Introduction: Adolescents with major depressive disorder (MDD) exhibit hypoactivity to positive stimuli and hyperactivity to negative stimuli in terms of neural responses. Automatic emotion regulation (AER) activates triple networks (i.e., the central control network, default mode network, and salience network). Based on previous studies, we hypothesized that adolescents with MDD exhibit dissociable spatiotemporal deficits during positive and negative AER. Methods: We first collected EEG data from 32 adolescents with MDD and 35 healthy adolescents while they performed an implicit emotional Go/NoGo task. Then, we characterized the spatiotemporal dynamics of cortical activity during AER. Results: In Go trials, MDD adolescents exhibited reduced N2 amplitudes, enhanced theta power for positive pictures, and stronger bottom-up information flow from the left orbitofrontal cortex (OFC) to the right superior frontal gyrus compared to top-down information flow than the controls. In contrast, in NoGo trials, MDD adolescents exhibited elevated P3 amplitudes, enhanced theta power, and stronger top-down information flows from the right middle frontal gyrus to the right OFC and the left insula than the controls. Conclusion: Overall, adolescents with MDD exhibited impaired automatic attention to positive emotions and impaired automatic response inhibition. These findings have potential implications for the clinical treatment of adolescents with MDD.

1.
Bress JN, Meyer A, Proudfit GH. The stability of the feedback negativity and its relationship with depression during childhood and adolescence. Dev Psychopathol. 2015 Jan;27(4 Pt 1):1285–94.
2.
Ho RA, Hall GB, Noseworthy MD, DeMatteo C. An emotional Go/No-Go fMRI study in adolescents with depressive symptoms following concussion. Int J Psychophysiol. 2018 Jul;132(Pt A):62–73.
3.
Ventriglio A, Bhugra D, Sampogna G, Luciano M, De Berardis D, Sani G, et al. From dysthymia to treatment-resistant depression: evolution of a psychopathological construct. Int Rev Psychiatry. 2020 May;32(5–6):471–6.
4.
De Berardis D, Fornaro M, Orsolini L, Ventriglio A, Vellante F, Di Giannantonio M. Emotional dysregulation in adolescents: implications for the development of severe psychiatric disorders, substance abuse, and suicidal ideation and behaviors. Brain Sci. 2020 Aug;10(9):591.
5.
Cohen-Gilbert JE, Thomas KM. Inhibitory control during emotional distraction across adolescence and early adulthood. Child Dev. 2013 Aug;84(6):1954–66.
6.
Hallquist MN, Geier CF, Luna B. Incentives facilitate developmental improvement in inhibitory control by modulating control-related networks. Neuroimage. 2018 May;172:369–80.
7.
Cole PM, Martin SE, Dennis TA. Emotion regulation as a scientific construct: methodological challenges and directions for child development research. Child Dev. 2004 Jul;75(2):317–33.
8.
Mauss IB, Cook CL, Gross JJ. Automatic emotion regulation during anger provocation. J Exp Soc Psychol. 2007 Sept;43(5):698–711.
9.
Rive MM, van Rooijen G, Veltman DJ, Phillips ML, Schene AH, Ruhé HG. Neural correlates of dysfunctional emotion regulation in major depressive disorder. A systematic review of neuroimaging studies. Neurosci Biobehav R. 2013 Dec;37(10 Pt 2):2529–53.
10.
Miller CH, Hamilton JP, Sacchet MD, Gotlib IH. Meta-analysis of functional neuroimaging of major depressive disorder in youth. JAMA Psychiat. 2015 Sept;72(10):1045–53.
11.
Rupprechter S, Romaniuk L, Series P, Hirose Y, Hawkins E, Sandu AL, et al. Blunted medial prefrontal cortico-limbic reward-related effective connectivity and depression. Brain. 2020 Jun;143(6):1946–56.
12.
McKlveen JM, Moloney RD, Scheimann JR, Myers B, Herman JP. “Braking” the prefrontal cortex: the role of glucocorticoids and Interneurons in stress adaptation and pathology. Biol Psychiat. 2019 Nov;86(9):669–81.
13.
Hölich A, Michenthaler P, Kasper S, Lanzenberger R. Circuit mechanisms of reward, anhedonia, and depression. Int J Neuropsychoph. 2019 Feb;22(2):10–118.
