Advertisement

Frontal Cortex Stimulation Reduces Vigilance to Threat: Implications for the Treatment of Depression and Anxiety

      Abstract

      Background

      The difficulty in treating mood disorders has brought about clinical interest in alternative treatments, such as transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). However, the optimal parameters for stimulation and underlying mechanisms of action are unclear. Psychiatric treatments have acute effects on emotional processing that predict later therapeutic action. Such effects have been proposed as cognitive biomarkers for screening novel treatments for depression and anxiety.

      Methods

      This study assessed the effect of tDCS on a battery of emotional processing measures sensitive to antidepressant action. To refine optimal stimulation parameters, DLPFC stimulation using two common electrode montages was compared with sham. Sixty healthy volunteers received 20 minutes of active or sham DLPFC stimulation before completing computerized emotional processing tasks, including a dot-probe measure of vigilance to threat.

      Results

      Relative to sham stimulation, participants receiving simultaneous anodal stimulation of left DLPFC and cathodal stimulation of right DLPFC (bipolar-balanced montage) showed reduced vigilance to threatening stimuli. There was no such significant effect when the cathode was placed on the supraorbital ridge (bipolar-unbalanced montage). There were no effects of tDCS on other measures of emotional processing.

      Conclusions

      Our findings provide the first experimental evidence that modulating activity in the DLPFC reduces vigilance to threatening stimuli. This significant reduction in fear vigilance is similar to that seen with anxiolytic treatments in the same cognitive paradigm. The finding that DLPFC tDCS acutely alters the processing of threatening information suggests a potential cognitive mechanism that could underwrite treatment effects in clinical populations.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Rush A.
        • Trivedi M.
        • Wisniewski S.
        • Nierenberg A.
        • Stewart J.
        • Warden D.
        • et al.
        Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR* D report.
        Am J Psychiatry. 2006; 163: 1905-1917
        • Kalu U.G.
        • Sexton C.E.
        • Loo C.K.
        • Ebmeier K.P.
        Transcranial direct current stimulation in the treatment of major depression: A meta-analysis.
        Psychol Med. 2012; 42: 1791-1800
        • Bindman L.J.
        • Lippold O.
        • Redfearn J.
        The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects.
        J Physiol. 1964; 172: 369-382
        • Nitsche M.A.
        • Fricke K.
        • Henschke U.
        • Schlitterlau A.
        • Liebetanz D.
        • Lang N.
        • et al.
        Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.
        J Physiol. 2003; 553: 293-301
        • Nitsche M.A.
        • Jaussi W.
        • Liebetanz D.
        • Lang N.
        • Tergau F.
        • Paulus W.
        Consolidation of human motor cortical neuroplasticity by D-cycloserine.
        Neuropsychopharmacology. 2004; 29: 1573-1578
        • Liebetanz D.
        • Nitsche M.A.
        • Tergau F.
        • Paulus W.
        Pharmacological approach to the mechanisms of transcranial DC‐stimulation‐induced after‐effects of human motor cortex excitability.
        Brain. 2002; 125: 2238-2247
        • Monte-Silva K.
        • Kuo M.-F.
        • Hessenthaler S.
        • Fresnoza S.
        • Liebetanz D.
        • Paulus W.
        • Nitsche M.A.
        Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.
        Brain Stimul. 2013; 6: 424-432
        • 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
        • George M.S.
        • Wassermann E.M.
        • Kimbrell T.A.
        • Little J.T.
        • Williams W.E.
        • Danielson A.L.
        • et al.
        Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: A placebo-controlled crossover trial.
        Am J Psychiatry. 2014; 154: 1752-1756
        • Boggio P.S.
        • Rigonatti S.P.
        • Ribeiro R.B.
        • Myczkowski M.L.
        • Nitsche M.A.
        • Pascual-Leone A.
        • Fregni F.
        A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression.
        Int J Neuropsychopharmacol. 2008; 11: 249-254
        • Loo C.K.
        • Alonzo A.
        • Martin D.
        • Mitchell P.B.
        • Galvez V.
        • Sachdev P.
        Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial.
        Br J Psychiatry. 2012; 200: 52-59
        • Brunoni A.R.
        • Valiengo L.
        • Baccaro A.
        • Zanão T.A.
        • de Oliveira J.F.
        • Goulart A.
        • et al.
        The sertraline vs electrical current therapy for treating depression clinical study results from a factorial, randomized, controlled trial sertraline vs electrical current therapy.
        JAMA Psychiatry. 2013; 70: 383-391
