Alberto J Espay1, Scott Ries2, Thomas Maloney2, Jennifer Vannest2, Erin Neefus2, Alok K Dwivedi2, Jane B Allendorfer2, Lawson R Wulsin2, W Curt LaFrance2, Anthony E Lang2, Jerzy P Szaflarski2. 1. From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada. alberto.espay@uc.edu. 2. From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
Abstract
OBJECTIVES: To evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults. METHODS: Fifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation. RESULTS: CBT markedly reduced tremor severity (p < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing (p = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression (r = 0.75, p < 0.01). CONCLUSIONS: Tremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.
OBJECTIVES: To evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults. METHODS: Fifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation. RESULTS: CBT markedly reduced tremor severity (p < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing (p = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression (r = 0.75, p < 0.01). CONCLUSIONS:Tremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.
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