title: Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.
abstract: To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD).
  
  
  
  Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 × 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month.
  
  
  
  Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms.
  
  
  
  In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects.
  
  
  
  NCT01080794.
  
  
  
  This study provides Class I evidence that in patients with PD with depression, M1 rTMS leads to improvement in motor function while DLPFC rTMS does not lead to improvement in depression compared to sham rTMS.
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Brys
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Fox
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Shashank
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Milton
authors.initials: M
authors.lastname: Biagioni
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dacpano
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pirraglia
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Allan
authors.initials: A
authors.lastname: Wu
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Hubert
authors.initials: H
authors.lastname: Fernandez
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Aparna
authors.initials: A
authors.lastname: Wagle Shukla
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Jau-Shin
authors.initials: JS
authors.lastname: Lou
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Gray
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: David K
authors.initials: DK
authors.lastname: Simon
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Rocco
authors.affiliation: From the New York University School of Medicine (M.B., S.A., M.B., G.D., P.K., A.D.R.), Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, New York; Berenson-Allen Center for Noninvasive Brain Stimulation (M.D.F., Z.G., A.P.-L.), Division of Cognitive Neurology, and Parkinson's Disease and Movement Disorders Center (D.K.S., A.P.-L.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Neurology (A.W.) and Ahmanson-Lovelace Brain Mapping Center (A.W.), University of California School of Medicine, Los Angeles; Cleveland Clinic (H.F.), Department of Neurology, OH; Toronto Western Research Institute (R.C.), University of Toronto, Ontario, Canada; University of Florida (A.W.S.), Department of Neurology, Gainesville; University of North Dakota School of Medicine (J.-S.L.), Department of Neurology, Grand Forks; and Center for Brain Health (E.P.), NYU School of Medicine, New York, NY. apleone@bidmc.harvard.edu.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000209:etiology* / Q000628:therapy*; D010300:Parkinson Disease / Q000150:complications* / Q000628:therapy; D017397:Prefrontal Cortex / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D016896:Treatment Outcome