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Neurophysiological predictors of non-response to rTMS in depression

Published:February 23, 2012DOI:https://doi.org/10.1016/j.brs.2011.12.003

      Abstract

      Background

      The application of rTMS in Depression has been very well investigated over the last few years. However, little is known about predictors of non-response associated with rTMS treatment.

      Objective

      This study examined neurophysiological parameters (EEG and ERP) in 90 depressed patients treated with rTMS and psychotherapy and sought to identify predictors of non-response.

      Methods

      This study is a multi-site open-label study assessing pre-treatment EEG and ERP measures associated with non-response to rTMS treatment.

      Results

      Non-responders were characterized by 1) Increased fronto-central theta EEG power, 2) a slower anterior individual alpha peak frequency, 3) a larger P300 amplitude, and 4) decreased pre-frontal delta and beta cordance. A discriminant analysis yielded a significant model, and subsequent ROC curve demonstrated an area under the curve of 0.814.

      Conclusions

      Several EEG variables demonstrated clear differences between R and NR such as the anterior iAPF, fronto-central Theta and pre-frontal cordance in the Delta and Beta band (representative of increased relative pre-frontal perfusion). The increased P300 amplitude as a predictor for non-response requires further study, since this was the opposite as hypothesized and there were no correlations of this measure with clinical improvement for the whole sample. Combining these biomarkers in a discriminant analysis resulted in a reliable identification of non-responders with low false positive rates. Future studies should prospectively replicate these findings and also further investigate appropriate treatments for the sub-groups of non-responders identified in this study, given that most of these biomarkers have also been found in antidepressant medication studies.

