Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? A pilot study

1 Universidade do Minho Escola de Psicologia Isadora Maria Santos Valente Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? A pilot study Jan 2023 Isadora Valente UMinho | 2023 Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? A pilot study ii Janeiro de 2023 Universidade do Minho Escola de Psicologia Isadora Maria Santos Valente Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? A pilot study Dissertação de Mestrado Mestrado em psicologia Aplicada Trabalho efetuado sob a orientação da Professora Doutora Sandra Carvalho e do Professor Doutor Diego Pinal iii Despacho RT - 31 /2019 - Anexo 3 Declaração a incluir na Tese de Doutoramento (ou equivalente) ou no trabalho de Mestrado DIREITOS DE AUTOR E CONDIÇÕES DE UTILIZAÇÃO DO TRABALHO POR TERCEIROS Este é um trabalho académico que pode ser utilizado por terceiros desde que respeitadas as regras e boas práticas internacionalmente aceites, no que concerne aos direitos de autor e direitos conexos. Assim, o presente trabalho pode ser utilizado nos termos previstos na licença abaixo indicada. Caso o utilizador necessite de permissão para poder fazer um uso do trabalho em condições não previstas no licenciamento indicado, deverá contactar o autor, através do RepositóriUM da Universidade do Minho. Atribuição-NãoComercial CC BY-NC https://creativecommons.org/licenses/by-nc/4.0/ [Esta licença permite que outros remisturem, adaptem e criem a partir do seu trabalho para fins não comerciais, e embora os novos trabalhos tenham de lhe atribuir o devido crédito e não possam ser usados para fins comerciais, eles não têm de licenciar esses trabalhos derivados ao abrigo dos mesmos termos.] iv Agradecimentos Primeiramente, gostaria de agradecer à minha orientadora, Dra. Sandra Carvalho, por todo o apoio e suporte que me providenciou ao longo deste projeto e pelos seus valiosos contributos que me inspiraram a querer aprender mais sobre esta área. Igualmente, gostaria de agradecer ao meu co-orientador, Dr. Diego Pinal, pela orientação e acompanhamento extraordinário que me providenciou ao longo deste ano, fundamental para a execução deste projeto e para o meu processo de aprendizagem. Gostaria igualmente de reconhecer e agradecer o apoio incansável da minha colega de equipa, Catarina Gomes, pela sua imensa disponibilidade e suporte ao longo desta dissertação. Gostaria de deixar um agradecimento aos meus amigos por todo o inestimável suporte e carinho, que foi fundamental no decorrer desta jornada. E finalmente, deixo um profundo agradecimento à minha família, pelo suporte incondicional ao longo do toda a minha jornada académica, aos quais eu devo a oportunidade privilegiada de poder seguir o meu percurso académico e profissional ambicionado. v DECLARAÇÃO DE INTEGRIDADE Declaro ter atuado com integridade na elaboração do presente trabalho académico e confirmo que não recorri à prática de plágio nem a qualquer forma de utilização indevida ou falsificação de informações ou resultados em nenhuma das etapas conducente à sua elaboração. Mais declaro que conheço e que respeitei o Código de Conduta Ética da Universidade do Minho. vi Existe evidência de assimetria inter-hemisférica em EEG de repouso em pessoas com depressão? Um estudo piloto Resumo A perturbação Depressiva Major (PDM), é notória pela sua alta comorbilidade com perturbações de ansiedade (PA). Assimetrias de alfa frontal (AAF) e de alfa parietal (AAP) em Eletroencefalograma (EEG), tem sido propostas como um potenciais marcadores de PDM e de PA. No entanto, nem todos os estudos reportaram a evidência neste sentido, sendo necessária mais investigação para testar esta hipótese. Neste estudo piloto examinamos AAF e AAP em EEG em estado de repouso em indivíduos com sintomatologia depressiva e ansiosa. Principais objetivos foram investigar se (1) indivíduos com sintomatologia depressiva diferem de indivíduos assintomáticos nos padrões de AAF e AAP; (2) se indivíduos com ansiedade comórbida apresentavam esses mesmos padrões. Embora não tenham sido encontradas diferenças entre AAF e AAP entre os grupos deprimidos e de assintomáticos, poder de alfa frontal à esquerda e poder de alfa parietal à direita foram encontrados em todos os grupos. A ansiedade comórbida não aparentou influenciar os padrões de assimetria encontrados nos grupos. Este estudo não corroborou AAF e AAP como marcadores capazes de diferenciar indivíduos com base na sua sintomatologia depressiva ou ansiosa. Estudos futuros deverão explorar estas hipóteses em amostras maiores. Palavras-Chave: Assimetria de alfa frontal, Assimetria de alfa parietal, Ansiedade Comórbida, Depressão major, EEG. Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? vii Abstract Major depressive disorder (MDD) is notoriously highly comorbid with anxiety disorders (AD). Electroencephalography (EEG) resting-state frontal alpha (FAA) and parietal alpha asymmetry (PAA) have been proposed to be a potential marker of MDD and AD. However, not all studies have found evidence for this and, further investingation is needed to test this alpha asymmetry hypothesis. In this pilot study, we examined resting-state EEG FAA and PAA in individuals experiencing depressive and anxious symptomology. The main aims were to investigate if (1) individuals with depressive symptoms differ from asymptomatic individuals in FAA and PAA patterns;(2) if individuals with comorbid anxiety showed these same patterns. Although we did not find FAA and PAA between depressive and asymptomatic groups, a left-sided FAA and right-sided PAA were found across all groups. Comorbid anxiety did not seem to influence the asymmetry patterns found among these groups. This study did not support FAA and PAA as markers able to differentiate individuals based on depressive or anxious symptomology. Future studies should explore these hypotheses in larger samples. Keywords: Comorbid Anxiety, EEG, Frontal Alpha Asymmetry, Major Depressive Disorder, Parietal Alpha Asymmetry. Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? viii Contents Background ...................................................................................................................................... 10 Major Depressive disorder prevalence and impact ......................................................................... 10 MDD issues and treatment difficulties ........................................................................................... 10 Neurobiology of Depression........................................................................................................... 11 Electroencephalography ................................................................................................................ 12 Frontal Alpha Asymmetry .............................................................................................................. 12 Parietal Alpha Asymmetry ............................................................................................................. 14 Study aims ....................................................................................................................................... 14 Methods ........................................................................................................................................... 15 Sample ......................................................................................................................................... 15 Experimental procedure ................................................................................................................ 16 Instruments .................................................................................................................................. 17 EEG Recording Procedure ............................................................................................................. 18 EEG Data Processing .................................................................................................................... 18 Statistical analysis ........................................................................................................................ 19 Results ............................................................................................................................................. 20 FAA differences between depressed and asymptomatic individuals ................................................ 20 FAA differences between Comorbid and Anxious individuals ........................................................... 22 PAA differences between Depressed and Asymptomatic individuals ............................................... 24 PAA differences between Comorbid and Anxious individuals ......................................................... 26 Discussion ........................................................................................................................................ 27 Frontal alpha asymmetries ............................................................................................................ 