14.
Kerestes R, Segreti MA, Pan LA, Phillips ML, Birmaher B, Brent DA. Altered neural function to happy faces in adolescents with and at risk for depression. J Affect Disorders. 2015 Mar;192:143–152.
15.
Young CB, Chen T, Nusslock R, Keller J, Schatzberg AF, Menon V. Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder. Transl Psychiat. 2016 May;6(5):e810.
16.
Zhang W, Chang S, Guo L, Zhang K, Wang J. The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies. J Affect Disord. 2013 Nov;151(2):531–9.
17.
Carl JR, Soskin DP, Kerns C, Barlow DH. Positive emotion regulation in emotional disorders: a theoretical review. Clin Psychol Rev. 2013 Apr;33(3):343–60.
18.
Light SN, Heller AS, Johnstone T, Kolden GG, Peterson MJ, Kalin NH, et al. Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder. Biol Psychiat. 2011 Jun;70(10):962–8.
19.
Wackerhagen C, Wüstenberg T, Mohnke S, Erk S, Veer IM, Kruschwitz JD, et al. Influence of familial risk for depression on cortico-limbic connectivity during implicit emotional processing. Neuropsychopharmacol. 2017 Jul;42(8):1729–38.
20.
Ernst M, Romeo RD, Andersen SL. Neurobiology of the development of motivated behaviors in adolescence: a window into a neural systems model. Pharmacol Biochem Be. 2009 Jun;93(3):199–211.
21.
Luking KR, Pagliaccio D, Luby JL, Barch DM. Reward processing and risk for depression across development. Trends Cogn Sci. 2016 Jun;20(6):456–68.
22.
Ghosal S, Hare BD, Duman RS. Prefrontal cortex GABAergic deficits and circuit dysfunction in the pathophysiology and treatment of chronic stress and depression. Curr Opin Behav Sci. 2017 Apr;14:1–8.
23.
Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011 Apr;16(4):383–406.
24.
Tupak SV, Dresler T, Guhn A, Ehlis A, Fallgatter AJ, Pauli P, et al. Implicit emotion regulation in the presence of threat: neural and autonomic correlates. Neuroimage. 2014 Jun;85 Pt 1:372–9.
25.
Shi H, Wang X, Yi J, Zhu X, Zhang X, Yang J, et al. Default mode network alterations during implicit emotional faces processing in first-episode, treatment-naive major depression patients. Front Psychol. 2015 Aug;6:1198.
26.
Urbain C, Sato J, Pang EW, Taylor M. The temporal and spatial brain dynamics of automatic emotion regulation in children. Dev Cogn Neurosci. 2017 Aug;26(C):62–8.
27.
Shen Q, Lal R, Luellen BA, Earnheart JC, Andrews AM, Luscher B. Gamma-aminobutyric acid-type A receptor deficits cause hypothalamic–pituitary–adrenal axis hyperactivity and antidepressant drug sensitivity reminiscent of melancholic forms of depression. Biol Psychiat. 2010 Sept;68(6):512–20.
28.
Chen CC, Kiebel SJ, Kilner JM, Ward NS, Stephan KE, Wang WJ, et al. A dynamic causal model for evoked and induced responses. Neuroimage. 2012 Jan;59(1):340–8.
29.
Chmielewski WX, Beste C. Testing interactive effects of automatic and conflict control processes during response inhibition: a system neurophysiological study. Neuroimage. 2017 Jun;146:1149–56.
30.
Mocaiber I, Pereira MG, Erthal FS, Machado-Pinheiro W, David IA, Cagy M, et al. Fact or fiction? An event-related potential study of implicit emotion regulation. Neurosci Lett. 2010 Jun;476(2):84–8.
31.
De Pretto M, Rochat L, Spierer L. Spatiotemporal brain dynamics supporting the immediate automatization of inhibitory control by implementation intentions. Sci Rep. 2017 Sept;7(1):10821.
32.
Wang Y, Li X. Temporal course of implicit emotion regulation during a priming-identify task: an ERP study. Sci Rep. 2017 Feb;7(1):41941.
33.
Burani K, Mulligan EM, Klawohn J, Luking KR, Nelson BD, Hajcak G. Longitudinal increases in reward-related neural activity in early adolescence: evidence from event-related potentials (ERPs). Dev Cogn Neurosci. 2019 Apr;36:100620.
