Scientific Updates

Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia: An fMRI Study

Authors: Kristina Simonyan, M.D., Ph.D., and Christy L. Ludlow, Ph.D.

The full article on this study was published in Cerebral Cortex (2010): March 1.

Abstract
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.

Lay summary of research
Although it is well known that patients with spasmodic dysphonia (SD) have uncontrolled spasms in their laryngeal muscles that interfere with speaking, it is not know what abnormalities in the brain produce those spasms. In this study, we wanted to find out what abnormalities occur in the brain during speaking but not during production of other types of sounds that do not produce spasms in SD patients. Also, we wanted to compared brain function when SD patients are speaking and having voice breaks with brain function in persons without SD to determine what brain abnormalities might produce spasms in the laryngeal muscles in SD. The differences in brain function between persons with normal speech and patients with SD were in the primary sensorimotor cortex (the part of the brain associated with laryngeal muscle and laryngeal sensory control), the superior temporal gyrus (the part of the brain associated with listening to speech) and the insula (the part of the brain associated with sensory and motor integration). Surprisingly, these differences in brain function occurred even when persons with SD were performing other types of sounds that did not produce spasms in the laryngeal muscles. In addition, the patients had reduced brain function in regions at the inner part of the brain (basal ganglia, thalamus) and in the cerebellum. Further, increases in brain function found in the part of the brain associated with laryngeal sensory control were related to the severity of voice breaks in speech in the persons with adductor SD. Finally, the brain function differences between persons without abductor and adductor SD were similar, except that the increase of brain function in the part of the brain associated with laryngeal muscle and laryngeal sensory control was greater in persons with abductor SD.  Overall, we found that the increase in function of the sensory cortex that has to do with laryngeal feedback to the brain, was the most impaired function in SD patients and may play an important role in the generation of muscle spasms in SD.

Focal White Matter Changes in Spasmodic Dysphonia: A Combined Diffusion Tensor Imaging and Neuropathological Study

Authors: Kristina Simonyan, Fernanda Tovar-Moll, John Ostuni, Mark Hallett, Victor F. Kalasinsky, Michael R. Lewin-Smith, Elisabeth J. Rushing, Alexander O. Vortmeyer, Christy L. Ludlow

The full article on this study was published in Brain (2008): 131(2), 447-459.

Abstract
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.

Lay Summary of Research
Spasmodic Dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are known, the brain abnormalities underlying this voice disorder remain unknown. Using magnetic resonance imaging (MRI) available in most hospitals, no brain abnormalities are seen in persons with SD. However, when some specialized techniques were used, referred to as Diffusion Tensor Imaging (DTI), we found structural brain differences in patients with SD in comparison with normal speakers. This study compared 20 SD patients and 20 healthy subjects using this specialized technique. The connecting pathways in the brain from the cortex down to the brain stem region, where the neurons controlling the laryngeal muscles can be found, were measured on both sides of the brain. In this study, the connecting pathway on the right side of the brain from the cortex to the brainstem showed some thinning suggesting that some of the fibers from cortical neurons going to the brainstem were either injured or losing their myelin covering.

We also studied a brain that was donated by an SD patient and their family and compared it with brains of people who had normal speech. No gross abnormalities could be seen in the brain of the SD patient in comparison with the three controls. However, when we closely examined the region that showed abnormalities on brain imaging with DTI, we found some thinning in the same region—the right internal capsule, which carries fibers from the laryngeal motor cortical region towards the brainstem motor nuclei for laryngeal muscle control. In addition, in regions of the basal ganglia, thalamus and cerebellum we also found clusters of mineral accumulations, which contained calcium, phosphorus, and iron. This indicates that some abnormal processes have occurred in the brains of persons with SD but does not tell us what caused those abnormalities.

This study is important because it is the first time we have found abnormalities that may underlie the development of the voice disorder in persons with spasmodic dysphonia. The next step will be to determine what has caused these abnormalities to occur. Studies of abnormalities in proteins that may have produced the build up of these deposits in the brain will be required to unravel the cause of SD.