Giovanni Battistella1, Kristina Simonyan2. 1. From the Memory and Aging Center (G.B.), Department of Neurology, University of California San Francisco; Department of Otolaryngology (K.S.), Massachusetts Eye and Ear; Department of Neurology (K.S.), Massachusetts General Hospital (K.S.); and Harvard Medical School (K.S.), Boston, MA. 2. From the Memory and Aging Center (G.B.), Department of Neurology, University of California San Francisco; Department of Otolaryngology (K.S.), Massachusetts Eye and Ear; Department of Neurology (K.S.), Massachusetts General Hospital (K.S.); and Harvard Medical School (K.S.), Boston, MA. kristina_simonyan@meei.harvard.edu.
Abstract
OBJECTIVES: To determine the directionality of regional interactions and influences of one region on another within the functionally abnormal sensorimotor network in isolated focal dystonia. METHODS: A total of 40 patients with spasmodic dysphonia with and without dystonic tremor of voice and 35 healthy controls participated in the study. Independent component analysis (ICA) of resting-state fMRI was used to identify 4 abnormally coupled brain regions within the functional sensorimotor network in all patients compared to controls. Follow-up spectral dynamic causal modeling (DCM) estimated regional effective connectivity between patients and controls and between patients with spasmodic dysphonia with and without dystonic tremor of voice to expand the understanding of symptomatologic variability associated with this disorder. RESULTS: ICA found abnormally reduced functional connectivity of the left inferior parietal cortex, putamen, and bilateral premotor cortex in all patients compared to controls, pointing to a largely overlapping pathophysiology of focal dystonia and dystonic tremor. DCM determined that the disruption of the sensorimotor network was both top-down, involving hyperexcitable parieto-putaminal influence, and interhemispheric, involving right-to-left hyperexcitable premotor coupling in all patients compared to controls. These regional alterations were associated with their abnormal self-inhibitory function when comparing patients with spasmodic dysphonia patients with and without dystonic tremor of voice. CONCLUSIONS: Abnormal hyperexcitability of premotor-parietal-putaminal circuitry may be explained by altered information transfer between these regions due to underlying deficient connectivity. Identification of brain regions involved in processing of sensorimotor information in preparation for movement execution suggests that complex network disruption is staged well before the dystonic behavior is produced by the primary motor cortex.
OBJECTIVES: To determine the directionality of regional interactions and influences of one region on another within the functionally abnormal sensorimotor network in isolated focal dystonia. METHODS: A total of 40 patients with spasmodic dysphonia with and without dystonic tremor of voice and 35 healthy controls participated in the study. Independent component analysis (ICA) of resting-state fMRI was used to identify 4 abnormally coupled brain regions within the functional sensorimotor network in all patients compared to controls. Follow-up spectral dynamic causal modeling (DCM) estimated regional effective connectivity between patients and controls and between patients with spasmodic dysphonia with and without dystonic tremor of voice to expand the understanding of symptomatologic variability associated with this disorder. RESULTS:ICA found abnormally reduced functional connectivity of the left inferior parietal cortex, putamen, and bilateral premotor cortex in all patients compared to controls, pointing to a largely overlapping pathophysiology of focal dystonia and dystonic tremor. DCM determined that the disruption of the sensorimotor network was both top-down, involving hyperexcitable parieto-putaminal influence, and interhemispheric, involving right-to-left hyperexcitable premotor coupling in all patients compared to controls. These regional alterations were associated with their abnormal self-inhibitory function when comparing patients with spasmodic dysphoniapatients with and without dystonic tremor of voice. CONCLUSIONS: Abnormal hyperexcitability of premotor-parietal-putaminal circuitry may be explained by altered information transfer between these regions due to underlying deficient connectivity. Identification of brain regions involved in processing of sensorimotor information in preparation for movement execution suggests that complex network disruption is staged well before the dystonic behavior is produced by the primary motor cortex.
Authors: Christian F Beckmann; Marilena DeLuca; Joseph T Devlin; Stephen M Smith Journal: Philos Trans R Soc Lond B Biol Sci Date: 2005-05-29 Impact factor: 6.237
Authors: Nicolas Mallet; Benjamin R Micklem; Pablo Henny; Matthew T Brown; Claire Williams; J Paul Bolam; Kouichi C Nakamura; Peter J Magill Journal: Neuron Date: 2012-06-21 Impact factor: 17.173
Authors: Cathérine C S Delnooz; Jaco W Pasman; Christian F Beckmann; Bart P C van de Warrenburg Journal: PLoS One Date: 2013-05-01 Impact factor: 3.240
Authors: Karl J Friston; Vladimir Litvak; Ashwini Oswal; Adeel Razi; Klaas E Stephan; Bernadette C M van Wijk; Gabriel Ziegler; Peter Zeidman Journal: Neuroimage Date: 2015-11-11 Impact factor: 6.556
Authors: Shabbir Hussain I Merchant; Eleni Frangos; Jacob Parker; Megan Bradson; Tianxia Wu; Felipe Vial-Undurraga; Giorgio Leodori; M C Bushnell; Silvina G Horovitz; Mark Hallett; Traian Popa Journal: Brain Date: 2020-06-01 Impact factor: 13.501
Authors: Kristina Simonyan; Stefan K Ehrlich; Richard Andersen; Jonathan Brumberg; Frank Guenther; Mark Hallett; Matthew A Howard; José Del R Millán; Richard B Reilly; Tanja Schultz; Davide Valeriani Journal: Mov Disord Date: 2022-08-10 Impact factor: 9.698
Authors: 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; Kristine Tanner Journal: Neurology Date: 2021-04-15 Impact factor: 11.800
Authors: Marenka Smit; Alberto Albanese; Monika Benson; Mark J Edwards; Holm Graessner; Michael Hutchinson; Robert Jech; Joachim K Krauss; Francesca Morgante; Belen Pérez Dueñas; Richard B Reilly; Michele Tinazzi; Maria Fiorella Contarino; Marina A J Tijssen Journal: Front Neurol Date: 2021-06-03 Impact factor: 4.003