      Keywords

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      References

        • Schutter D.J.
        Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder.
        Psychol Med. 2010; 27: 1-7
        • Schutter D.J.
        Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: A meta-analysis.
        Psychol Med. 2009; 39: 65-75
        • Fitzgerald P.B.
        • Hoy K.
        • Gunewardene R.
        • Slack C.
        • Ibrahim S.
        • Bailey M.
        • et al.
        A randomized trial of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in treatment-resistant major depression.
        Psychol Med. 2010; 7: 1-10
        • Fitzgerald P.B.
        • Hoy K.
        • Daskalakis Z.J.
        • Kulkarni J.
        A randomized trial of the anti-depressant effects of low- and high-frequency transcranial magnetic stimulation in treatment-resistant depression.
        Depress Anxiety. 2009; 26: 229-234
        • Fitzgerald P.B.
        • Brown T.L.
        • Marston N.A.U.
        • Daskalakis Z.J.
        • de Castella A.
        • Kulkarni J.
        Transcranial magnetic stimulation in the treatment of depression: A double-blind, placebo-controlled trial.
        Arch Gen Psychiatry. 2003; 60: 1002
        • Shimizu E.
        • Hashimoto K.
        • Okamura N.
        • Koike K.
        • Komatsu N.
        • Kumakiri C.
        • et al.
        Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants.
        Biol Psychiatry. 2003; 54: 70-75
        • Duman R.S.
        • Monteggia L.M.
        A neurotrophic model for stress-related mood disorders.
        Biol Psychiatry. 2006; 59: 1116-1127
        • Zanardini R.
        • Gazzoli A.
        • Ventriglia M.
        • Perez J.
        • Bignotti S.
        • Rossini P.M.
        • et al.
        Effect of repetitive transcranial magnetic stimulation on serum brain derived neurotrophic factor in drug resistant depressed patients.
        J Affect Disord. 2006; 91: 83-86
        • Yukimasa T.
        • Yoshimura R.
        • Tamagawa A.
        • Uozumi T.
        • Shinkai K.
        • Ueda N.
        • et al.
        High-Frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors.
        Pharmacopsychiatry. 2006; 39: 52-59
        • Angelucci F.
        • Brenè S.
        • Mathé A.A.
        BDNF in schizophrenia, depression and corresponding animal models.
        Mol Psychiatry. 2005; 10: 345-352
        • Teneback C.C.
        • Nahas Z.
        • Speer A.M.
        • Molloy M.
        • Stallings L.E.
        • Spicer K.M.
        • et al.
        Changes in prefrontal cortex and paralimbic activity in depression following two weeks of daily left prefrontal TMS.
        J Neuropsychiatry Clin Neurosci. 1999; 11: 426-435
        • Baeken C.
        • De Raedt R.
        • Van Hove C.
        • Clerinx P.
        • De Mey J.
        • Bossuyt A.
        Hf-RTMS treatment in medication-resistant melancholic depression: Results from 18FDG-PET brain imaging.
        CNS Spectr. 2009; 14: 439-448
        • Langguth B.
        • Wiegand R.
        • Kharraz A.
        • Landgrebe M.
        • Marienhagen J.
        • Frick U.
        • et al.
        Pre-Treatment anterior cingulate activity as a predictor of antidepressant response to repetitive transcranial magnetic stimulation (rTMS).
        Neuro Endocrinol Lett. 2007; 28: 633-638
        • Li C.T.
        • Wang S.J.
        • Hirvonen J.
        • Hsieh J.C.
        • Bai Y.M.
        • Hong C.J.
        • et al.
        Antidepressant mechanism of add-on repetitive transcranial magnetic stimulation in medication-resistant depression using cerebral glucose metabolism.
        J Affect Disord. 2010; 127: 219-229
        • Kito S.
        • Fujita K.
        • Koga Y.
        Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression.
        Neuropsychobiology. 2008; 58: 29-36
        • Pizzagalli D.A.
        Frontocingulate dysfunction in depression: Toward biomarkers of treatment response.
        Neuropsychopharmacology. 2011; 36: 183-206
        • Simon G.E.
        • Perlis R.H.
        Personalized medicine for depression: Can we match patients with treatments?.
        Am J Psychiatry. 2010; 167: 1445-1455
        • Bagby R.M.
        • Ryder A.G.
        • Cristi C.
        Psychosocial and clinical predictors of response to pharmacotherapy for depression.
        J Psychiatry Neurosci. 2002; 27: 250-257
        • Spronk D.
        • Arns M.
        • Barnett K.J.
        • Cooper N.J.
        • Gordon E.
        An investigation of EEG, genetic and cognitive markers of treatment response to antidepressant medication in patients with major depressive disorder: A pilot study.
        J Affect Disord. 2011; 128: 41-48
        • Williams L.M.
        • Rush A.J.
        • Koslow S.H.
        • Wisniewski S.R.
        • Cooper N.J.
        • Nemeroff C.B.
        • et al.
        International study to predict optimized treatment for depression (ispot-d), a randomized clinical trial: Rationale and protocol.
        Trials. 2011; 12: 4
        • Knott V.
        • Mahoney C.
        • Kennedy S.
        • Evans K.
        Pre-Treatment EEG and it’s relationship to depression severity and paroxetine treatment outcome.
        Pharmacopsychiatry. 2000; 33: 201-205
        • Knott V.J.
        • Telner J.I.
        • Lapierre Y.D.
        • Browne M.
        • Horn E.R.
        Quantitative EEG in the prediction of antidepressant response to imipramine.
        J Affect Disord. 1996; 39: 175-184
        • Iosifescu D.V.
        • Greenwald S.
        • Devlin P.
        • Mischoulon D.
        • Denninger J.W.
        • Alpert J.E.
        • et al.
        Frontal EEG predictors of treatment outcome in major depressive disorder.
        Eur Neuropsychopharmacol. 2009; 19: 772-777
        • Ulrich G.
        • Renfordt E.
        • Zeller G.
        • Frick K.
        Interrelation between changes in the EEG and psychopathology under pharmacotherapy for endogenous depression. A contribution to the predictor question.
        Pharmacopsychiatry. 1984; 17: 178-183
        • Conca A.
        • Swoboda E.
        • König P.
        • Koppi S.
        • Beraus W.
        • Künz A.
        • et al.
        Clinical impacts of single transcranial magnetic stimulation (sTMS) as an add-on therapy in severely depressed patients under SSRI treatment.
        Hum Psychopharmacol. 2000; 15: 429-438
        • Arns M.
        • Spronk D.
        • Fitzgerald P.B.
        Potential differential effects of 9 Hz rTMS and 10 Hz rTMS in the treatment of depression.
        Brain Stimulation. 2010; : 124-126
        • Bruder G.E.
        • Stewart J.W.
        • Tenke C.E.
        • McGrath P.J.
        • Leite P.
        • Bhattacharya N.
        • et al.
        Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant.
        Biol Psychiatry. 2001; 49: 416-425
        • Bruder G.E.
        • Tenke C.E.
        • Stewart J.W.
        • Towey J.P.
        • Leite P.
        • Voglmaier M.
        • et al.
        Brain event-related potentials to complex tones in depressed patients: Relations to perceptual asymmetry and clinical features.
        Psychophysiology. 1995; 32: 373-381
        • Ancy J.
        • Gangadhar B.N.
        • Janakiramaiah N.
        ‘Normal’ P300 amplitude predicts rapid response to ECT in melancholia.
        J Affect Disord. 1996; 41: 211-215
        • Kalayam B.
        • Alexopoulos G.S.
        Prefrontal dysfunction and treatment response in geriatric depression.
        Arch Gen Psychiatry. 1999; 56: 713
        • Vandoolaeghe E.
        • van Hunsel F.
        • Nuyten D.
        • Maes M.
        Auditory event related potentials in major depression: Prolonged P300 latency and increased P200 amplitude.
        J Affect Disord. 1998; 48: 105-113
        • Cook I.A.
        • Hunter A.M.
        • Abrams M.
        • Siegman B.
        • Leuchter A.F.
        Midline and right frontal brain function as a physiologic biomarker of remission in major depression.
        Psychiatry Res Neuroimaging. 2009;
        • Leuchter A.F.
        • Uijtdehaage S.H.
        • Cook I.A.
        • O’Hara R.
        • Mandelkern M.
        Relationship between brain electrical activity and cortical perfusion in normal subjects.
        Psychiatry Res. 1999; 90: 125-140
        • Henry J.D.
        • Crawford J.R.
        The short-form version of the depression anxiety stress scales (DASS-21): Construct validity and normative data in a large non-clinical sample.
        Br J Clin Psychol. 2005; 44: 227-239
        • Williams L.M.
        • Simms E.
        • Clark C.R.
        • Paul R.H.
        • Rowe D.
        • Gordon E.
