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Archival Report| Volume 7, ISSUE 3, P302-311, March 2022

Reduction in Left Frontal Alpha Oscillations by Transcranial Alternating Current Stimulation in Major Depressive Disorder Is Context Dependent in a Randomized Clinical Trial

  • Justin Riddle
    Affiliations
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Morgan L. Alexander
    Affiliations
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Crystal Edler Schiller
    Affiliations
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • David R. Rubinow
    Affiliations
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Flavio Frohlich
    Correspondence
    Address correspondence to Flavio Frohlich, Ph.D.
    Affiliations
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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      Abstract

      Background

      Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for noninvasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind, placebo-controlled clinical trial.

      Methods

      In this current study, we aimed to replicate successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. Eighty-four participants were randomized to receive verum or sham IAF-tACS. Electrical brain activity was recorded during rest and while viewing emotionally salient images before and after stimulation to investigate whether the modulation of alpha oscillation by tACS exhibited specificity with regard to valence.

      Results

      In agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared with placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants.

      Conclusions

      Together, these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD.

      Keywords

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      References

        • Davidson R.J.
        Anterior cerebral asymmetry and the nature of emotion.
        Brain Cogn. 1992; 20: 125-151
        • Harmon-Jones E.
        • Gable P.A.
        On the role of asymmetric frontal cortical activity in approach and withdrawal motivation: An updated review of the evidence.
        Psychophysiology. 2018; 55e12879
        • Messerotti Benvenuti S.
        • Buodo G.
        • Mennella R.
        • Dal Bò E.
        • Palomba D.
        Appetitive and aversive motivation in depression: The temporal dynamics of task-elicited asymmetries in alpha oscillations.
        Sci Rep. 2019; 9: 17129
        • Allen J.J.
        • Urry H.L.
        • Hitt S.K.
        • Coan J.A.
        The stability of resting frontal electroencephalographic asymmetry in depression.
        Psychophysiology. 2004; 41: 269-280
        • Pascual-Leone A.
        • Rubio B.
        • Pallardó F.
        • Catalá M.D.
        Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression.
        Lancet. 1996; 348: 233-237
        • Grimm S.
        • Beck J.
        • Schuepbach D.
        • Hell D.
        • Boesiger P.
        • Bermpohl F.
        • et al.
        Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: An fMRI study in severe major depressive disorder.
        Biol Psychiatry. 2008; 63: 369-376
        • Perera T.
        • George M.S.
        • Grammer G.
        • Janicak P.G.
        • Pascual-Leone A.
        • Wirecki T.S.
        The clinical TMS society consensus review and treatment recommendations for TMS therapy for major depressive disorder.
        Brain Stimul. 2016; 9: 336-346
        • O’Reardon J.P.
        • Solvason H.B.
        • Janicak P.G.
        • Sampson S.
        • Isenberg K.E.
        • Nahas Z.
        • et al.
        Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial.
        Biol Psychiatry. 2007; 62: 1208-1216
        • Goldman R.I.
        • Stern J.M.
        • Engel Jr., J.
        • Cohen M.S.
        Simultaneous EEG and fMRI of the alpha rhythm.
        Neuroreport. 2002; 13: 2487-2492
        • Leuchter A.F.
        • Cook I.A.
        • Jin Y.
        • Phillips B.
        The relationship between brain oscillatory activity and therapeutic effectiveness of transcranial magnetic stimulation in the treatment of major depressive disorder.
        Front Hum Neurosci. 2013; 7: 37
        • Alexander M.L.
        • Alagapan S.
        • Lugo C.E.
        • Mellin J.M.
        • Lustenberger C.
        • Rubinow D.R.
        • Fröhlich F.
        Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD).
        Transl Psychiatry. 2019; 9: 106
        • Ali M.M.
        • Sellers K.K.
        • Fröhlich F.
        Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance.
        J Neurosci. 2013; 33: 11262-11275
        • Fingelkurts A.A.
        • Fingelkurts A.A.
        • Rytsälä H.
        • Suominen K.
        • Isometsä E.
        • Kähkönen S.
        Impaired functional connectivity at EEG alpha and theta frequency bands in major depression.
        Hum Brain Mapp. 2007; 28: 247-261
        • Dell’Acqua C.
        • Ghiasi S.
        • Messerotti Benvenuti S.M.
        • Greco A.
        • Gentili C.
        • Valenza G.
        Increased functional connectivity within alpha and theta frequency bands in dysphoria: A resting-state EEG study.
        J Affect Disord. 2021; 281: 199-207
        • Mohammadi Y.
        • Moradi M.H.
        Prediction of depression severity scores based on functional connectivity and complexity of the EEG signal.
        Clin EEG Neurosci. 2021; 52: 52-60
        • Jeong H.G.
        • Ko Y.H.
        • Han C.
        • Kim Y.K.
        • Joe S.H.
        Distinguishing quantitative electroencephalogram findings between adjustment disorder and major depressive disorder.
        Psychiatry Investig. 2013; 10: 62-68
        • Leuchter A.F.
        • Cook I.A.
        • Hunter A.M.
        • Cai C.
        • Horvath S.
        Resting-state quantitative electroencephalography reveals increased neurophysiologic connectivity in depression.
