title: Cognitive safety of dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression.
abstract: The most widely used target for repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD) is the dorsolateral prefrontal cortex (DLPFC). Despite convergent evidence that the dorsomedial prefrontal cortex (DMPFC) may be a promising alternative target for rTMS in TRD, its cognitive safety profile has not previously been assessed. Here, we applied 20 sessions of rTMS to the DMPFC in 21 TRD patients. Before and after treatment, a battery of neuropsychological tasks was administered to evaluate changes in cognition across three general cognitive domains: learning and memory, attention and processing speed, and cognitive flexibility. Subjects also completed the 17-item Hamilton Rating Scale for Depression (HamD17) prior to and following treatment to measure changes in severity of depressive symptoms, and to assess the relationship between mood and cognitive performance over the course of treatment. No serious adverse effects or significant deterioration in cognitive performance were observed. Overall, subjects improved significantly on Stroop Inhibition/Switching and on Trails B, and this improvement was independent of the degree of improvement in depression symptoms. No domains or items significantly predicted clinical outcome, with the exception of baseline performance on Visual Elevator Accuracy. Clinical improvement correlated to improved performance in the overall domain of attention and processing speed, although this effect was not evident following covariate adjustment. DMPFC-rTMS did not produce any detectable cognitive adverse effects during treatment of TRD. Performance did not deteriorate significantly on any measures. Taken together, the present findings support the tolerability and cognitive safety of DMPFC-rTMS in refractory depression.
authors.affiliation: MRI-Guided rTMS Clinic, Department of Psychiatry, University Health Network, 399 Bathurst Street, Room 7M-415, Toronto, Ontario, Canada M5T 2S8; Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, 1 King׳s College Circle, Room 2374, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Laura
authors.initials: L
authors.lastname: Schulze
authors.affiliation: Toronto Western Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wheeler
authors.affiliation: Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, 1 King׳s College Circle, Room 2374, Toronto, Ontario, Canada M5S 1A8; Toronto Western Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8.
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: McAndrews
authors.affiliation: MRI-Guided rTMS Clinic, Department of Psychiatry, University Health Network, 399 Bathurst Street, Room 7M-415, Toronto, Ontario, Canada M5T 2S8.
authors.forename: Chloe J E
authors.initials: CJ
authors.lastname: Solomon
authors.affiliation: MRI-Guided rTMS Clinic, Department of Psychiatry, University Health Network, 399 Bathurst Street, Room 7M-415, Toronto, Ontario, Canada M5T 2S8; Department of Psychiatry, University of Toronto, 250 College Street, Floor 8, Toronto, Ontario, Canada M5T 1R8; Toronto Western Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8.
authors.forename: Peter
authors.initials: P
authors.lastname: Giacobbe
authors.affiliation: MRI-Guided rTMS Clinic, Department of Psychiatry, University Health Network, 399 Bathurst Street, Room 7M-415, Toronto, Ontario, Canada M5T 2S8; Department of Psychiatry, University of Toronto, 250 College Street, Floor 8, Toronto, Ontario, Canada M5T 1R8; Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, 1 King׳s College Circle, Room 2374, Toronto, Ontario, Canada M5S 1A8; Toronto Western Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. Electronic address: jonathan.downar@uhn.ca.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Downar
mesh_terms: D000328:Adult; D000339:Affect; D000368:Aged; D003071:Cognition; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000523:psychology* / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000523:psychology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000627:therapeutic use; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011619:Psychotropic Drugs
keywords: Cognition; Dorsomedial prefrontal cortex (DMPFC); Major depression; Neurostimulation; Repetitive transcranial magnetic stimulation (rTMS); Safety