        The test-retest reliability of a standardized neurocognitive and neurophysiological test battery: “Neuromarker”.
        Int J Neurosci. 2005; 115: 1605-1630
        • Arns M.
        • Gunkelman J.
        • Breteler M.
        • Spronk D.
        EEG phenotypes predict treatment outcome to stimulants in children with ADHD.
        J Integr Neurosci. 2008; 7: 421-438
        • Spronk D.
        • Arns M.
        • Bootsma A.
        • van Ruth R.
        • Fitzgerald P.B.
        Long-Term effects of left frontal rTMS on EEG and erps in patients with depression.
        Clin EEG Neurosci. 2008; 39: 118-124
        • Clark C.R.
        • Paul R.H.
        • Williams L.M.
        • Arns M.
        • Fallahpour K.
        • Handmer C.
        • et al.
        Standardized assessment of cognitive functioning during development and aging using an automated touchscreen battery.
        Arch Clin Neuropsychol. 2006; 21: 449-467
        • Paul R.H.
        • Gunstad J.
        • Cooper N.
        • Williams L.M.
        • Clark C.R.
        • Cohen R.A.
        • et al.
        Cross-Cultural assessment of neuropsychological performance and electrical brain function measures: Additional validation of an international brain database.
        Int J Neurosci. 2007; 117: 549-568
        • Niedermeyer E.
        • Da Silva F.H.L.
        Electroencephalography: Basic principles, clinical applications, and related fields.
        Lippincott Williams & Wilkins, 2004
        • Fitzgerald P.B.
        • Hoy K.
        • McQueen S.
        • Herring S.
        • Segrave R.
        • Been G.
        • et al.
        Priming stimulation enhances the effectiveness of low-frequency right prefrontal cortex transcranial magnetic stimulation in major depression.
        J Clin Psychopharmacol. 2008; 28: 52-58
        • Mizumasa T.
        • Hirakata H.
        • Yoshimitsu T.
        • Hirakata E.
        • Kubo M.
        • Kashiwagi M.
        • et al.
        Dialysis-Related hypotension as a cause of progressive frontal lobe atrophy in chronic hemodialysis patients: A 3-year prospective study.
        Nephron Clin Pract. 2004; 97: c23-30
        • Doppelmayr M.
        • Klimesch W.
        • Pachinger T.
        • Ripper B.
        Individual differences in brain dynamics: Important implications for the calculation of event-related band power.
        Biol Cybern. 1998; 79: 49-57
        • Lansbergen M.
        • Arns M.
        • van Dongen-Boomsma M.
        • Spronk D.
        • Buitelaar J.K.
        The increase in theta/beta ratio on resting state EEG in boys with attention-deficit/hyperactivity disorder is mediated by slow alpha peak frequency.
        Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35: 47-52
        • Gratton G.
        • Coles M.G.
        • Donchin E.
        A new method for off-line removal of ocular artifact.
        Electroencephalogr Clin Neurophysiol. 1983; 55: 468-484
        • Leuchter A.F.
        • Cook I.A.
        • Lufkin R.B.
        • Dunkin J.
        • Newton T.F.
        • Cummings J.L.
        • et al.
        Cordance: A new method for assessment of cerebral perfusion and metabolism using quantitative electroencephalography.
        Neuroimage. 1994; 1: 208-219
        • Riedel M.
        • Möller H.J.
        • Obermeier M.
        • Schennach-Wolff R.
        • Bauer M.
        • Adli M.
        • et al.
        Response and remission criteria in major depression–a validation of current practice.
        J Psychiatr Res. 2010; 44: 1063-1068
        • Ishii R.
        • Shinosaki K.
        • Ukai S.
        • Inouye T.
        • Ishihara T.
        • Yoshimine T.
        • et al.
        Medial prefrontal cortex generates frontal midline theta rhythm.
        Neuroreport. 1999; 10: 675-679
        • Asada H.
        • Fukuda Y.
        • Tsunoda S.
        • Yamaguchi M.
        • Tonoike M.
        Frontal midline theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex in humans.
        Neurosci Lett. 1999; 274: 29-32
        • Hegerl U.
        • Himmerich H.
        • Engmann B.
        • Hensch T.
        Mania and attention-deficit/hyperactivity disorder: Common symptomatology, common pathophysiology and common treatment?.
        Curr Opin Psychiatry. 2010; 23: 1-7
        • Arns M.
        • Gunkelman J.
        • Olbrich S.
        • Sander C.
        • Hegerl U.
