• brain

    The Functional Connectome of Speech Control

    PLoS Biology 2015

  • JNeurosci

    Functional but not structural networks of the human laryngeal motor cortex show left hemispheric lateralization during syllable

    Journal of Neuroscience 2009

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  • ALA2019

    American Laryngological Association 2019

    Alexis Worthley: Outstanding Paper Award and Travel Award

  • stars

    Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia

    Journal of Neuroscience 2017

  • peacock2

    High-frequency brain networks undergo modular breakdown during epileptic seizures

    Epilepsia 2016

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    Happy Birthday!

  • pathology

    Focal white matter changes in laryngeal dystonia

    Brain 2008

  • modeling

    Dopamine drives left-hemispheric lateralization of neural networks during human speech

    Journal of Comparative Neurology 2018

  • DystoniaNet
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    Team work

We investigate neural mechanisms of isolated focal dystonia and tremor to determine the disorder-specific pathophysiology and develop novel diagnostic tools and therapeutic strategies for these patients. We use a variety of experimental approaches, including multimodal neuroimaging, advanced machine-learning, clinical-behavioral testing, neuropathology, and genetics. Explore our website to learn more about our researchdiscoveries and team.
The Dystonia and Speech Motor Control Laboratory is supported by supported by the National Institutes of Health - National Institute on Deafness and Other Communication Disorders (NIDCD) and National Institute of Neurological Disorders and Stroke (NINDS), Department of Defense, Amazon Web Services, Jazz Pharmaceuticals, Mass General Brigham Innovation.

