Disturbance in long distance gamma coherence in bipolar disorder Ayşegül Özerdem a,b,c, ⁎, Bahar Güntekin d , Ertuğrul Saatçi e , Zeliha Tunca a , Erol Başar d a Department of Psychiatry, Dokuz Eylul University Medical School, Turkey b Department of Neuroscience, Dokuz Eylul University Health Sciences Institute, Turkey c Multidisciplinary Brain Dynamics Research Center, Dokuz Eylul University, Izmir, Turkey d Brain Dynamics, Cognition, and Complex Systems Research Center, Istanbul Kultur University, Istanbul, Turkey e Computer Engineering Department, Faculty of Engineering and Architecture, Istanbul Kultur University, Istanbul, Turkey abstract article info Article history: Received 25 December 2009 Received in revised form 7 April 2010 Accepted 7 April 2010 Available online xxxx Keywords: Bipolar disorder Event-related oscillations Gamma coherence Mania Neurocognitive functioning Valproate The aim of this study was to investigate long distance event-related gamma (28–48 Hz) coherence in mania before and after valproate monotherapy. Gamma coherence in response to visual oddball paradigm in ten medication-free, manic patients was studied before and after six weeks of valproate monotherapy in comparison to ten controls. Inter-hemispheric F 3 –F 4 ,C 3 –C 4 ,T 3 –T 4 ,T 5 –T 6 ,P 3 –P 4 ,O 1 –O 2 and intra-hemispheric F 3 –P 3 ,F 4 –P 4 ,F 3 –T 5 ,F 4 –T 6 ,F 3 –O 1 ,F 4 –O 2 ,C 3 –O 1 ,C 2 –O 4 electrode pairs were included in the analysis. Repeated measures ANOVA revealed a significant difference between groups with regard to pre-treatment coherence values (p: 0.018). The coherence to the target stimuli at the right fronto-temporal location was significantly reduced by 35.41% in the patients compared to controls (p: 0.003). Patients showed significantly lower pre- treatment coherence values in response to non-target stimuli compared to controls at the right fronto- temporal (28.51%, p: 0.004), right fronto-occipital (23.71%, p: 0.024), and right centro-occipital (25.69%, p: 0.029) locations. After six weeks of valproate monotherapy, manic symptoms improved significantly. Post- treatment change in target and non-target coherence values was statistically non-significant. EEG coherence is a measure of functional connectivity in the brain. Event-related gamma oscillations are essential for brain electrical activity. The results show that acute mania presents right sided long distance connectivity disturbance, thus pointing to the potential importance of measuring oscillatory responses in the search for consistent neurobiological markers in such a complicated condition as bipolar disorder. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Mania is the core feature of bipolar disorder. Besides symptoms related to mood, behavior, energy and sleep–wake cycle, mania involves disordered thought, disturbance in attentional measures, complex processing, memory and emotional processing (Quraishi and Frangou, 2002). We have previously reported abnormally increased left frontal delta in euthymic states (Özerdem et al., 2008b) and increased occipital beta activity in manic states (Özerdem et al., 2008a) in response to visual oddball paradigm. The latter finding (Özerdem et al., 2008a) was suggested to be compensatory to a presumed disrupted connectivity in the brain's integrative functioning. Generation of beta oscillations requires involvement of gamma-induced synchrony (Whittington et al., 2000). Patients in the manic or mixed state were shown to have deficits in auditory EEG synchronization in beta (20 Hz) and gamma (30, 40, and 50 Hz) range activity during click entrainment paradigm (O'Donnell et al., 2004). The degree of resting state long-range synchrony was found to be significantly reduced in manic patients compared to healthy controls in all frequency bands (Bhattacharya, 2001), whereas euthymic medicated patients displayed increased delta, and decreased beta synchronization in the frontal region (Chen et al., 2008). For almost a decade, the concept and methods of the emerging field of “oscillatory brain dynamics” have increased rapidly (Başar Eroğlu et al. 2008; Güntekin et al. 2008; Yener et al. 2008), as summarized in a recent review of brain oscillations in pathology conditions (Başar and Güntekin, 2008). As one of the assessment models of oscillatory activity EEG coherence describes the coupling of or relationship between signals in a given frequency band. Varying degrees of spatial coherence occur over long distances as parallel processing (Başar, 1980; Miltner et al., 1999; Schürmann, et al., 2000). EEG coherence is considered an important large-scale measure of functional relationships or synchro- nized functioning between pairs of cortical regions, and therefore, the Progress in Neuro-Psychopharmacology & Biological Psychiatry xxx (2010) xxx–xxx Abbreviations: ANOVA, Analysis of variance; C xy (f), The magnitude-squared coherence, as a function of the frequency; DSM-IV, Diagnostic and Statistical Manual of Psychiatric Disorders-fourth edition; EOG, Electro-occulography; EEG, Electro-encephalography; f, Frequency; GABA, Gamma amino butyric acid; HAM-D 21, 21-item Hamilton Depression Rating Scale; LOCF, Last observation carried forward; PSD, Power spectral density; SCID-I, Structured Interview for DSM-IV; SD, Standard deviation; SPSS, The Statistical Package for Social Studies; YMRS, Young Mania Rating Scale. ⁎ Corresponding author. Mailing Address: Dokuz Eylul University Medical School, Department of Psychiatry, Narlidere, 35340 Izmir, Turkey. Tel.: + 90 232 412 4152; fax: +90 232 412 4169. E-mail address: aysegul.ozerdem@deu.edu.tr (A. Özerdem). PNP-07587; No of Pages 5 0278-5846/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2010.04.001 Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp ARTICLE IN PRESS Please cite this article as: Özerdem A, et al, Disturbance in long distance gamma coherence in bipolar disorder, Prog Neuro-Psychopharmacol Biol Psychiatry (2010), doi:10.1016/j.pnpbp.2010.04.001