        EEG vigilance and phenotypes in neuropsychiatry: Implications for intervention.
        in: Coben R. Evans J. Neuromodulation and neurofeedback: Techniques and applications. Elsevier, 2010
        • Ulrich G.
        • Fürstenberg U.
        Quantitative assessment of dynamic electroencephalogram (EEG) organization as a tool for subtyping depressive syndromes.
        Eur Psychiatry. 1999; 14: 217-229
        • Hegerl U.
        • Wilk K.
        • Olbrich S.
        • Schoenknecht P.
        • Sander C.
        Hyperstable regulation of vigilance in patients with major depressive disorder.
        World J Biol Psychiatry. 2011; ([Epub ahead of print])
        • Bschor T.
        • Müller-Oerlinghausen B.
        • Ulrich G.
        Decreased level of EEG-vigilance in acute mania as a possible predictor for a rapid effect of methylphenidate: A case study.
        Clin Electroencephalogr. 2001; 32: 36-39
        • Schoenknecht P.
        • Olbrich S.
        • Sander C.
        • Spindler P.
        • Hegerl U.
        Treatment of acute mania with modafinil monotherapy.
        Biol Psychiatry. 2010; 67: e55-e57
        • Sander C.
        • Arns M.
        • Olbrich S.
        • Hegerl U.
        EEG-vigilance and response to stimulants in paediatric patients with attention deficit/hyperactivity disorder.
        Clin Neurophysiol. 2010; 8: 1511-1518
        • Suffin S.C.
        • Emory W.H.
        Neurometric subgroups in attentional and affective disorders and their association with pharmacotherapeutic outcome.
        Clin Electroencephalogr. 1995; 26: 76-83
        • Debattista C.
        • Kinrys G.
        • Hoffman D.
        • Goldstein C.
        • Zajecka J.
        • Kocsis J.
        • et al.
        The use of referenced-EEG (rEEG) in assisting medication selection for the treatment of depression.
        J Psychiatr Res. 2011; 45: 64-75
        • Itil T.M.
        • Marasa J.
        • Saletu B.
        • Davis S.
        • Mucciardi A.N.
        Computerized EEG: Predictor of outcome in schizophrenia.
        J Nerv Ment Dis. 1975; 160: 118-203
        • Jin Y.
        • Potkin S.G.
        • Kemp A.S.
        • Huerta S.T.
        • Alva G.
        • Thai T.M.
        • et al.
        Therapeutic effects of individualized alpha frequency transcranial magnetic stimulation (alphaTMS) on the negative symptoms of schizophrenia.
        Schizophr Bull. 2006; 32: 556-561
        • Bruder G.E.
        • Kayser J.
        • Tenke C.E.
        • Leite P.
        • Schneier F.R.
        • Stewart J.W.
        • et al.
        Cognitive ERPs in depressive and anxiety disorders during tonal and phonetic oddball tasks.
        Clin Electroencephalogr. 2002; 33: 119-124
        • Leuchter A.F.
        • Cook I.A.
        • Marangell L.B.
        • Gilmer W.S.
        • Burgoyne K.S.
        • Howland R.H.
        • et al.
        Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in major depressive disorder: Results of the BRITE-MD study.
        Psychiatry Res. 2009; 169: 124-131
        • Keller M.B.
        • McCullough J.P.
        • Klein D.N.
        • Arnow B.
        • Dunner D.L.
        • Gelenberg A.J.
        • et al.
        A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.
        N Engl J Med. 2000; 342: 1462-1470
        • George M.S.
        • Lisanby S.H.
        • Avery D.
        • McDonald W.M.
        • Durkalski V.
        • Pavlicova M.
        • et al.
        Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial.
        Arch Gen Psychiatry. 2010; 67: 507-516
        • Brakemeier E.L.
        • Luborzewski A.
        • Danker-Hopfe H.
        • Kathmann N.
        • Bajbouj M.
        Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS).
        J Psychiatr Res. 2007; 41: 395-403
        • Fregni F.
        • Marcolin M.A.
        • Myczkowski M.
        • Amiaz R.
        • Hasey G.
        • Rumi D.O.
        • et al.
        Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation.
        Int J Neuropsychopharmacol. 2006; 9: 641-654
        • Clemens B.
        • Ménes A.
        • Piros P.
        • Bessenyei M.
        • Altmann A.
        • Jerney J.
        • et al.
        Quantitative EEG effects of carbamazepine, oxcarbazepine, valproate, lamotrigine, and possible clinical relevance of the findings.
        Epilepsy Res. 2006; 70: 190-199