27 Anxiety influence in FAA ................................................................................................................ 28 Parietal alpha asymmetries ........................................................................................................... 29 Anxiety influence on PAA ............................................................................................................... 30 Limitations.................................................................................................................................... 30 Bibliography ..................................................................................................................................... 32 Approval declaration by the ethics committee………………………………………………………………………….39 Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? ix Tables Table 1. Demographics of depressed and asymptomatic participants................................................. 16 Table 2. Demographics of Comorbid and Anxious participants ........................................................... 17 Table 3. Differences between groups for age, gender and Beck Anxiety Inventory Scale ...................... 21 Table 4. Variables correlation with Interhemispheric asymmetry ........................................................ 21 Table 5. Differences in FAA and PAA between participants with/without depressive symptomology .... 23 Figures Figure 1 Linear graphs for Depressed and Asymptomatic groups examining FAA ............................... 22 Figure 2 Linear graphs for Comorbid and Anxious groups examining FAA ...........................................24 Figure 3 Linear graphs for Depressed and Asymptomatic groups examining PAA ............................... 25 Figure 4 Linear graphs for Comorbid and Anxious groups examining PAA .......................................... 26 Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 16 (see table 1): the depressed group ( n = 11; 9 females; age M = 21.6; SD =1.9) experiencing depressive symptomatology (BDI scores ≥ 10), and an Asymptomatic group ( n = 18; 15 females; age M = 20.3; SD = 1.7) free from depressive symptomatology (BDI scores <10). To explore the influence of anxiety over the dependent variable (i.e., interhemispheric alpha power), in a second analysis participants were reorganized into a Comorbid group ( n = 10; 9 females; age M = 21.6; SD = 1.9), with clinical levels of depressive and anxiety symptomatology (BDI scores ≥ 10 and BAI scores ≥ 8) and an Anxious group ( n = 13; 11 females; age M = 20.3; SD =2), including participants that had clinical anxiety but no clinical depressive symptomatology (BAI scores ≥ 8 and BDI scores <10) (see table 2). Experimental procedure All data collection took place at the Psychological Neuroscience Laboratory at the University of Minho, in Portugal. Participants were initially briefed on the study protocol and provided with any clarification regarding safety and data collection concerns. Following the signature of the informed consent, all volunteers were asked to complete a questionnaire collecting: demographic data, medication status, use of illicit substances and clinical information. Participants were then asked to complete selfreport psychometric instruments followed by the EEG recording, with each session taking approximately 40 minutes. Table 1 Demographics of depressed and asymptomatic participants Asymptomatic ( n= 18 ) Currently Depressed ( n= 11) Variables Range Range Age (M ±SD) 20.8 ±2.4 18 - 27 21.8 ±2.9 18 - 28 Sex, n(%) Female 15 (83.34) - 9 (81.82) - Male 3 (16.67) - 2 (18.2) - Years of education 13.59 ± 1.9 9 - 17 14.2 ±1.7 12 - 16 BDI-II (M±SD) 3.7 ± 2.7 0 - 9 19.3 ± 9.9 10 - 45 BAI -II (M±SD) 11.9 ± 7.7 1 - 31 19.5 ±10.1 2 - 43 Note: Education level data was missing for three participants of the total sample; Years of education data was missing for three participants of the total sample. Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 17 Table 2 Demographics of Comorbid and Anxious participants Comorbid ( n= 10 ) Anxious ( n=13 ) Variables Range Range Age, years ( M ±SD ) 21.2 ± 2.1) 18 – 24 20.7 ±2.6) 18 – 27 Sex, n (%) Female 9 (90) - 11(84.62) - Male 1 (10) - 2 (15.4) - Years of education ( M ±SD ) 14.5 ±1.6 12 – 16 13.5 ± 2.1 9 - 17 BDI-II ( M±SD ) 20.1 ±10.1 10 – 45 4.5 ±2.6 0 - 9 BAI -II ( M ±SD ) 21.3±8.8 12 - 43 15 ±6.8 7 - 31 Note: Education level data was missing for three participants of the total sample; Years of education data was missing for two participants of the total sample. Instruments Beck Depression Inventory-II Participants completed the validated Portuguese version (Campos & Gonçalves, 2011) of the Beck Depression Inventory-II (BDI; Beck et al., 1961). This inventory is composed of 21 self-report items measuring characteristics, attitudes, and symptoms of depression. It assesses the presence and severity of depressive symptomatology. Total inventory score ranges from 0 to 63 with higher scores indicating higher depressive symptomatology. Item scores range between 0 to 3, organized by the frequency in which respondents experienced reported symptoms, ranging from affective, cognitive, and somatic complaints (irritability, hopelessness, sleep, concentration) during the last week. BDI has shown high internal consistency, with a Cronbach’s alpha of .86 being among the most widely used methods to classify depression (Beck et al., 1961). Beck Anxiety Inventory Participants completed the Portuguese version of Beck Anxiety Inventory (BAI; Quintão et al., 2013); to determine the presence and severity of anxiety. This inventory is composed of 21 - self-repot items scored from 0 to 3, organized by the frequency of the symptoms (e.g., agitation, fear, nervousness) experienced during the last week. The total score ranges from 0 to 63, scaling anxiety in terms of severity. Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 18 The original instrument has proven high internal consistency (α = .92) and acceptable test-retest reliability over a week, r (81) = .75 (Beck, Steer, et al., 1988). The validated Portuguese version holds good psychometric properties as a unidimensional measure, with a good model fit person reliability (.79) and high item reliability (.99). Hence, it has shown good specificity quality, providing less overlap between symptoms of depression and anxiety (Beck, Epstein, et al., 1988). EEG Recording Procedure Participants were comfortably seated and instructed to stay still, relaxed, and to avoid excessive blinking and movement when possible. Data was recorded in continuous mode and indications were given verbally to participants to when to open or to close their eyes. A portable 20-channel low-density EEG cap was used due to its quick applicability and easy portability, making it appropriate for clinical settings. The resting-state EEG recordings lasted about 18 minutes in total, divided in alternative blocks of 3 mins for each condition: eyes-open (EO) and eyes closed (EC). Block were presented in one of two counterbalanced orders (EO EC EO EC EO EC or EC EO EC EO EC EO). The recording resulted in a total of 9 minutes of EEG data, per condition. A 20-channel Starstim (Neuroelectric, Barcelona, Spain) device was used, with electrodes placed following the 10/20 international system (Jasper, 1958). Electrooculogram (EOG) was recorded from two bipolar channels and impedances were kept below 5 kΩ. Data was collected using a 500Hz of continuous digitalization rate, with a bandpass filter of 0.001 – 100 Hz. The electrodes covering the scalp included frontal (Fp1, Fp2, F3, F4, F7, F8, Fz), central (C3, C4, Cz) temporal (T7, T8), parietal (P3, P4, P7, P8, Pz), and occipital (O1, O2, Oz) sites. The analyzed frequency band was defined within the alpha (8–13 Hz) range. EEG Data Processing Stored EEG data was preprocessed in MATLAB R2021b, using the EEGlab toolbox (Delorme & Makeig, 2004). All channels were then bandpass filtered (0.5 to 45 Hz) using a 4thorder phaseshift free Butterworth filter. Data were visually inspected for major artifacts compromising all channels and rejection data periods was applied when necessary, removing 1.7% of the total data at this stage. Next, followed automated detection and elimination of electrodes with low correlation (r ≤ 0.8) with neighbouring electrodes and of electrodes with a flat signal lasting longer than 5 seconds. Then, correction of large transient artifacts in the data was performed using artifact subspace reconstruction via Clean Raw Data EEGlab plugin. Independent Component Analysis (ICA) was performed and IC label EEGlab plugin (PionTonachini et al., 2019) used to aid in the inspection of the resulting independent components. Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 19 Components with a 20% or lower probability of containing brain activity, and a residual variance superior to 20%, were removed from data reconstruction. Further, visual inspection of the spectrum frequency density was made to determine signal quality and channels were removed if they significantly deviated from expected normal spectral power (e.g., power distribution following 1/f law). All removed channels were then interpolated. Then, preprocessed data was segmented into 2-second non-overlapping epochs, whereas segments containing artifacts were removed if they had: (1) values of ±100µV; (2) contained trends with slopes exceeding 75µV ; (3) improbable data points or abnormal distributions with a single channel limit of 5 SDs; (4) spectral power in frequencies from 0 to 2 Hz outside the range from 50 to - 50 dB, or outside the range 25 to -100 dB from frequencies between 20 and 40 Hz. Finally, data for participants with a minimum of 30 artifact-free data epochs (i.e., 1 min) was used for power spectral density (PSD) calculations using the p-welch function from the Signal Processing Toolbox, in MATLAB, through Welch’s overlapped segment averaging estimator using a Hamming window. Afterward, the eight power values (0.5 Hz resolution) in the alpha frequency band (8–12 Hz) were extracted and averaged for each analyzed electrode (i.e., F3, F4, F7, F8; P3, P4; P7, P8), separately. Averaged alpha power values were then transformed by calculating their natural logarithm. FAA and PAA were calculated using the laterality quoficient (LQ; Reznik & Allen, 2018) function: ln (right electrode) – ln(left electrode), which enables calculation of an interhemispheric asymmetry index based on the difference between homologs electrodes [e.g. ln(F4) – ln(F3)]. Statistical analysis All calculations were conducted in IBM SPSS Statistics Inc. 28.0 Software. For the missing data treatment, an analysis of the data matrix was run, indicating a total of 0.74% of missing values across the BAI and BDI observations. Little’s missing completely at Random Test (MCAR) demonstrated that this data was missing in a random way (χ2 = 156.23; df =159, p =.547); hence an Expected Maximization Analysis procedure as implemented in SPSS was run to estimate missing values. In order to reduce the effect of extreme values in the analysis, individual scores deviating from the analysed variables mean (i.e, BDI, BAI, Alpha PSD at each electrode) at least 2.2 times the interquartile range were considered univariate outliers (Hoaglin et al., 1986; Hoaglin & Iglewicz, 1987) and were winsorized before the statistical analysis (Tukey, 1962). For statistical tests, the alpha level was kept at α ≤ 0.05. To examine between groups differences, a series of independent sample t-tests were run to assess BAI scores and age; while a chi-square test for Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 20 gender differences (see table 3). Additionally, to investigate gender, age, BAI and BDI scores influence on the dependent variables (e.g. FAA and PAA scores) for each condition, a Pearson’s correlation was run for age, BAI, and BDI scores, and a point-biserial correlation test was run for gender (see table 4). Depressed and asymptomatic groups differ significantly in BAI scores , t (27)= -2.22, p = 0.35, therefore, these scores were used as a covariate in ANCOVA analysis for these groups. Additionally, a marginal significance was observed between the Anxious and Comorbid group , t (27)= -1.92, p = .068, whereas Comorbid group showed slightly increased levels of anxiety. No other confounding variables were found to influence the data. To examine interhemispheric asymmetry, a series of two-way mixed repeated measures ANCOVAs were run for all electrodes pairs (i.e., F3/F4; F7/F8; P3/P4; P7/P8), with the between-subjects factor Group (i.e., depressed vs asymptomatic) and the within-factor as Hemisphere (i.e., right versus left electrode) tested independently for each condition (i.e., EC and EO). To explore the influence of anxiety on interhemispheric asymmetries, two-way mixed repeated measures ANOVA were run for the same electrode pairs, with the between-subjects factor Group (i.e., comorbid versus anxious) and the withinfactor Hemisphere (i.e., right versus left homologous electrode), tested independently for each condition (i.e., EC and EO). Results FAA differences between depressed and asymptomatic individuals To analyse alpha lateralization over frontal hemispheres at both pairs of electrodes (F3/F4 and F7/F8), two-way mixed repeated measure ANCOVAs were performed with Group as the between-subjects factor and hemisphere as a within-subjects factor. A main effect of factor Hemisphere was found at the F3/F4 sites, showing greater alpha power over the left (F3) compared to the right (F4) hemisphere in both EC, F (1, 26) = 41.888, p < .001, η2 = .617, and EO conditions, F (1, 26) = 63.882, p < .001, η2 = .711, irrespective of depressive status. No main effect of Group factor was found (EC: F (1, 26) = .419, p = .523; EO: F(1, 26) = .067, p= .797). There was no statistically significant interaction between Group and Hemisphere factor for frontal alpha power (EC: F (1, 26) = .262, p = .613; EO: F (1, 26) = .536, p= .471; see figure 1). Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 21 Table 3 Differences between groups for age, gender and Beck Anxiety Inventory Scale Age BAI Gender t p t p χ2 p Depressed vs Asymthomatic -1.05 .303 -2.22 .0.35** .011 .920 Comorbid vs Anxious .42 .677 1.92 .068* .144 .704 **Statistically significant, p <. 05 *Marginally significant Table 4 Variables correlation with Interhemispheric asymmetry Age BAI BDI Gender LQ electrodes Condition r p r p r p rpb p F3/F4 EC .041 .835 -.056 .772 -.079 .684 .109 .572 EO -.027 .890 .057 .770 -.039 .840 -.054 .781 F7/F8 EC .020 .919 -.038 .846 -.194 .314 .158 .412 EO -.004 .983 .012 .953 -.328 .082* .024 .903 P3/P4 EC -.121 .538 .126 .516 .010 .958 .073 .709 EO -.055 .782 .310 .101 .287 .131 -.188 .328 P7/P8 EC .130 .508 .064 .742 .277 .146 .204 .288 EO .054 .783 .131 .498 .185 .336 -.047 .807 *Marginally significant F7/F8 electrodes pair analysis followed the same trend, showing a main effect of factor Hemisphere in both conditions (EC, F (1, 26) = 44.969, p< .001, η2 =-634; EO, F (1, 26) = 41.557, p <.001, η2 =.615), with greater alpha power over the left (F7) relative to the right (F8) side. No main effect of Group factor was found for EO, F (1, 26) = .227, p = .638, neither for EC, F (1, 26) = .524, p = .476, condition. Furthermore, no interaction effects were found between Group and Hemisphere factor in either Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 22 Figure 1 Mixed repeated measures ANCOVA linear graph for Depressed and Asymptomatic groups examining FAA Note. Four mixed repeated measures ANCOVA linear graphs for Depressed and Asymptomatic groups, showing estimated means of alpha power values (at Y axis) at F3/F4 and F7/F8 pair of electrodes (at X axis), for both EC and EO conditions. condition (EC: F(1, 26) = .032,p= .859; EO: F(1, 26) = .501,p= .485; see figure 1). Notwithstanding, exploratory analyses performed outside the main analysis, detected a potential lateralization effect at F7/F8 electrodes (see table 5). An independent-sample t-tests detected a marginally significant difference between depressed and asymptomatic groups in EO condition, t(27)= 1.934, p = 0.64, suggesting an increased tendency for left-sided asymmetry in the depressed group (M = -.908, SD = .21), compared to the asymptomatic group (M = -.755, SD =.20) for when the eyes are open. Although ANCOVA did not corroborated this lateralization effect, these tests suggest potential alpha power trend over F7 site in depressed individuals. FAA differences between Comorbid and Anxious individuals Only a small portion of the asymptomatic group participants reported not experiencing clinical levels of anxiety (n = 5). Thus, the mean BAI score for this group was within the mild range Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 23 (M=11.94, SD=7.7). To test for anxiety influence in FAA, tests were run contrasting individuals scoring at the clinical range of both BDI and BAI symptomatology (i.e., Comorbid group, n = 10) and individuals scoring at clinical range in BAI (i.e., Anxious group, n =13). A two-way mixed ANOVA showed a main effect of Hemisphere factor for the F3/F4 pair, showing greater alpha power over the left hemisphere in both EC, F (1, 21) = 191.096, p < .001, η2 =.901, and EO conditions, F( 1, 21) = 241.213, p< .001 η2 =.92. However, no differences in alpha power distribution were found among the anxious and comorbid individuals in either EC, F (1, 21) = .409, p = .529, or EO conditions, F (1, 21) = .034, p= .856. Also, no statistically significant interaction was found between Groups and Hemisphere factors (EC, F (1, 21) = .573, p = .015; EO, F (1, 21) = .246, p= .625; see figure 2). A second two-way mixed ANOVA showed a main effect of Hemisphere factor for the F7/F8 pair, showing greater alpha power over the left hemisphere in both EC, F (1, 21) = 184.43, p < .001, η2 =.898., and EO conditions, F( 1, 21) = 150.008, p< .001, η2 =.877. However, no differences in alpha power Table 5 Differences in FAA and PAA between participants with and without depressive symptomology Asymptomatic ( n = 18) Depressed ( n=11 ) t-test Frontal Alpha Asymmetry M SD M SD t p F3/F4 EC -.51 .15 -.57 .13 1.11 .28 EO -.5 .15 -.56 .14 1.01 .32 F7/F8 EC -.63 .14 .-.68 .1 .98 .33 EO -.76 .2 -.91 .21 1.93 .06* Parietal Alpha Asymetry P3/P4 EC .7 .21 .71 .13 -.05 .96 EO .28 .19 .32 .19 -.55 .59 P7/P8 EC 1.06 .4 1.23 .63 -.91 .37 EC .53 .19 .56 .23 -.38 .71 Note. Sample t-tests were run to assess differences between of FAA and PAA values at difference set of electrodes, between depressed and asymptomatic groups. p - value < .05 *Marginally significant Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 24 Figure 2 Mixed repeated measures ANOVA linear graph for Comorbid and Anxious groups examining FAA Note . Four mixed repeated measures ANOVA linear graphs for Comorbid and Anxious groups, showing estimated means of alpha power values (at Y axis) at F3/F4 and F7/F8 pair of electrodes (at X axis), for both EC and EO conditions. distribution were found between the anxious and comorbid groups in either EC, F (1, 21) = .323, p = .576, or EO conditions, F (1, 21) = .016, p = .900. Also, no statistically significant interaction was found between Group and Hemisphere factors (EC, F (1, 21) = .040, p = .843; EO F (1, 21) = .478, p= .497; see figure 2). PAA differences between Depressed and Asymptomatic individuals A two-way mixed ANCOVA showed a main effect for the factor Hemisphere (at P3/P4 electrodes) in the EC condition F (1, 26) = 42.490, p < .001, η2 =.620,showing greater alpha power over the right hemisphere. However, for the EO condition F (1, 26) = 2.22, p < .148 no main effect was found for the factor Hemisphere. Additionally, no main effects of Group were found (EC: F (1, 26) = .204, p = .655; EO: F (1, 26) = .0.13, p= .909). No interaction effect was found between Group and Hemisphere factors Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 25 on parietal alpha power in any condition (EC, F (1, 26) = .345, p = .562; E0 , F (1, 26) = .153, p = .699; see figure 3) . For the P7/P8 electrodes pair, a two-way mixed ANCOVA showed a main effect for the factor Hemisphere in the EC condition F (1, 26) = 35.436, p <.001, η2 =.577, showing greater alpha power over the right hemisphere. However, for the EO condition, F (1, 26) = 30.28, p <.001, no main effect was found for the factor Hemisphere. Also no main effects of Group were found in neither condition, EC: F (1, 26) =. 203, p= .656; EO: F (1, 26) = .41, p = 842. No interaction effect was found between Group and Hemisphere on parietal alpha power in any condition (EC, F (1, 26) = .515 , p =.480; E0 ,F (1, 26) = .002, p = .966; see figure 3). Figure 3 Mixed repeated measures ANCOVA linear graph for Depressed and Asymptomatic groups examining PAA Note . Four mixed repeated measures ANCOVA linear graphs for Depressed and Asymptomatic groups, showing estimated means of alpha power values (at Y axis) at P3/P4 and P7/P8 pair of electrodes (at X axis), for both EC and EO conditions. Is there evidence for resting-state EEG interhemispheric imbalance in people with depression? 32 BIBLIOGRAPHY Al-Ezzi, A., Selman, N. K., Faye, I., & Gunaseli, E. (2020). 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Psychophysiology , 30 (1), 82–89. https://doi.org/10.1111/J.1469-8986.1993.TB03207.X SECVS Subcomissão de Ética para as Ciências da Vida e da Saúde Identificação do documento: SECVS 174/2017 Título do projeto: Transcranial Direct Current Stimulation as add-on treatment to Cognitive-Behavior Therapy in first episode Major Depression drug-naive patients (ESAP Trial) Investigador(a) responsável: Sandra Carvalho, da Escola de Psicologia da Universidade do Minho Outros investigadores: Jorge Leite, da Escola de Psicologia da Universidade do Minho e do Instituto de Desenvolvimento Humano Portucalense (INPP) da Universidade Portucalense; Óscar F. Gonçalves da Escola de Psicologia da Universidade do Minho Subunidade orgânica: Centro de Investigação em Psicologia (CIPsi), Universidade do Minho, Braga, Portugal PARECER A Subcomissão de Ética para as Ciências da Vida e da Saúde (SECVS) analisou o processo relativo ao projeto intitulado Transcranial Direct Current Stimulation as add-on treatment to Cognitive-Behavior Therapy in first episode Major Depression drug-naive patients (ESAP Trial). Os documentos apresentados revelam que o projeto obedece aos requisitos exigidos para as boas práticas na experimentação com humanos, em conformidade com o Guião para submissão de processos a apreciar pela Subcomissão de Ética para as Ciências da Vida e da Saúde. Face ao exposto, a SECVS nada tem a opor à realização do projeto. Braga, 30 de janeiro de 2018. A Presidente Maria Cecília de Lemos Pinto Estrela Leão