The research focus of the Simonyan Laboratory is two-fold: identification of the central mechanisms responsible for speech production and elucidation of the pathophysiology of neurological voice and speech disorders.
Our earlier contributions involved identification of the extensive projection system of the laryngeal motor cortex in the rhesus monkey using neuroanatomical tract tracing. Using multimodal neuroimaging, our laboratory later played a central role in i) identification of the laryngeal motocortical representation in humans; ii) defining the functional connectome of speech production, and iii) elucidation of the mechanisms of dopaminergic neurotransmission during speaking, as well as those underlying left-hemispheric lateralization of speech networks. We are currently focused on examining temporal characteristics of laryngeal motocortical activity and the modulatory role of different neurotransmitters on neural networks controlling speech production. To this end, we are developing multi-compartmental neural population models to test specific hypotheses about speech motor control, which have remained extremely challenging to address due to either invasiveness of the applied methods or technical limitations.
Our contributions to the understanding of the pathophysiology of neurological speech disorders include a comprehensive mapping of brain functional, structural and dopaminergic alterations as well as identification of neuropathological changes in spasmodic dysphonia (laryngeal dystonia) and voice tremor. We demonstrated that focal dystonia is a disorder of large-scale functional neural networks, where abnormal regional interactions may contribute to network-wide alterations. We also established that abnormal sensory discrimination thresholds in patients with focal dystonias represent a common endophenotypic trait of this disorder. We further showed that clinically and genetically distinct forms of spasmodic dysphonia can be accurately classified based on cortical sensorimotor abnormalities, the latter serving as potential objective diagnostic markers for this disorder. Our laboratory described the first spasmodic dysphonia patient with a causative DYT25 (GNAL) mutation and determined the polygenic risk of focal dystonia. Most recently, we delineated the first effective use of a novel oral medication, sodium oxybate (Xyrem®), in patients with spasmodic dysphonia and voice tremor.
The Simonyan laboratory currently uses multi-modal neuroimaging, machine learning, and neural population modeling to determine and validate phenotype- and genotype-specific neural markers of dystonia as well as the endophenotypic markers of its development. We are also working on the identification of the primary neural determinants of clinical response to sodium oxybate in patients with dystonia and tremor as a potential new therapeutic option. Another goal is to delineate abnormal neurotransmission in dystonia, which would ultimately help identify other novel pharmacological targets. We are applying several genetic strategies, including next-generation sequencing in dystonia families and singleton cases as well as genome-wide association studies in isolated populations, in order to identify new genes and risk factors of spasmodic dysphonia.
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Tweets by @SimonyanLab
- Excited to share some of my dissertation research from the @GuentherLab, now out in #JSLHR! Shout outs to @LizHellerMurray @MMasapollo @sqcai @jay2our @alf_nie! t.co/aJ3e2oZk7w
- Great paper in Brain. Wonder how the pathways for essential tremor and dystonic tremor differ? @DBSThinkTank @leaddbs @UFMDFellowship @brainstimj @JNeuromod t.co/Z7oS8UQ2ox t.co/1u6nx1eFY3
- Big news! We are extremely proud to announce that @dmrf has partnered with @FrontiersIn to launch the first ever scientific journal dedicated to #dystonia. Chief editors are Dr. Roy V. Sillitoe and Dr. Aasef Shaikh. Learn more: t.co/H11DrwUN5U @SillitoeLab @cwru t.co/DiH2Wv6DGS
- Today we announce the launch of a new Frontiers partner journal Dystonia, the official journal of Dystonia Medical Research Foundation @dmrf. The journal is led by chief editors Dr. Roy Sillitoe @SillitoeLab and Dr. Aasef Shaikh from @cwru. #OpenAccess #FrontiersOApartners