title: Abnormal brain oscillations persist after recovery from bipolar depression.
abstract: When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20-40Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21-50Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11-27Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.
authors.affiliation: Department of clinical neurosciences, scientific institute Ospedale San Raffaele, university Vita-Salute San Raffaele, San Raffaele Turro, 20, via Stamira d'Ancona, 20127 Milano, Italy. Electronic address: canali.paola@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Canali
authors.affiliation: Department of biomedical and clinical sciences "L. Sacco", università degli Studi di Milano, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Casarotto
authors.affiliation: Department of biomedical and clinical sciences "L. Sacco", università degli Studi di Milano, Milano, Italy; Fondazione Europea di Ricerca Biomedica, FERB Onlus, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rosanova
authors.affiliation: Department of clinical neurosciences, scientific institute Ospedale San Raffaele, university Vita-Salute San Raffaele, San Raffaele Turro, 20, via Stamira d'Ancona, 20127 Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sferrazza-Papa
authors.affiliation: Institute of science and technology, Federal university of São Paulo, 330, Rua Talim, São José dos Campos, Brazil.
authors.forename: A G
authors.initials: AG
authors.lastname: Casali
authors.affiliation: Coma science group, GIGA research & neurology department, university hospital of Liège, Liège, Belgium; Center for sleep and consciousness, Postle laboratory, department of psychology and psychiatry, university of Wisconsin, Madison, WI, USA.
authors.forename: O
authors.initials: O
authors.lastname: Gosseries
authors.affiliation: Department of biomedical and clinical sciences "L. Sacco", università degli Studi di Milano, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Massimini
authors.affiliation: Department of clinical neurosciences, scientific institute Ospedale San Raffaele, university Vita-Salute San Raffaele, San Raffaele Turro, 20, via Stamira d'Ancona, 20127 Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Smeraldi
authors.affiliation: Department of clinical neurosciences, scientific institute Ospedale San Raffaele, university Vita-Salute San Raffaele, San Raffaele Turro, 20, via Stamira d'Ancona, 20127 Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Department of clinical neurosciences, scientific institute Ospedale San Raffaele, university Vita-Salute San Raffaele, San Raffaele Turro, 20, via Stamira d'Ancona, 20127 Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D004569:Electroencephalography / Q000379:methods; D055724:Electrophysiological Phenomena; D005260:Female; D006801:Humans; D008297:Male; D010789:Phototherapy / Q000009:adverse effects / Q000379:methods; D011569:Psychiatric Status Rating Scales; D011580:Psychological Techniques; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods; D055815:Young Adult
keywords: Biomarkers; Bipolar disorder; GABAergic circuits; Gamma oscillations; TMS/EEG