title: Effect of rTMS on brain activation in schizophrenia with negative symptoms: A proof-of-principle study.
abstract: BACKGROUND
  Prefrontal cortical dysfunction is frequently reported in schizophrenia and is thought to underlie negative symptoms of schizophrenia. Repetitive Transcranial Magnetic Stimulation (rTMS) can modulate neuronal activity and has been shown to improve negative symptoms in patients with schizophrenia, but the underlying neural mechanism is unknown.
  
  
  OBJECTIVE
  To examine whether 3weeks of 10Hz rTMS treatment of the bilateral dorsolateral prefrontal cortex (DLPFC) would improve frontal brain activation in patients with negative symptoms of schizophrenia, as measured by functional magnetic resonance imaging (fMRI) during the Tower of London (ToL) task.
  
  
  METHODS
  24 patients with the diagnosis of schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale≥15) participated. Patients were randomized to a 3-week (15day) course of active or sham rTMS. All patients performed the ToL task during fMRI scanning both pre-treatment and post-treatment. Differences in brain activation between the two groups were compared non-parametrically.
  
  
  RESULTS
  After rTMS treatment, brain activity in the active group increased in the right DLPFC and the right medial frontal gyrus as compared to the sham group. In addition, the groups significantly differed with regard to activation change in the left posterior cingulate, with decreased activation in the active and increased activation in the sham group.
  
  
  CONCLUSIONS
  Treatment with rTMS over the DLPFC may have the potential for increasing task-related activation in frontal areas in patients with schizophrenia. Effects of different rTMS parameters and fMRI tasks targeting relevant brain circuitry deserve further investigation.
  
  
  BACKGROUND
  Nederlands Trial Register, registration number: NTR1261.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Rob Giel Research Center, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands. Electronic address: j.j.l.a.s.n.dlabac@umcg.nl.
authors.forename: Jozarni J
authors.initials: JJ
authors.lastname: Dlabac-de Lange
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands.
authors.forename: Edith J
authors.initials: EJ
authors.lastname: Liemburg
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands; Lentis Psychiatric Institute, Lentis Research, Hereweg 80, 9725 AG Groningen, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Bais
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands.
authors.forename: Remco J
authors.initials: RJ
authors.lastname: Renken
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Rob Giel Research Center, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands; Lentis Psychiatric Institute, Lentis Research, Hereweg 80, 9725 AG Groningen, The Netherlands.
authors.forename: Henderikus
authors.initials: H
authors.lastname: Knegtering
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Psychology, Grote Kruisstraat 2/1, 9712 TS Groningen, The Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Aleman
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008606:Mental Processes / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000503:physiopathology* / Q000628:therapy*; D012565:Schizophrenic Psychology; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents
keywords: Functional; MRI; Prefrontal cortex; Repetitive; Schizophrenia; Tower of London; Transcranial Magnetic Stimulation