Skip to main content Accessibility help

Drug-free patients with major depression show an increased electrophysiological response to valid and invalid feedback

  • G. W. Mies (a1), F. M. van der Veen (a1), J. H. M. Tulen (a1), T. K. Birkenhäger (a1), M. W. Hengeveld (a1) and M. W. van der Molen (a2)...



Depressed patients are biased in their response to negative information. They have been found to show a maladaptive behavioral and aberrant electrophysiological response to negative feedback. The aim of this study was to investigate the behavioral and electrophysiological response to feedback validity in drug-free depressed patients.


Fifteen drug-free in-patients with unipolar major depression disorder (MDD) and 30 demographically matched controls performed a time-estimation task in which they received valid and invalid (i.e. related and unrelated to performance) positive and negative feedback. The number of behavioral adjustments to the feedback and the feedback-related negativity (FRN) were measured.


Patients made fewer correct adjustments after valid negative feedback than controls, and their FRNs were larger. Neither patients nor controls adjusted their time estimates following invalid negative feedback.


The FRN results suggest that depressed drug-free in-patients have an atypical rostral anterior cingulate response to feedback that is independent of feedback validity. Their behavioral response to invalid negative feedback, however, is not impaired. This study confirms the notion that the behavioral responses of depressed individuals to negative feedback are context dependent.


Corresponding author

*Address for correspondence: Dr F. M. van der Veen, Department of Psychiatry, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. (Email:


