent studies found changes in brain function in patients with the disorder that may play a role in its development.
People between 21 and 80 years of age with adductor spasmodic dysphonia may be eligible for this study. Candidates are screened with the following procedures:
Medical history and physical examination.
Nasolaryngoscopy to examine the larynx. For this test, the inside of the subject s nose is sprayed with a decongestant and a small, flexible tube called a nasolaryngoscope is passed through the nose to the back of the throat to allow examination of the larynx. The subject may be asked to talk, sing, whistle and say prolonged vowels during the procedure. The nasolaryngoscope is connected to a camera that records the movement of the vocal cords during these tasks.
Voice and speech recording to measure the type and severity of voice disorder. Subjects are asked questions about their voice disorder and their voice is recorded while they repeat sentences and sounds.
Participants undergo positron emission tomography (PET) and magnetic resonance imaging (MRI) of the brain, as follows:
PET: A catheter is placed in a vein in the subject s arm to inject a radioactive substance called a tracer that is detected by the PET scanner and provides information on brain function. [11C]flumazenil is used in one scanning session and [11C]raclopride is used in another. For the s
Detailed Summary:
Spasmodic dysphonia (SD) and writer s cramp (WC) are primary focal dystonias with selective impairment of voluntary control of speaking and writing, respectively. Although the pathophysiology of SD and WC is unknown, dystonia is considered to be a disorder of basal ganglia that leads to secondary cortical and subcortical sensorimotor dysfunction. Results of recent neuroimaging studies have established microstructural abnormalities, as well as alterations of functional activity and neurotransmission within the basal ganglia-thalamo-cortical circuitry during symptom production in these patients. Abnormal functional relationships between these brain regions may play an important role in the pathophysiology of dystonia. However, the organization of functional networks and the neurochemical correlates underpinning their abnormalities have not, to date, been fully investigated. A few pharmacological reports of patients have provided indirect evidence of the contributing role of the major basal ganglia neurotransmitters, >=-aminobutyric acid (GABA) and dopamine, to the pathophysiology of this disorder. We identified decreased D2/D3 receptor binding at rest and abnormal dopamine release during both symptomatic and asymptomatic tasks in SD and WC compared to controls. We also identified altered GABAergic transmission, especially involving the laryngeal and hand sensorimotor cortex. These changes in neurotransmission may, in turn, be coupled with abnormalities of network functional activity in these patients and thus contribute to the pathophysiology of this disorder. There is, therefore, a critical need to further investigate the contribution of dopaminergic transmission via D1-family receptors as well as dopaminergic function of substantia nigra, pars compacta (SNc), in order to fully characterize abnormalities of dopaminergic neurotransmission in this disorder. Filling this knowledge gap is essential for development of effec
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Current Primary Outcome: Identify GABAergic and dopaminergic transmission in patients with spasmodic dysphonia and healthy subjects
Original Primary Outcome:
Current Secondary Outcome: Determine the functional brain networks during speech and at rest in patients with spasmodic dysphonia compared to healthy subjects.
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: July 10, 2008
Date Started: July 9, 2008
Date Completion: September 21, 2016
Last Updated: April 21, 2017
Last Verified: September 21, 2016