Recent Publications

Multimodal collaborative brain-computer interfaces aid human-machine team decision-making in a pandemic scenario
Davide Valeriani, Lena C. O'Flynn, Alexis Worthley, Azadeh Hamzehei Sichani, and Kristina Simonyan. 2022. “Multimodal collaborative brain-computer interfaces aid human-machine team decision-making in a pandemic scenario.” Journal of Neural Engineering, Sep 30.Abstract
Objective: Critical decisions are made by effective teams that are characterized by individuals who trust each other and know how to best integrate their opinions. Here, we introduce a multimodal BCI to help collaborative teams of humans and an artificial agent achieve more accurate decisions in assessing danger zones during a pandemic scenario. Approach: Using high-resolution simultaneous EEG/fMRI, we first disentangled the neural markers of decision-making confidence and trust and then employed machine-learning to decode these neural signatures for BCI-augmented team decision-making. We assessed the benefits of BCI on the team's decision-making process compared to the performance of teams of different sizes using the standard majority or weighing individual decisions. Main results: We showed that BCI-assisted teams are significantly more accurate in their decisions than traditional teams, as the BCI is capable of capturing distinct neural correlates of confidence on a trial-by-trial basis. Accuracy and subjective confidence in the context of collaborative BCI engaged parallel, spatially distributed, and temporally distinct neural circuits, with the former being focused on incorporating perceptual information processing and the latter involving action planning and executive operations during decision making. Among these, the superior parietal lobule emerged as a pivotal region that flexibly modulated its activity and engaged premotor, prefrontal, visual, and subcortical areas for shared spatial-temporal control of confidence and trust during decision-making. Significance: Multimodal, collaborative BCIs that assist human-artificial agent teams may be utilized in critical settings for augmented and optimized decision-making strategies.
Functional Neural Networks in Writer's Cramp as Determined by Graph-Theoretical Analysis
Jana Schill, Kirsten E. Zeuner, Arne Knutzen, Inken Tödt, Kristina Simonyan, and Karsten Witt. 2021. “Functional Neural Networks in Writer's Cramp as Determined by Graph-Theoretical Analysis.” Frontiers in Neurology, 12, Pp. 2106.Abstract
Dystonia, a debilitating neurological movement disorder, is characterized by involuntary muscle contractions and develops from a complex pathophysiology. Graph theoretical analysis approaches have been employed to investigate functional network changes in patients with different forms of dystonia. In this study, we aimed to characterize the abnormal brain connectivity underlying writer's cramp, a focal hand dystonia. To this end, we examined functional magnetic resonance scans of 20 writer's cramp patients (11 females/nine males) and 26 healthy controls (10 females/16 males) performing a sequential finger tapping task with their non-dominant (and for patients non-dystonic) hand. Functional connectivity matrices were used to determine group averaged brain networks. Our data suggest that in their neuronal network writer's cramp patients recruited fewer regions that were functionally more segregated. However, this did not impair the network's efficiency for information transfer. A hub analysis revealed alterations in communication patterns of the primary motor cortex, the thalamus and the cerebellum. As we did not observe any differences in motor outcome between groups, we assume that these network changes constitute compensatory rerouting within the patient network. In a secondary analysis, we compared patients with simple writer's cramp (only affecting the hand while writing) and those with complex writer's cramp (affecting the hand also during other fine motor tasks). We found abnormal cerebellar connectivity in the simple writer's cramp group, which was less prominent in complex writer's cramp. Our preliminary findings suggest that longitudinal research concerning cerebellar connectivity during WC progression could provide insight on early compensatory mechanisms in WC.
Laryngeal Dystonia: Multidisciplinary Update on Terminology, Pathophysiology, and Research Priorities
Kristina Simonyan, Julie Barkmeier-Kraemer, Andrew Blitzer, Mark Hallett, John F Houde, Teresa Jacobson Kimberley, Laurie J Ozelius, Michael J Pitman, Robert Mark Richardson, Nutan Sharma, and Kristine Tanner. 2021. “Laryngeal Dystonia: Multidisciplinary Update on Terminology, Pathophysiology, and Research Priorities.” Neurology, 96, 21, Pp. 989-1001.Abstract
OBJECTIVE: To delineate research priorities for improving clinical management of laryngeal dystonia, the NIH convened a multidisciplinary panel of experts for a 1-day workshop to examine the current progress in understanding its etiopathophysiology and clinical care. METHODS: The participants reviewed the current terminology of disorder and discussed advances in understanding its pathophysiology since a similar workshop was held in 2005. Clinical and research gaps were identified, and recommendations for future directions were delineated. RESULTS: The panel unanimously agreed to adopt the term "laryngeal dystonia" instead of "spasmodic dysphonia" to reflect the current progress in characterizations of this disorder. Laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonia. Its etiology remains unknown, whereas the pathophysiology likely involves large-scale functional and structural brain network disorganization. Current challenges include the lack of clinically validated diagnostic markers and outcome measures and the paucity of therapies that address the disorder pathophysiology. CONCLUSION: Research priorities should be guided by challenges in clinical management of laryngeal dystonia. Identification of disorder-specific biomarkers would allow the development of novel diagnostic tools and unified measures of treatment outcome. Elucidation of the critical nodes within neural networks that cause or modulate symptoms would allow the development of targeted therapies that address the underlying pathophysiology. Given the rarity of laryngeal dystonia, future rapid research progress may be facilitated by multicenter, national and international collaborations.
Suicidal Ideations and Attempts in Patients with Isolated Dystonia
Alexis Worthley and Kristina Simonyan. 2021. “Suicidal Ideations and Attempts in Patients with Isolated Dystonia.” Neurology, 96, 11, Pp. e1551-e1560.Abstract
OBJECTIVE: To evaluate the hypothesis that individuals with isolated dystonia are at an increased risk for suicidal behavior, we administered an anonymous electronic survey to patients with dystonia, asking them about their history of suicidal ideations and suicide attempt. METHODS: A total of 542 patients with dystonia completed an online 97-question survey, which captured the demographics of suicidal behavior and major psychiatric disorders in these patients. Statistical analyses examined the prevalence of suicidal behavior in patients with dystonia compared to the prevalence of suicidal ideations and attempt in the general global population and assessed the significance of risk associations between suicidality and psychiatric history in these patients. RESULTS: Overall, 32.3% of patients with isolated dystonia reported a lifetime history of suicidal behavior, which was significantly different from the reported rates of suicidal ideation (9.2%) and attempt (2.7%) in the general global population. The prevalence of suicidality was higher in patients with multifocal/segmental and generalized forms of dystonia (range of 46%-50%) compared to patients with focal dystonias (range of 26.1%-33.3%). The highest suicidal ideation-to-attempt ratio of 4:1 was found in patients with generalized dystonia. Suicidality in patients with focal dystonia was significantly associated with their history of depression and anxiety disorders. CONCLUSION: Patients with isolated dystonia have an increased, albeit unrecognized, prevalence of suicidal behavior compared to the general global population. The screening for suicidal risk should be incorporated as part of the clinical evaluation of patients with dystonia to prevent their suicide-induced injury and death.
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