Hide All
Beats, BC, Sahakian, BJ, Levy, R (1996). Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed. Psychological Medicine 26, 591603.
Beck, AT (1979). Cognitive Theory of Depression. John Wiley and Sons: New York.
Bush, G, Luu, P, Posner, MI (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences 4, 215222.
Chiu, PH, Deldin, PJ (2007). Neural evidence for enhanced error detection in major depressive disorder. American Journal of Psychiatry 164, 608616.
Cohen, J (1988). Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates: Hillsdale, NJ.
Compton, RJ, Lin, M, Vargas, G, Carp, J, Fineman, SL, Quandt, LC (2008). Error detection and posterror behavior in depressed undergraduates. Emotion 8, 5867.
Davidson, RJ, Pizzagalli, D, Nitschke, JB, Putnam, K (2002). Depression: perspectives from affective neuroscience. Annual Review of Psychology 53, 545574.
De Bruijn, ER, Hulstijn, W, Verkes, RJ, Ruigt, GS, Sabbe, BG (2004). Drug-induced stimulation and suppression of action monitoring in healthy volunteers. Psychopharmacology (Berlin) 177, 151160.
De Bruijn, ER, Sabbe, BG, Hulstijn, W, Ruigt, GS, Verkes, RJ (2006). Effects of antipsychotic and antidepressant drugs on action monitoring in healthy volunteers. Brain Research 1105, 122129.
Douglas, KM, Porter, RJ, Frampton, CM, Gallagher, P, Young, AH (2009). Abnormal response to failure in unmedicated major depression. Journal of Affective Disorders 119, 9299.
Ekman, P, Friesen, WV (1978). Facial Action Coding System: A Technique for the Measurement of Facial Movement. Consulting Psychologists Press: Palo Alto, CA.
Elliott, R, Sahakian, BJ, Herrod, JJ, Robbins, TW, Paykel, ES (1997). Abnormal response to negative feedback in unipolar depression: evidence for a diagnosis specific impairment. Journal of Neurology, Neurosurgery and Psychiatry 63, 7482.
Elliott, R, Sahakian, BJ, McKay, AP, Herrod, JJ, Robbins, TW, Paykel, ES (1996). Neuropsychological impairments in unipolar depression: the influence of perceived failure on subsequent performance. Psychological Medicine 26, 975989.
Eppinger, B, Kray, J, Mock, B, Mecklinger, A (2008). Better or worse than expected? Aging, learning, and the ERN. Neuropsychologia 46, 521539.
Eshel, N, Roiser, JP (2010). Reward and punishment processing in depression. Biological Psychiatry 68, 118124.
Evers, EA, Cools, R, Clark, L, van der Veen, FM, Jolles, J, Sahakian, BJ, Robbins, TW (2005). Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning. Neuropsychopharmacology 30, 11381147.
Fallgatter, AJ, Herrmann, MJ, Roemmler, J, Ehlis, AC, Wagener, A, Heidrich, A, Ortega, G, Zeng, Y, Lesch, KP (2004). Allelic variation of serotonin transporter function modulates the brain electrical response for error processing. Neuropsychopharmacology 29, 15061511.
Fladung, AK, Baron, U, Gunst, I, Kiefer, M (2010). Cognitive reappraisal modulates performance following negative feedback in patients with major depressive disorder. Psychological Medicine 40, 17031710.
Foti, D, Weinberg, A, Dien, J, Hajcak, G (2010). Parsing event-related potentials to rewards and non-rewards using temporal-spatial PCA: the feedback negativity is the absence of a reward-related positivity. SPR 50th Annual Meeting, Portland, OR, USA.
Gehring, WJ, Himle, J, Nisenson, LG (2000). Action-monitoring dysfunction in obsessive-compulsive disorder. Psychological Science 11, 16.
Gratton, G, Coles, MG, Donchin, E (1983). A new method for off-line removal of ocular artifact. Electroencephalography and Clinical Neurophysiology 55, 468484.
Hajcak, G, McDonald, N, Simons, RF (2003). Anxiety and error-related brain activity. Biological Psychology 64, 7790.
Hajcak, G, McDonald, N, Simons, RF (2004). Error-related psychophysiology and negative affect. Brain and Cognition 56, 189197.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.
Holmes, AJ, Pizzagalli, DA (2008). Spatiotemporal dynamics of error processing dysfunctions in major depressive disorder. Archives of General Psychiatry 65, 179188.
Holmes, AJ, Pizzagalli, DA (2010). Effects of task-relevant incentives on the electrophysiological correlates of error processing in major depressive disorder. Cognitive, Affective and Behavioral Neuroscience 10, 119128.
Jocham, G, Ullsperger, M (2009). Neuropharmacology of performance monitoring. Neuroscience and Biobehavioral Reviews 33, 4860.
Johannes, S, Wieringa, BM, Nager, W, Dengler, R, Munte, TF (2001 a). Oxazepam alters action monitoring. Psychopharmacology (Berlin) 155, 100106.
Johannes, S, Wieringa, BM, Nager, W, Rada, D, Dengler, R, Emrich, HM, Munte, TF, Dietrich, DE (2001 b). Discrepant target detection and action monitoring in obsessive-compulsive disorder. Psychiatry Research 108, 101110.
Koolschijn, PC, van Haren, NE, Lensvelt-Mulders, GJ, Hulshoff Pol, HE, Kahn, RS (2009). Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Human Brain Mapping 30, 37193735.
Luu, P, Collins, P, Tucker, DM (2000). Mood, personality, and self-monitoring: negative affect and emotionality in relation to frontal lobe mechanisms of error monitoring. Journal of Experimental Psychology: General 129, 4360.
Mathewson, KJ, Dywan, J, Snyder, PJ, Tays, WJ, Segalowitz, SJ (2008). Aging and electrocortical response to error feedback during a spatial learning task. Psychophysiology 45, 936948.
Mayberg, HS (1997). Limbic-cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry and Clinical Neurosciences 9, 471481.
Mayberg, HS (2003). Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. British Medical Bulletin 65, 193207.