34.
Kujawa A, Kessel EM, Carroll A, Arfer KB, Klein DN. Social processing in early adolescence: associations between neurophysiological, self-report, and behavioral measures. Biol Psychol. 2017 Sept;128:55–62.
35.
Trinkl M, Greimel E, Bartling J, Grünewald B, Schulte-Körne G, Grossheinrich N. Right-lateralization of N2-amplitudes in depressive adolescents: an emotional go/nogo study. J Child Psychol P. 2015 Jan;56(1):76–86.
36.
Alloy LB, Olino T, Freed RD, Nusslock R. Role of reward sensitivity and processing in major depressive and bipolar spectrum disorders. Behav Ther. 2016 Sept;47(5):600–21.
37.
Zhang J, Feng C, Mai X. Automatic emotion regulation in response inhibition: the temporal dynamics of emotion counterregulation during a go/nogo task. Psychophysiology. 2016 Aug;53(12):1909–17.
38.
Zhang W, Lu J, Wang TZ. Time course of automatic emotion regulation during a facial Go/Nogo task. Biol Psychol. 2012 Feb;89(2):444–9.
39.
Albert J, Lopez-Martin S, Tapia M, Montoya D, Carretie L. The role of the anterior cingulate cortex in emotional response inhibition. Hum Brain Mapp. 2012 Sept;33(9):2147–60.
40.
Messerotti Benvenuti S, Sarlo M, Buodo G, Mento G, Palomba D. Influence of impulsiveness on emotional modulation of response inhibition: an ERP study. Clin Neurophysiol. 2015 Oct;126(10):1915–25.
41.
Bartholomew ME, Heller W, Miller GA. Inhibitory control of emotional processing: theoretical and empirical considerations. Int J Psychophysiol. 2019 Apr;163:5–10.
42.
Lewis MD, Granic I, Lamm C. Behavioral differences in aggressive children linked with neural mechanisms of emotion regulation. Ann NY Acad Sci. 2006 Dec;1094:164–77.
43.
Spronk M, Jonkman LM, Kemner C. Response inhibition and attention processing in 5- to 7-year-old children with and without symptoms of ADHD: an ERP study. Clin Neurophysiol. 2008 Jun;119(12):2738–52.
44.
Hultman R, Mague SD, Li Q, Katz BM, Michel N, Lin L, et al. Dysregulation of prefrontal cortex-mediated slow-evolving limbic dynamics drives stress-induced emotional pathology. Neuron. 2016 Jun;91(2):439–52.
45.
Maalouf FT, Clark L, Tavitian L, Sahakian BJ, Brent D, Phillips ML. Bias to negative emotions: a depression state-dependent marker in adolescent major depressive disorder. Psychiat Res. 2012 Jun;198(1):28–33.
46.
Başar E, Güntekin B, Öniz A. Principles of oscillatory brain dynamics and a treatise of recognition of faces and facial expressions. Prog Brain Res. 2006 Jun;159:43–62.
47.
Woltering S, Liu Z, Rokeach A, Tannock R. Neurophysiological differences in inhibitory control between adults with ADHD and their peers. Neuropsychologia. 2013 Aug;51(10):1888–95.
48.
Aftanas LI, Reva NV, Varlamov AA, Pavlov SV, Makhnev VP. Analysis of evoked EEG synchronization and desynchronization in conditions of emotional activation in humans: temporal and topographic characteristics. Neurosci Behav Physiol. 2004 Oct;34(8):859–67.
49.
Paul K, Pourtois G. Mood congruent tuning of reward expectation in positive mood: evidence from FRN and theta modulations. Scanning. 2017 May;12(5):765–74.
50.
Knyazev GG, Barchard KA, Razumnikova OM, Mitrofanova LG. The relationship of positive and negative expressiveness to the processing of emotion information. Scand J Psychol. 2012 Jun;53(3):206–15.
51.
Knyazev GG, Slobodskoj-Plusnin JY, Bocharov AV. Gender differences in implicit and explicit processing of emotional facial expressions as revealed by event-related theta synchronization. Emotion. 2010 Oct;10(5):678–87.
52.