        PLoS One. 2012; 7e32508
        • Riddle J.
        • Alexander M.L.
        • Schiller C.E.
        • Rubinow D.R.
        • Frohlich F.
        Reward-based decision-making engages distinct modes of cross-frequency coupling [published online ahead of print Oct 8].
        Cerebral Cortex. 2021;
        • Riddle J.
        • McFerren A.
        • Frohlich F.
        Causal role of cross-frequency coupling in distinct components of cognitive control.
        Prog Neurobiol. 2021; 202: 102033
        • Riddle J.
        • Rubinow D.R.
        • Girdler S.
        • Frohlich F.
        Disinhibition of right inferior frontal gyrus underlies alpha asymmetry in women with low testosterone.
        Biol Psychol. 2021; 161: 108061
        • Fröhlich F.
        Experiments and models of cortical oscillations as a target for noninvasive brain stimulation.
        Prog Brain Res. 2015; 222: 41-73
        • Huang Y.
        • Datta A.
        • Bikson M.
        • Parra L.C.
        Realistic volumetric-approach to simulate transcranial electric stimulation-ROAST-A fully automated open-source pipeline.
        J Neural Eng. 2019; 16056006
        • Lang P.J.
        • Bradley M.M.
        • Cuthbert B.N.
        International affective picture system (IAPS): Technical manual and affective ratings.
        NIMH Center for the Study of Emotion and Attention. 1997; 1: 3
        • Voytek B.
        • Kramer M.A.
        • Case J.
        • Lepage K.Q.
        • Tempesta Z.R.
        • Knight R.T.
        • Gazzaley A.
        Age-related changes in 1/f neural electrophysiological noise.
        J Neurosci. 2015; 35: 13257-13265
        • Riddle J.
        • Vogelsang D.A.
        • Hwang K.
        • Cellier D.
        • D’Esposito M.
        Distinct oscillatory dynamics underlie different components of hierarchical cognitive control.
        J Neurosci. 2020; 40: 4945-4953
        • Van Der Vinne N.
        • Vollebregt M.A.
        • Van Putten M.J.A.M.
        • Arns M.
        Frontal alpha asymmetry as a diagnostic marker in depression: Fact or fiction? A meta-analysis.
        NeuroImage Clin. 2017; 16: 79-87
        • Nusslock R.
        • Walden K.
        • Harmon-Jones E.
        Asymmetrical frontal cortical activity associated with differential risk for mood and anxiety disorder symptoms: An RDoC perspective.
        Int J Psychophysiol. 2015; 98: 249-261
        • Husain M.
        • Roiser J.P.
        Neuroscience of apathy and anhedonia: A transdiagnostic approach.
        Nat Rev Neurosci. 2018; 19: 470-484
        • Berkman E.T.
        • Lieberman M.D.
        Approaching the bad and avoiding the good: Lateral prefrontal cortical asymmetry distinguishes between action and valence.
        J Cogn Neurosci. 2010; 22: 1970-1979
        • Harmon-Jones E.
        Early Career Award. Clarifying the emotive functions of asymmetrical frontal cortical activity.
        Psychophysiology. 2003; 40: 838-848
        • Jesulola E.
        • Sharpley C.F.
        • Bitsika V.
        • Agnew L.L.
        • Wilson P.
        Frontal alpha asymmetry as a pathway to behavioural withdrawal in depression: Research findings and issues.
        Behav Brain Res. 2015; 292: 56-67
        • De Pascalis V.
        • Cozzuto G.
        • Caprara G.V.
        • Alessandri G.
        Relations among EEG-alpha asymmetry, BIS/BAS, and dispositional optimism.
        Biol Psychol. 2013; 94: 198-209
        • Coan J.A.
        • Allen J.J.
        Frontal EEG asymmetry and the behavioral activation and inhibition systems.
        Psychophysiology. 2003; 40: 106-114
        • Nusslock R.
        • Alloy L.B.
        Reward processing and mood-related symptoms: An RDoC and translational neuroscience perspective.
        J Affect Disord. 2017; 216: 3-16
        • Vrieze E.
        • Pizzagalli D.A.
        • Demyttenaere K.
        • Hompes T.
        • Sienaert P.
        • de Boer P.
        • et al.
        Reduced reward learning predicts outcome in major depressive disorder.
        Biol Psychiatry. 2013; 73: 639-645
        • Admon R.
        • Pizzagalli D.A.
        Dysfunctional reward processing in depression.
        Curr Opin Psychol. 2015; 4: 114-118
        • Schlaepfer T.E.
        • Cohen M.X.
        • Frick C.
        • Kosel M.
        • Brodesser D.
        • Axmacher N.
        • et al.
        Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.
        Neuropsychopharmacology. 2008; 33: 368-377
        • Russo G.B.
        • Tirrell E.
        • Busch A.
        • Carpenter L.L.
        Behavioral activation therapy during transcranial magnetic stimulation for major depressive disorder.
        J Affect Disord. 2018; 236: 101-104
        • Lang P.J.
        • Bradley M.M.
        Emotion and the motivational brain.
        Biol Psychol. 2010; 84: 437-450
        • Bergmann T.O.
        • Karabanov A.
        • Hartwigsen G.
        • Thielscher A.
        • Siebner H.R.
        Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives.
        Neuroimage. 2016; 140: 4-19
        • Noury N.
        • Siegel M.
        Phase properties of transcranial electrical stimulation artifacts in electrophysiological recordings.
        Neuroimage. 2017; 158: 406-416
        • Hanslmayr S.
        • Matuschek J.
        • Fellner M.C.
        Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation.
        Curr Biol. 2014; 24: 904-909
        • Wang J.X.
        • Rogers L.M.
        • Gross E.Z.
        • Ryals A.J.
        • Dokucu M.E.
        • Brandstatt K.L.
        • et al.
        Targeted enhancement of cortical-hippocampal brain networks and associative memory.
        Science. 2014; 345: 1054-1057
        • Riddle J.
        • Rubinow D.R.
        • Frohlich F.
        A case study of weekly tACS for the treatment of major depressive disorder.
        Brain Stimul. 2020; 13: 576-577