Mies, GW, van der Molen, MW, Smits, M, Hengeveld, MW, van der Veen, FM (2011). The anterior cingulate cortex responds differently to the validity and valence of feedback in a time-estimation task. NeuroImage. Published online: 13 April 2011. doi:10.1016/j.neuroimage.2011.04.015.
Mies, GW, van der Veen, FM, Tulen, JHM, Hengeveld, MW, van der Molen, MW (in press). Cardiac and electrophysiological responses to valid and invalid feedback in a time-estimation task. Journal of Psychophysiology.
Miltner, WHR, Braun, CH, Coles, MGH (1997). Event-related brain potentials following incorrect feedback in a time-estimation task: evidence for a ‘generic’ neural system for error detection. Journal of Cognitive Neuroscience 9, 788798.
Murphy, FC, Michael, A, Robbins, TW, Sahakian, BJ (2003). Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance. Psychological Medicine 33, 455467.
Nieuwenhuis, S, Slagter, HA, von Geusau, NJ, Heslenfeld, DJ, Holroyd, CB (2005). Knowing good from bad: differential activation of human cortical areas by positive and negative outcomes. European Journal of Neuroscience 21, 31613168.
Olvet, DM, Klein, DN, Hajcak, G (2010). Depression symptom severity and error-related brain activity. Psychiatry Research 179, 3037.
Pizzagalli, DA (2011). Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 36, 183206.
Riba, J, Rodriguez-Fornells, A, Morte, A, Munte, TF, Barbanoj, MJ (2005). Noradrenergic stimulation enhances human action monitoring. Journal of Neuroscience 25, 43704374.
Ridderinkhof, KR, Ullsperger, M, Crone, EA, Nieuwenhuis, S (2004). The role of the medial frontal cortex in cognitive control. Science 306, 443447.
Ruchsow, M, Herrnberger, B, Beschoner, P, Gron, G, Spitzer, M, Kiefer, M (2006). Error processing in major depressive disorder: evidence from event-related potentials. Journal of Psychiatric Research 40, 3746.
Ruchsow, M, Herrnberger, B, Wiesend, C, Gron, G, Spitzer, M, Kiefer, M (2004). The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials. Psychophysiology 41, 833840.
Santesso, DL, Steele, KT, Bogdan, R, Holmes, AJ, Deveney, CM, Meites, TM, Pizzagalli, DA (2008). Enhanced negative feedback responses in remitted depression. Neuroreport 19, 10451048.
Schrijvers, D, de Bruijn, ER, Maas, Y, De Grave, C, Sabbe, BG, Hulstijn, W (2008). Action monitoring in major depressive disorder with psychomotor retardation. Cortex 44, 569579.
Schrijvers, D, De Bruijn, ER, Maas, YJ, Vancoillie, P, Hulstijn, W, Sabbe, BG (2009). Action monitoring and depressive symptom reduction in major depressive disorder. International Journal of Psychophysiology 71, 218224.
Sharbrough, F, Chatrian, G-E, Lesser, RP, Luders, H, Nuwer, M, Picton, TW (1991). American Electroencephalographic Society guidelines for standard electrode position nomenclature. Journal of Clinical Neurophysiology 8, 200202.
Steele, JD, Kumar, P, Ebmeier, KP (2007). Blunted response to feedback information in depressive illness. Brain 130, 23672374.
Steffens, DC, Wagner, HR, Levy, RM, Horn, KA, Krishnan, KR (2001). Performance feedback deficit in geriatric depression. Biological Psychiatry 50, 358363.
Stern, ER, Liu, Y, Gehring, WJ, Lister, JJ, Yin, G, Zhang, J, Fitzgerald, KD, Himle, JA, Abelson, JL, Taylor, SF (2010). Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder. Psychophysiology 47, 913920.
Taylor Tavares, JV, Clark, L, Furey, ML, Williams, GB, Sahakian, BJ, Drevets, WC (2008). Neural basis of abnormal response to negative feedback in unmedicated mood disorders. NeuroImage 42, 11181126.
Tucker, DM, Luu, P, Frishkoff, G, Quiring, J, Poulsen, C (2003). Frontolimbic response to negative feedback in clinical depression. Journal of Abnormal Psychology 112, 667678.
van den Bosch, RJ, Rombouts, RP, van Asma, MJ (1996). What determines Continuous Performance Task performance? Schizophrenia Bulletin 22, 643651.
van der Elst, W, van Boxtel, MP, van Breukelen, GJ, Jolles, J (2008). A large-scale cross-sectional and longitudinal study into the ecological validity of neuropsychological test measures in neurologically intact people. Archives of Clinical Neuropsychology 23, 787800.
van der Veen, F, Evers, E, Mies, G, Vuurman, E, Jolles, J (2009). Acute tryptophan depletion selectively attenuates cardiac slowing in an Eriksen flanker task. Journal of Psychopharmacology 24, 14551463.
van der Veen, FM, Mies, GW, van der Molen, MW, Evers, EA (2008). Acute tryptophan depletion in healthy males attenuates phasic cardiac slowing but does not affect electro-cortical response to negative feedback. Psychopharmacology (Berlin) 199, 255263.
van der Veen, FM, Roder, CH, Mies, GW, van der Lugt, A, Smits, M (2011). Remedial action and feedback processing in a time-estimation task: evidence for a role of the rostral cingulate zone in behavioral adjustments without learning. NeuroImage 54, 447454.
van Tol, MJ, van der Wee, NJ, van den Heuvel, OA, Nielen, MM, Demenescu, LR, Aleman, A, Renken, R, van Buchem, MA, Zitman, FG, Veltman, DJ (2010). Regional brain volume in depression and anxiety disorders. Archives of General Psychiatry 67, 10021011.
Wechsler, D (1997). Wechsler Adult Intelligence Scale-III (WAIS-III). Psychological Corporation: San Antonio, TX.
Wild-Wall, N, Willemssen, R, Falkenstein, M (2009). Feedback-related processes during a time-production task in young and older adults. Clinical Neurophysiology 120, 407413.
Wu, Y, Zhou, X (2009). The P300 and reward valence, magnitude, and expectancy in outcome evaluation. Brain Research 1286, 114122.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed