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Randomized, Sham-Controlled Trial of Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Tics in Adolescents With Tourette Syndrome

      Abstract

      Background

      Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention—real-time functional magnetic resonance imaging neurofeedback from the SMA—for reduction of tics in adolescents with TS.

      Methods

      Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback.

      Results

      All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA.

      Conclusions

      This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action.

      Keywords

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      References

        • Scahill L.
        • Dalsgaard S.
        • Bradbury K.
        The prevalence of Tourette syndrome and ints relationship to clinical features.
        in: Martino D. Leckman J.F. Tourette Syndrome. Oxford University Press, New York, NY2013: 121-136
        • Bloch M.H.
        • Leckman J.F.
        Clinical course of Tourette syndrome.
        J Psychosom Res. 2009; 67: 497-501
        • Woods D.W.
        • Piacentini J.C.
        • Chang S.W.
        • Deckersbach T.
        • Ginsburg G.S.
        • Peterson A.L.
        • et al.
        Managing Tourette Syndrome: A Behavioral Intervention.
        Oxford University Press, New York, NY2008
        • Piacentini J.
        • Woods D.W.
        • Scahill L.
        • Wilhelm S.
        • Peterson A.L.
        • Chang S.
        • et al.
        Behavior therapy for children with Tourette disorder: A randomized controlled trial.
        JAMA. 2010; 303: 1929-1937
        • Murphy T.K.
        • Lewin A.B.
        • Storch E.A.
        • Stock S.
        Practice parameter for the assessment and treatment of children and adolescents with tic disorders.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 1341-1359
        • Weisman H.
        • Qureshi I.A.
        • Leckman J.F.
        • Scahill L.
        • Bloch M.H.
        Systematic review: Pharmacological treatment of tic disorders - Efficacy of antipsychotic and alpha-2 adrenergic agonist agents.
        Neurosci Biobehav Rev. 2013; 37: 1162-1171
        • Himle M.B.
        • Woods D.W.
        • Bunaciu L.
        Evaluating the role of contingency in differentially reinforced tic suppression.
        J Appl Behav Anal. 2008; 41: 285-289
        • Alegria A.A.
        • Wulff M.
        • Brinson H.
        • Barker G.J.
        • Norman L.J.
        • Brandeis D.
        • et al.
        Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder.
        Hum Brain Mapp. 2017; 38: 3190-3209
        • Goldway N.
        • Ablin J.
        • Lubin O.
        • Zamir Y.
        • Keynan J.N.
        • Or-Borichev A.
        • et al.
        Volitional limbic neuromodulation has a multifaceted clinical benefit in Fibromyalgia patients.
        Neuroimage. 2019; 186: 758-770
        • Mehler D.M.A.
        • Sokunbi M.O.
        • Habes I.
        • Barawi K.
        • Subramanian L.
        • Range M.
        • et al.
        Targeting the affective brain—a randomized controlled trial of real-time fMRI neurofeedback in patients with depression.
        Neuropsychopharmacology. 2018; 43: 2578-2585
        • Ramot M.
        • Kimmich S.
        • Gonzalez-Castillo J.
        • Roopchansingh V.
        • Popal H.
        • White E.
        • et al.
        Direct modulation of aberrant brain network connectivity through real-time neurofeedback.
        Elife. 2017; 6e28974
        • Young K.D.
        • Siegle G.J.
        • Zotev V.
        • Phillips R.
        • Misaki M.
        • Yuan H.
        • et al.
        Randomized clinical trial of real-time fMRI amygdala neurofeedback for major depressive disorder: Effects on symptoms and autobiographical memory recall.
        Am J Psychiatry. 2017; 174: 748-755
        • Zhao Z.
        • Yao S.
        • Li K.
        • Sindermann C.
        • Zhou F.
        • Zhao W.
        • et al.
        Real-time functional connectivity-informed neurofeedback of amygdala-frontal pathways reduces anxiety.
        Psychother Psychosom. 2019; 88: 5-15
        • Zilverstand A.
        • Sorger B.
        • Slaats-Willemse D.
        • Kan C.C.
        • Goebel R.
        • Buitelaar J.K.
        fMRI neurofeedback training for increasing anterior cingulate cortex activation in adult attention deficit hyperactivity disorder. An exploratory randomized, single-blinded study.
        PLoS One. 2017; 12e0170795
        • Subramanian L.
        • Morris M.B.
        • Brosnan M.
        • Turner D.L.
        • Morris H.R.
        • Linden D.E.
        Functional magnetic resonance imaging neurofeedback-guided motor imagery training and motor training for Parkinson's disease: Randomized trial.
        Front Behav Neurosci. 2016; 10: 111
        • Robertson M.M.
        • Eapen V.
        • Singer H.S.
        • Martino D.
        • Scharf J.M.
        • Paschou P.
        • et al.
        Gilles de la Tourette syndrome.
        Nat Rev Des Primers. 2017; 3: 16097
        • Fried I.
        • Katz A.
        • McCarthy G.
        • Sass K.J.
        • Williamson P.
        • Spencer S.S.
        • et al.
        Functional organization of human supplementary motor cortex studied by electrical stimulation.
        J Neurosci. 1991; 11: 3656-3666
        • Biswal B.
