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A recent expert consensus labelled the incidence of tremor as a core feature of dystonia that can affect body regions both symptomatic and asymptomatic to dystonic features. We are only beginning to understand the neural network-level signatures that relate to clinical features of dystonic tremor. At the same time, clinical features of dystonic tremor can resemble that of essential tremor and present a diagnostic confound for clinicians. Here, we examined network-level functional activation and connectivity in patients with dystonic tremor and essential tremor. The dystonic tremor group included primarily cervical dystonia patients with dystonic head tremor and the majority had additional upper-limb tremor. The experimental paradigm included a precision grip-force task wherein online visual feedback related to force was manipulated across high and low spatial feedback levels. Prior work using this paradigm in essential tremor patients produced exacerbation of grip-force tremor and associated changes in functional activation. As such, we directly compared the effect of visual feedback on grip-force tremor and associated functional network-level activation and connectivity between dystonic tremor and essential tremor patient cohorts to better understand disease-specific mechanisms. Increased visual feedback similarly exacerbated force tremor during the grip-force task in dystonic tremor and essential tremor cohorts. Patients with dystonic tremor and essential tremor were characterized by distinct functional activation abnormalities in cortical regions but not in the cerebellum. We examined seed-based functional connectivity from the sensorimotor cortex, globus pallidus internus, ventral intermediate thalamic nucleus, and dentate nucleus, and observed abnormal functional connectivity networks in dystonic tremor and essential tremor groups relative to controls. However, the effects were far more widespread in the dystonic tremor group as changes in functional connectivity were revealed across cortical, subcortical, and cerebellar regions independent of the seed location. A unique pattern for dystonic tremor included widespread reductions in functional connectivity compared to essential tremor within higher-level cortical, basal ganglia, and cerebellar regions. Importantly, a receiver operating characteristic determined that functional connectivity z-scores were able to classify dystonic tremor and essential tremor with 89% area under the curve, whereas combining functional connectivity with force tremor yielded 94%. These findings point to network-level connectivity as an important feature that differs substantially between dystonic tremor and essential tremor and should be further explored in implementing appropriate diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.1093\/brain\/awz085","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T16:22:00Z","timestamp":1552580520000},"page":"1644-1659","source":"Crossref","is-referenced-by-count":71,"title":["Network-level connectivity is a critical feature distinguishing dystonic tremor and essential tremor"],"prefix":"10.1093","volume":"142","author":[{"given":"Jesse C","family":"DeSimone","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-0785","authenticated-orcid":false,"given":"Derek B","family":"Archer","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Vaillancourt","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA"},{"name":"Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA"},{"name":"Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Wagle Shukla","sequence":"first","affiliation":[{"name":"Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA"},{"name":"Fixel Center for Neurological Disease, College of Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"2020040720052299800_awz085-B1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.25475","article-title":"Phenomenology and classification of dystonia: a consensus update","volume":"28","author":"Albanese","year":"2013","journal-title":"Mov Disord"},{"key":"2020040720052299800_awz085-B2","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1093\/brain\/awx338","article-title":"A widespread visually-sensitive functional network relates to symptoms in essential tremor","volume":"141","author":"Archer","year":"2018","journal-title":"Brain"},{"key":"2020040720052299800_awz085-B3","doi-asserted-by":"crossref","first-page":"9740","DOI":"10.1523\/JNEUROSCI.2300-09.2009","article-title":"Cerebellothalamocortical connectivity regulates penetrance in dystonia","volume":"29","author":"Argyelan","year":"2009","journal-title":"J Neurosci"},{"key":"2020040720052299800_awz085-B4","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/ene.13067","article-title":"Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia","volume":"23","author":"Battistella","year":"2016","journal-title":"Eur J Neurol"},{"key":"2020040720052299800_awz085-B5","first-page":"1203","article-title":"Isolated focal dystonia as a disorder of large-scale functional networks","volume":"27","author":"Battistella","year":"2017","journal-title":"Cereb Cortex"},{"key":"2020040720052299800_awz085-B6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"key":"2020040720052299800_awz085-B7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/mds.27121","article-title":"Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society","volume":"33","author":"Bhatia","year":"2018","journal-title":"Mov Disord"},{"key":"2020040720052299800_awz085-B8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.11138\/FNeur\/2018.33.1.045","article-title":"A role for accelerometry in the differential diagnosis of tremor syndromes","volume":"33","author":"Bove","year":"2018","journal-title":"Funct Neurol"},{"issue":"Pt 1","key":"2020040720052299800_awz085-B9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/brain\/117.1.39","article-title":"Rapid wrist movements in patients with essential tremor. 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