Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia
- 353 Downloads
Tremor, affecting a dystonic body part, is a frequent feature of adult-onset dystonia. However, our understanding of dystonic tremor pathophysiology remains ambiguous as its interplay with the main co-occurring disorder, dystonia, is largely unknown. We used a combination of functional MRI, voxel-based morphometry and diffusion-weighted imaging to investigate similar and distinct patterns of brain functional and structural alterations in patients with dystonic tremor of voice (DTv) and isolated spasmodic dysphonia (SD). We found that, compared to controls, SD patients with and without DTv showed similarly increased activation in the sensorimotor cortex, inferior frontal (IFG) and superior temporal gyri, putamen and ventral thalamus, as well as deficient activation in the inferior parietal cortex and middle frontal gyrus (MFG). Common structural alterations were observed in the IFG and putamen, which were further coupled with functional abnormalities in both patient groups. Abnormal activation in left putamen was correlated with SD onset; SD/DTv onset was associated with right putaminal volumetric changes. DTv severity established a significant relationship with abnormal volume of the left IFG. Direct patient group comparisons showed that SD/DTv patients had additional abnormalities in MFG and cerebellar function and white matter integrity in the posterior limb of the internal capsule. Our findings suggest that dystonia and dystonic tremor, at least in the case of SD and SD/DTv, are heterogeneous disorders at different ends of the same pathophysiological spectrum, with each disorder carrying a characteristic neural signature, which may potentially help development of differential markers for these two conditions.
KeywordsDystonic tremor Laryngeal dystonia fMRI Tbss VBM
We thank Amanda Pechman, BA, Ian M. Farwell, MSG, and Heather Alexander, BA, for help with patient recruitment and data acquisition.
KS designed the study; DNK, GB, ERT, MC collected the data; DNK, GB, VK, ERT, MC, AR and KS analyzed the data; DNK wrote the first draft of the manuscript; KS, GB, VK, ERT, MC and AR revised and critiqued the paper.
Compliance with ethical standards
Conflict of interest
Diana N. Kirke declares that she has no conflict of interest. Diana N. Kirke was supported by a research fellowship grant from the Foundation for Surgery Reg Worcester Research Fellowship Scholarship, Royal Australasian College of Surgeons.
Giovanni Battistella declares that he has no conflict of interest.
Veena Kumar declares that she has no conflict of interest.
Estee Rubien-Thomas declares that she has no conflict of interest.
Melissa Choy declares that she has no conflict of interest.
Anna Rumbach declares that she has no conflict of interest.
Kristina Simonyan declares that she has no conflict of interest. Kristina Simonyan received grants from National Institute on Deafness and Other Communication Disorders, National Institutes of Health (R01DC011805, R01DC012434, R01DC007658), National Institute of Neurological Disorders and Stroke, National Institutes of Health (R01NS088160). Kristina Simonyan serves on the Medical and Scientific Advisory Council of the Dystonia Medical Research Foundation.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
This study was funded by the National Institute on Deafness and Other Communication Disorders, National Institutes of Health (grant number R01DC012545) to KS. DNK was supported by a research fellowship grant from the Foundation for Surgery Reg Worcester Research Fellowship Scholarship, Royal Australasian College of Surgeons.
- Basho, S., Palmer, E. D., Rubio, M. A., Wulfeck, B., & Muller, R. A. (2007). Effects of generation mode in fMRI adaptations of semantic fluency: paced production and overt speech. Neuropsychologia, 45(8), 1697–1706. doi: 10.1016/j.neuropsychologia.2007.01.007.CrossRefPubMedPubMedCentralGoogle Scholar
- Berardelli, A., Rothwell, J. C., Day, B. L., & Marsden, C. D. (1985). Pathophysiology of blepharospasm and oromandibular dystonia. Brain, 108 (Pt 3), 593–608.Google Scholar
- Crosson, B., Benefield, H., Cato, M. A., Sadek, J. R., Moore, A. B., Wierenga, C. E., et al. (2003). Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes. Journal of the International Neuropsychological Society, 9(7), 1061–1077. doi: 10.1017/S135561770397010X.PubMedGoogle Scholar
- Defazio, G., Conte, A., Gigante, A. F., Fabbrini, G., & Berardelli, A. (2015). Is tremor in dystonia a phenotypic feature of dystonia? American academy of neurology(84), 1053–1059.Google Scholar
- Deuschl, G., Bain, P., & Brin, M. (1998). Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Movement Disorders, 13 Suppl 3, 2–23.Google Scholar
- Ramdhani, R. A., & Simonyan, K. (2013). Primary dystonia: conceptualizing the disorder through a structural brain imaging lens. Tremor Other Hyperkinet Mov (N Y), 3.Google Scholar
- Simonyan, K., & Ludlow, C. L. (2010). Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Cerebral Cortex, 20(11), 2749–2759. doi: 10.1093/cercor/bhq023.
- Simonyan, K., & Ludlow, C. L. (2012). Abnormal structure-function relationship in spasmodic dysphonia. Cerebral Cortex, 22(2), 417–25. doi: 10.1093/cercor/bhr120.
- Simonyan, K., Tovar-Moll, F., Ostuni, J., Hallett, M., Kalasinsky, V. F., Lewin-Smith, M. R., et al. (2008). Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. Brain, 131(Pt 2), 447–459. doi: 10.1093/brain/awm303.CrossRefPubMedGoogle Scholar
- Simonyan, K., Ostuni, J., Ludlow, C. L., & Horwitz, B. (2009). Functional but not structural networks of the human laryngeal motor cortex show left hemispheric lateralization during syllable but not breathing production. The Journal of Neuroscience, 29(47), 14912–14923. doi: 10.1523/JNEUROSCI.4897-09.2009.CrossRefPubMedPubMedCentralGoogle Scholar
- Simonyan, K., Berman, B. D., Herscovitch, P., & Hallett, M. (2013). Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia. The Journal of Neuroscience, 33(37), 14705–14714. doi: 10.1523/JNEUROSCI.0407-13.