        • Ulmer J.L.
        • Krippendorf R.L.
        • Harsch H.H.
        • Daniels D.L.
        • Hyde J.S.
        • et al.
        Abnormal cerebral activation associated with a motor task in Tourette syndrome.
        Am J Neuroradiol. 1998; 19: 1509-1512
        • Braun A.R.
        • Stoetter B.
        • Randolph C.
        • Hsiao J.K.
        • Vladar K.
        • Gernert J.
        • et al.
        The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls.
        Neuropsychopharmacology. 1993; 9: 277-291
        • Bohlhalter S.
        • Goldfine A.
        • Matteson S.
        • Garraux G.
        • Hanakawa T.
        • Kansaku K.
        • et al.
        Neural correlates of tic generation in Tourette syndrome: An event-related functional MRI study.
        Brain. 2006; 129: 2029-2037
        • Stern E.
        • Silbersweig D.A.
        • Chee K.-Y.
        • Holmes A.
        • Robertson M.M.
        • Trimble M.
        • et al.
        A functional neuroanatomy of tics in Tourette syndrome.
        Arch Gen Psychiatry. 2000; 57: 741-748
        • Hampson M.
        • Tokoglu F.
        • King R.A.
        • Constable R.T.
        • Leckman J.F.
        Brain areas coactivating with motor cortex during chronic motor tics and intentional movements.
        Biol Psychiatry. 2009; 65: 594-599
        • Neuner I.
        • Werner C.J.
        • Arrubla J.
        • Stocker T.
        • Ehlen C.
        • Wegener H.P.
        • et al.
        Imaging the where and when of tic generation and resting state networks in adult Tourette patients.
        Front Hum Neurosci. 2014; 8: 362
        • Papoutsi M.
        • Weiskopf N.
        • Langbehn D.
        • Reilmann R.
        • Rees G.
        • Tabrizi S.J.
        Stimulating neural plasticity with real-time fMRI neurofeedback in Huntington's disease: A proof of concept study.
        Hum Brain Mapp. 2018; 39: 1339-1353
        • Subramanian L.
        • Hindle J.V.
        • Johnston S.
        • Roberts M.V.
        • Husain M.
        • Goebel R.
        • et al.
        Real-time functional magnetic resonance imaging neurofeedback for treatment of Parkinson's disease.
        J Neurosci. 2011; 31: 16309-16317
        • Leckman J.F.
        • Riddle M.A.
        • Hardin M.T.
        • Ort S.I.
        • Swartz K.L.
        • Stevenson J.
        • et al.
        The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale of tic severity.
        J Am Acad Child Adolesc Psychiatry. 1989; 28: 566-573
        • Kaufman J.
        • Birmaher B.
        • Brent D.
        • Rao U.
        • Flynn C.
        • Moreci P.
        • et al.
        Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data.
        J Am Acad Child Adolesc Psychiatry. 1997; 36: 980-988
        • Kaufman A.S.
        • Kaufman N.L.
        Kaufman Brief Intelligence Test: Manual.
        American Guidance Service, Circle Pines, MN1990
        • Leckman J.F.
        • King R.A.
        • Scahill L.
        • Findley D.
        • Ort S.I.
        • Cohen D.J.
        Yale approach to assessment and treatment.
        in: Leckman J.F. Cohen D.J. Tourette's Syndrome—Tics, Obsessions, Compulsions: Developmental Psychopathology and Clinical Care. Wiley, New York, NY1999: 285-309
        • Jeon S.
        • Walkup J.T.
        • Woods D.W.
        • Peterson A.
        • Piacentini J.
        • Wilhelm S.
        • et al.
        Detecting a clinically meaningful change in tic severity in Tourette syndrome: A comparison of three methods.
        Contemp Clin Trials. 2013; 36: 414-420
        • Guy W.
        Clinical Global Impression Scales (CGI). ECDEU Assessment Manual for Psychopharmacology (Publication 76-338).
        Department of Health, Education, and Welfare, Washington, DC1976
        • Scheinost D.
        • Hampson M.
        • Qiu M.
        • Bhawnani J.
        • Constable R.T.
        • Papademetris X.
        A graphics processing unit accelerated motion correction algorithm and modular system for real-time fMRI.
        Neuroinformatics. 2013; 11: 291-300
        • Rance M.
        • Walsh C.
        • Sukhodolsky D.G.
        • Pittman B.
        • Qiu M.
        • Kichuk S.A.
        • et al.
        Time course of clinical change following neurofeedback.
        Neuroimage. 2018; 181: 807-913
        • Sepulveda P.
        • Sitaram R.
        • Rana M.
        • Montalba C.
        • Tejos C.
        • Ruiz S.
        How feedback, motor imagery, and reward influence brain self-regulation using real-time fMRI.
        Hum Brain Mapp. 2016; 37: 3153-3171

      Linked Article

      • Potential New Tourette Syndrome Treatments: Will Real-Time Neurofeedback Have a Role?
        Biological PsychiatryVol. 87Issue 12
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          Tourette syndrome (TS), also known as Tourette’s disorder, is a neurodevelopmental disorder with onset in early childhood characterized by multiple motor tics and at least one vocal tic that have been present for longer than 1 year. TS is a model neuropsychiatric disorder, in that the vast majority of affected individuals, whether ascertained in clinical or community settings, experience at least one co-occurring psychiatric disorder, such as attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and/or mood, anxiety, and specific learning disorders (1).
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