        • Nasseri P.
        • Nitsche M.A.
        • Ekhtiari H.
        A framework for categorizing electrode montages in transcranial direct current stimulation.
        Front Hum Neurosci. 2015; 9: 54
        • Blumberger D.M.
        • Tran L.C.
        • Fitzgerald P.B.
        • Hoy K.E.
        • Daskalakis Z.J.
        A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression.
        Front Psychiatry. 2012; 3: 17
        • Nitsche M.A.
        • Cohen L.G.
        • Wassermann E.M.
        • Priori A.
        • Lang N.
        • Antal A.
        • et al.
        Transcranial direct current stimulation: State of the art 2008.
        Brain Stimul. 2008; 1: 206-223
        • Harmer C.J.
        • Goodwin G.M.
        • Cowen P.J.
        Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action.
        Br J Psychiatry. 2009; 195: 102-108
        • Beck A.T.
        Cognitive Therapy of Depression.
        Guilford Press, New York1979
        • Harmer C.J.
        • Hill S.A.
        • Taylor M.J.
        • Cowen P.J.
        • Goodwin G.M.
        Toward a neuropsychological theory of antidepressant drug action: increase in positive emotional bias after potentiation of norepinephrine activity.
        Am J Psychiatry. 2003; 160: 990-992
        • Tranter R.
        • Bell D.
        • Gutting P.
        • Harmer C.
        • Healy D.
        • Anderson I.M.
        The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients.
        J Affect Disord. 2009; 118: 87-93
        • Reinecke A.
        • Waldenmaier L.
        • Cooper M.J.
        • Harmer C.J.
        Changes in automatic threat processing precede and predict clinical changes with exposure-based cognitive-behavior therapy for panic disorder.
        Biol Psychiatry. 2013; 73: 1064-1070
        • Harmer C.
        • O’Sullivan U.
        • Favaron E.
        • Massey-Chase R.
        • Ayres R.
        • Reinecke A.
        • et al.
        Effect of acute antidepressant administration on negative affective bias in depressed patients.
        Am J Psychiatry. 2009; 166: 1178-1184
        • Beck A.
        Cognitive Therapy and the Emotional Disorders.
        Meridian, New York1976
        • Mogg K.
        • Millar N.
        • Bradley B.P.
        Biases in eye movements to threatening facial expressions in generalized anxiety disorder and depressive disorder.
        J Abnorm Psychol. 2000; 109: 695
        • Mogg K.
        • Bradley B.P.
        • Williams R.
        Attentional bias in anxiety and depression: The role of awareness.
        Br J Clin Psychol. 1995; 34: 17-36
        • Gotlib I.H.
        • Krasnoperova E.
        • Yue D.N.
        • Joormann J.
        Attentional biases for negative interpersonal stimuli in clinical depression.
        J Abnorm Psychol. 2004; 113: 127
        • Phillips M.L.
        • Drevets W.C.
        • Rauch S.L.
        • Lane R.
        Neurobiology of emotion perception II: Implications for major psychiatric disorders.
        Biol Psychiatry. 2003; 54: 515-528
        • Leppänen J.M.
        Emotional information processing in mood disorders: A review of behavioral and neuroimaging findings.
        Curr Opin Psychiatry. 2006; 19: 34-39
        • Brunoni A.R.
        • Zanao T.A.
        • Vanderhasselt M.-A.
        • Valiengo L.
        • de Oliveira J.F.
        • Boggio P.S.
        • et al.
        Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression.
        Neuromodulation. 2014; 17: 138-142
        • Bishop S.
        • Duncan J.
        • Brett M.
        • Lawrence A.D.
        Prefrontal cortical function and anxiety: Controlling attention to threat-related stimuli.
        Nat Neurosci. 2004; 7: 184-188
        • Bishop S.J.
        • Jenkins R.
        • Lawrence A.D.
        Neural processing of fearful faces: Effects of anxiety are gated by perceptual capacity limitations.
        Cereb Cortex. 2007; 17: 1595-1603
        • Bishop S.J.
        Trait anxiety and impoverished prefrontal control of attention.
        Nat Neurosci. 2008; 12: 92-98
        • Harmer C.
        • Thilo K.
        • Rothwell J.
        • Goodwin G.
        Transcranial magnetic stimulation of medial–frontal cortex impairs the processing of angry facial expressions.
        Nat Neurosci. 2001; 4: 17-18
        • Clarke P.J.
        • Browning M.
        • Hammond G.
        • Notebaert L.
        • MacLeod C.
        The causal role of the dorsolateral prefrontal cortex in the modification of attentional bias: Evidence from transcranial direct current stimulation.
        Biol Psychiatry. 2014; 76: 946-952
        • Nitsche M.A.
        • Koschack J.
        • Pohlers H.
        • Hullemann S.
        • Paulus W.
        • Happe S.
        Effects of frontal transcranial direct current stimulation on emotional processing and mood in healthy humans.
        Front Psychiatry. 2012; 3: 58
      1. Neuroconn (2012): DC-STIMULATOR for tDCS. http://www.neuroconn.de/dc-stimulator_en/. Accessed November 28, 2012.

