Modulation of Cortical Activity by Transcranial Direct Current Stimulation in Patients with Affective Disorder

Transcranial direct current stimulation (tDCS) has been shown to have antidepressant efficacy in patients experiencing a major depressive episode, but little is known about the underlying neurophysiology. The purpose of our study was to investigate the acute effects of tDCS on cortical activity using electroencephalography (EEG) in patients with an affective disorder. Eighteen patients diagnosed with an affective disorder and experiencing a depressive episode participated in a sham-controlled study of tDCS, each receiving a session of active (2 mA for 20 minutes) and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC). The effects of tDCS on EEG activity were assessed after each session using event-related potentials (ERP) and measurement of spectral activity during a visual working memory (VWM) task. We observed task and intervention dependent effects on both ERPs and task-related alpha and theta activity, where active compared to sham stimulation resulted in a significant reduction in the N2 amplitude and reduced theta activity over frontal areas during memory retrieval. In summary a single session of anodal tDCS stimulation to the left DLPFC during a major depressive episode resulted in modulated brain activity evident in task-related EEG. Effects on the N2 and frontal theta activity likely reflect modulated activity in the medial frontal cortex and hence indicate that the after-effects of tDCS extend beyond the direct focal effects to the left DLPFC.

[1]  Michael Breakspear,et al.  Effects of mnemonic load on cortical activity during visual working memory: linking ongoing brain activity with evoked responses. , 2013, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[2]  L. Merabet,et al.  Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions , 2012, Brain Stimulation.

[3]  F. L. D. Silva,et al.  Event-related EEG/MEG synchronization and desynchronization: basic principles , 1999, Clinical Neurophysiology.

[4]  Christoph Mulert,et al.  Transcranial direct current stimulation in a patient with therapy-resistant major depression , 2009, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[5]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[6]  K. R. Ridderinkhof,et al.  Electrophysiological correlates of anterior cingulate function in a go/no-go task: Effects of response conflict and trial type frequency , 2003, Cognitive, affective & behavioral neuroscience.

[7]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[8]  Paul B. Fitzgerald,et al.  Upper alpha activity during working memory processing reflects abnormal inhibition in major depression. , 2010, Journal of affective disorders.

[9]  M. Vergari,et al.  Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients , 2012, European Psychiatry.

[10]  Edward Awh,et al.  The bouncer in the brain , 2008, Nature Neuroscience.

[11]  A. Brunoni,et al.  Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis , 2014, Brain and Cognition.

[12]  Valerie Kirsch,et al.  Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: A standardized low resolution tomography (sLORETA) study , 2011, NeuroImage.

[13]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[14]  M. Saarinen,et al.  Memory and metamemory functioning among depressed patients. , 1999, Applied neuropsychology.

[15]  A. Antal,et al.  Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans , 2008, Brain Stimulation.

[16]  R. McIntyre,et al.  The neurobiology of the EEG biomarker as a predictor of treatment response in depression , 2012, Neuropharmacology.

[17]  Arnaud Delorme,et al.  Frontal midline EEG dynamics during working memory , 2005, NeuroImage.

[18]  F. Fregni,et al.  Effects of non-pharmacological pain treatments on brain states , 2013, Clinical Neurophysiology.

[19]  O. Jensen,et al.  Frontal theta activity in humans increases with memory load in a working memory task , 2002, The European journal of neuroscience.

[20]  F. Fregni,et al.  The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. , 2013, JAMA psychiatry.

[21]  F. Fregni,et al.  Feasibility of focal transcranial DC polarization with simultaneous EEG recording: Preliminary assessment in healthy subjects and human epilepsy , 2012, Epilepsy & Behavior.

[22]  Colleen Loo,et al.  Transcranial direct current stimulation: a new tool for the treatment of depression? , 2009, Journal of affective disorders.

[23]  M. Nitsche,et al.  Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence , 2013, Journal of Physiology-Paris.

[24]  Sergio P. Rigonatti,et al.  Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory , 2005, Experimental Brain Research.

[25]  Felipe Fregni,et al.  Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder , 2013, Neuroscience Letters.

[26]  H. Möller,et al.  Prefrontal Transcranial Direct Current Stimulation Changes Connectivity of Resting-State Networks during fMRI , 2011, The Journal of Neuroscience.

[27]  Tsvetomira Tsoneva,et al.  EEG-rhythm dynamics during a 2-back working memory task and performance , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[28]  Klaus Linkenkaer-Hansen,et al.  Breakdown of Long-Range Temporal Correlations in Theta Oscillations in Patients with Major Depressive Disorder , 2005, The Journal of Neuroscience.

[29]  Klaus P. Ebmeier,et al.  Transcranial direct current stimulation in the treatment of major depression: a meta-analysis , 2012, Psychological Medicine.

[30]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[31]  Á. Pascual-Leone,et al.  Technology Insight: noninvasive brain stimulation in neurology—perspectives on the therapeutic potential of rTMS and tDCS , 2007, Nature Clinical Practice Neurology.

