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Affected Brain Regions (for Point 1)

Simonyan, K., Tovar-Moll, F., Ostuni, J., Hallett, M., Kalasinsky, V. F., Lewin-Smith, M. R.,. . . Ludlow, C. L. (2007). Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. Brain, 131(2), 447-459. doi:10.1093/brain/awm303

Diffusion tensor imaging has been used to identify brain differences between SD patients and healthy individuals and to target those brain regions for neuropathological examination in SD patients. The location of these brain abnormalities makes them specific to SD; they are located in the corticobulbar/corticospinal tract and its main input/output structures (the basal ganglia, thalamus, and cerebellum). It is suggested that SD may be associated with alterations in connectivity of the corticobulbar tract coming from the laryngeal/orofacial motor cortex to the brainstem phonatory nuclei. The basal ganglia balances excitation and inhibition of the thalamo-cortical circuit involved in motor execution; this balance is thought to be altered in task-specific dystonias due to reduced GABAergic metabolism and dopaminergic receptor binding--this leads to excessive motor cortical excitation. The cerebellum is involved in motor control via the ventrolateral thalamus and has a modulatory role in coordination of voice and speech production; cerebellar dysfunction and atrophy have been reported in a group of patients with dystonia, suggesting that this disorder may arise from cerebellar disorganization. Together these affected brain regions result in problems in linguistic output.

Abnormal Structure–Function Relationship in Spasmodic Dysphonia (for Point 3)

Simonyan, K., and C. L. Ludlow. "Abnormal Structure-Function Relationship in Spasmodic Dysphonia." Cerebral Cortex 22.2 (2011): 417-25. Web.

In studies that have measured grey matter volume and cortical thickness and examined the measures for relationships with blood oxygen level-dependent signal change during speech production, it has been found that the left anterior insula in SD patients has decreased cortical thickness. Yet this part of the insula also has been found to have increased functional activation, positive relationships between cortical thickness measurements/brain activation, and SD symptom severity with no volumetric changes.The insula is involved in a wide variety of behaviors, including voice and speech control. This is due in part to its direct connections with the laryngeal motor cortex, inferior frontal gyrus, auditory, and cingulate cortexes. While several studies have suggested that it is involved in motor planning of speech production, this view also associates the anterior insula with the temporal processing of auditory stimuli and the control of automatic aspects of speech production.

Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia (for Point 4)

Simonyan, Kristina, and Christy L. Ludlow. "Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia: An FMRI Study." Cerebral Cortex. Oxford University Press, 01 Mar. 2010. Web. 28 Apr. 2017.

In fMRI studies that have aimed to identify symptom-specific functional brain activation abnormalities in SD, it has been found that increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production. This suggests that abnormally increased extent and intensity of activation in this region may represent a disorder-specific phenomenon. Despite increased activation extent in the sensorimotor cortex in SD patients, some studies have found a lack of correlation in brain activation intensity between the primary motor and somatosensory cortices, which points to an impaired link between these two regions. As the sensory system plays an important role in driving the motor system, abnormal functional activation and correlations of the primary somatosensory cortex with other brain regions in SD patients may reflect the altered processing of sensory feedback, which, in turn, may affect motor control and sensorimotor functional integration during voice production in these patients.

Brainstem pathology in spasmodic dysphonia (for Point 2)

Simonyan, Kristina, Christy L. Ludlow, and Alexander O. Vortmeyer. "Brainstem Pathology in Spasmodic Dysphonia." The Laryngoscope. Wiley Subscription Services, Inc., A Wiley Company, 30 Sept. 2009. Web. 28 Apr. 2017.

Studies that have examined postmortem brainstem tissue from SD patients have found a presence of small clusters of microglia/macrophages activation in the reticular formation surrounding the lower brainstem nuclei involved in the control of laryngeal functions and mild neuronal degeneration and depigmentation in the substantia nigra and the locus coeruleus in SD patients compared to controls. The presence of small clusters of microglia/macrophages activation in the brainstem reticular formation of SD patients may represent a disorder-specific neuropathological process, because of their location in the area of the nuclei responsible for sensory (solitary tract and spinal trigeminal nuclei) and motor (nucleus ambiguus) control of voice production. Mild neuronal degeneration and depigmentation of the pars compact of the substantia nigra and the locus coeruleus is also similar to those reported in patients with idiopathic cervical dystonia, Meige’s syndrome and torsion dystonia. So the involvement of the substantia nigra and the locus coeruleus may represent a common neuropathogenic process in both early- and late-onset primary dystonias.