        • Harmer C.
        • Bhagwagar Z.
        • Perrett D.
        • Vollm B.
        • Cowen P.
        • Goodwin G.
        Acute SSRI administration affects the processing of social cues in healthy volunteers.
        Neuropsychopharmacology. 2003; 28: 148-152
        • Schneider W.
        • Eschman A.
        • Zuccolotto A.
        • Burgess S.
        E-prime.
        Psychology Software Tools, Pittsburgh2002
        • Mogg K.
        • Garner M.
        • Bradley B.P.
        Anxiety and orienting of gaze to angry and fearful faces.
        Biol Psychol. 2007; 76: 163-169
        • Whalen P.J.
        • Shin L.M.
        • McInerney S.C.
        • Fischer H.
        • Wright C.I.
        • Rauch S.L.
        A functional MRI study of human amygdala responses to facial expressions of fear versus anger.
        Emotion. 2001; 1: 70-83
        • Blair R.
        • Morris J.S.
        • Frith C.D.
        • Perrett D.I.
        • Dolan R.J.
        Dissociable neural responses to facial expressions of sadness and anger.
        Brain. 1999; 122: 883-893
        • Gorka S.M.
        • Fitzgerald D.A.
        • Labuschagne I.
        • Hosanagar A.
        • Wood A.G.
        • Nathan P.J.
        • Phan K.L.
        Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder.
        Neuropsychopharmacology. 2015; 40: 278-286
        • Carlson J.M.
        • Mujica-Parodi L.R.
        • Harmon-Jones E.
        • Hajcak G.
        The orienting of spatial attention to backward masked fearful faces is associated with variation in the serotonin transporter gene.
        Emotion. 2012; 12: 203-207
        • Morris J.S.
        • Öhman A.
        • Dolan R.J.
        Conscious and unconscious emotional learning in the human amygdala.
        Nature. 1998; 393: 467-470
        • Bradley B.P.
        • Mogg K.
        • Falla S.J.
        • Hamilton L.R.
        Attentional bias for threatening facial expressions in anxiety: Manipulation of stimulus duration.
        Cogn Emot. 1998; 12: 737-753
        • Mogg K.
        • Bradley B.
        • Miles F.
        • Dixon R.
        Brief report time course of attentional bias for threat scenes: Testing the vigilance‐avoidance hypothesis.
        Cogn Emot. 2004; 18: 689-700
        • Murphy S.E.
        • Yiend J.
        • Lester K.J.
        • Cowen P.J.
        • Harmer C.J.
        Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers.
        Int J Neuropsychopharmacol. 2009; 12: 169-179
        • Mogg K.
        • Bradley B.P.
        • De Bono J.
        • Painter M.
        Time course of attentional bias for threat information in non-clinical anxiety.
        Behav Res Ther. 1997; 35: 297-303
        • Mogg K.
        • Bradley B.P.
        • Williams R.
        • Mathews A.
        Subliminal processing of emotional information in anxiety and depression.
        J Abnorm Psychol. 1993; 102: 304
        • Murphy S.
        • Downham C.
        • Cowen P.
        • Harmer C.
        Direct effects of diazepam on emotional processing in healthy volunteers.
        Psychopharmacology (Berl). 2008; 199: 503-513
        • Reinecke A.
        • Cooper M.
        • Favaron E.
        • Massey-Chase R.
        • Harmer C.
        Attentional bias in untreated panic disorder.
        Psychiatry Res. 2011; 185: 387-393
        • Sartorius N.
        • Üstün T.B.
        • Lecrubier Y.
        • Wittchen H.-U.
        Depression comorbid with anxiety: Results from the WHO study on psychological disorders in primary health care.
        Br J Psychiatry Suppl. 1996; 30: 38-43
        • Brunoni A.R.
        • Vanderhasselt M.-A.
        • Boggio P.S.
        • Fregni F.
        • Dantas E.M.
        • Mill J.G.
        • et al.
        Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol.
        Psychoneuroendocrinology. 2013; 38: 58-66
        • Davis M.
        • Whalen P.J.
        The amygdala: Vigilance and emotion.
        Mol Psychiatry. 2001; 6: 13-34
        • Forster S.
        • Nunez Elizalde A.O.
        • Castle E.
        • Bishop S.J.
        Unraveling the anxious mind: Anxiety, worry, and frontal engagement in sustained attention versus off-task processing.
        Cereb Cortex. 2015; 25: 609-618
        • Koster E.H.
        • Crombez G.
        • Verschuere B.
        • De Houwer J.
        Selective attention to threat in the dot probe paradigm: Differentiating vigilance and difficulty to disengage.
        Behav Res Ther. 2004; 42: 1183-1192
        • Batsikadze G.
        • Moliadze V.
        • Paulus W.
        • Kuo M.F.
        • Nitsche M.A.
        Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.
        J Physiol. 2013; 591: 1987-2000