[32]  P. Fitzgerald,et al.  Testing the limits: Investigating the effect of tDCS dose on working memory enhancement in healthy controls , 2013, Neuropsychologia.

[33]  Klaus P. Ebmeier,et al.  Pattern of impaired working memory during major depression. , 2006, Journal of affective disorders.

[34]  M. Nitsche,et al.  Serotonin Affects Transcranial Direct Current–Induced Neuroplasticity in Humans , 2009, Biological Psychiatry.

[35]  J. Ushiba,et al.  Modulation of event-related desynchronization during motor imagery with transcranial direct current stimulation (tDCS) in patients with chronic hemiparetic stroke , 2012, Experimental Brain Research.

[36]  E. Vogel,et al.  Discrete capacity limits in visual working memory , 2010, Current Opinion in Neurobiology.

[37]  Alexander Neumeister,et al.  Evidence for continuing neuropsychological impairments in depression. , 2004, Journal of affective disorders.

[38]  Steven Woltering,et al.  Developmental change in EEG theta activity in the medial prefrontal cortex during response control , 2014, NeuroImage.

[39]  N. Müller,et al.  Behavioral and Electrophysiological Effects of Transcranial Direct Current Stimulation of the Parietal Cortex in a Visuo-Spatial Working Memory Task , 2012, Front. Psychiatry.

[40]  Y. Kim,et al.  Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory , 2008, Neuroreport.

[41]  O. Tzeng,et al.  Unleashing Potential: Transcranial Direct Current Stimulation over the Right Posterior Parietal Cortex Improves Change Detection in Low-Performing Individuals , 2012, The Journal of Neuroscience.

[42]  M. Lavidor,et al.  Modulating oscillatory brain activity correlates of behavioral inhibition using transcranial direct current stimulation , 2012, Clinical Neurophysiology.

[43]  Walter Paulus,et al.  Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases , 2014, NeuroImage.

[44]  A. Antal,et al.  Increasing Human Brain Excitability by Transcranial High-Frequency Random Noise Stimulation , 2008, The Journal of Neuroscience.

[45]  W. Klimesch,et al.  EEG alpha oscillations: The inhibition–timing hypothesis , 2007, Brain Research Reviews.

[46]  M F Huque,et al.  Some comments on frequently used multiple endpoint adjustment methods in clinical trials. , 1997, Statistics in medicine.

[47]  Matti Laine,et al.  The effects of memory load on event-related EEG desynchronization and synchronization , 2000, Clinical Neurophysiology.

[48]  P. Schestatsky,et al.  Simultaneous EEG Monitoring During Transcranial Direct Current Stimulation , 2013, Journal of visualized experiments : JoVE.

[49]  Felipe Fregni,et al.  Visual memory improved by non-invasive brain stimulation , 2010, Brain Research.

[50]  H. Bekkering,et al.  Modulation of activity in medial frontal and motor cortices during error observation , 2004, Nature Neuroscience.

[51]  Giulio Ruffini,et al.  Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields , 2014, NeuroImage.

[52]  C. Carter,et al.  The anterior cingulate as a conflict monitor: fMRI and ERP studies , 2002, Physiology & Behavior.

[53]  M. Nitsche,et al.  Physiological Basis of Transcranial Direct Current Stimulation , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[54]  J. Thorne,et al.  Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence , 2011, BMC Neuroscience.

[55]  R. Dolan,et al.  Peak Frequency in the Theta and Alpha Bands Correlates with Human Working Memory Capacity , 2010, Front. Hum. Neurosci..

[56]  W. Klimesch EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis , 1999, Brain Research Reviews.

[57]  H. Asada,et al.  Frontal midline theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex in humans , 1999, Neuroscience Letters.

[58]  Anthony R. McIntosh,et al.  Limbic–frontal circuitry in major depression: a path modeling metanalysis , 2004, NeuroImage.

[59]  R. de Raedt,et al.  tDCS over the Left Prefrontal Cortex Enhances Cognitive Control for Positive Affective Stimuli , 2013, PloS one.

[60]  Donel M. Martin,et al.  Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial , 2012, British Journal of Psychiatry.

[61]  S. Lisanby,et al.  Somatic Treatments for Mood Disorders , 2012, Neuropsychopharmacology.

[62]  J. Matias Palva,et al.  Localization of Cortical Phase and Amplitude Dynamics during Visual Working Memory Encoding and Retention , 2011, The Journal of Neuroscience.

[63]  Atsushi Matsuo,et al.  Influence of transcranial direct current stimulation of the dorsolateral prefrontal cortex on pain related emotions: A study using electroencephalographic power spectrum analysis , 2012, Neuroscience Letters.

[64]  M. Breakspear,et al.  Impact of Load-Related Neural Processes on Feature Binding in Visuospatial Working Memory , 2011, PloS one.

[65]  K. R. Ridderinkhof,et al.  The Role of the Medial Frontal Cortex in Cognitive Control , 2004, Science.

[66]  Jonathan R. Folstein,et al.  Influence of cognitive control and mismatch on the N2 component of the ERP: a review. , 2007, Psychophysiology.