Li L, Zhao D. Age-related interregion EEG coupling changes during the control of bottom-up and top-down attention. Front Aging Neurosci. 2015 Sept;7:223.
53.
Wang X, Wu H, Huang J, Gao C, Yin Y, Tang X, et al. Reward mechanism of depressive episodes in bipolar disorder: enhanced theta power in feedback-related negativity. J Affect Disord. 2021 Sept;292:217–22.
54.
Auerbach RP, Stewart JG, Stanton CH, Mueller EM, Pizzagalli DA. Emotion-processing biases and resting EEG activity in depressed adolescents. Depress Anxiety. 2015 Sept;32(9):693–701.
55.
Padrão G, Mallorquí A, Cucurell D, Marco-Pallares J, Rodriguez-Fornells A, DemPadrão G, et al. Neurophysiological differences in reward processing in anhedonics. Cogn Affect Behav Neurosci. 2013 Mar;13(1):102–15.
56.
Chmielewski WX, Mückschel M, Dippel G, Beste C. Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks. Brain Struct Funct. 2016;221(8):3949–61.
57.
Dippel G, Mückschel M, Ziemssen T, Beste C. Demands on response inhibition processes determine modulations of theta band activity in superior frontal areas and correlations with pupillometry: implications for the norepinephrine system during inhibitory control. Neuroimage. 2017 Aug;157:575–85.
58.
Kirmizi-Alsan E, Bayraktaroglu Z, Gurvit H, Keskin YH, Emre M, Demiralp T. Comparative analysis of event-related potentials during Go/NoGo and CPT: decomposition of electrophysiological markers of response inhibition and sustained attention. Brain Res. 2006 Jun;1104(1):114–28.
59.
Popov T, Westner BU, Silton RL, Sass SM, Spielberg JM, Rockstroh B, et al. Time course of brain network reconfiguration supporting inhibitory control. J Neurosci. 2018 May;38(18):4348–56.
60.
Baskaran A, Milev R, McIntyre RS. The neurobiology of the EEG biomarker as a predictor of treatment response in depression. Neuropharmacology. 2012 Sept;63(4):507–13.
61.
Hosseinifard B, Moradi MH, Rostami R. Classifying depression patients and normal subjects using machine learning techniques and nonlinear features from EEG signal. Comput Meth Prog Bio. 2013 Mar;109(3):339–45.
62.
Pizzagalli DA, Webb CA, Dillon DG, Tenke CE, Kayser J, Goer F, et al. Pretreatment rostral anterior cingulate cortex theta activity in relation to symptom improvement in depression a randomized clinical trial. JAMA Psychiat. 2018 Apr;75(6):547–54.
63.
Liu Z, Woltering S, Lewis MD. Developmental change in EEG theta activity in the medial prefrontal cortex during response control. Neuroimage. 2014 Jun;85 Pt 2:873–87.
64.
Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011 Jun;15(10):483–506.
65.
Oosterwijk S, Lindquist KA, Anderson E, Dautoff R, Moriguchi Y, Barrett LF. States of Mind: emotions, body feelings, and thoughts share distributed neural networks. Neuroimage. 2012 Sept;62(3):2110–28.
66.
Taylor MJ, Robertson A, Keller AE, Sato J, Urbain C, Pang EW. Inhibition in the face of emotion: characterization of the spatial-temporal dynamics that facilitate automatic emotion regulation. Hum Brain Mapp. 2018 Jul;39(7):2907–16.
67.
Fogelson N, Diaz-Brage P, Li L, Peled A, Klein E. Functional connectivity abnormalities during processing of predictive stimuli in patients with major depressive disorder. Brain Res. 2020 Jan;1727(C):146543.
68.
Lu Q, Bi K, Liu C, Luo G, Tang H, Yao Z. Predicting depression based on dynamic regional connectivity: a windowed Granger causality analysis of MEG recordings. Brain Res. 2013 Jun;1535:52–60.
69.
Zhang W, Li H, Pan X. Positive and negative affective processing exhibit dissociable functional hubs during the viewing of affective pictures. Hum Brain Mapp. 2015 Feb;36(2):415–26.
70.
First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM–IV–TR axis I disorders patient edition. New York (NY): Biometrics Research; 2002.
71.
First MB, Miriam G, Spitzer RL, Williams JBW, Lorna B. Structured clinical interview for DSM–IV axis II personality disorders. Washington (DC): American Psychiatric Press; 1997.
72.
Beck AT, Steer RA, Brown GK. Beck depression inventory-second edition manual. San Antonio (TX): The Psychological Corporation; 1996.
73.
Liu W, Wang L, Zhu Y, Li M, Chan RC. Clinical utility of the Snaith-Hamilton-Pleasure scale in the Chinese settings. BMC Psychiat. 2012 Oct;12(1):184.
74.
Lundqvist D, Flykt A, Öhman A. The Karolinska directed emotional faces (KDEF). CD-ROM from department of clinical neuroscience, psychology section. Karolinska Institute; 1998.
75.
Tadel F, Baillet S, Mosher JC, Pantazis D, Leahy RM. Brainstorm: a user-friendly application for MEG/EEG analysis. Comput Intel Neurosci. 2011 Jan;2011:879716.
76.
Uusitalo MA, Ilmoniemi RJ. Signal-space projection method for separating MEG or EEG into components. Med Biol Eng Comp. 1997 Mar;35(2):135–40.
77.
Codispoti M, Ferrari V, Junghöfer M, Schupp HT. The categorization of natural scenes: brain attention networks revealed by dense sensor ERPs. Neuroimage. 2006 Aug;32(2):583–91.
78.
Pantazis D, Nichols TE, Baillet S, Leahy RM. A comparison of random field theory and permutation methods for the statistical analysis of MEG data. Neuroimage. 2005 Apr;25(2):383–94.
79.
Philip NS, Barredo J, Aiken E, Carpenter LL. Neuroimaging mechanisms of therapeutic transcranial magnetic stimulation for major depressive disorder. Biol Psychiat Cogn Neurosci Neuroimaging. 2018 Mar;3(3):211–22.
80.
Gross J, Kujala J, Hamalainen M, Timmermann L, Schnitzler A, Salmelin R. Dynamic imaging of coherent sources: studying neural interactions in the human brain. P Natl Acad Sci USA. 2001 Jan;98(2):694–9.
81.
Gramfort A, Papadopoulo T, Olivi E, Clerc M. OpenMEEG: opensource software for quasistatic bioelectromagnetics. Biomed Eng Online. 2010 Sept;9(1):45.
82.
Oostenveld R, Fries P, Maris E, Schoffelen JM. FieldTrip: open source software for advanced analysis of MEG, EEG, and invasive electrophysiological data. Comput Intel Neurosci. 2011;2011:156869.
83.
Wyczesany M, Ferdek MA, Grzybowski SJ. Cortical functional connectivity is associated with the valence of affective states. Brain Cogn. 2014 Oct;90:109–15.
84.
Kaya S, McCabe C. What role does the prefrontal cortex play in the processing of negative and positive stimuli in adolescent depression?Brain Sci. 2019 May;9(5):104.
85.
Almeida JRC, Kronhaus DM, Sibille EL, Langenecker SA, Versace A, LaBarbara EJ, et al. Abnormal left-sided orbitomedial prefrontal cortical-amygdala connectivity during happy and fear face processing: a potential neural mechanism of female MDD. Front Psychiatry. 2011 Aug;2:69–83.
86.
Hakamata Y, Lissek S, Bar-Haim Y, Britton JC, Fox N, Leibenluft E, et al. Attention bias modification treatment: a meta-analysis toward the establishment of novel treatment for anxietyfication treatment: a meta-analysis toward the establishment of novel treatment for anxiety. Biol Psychiatry. 2010 Jul;68(11):982–90.
87.
Young KS, Sandman CF, Craske MG. Positive and negative emotion regulation in adolescence: links to anxiety and depression. Brain Sci. 2019 Mar;9(4):76.
88.
Paret C, Goldway N, Zich C, Keynan J, Hendler T, Linden D, et al. Current progress in real-time functional magnetic resonance-based neurofeedback: methodological challenges and achievements. Neuroimage. 2019 Nov;202:116107–16.
89.
Yadollahpour A, Jalilifar M, Rashidi S. Transcranial direct current stimulation for the treatment of depression: a comprehensive review of the recent advances. Int J Ment Health Ad. 2017 Apr;15(2):434–43.
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