Hostname: page-component-69cd664f8f-fq6ln Total loading time: 0 Render date: 2025-03-12T23:12:44.143Z Has data issue: false hasContentIssue false
  • English
  • Français

Differential frontal–striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive–compulsive disorder

Published online by Cambridge University Press:  27 January 2009

P. L. Remijnse ,
M. M. A. Nielen ,
A. J. L. M. van Balkom ,
G.-J. Hendriks ,
W. J. Hoogendijk ,
H. B. M. Uylings  and
D. J. Veltman
P. L. Remijnse*
Affiliation:
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands Amsterdam, The Netherlands
M. M. A. Nielen
Affiliation:
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands
A. J. L. M. van Balkom
Affiliation:
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands Out-patient Academic Clinic for Anxiety and Mood Disorders, GGZ Buitenamstel, Amsterdam, The Netherlands
G.-J. Hendriks
Affiliation:
Out-patient Clinic for Anxiety Disorders, GGZ Nijmegen, The Netherlands Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
W. J. Hoogendijk
Affiliation:
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands Out-patient Academic Clinic for Anxiety and Mood Disorders, GGZ Buitenamstel, Amsterdam, The Netherlands
H. B. M. Uylings
Affiliation:
Amsterdam, The Netherlands Department of Anatomy and Neuroscience, VU University Medical Center, Amsterdam, The Netherlands School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands
D. J. Veltman
Affiliation:
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands Amsterdam, The Netherlands Out-patient Academic Clinic for Anxiety and Mood Disorders, GGZ Buitenamstel, Amsterdam, The Netherlands
*
*Address for correspondence: P. L. Remijnse, M.D., VU University Medical Center, Department of Anatomy and Neurosciences, room G102B, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Several lines of research suggest a disturbance of reversal learning (reward and punishment processing, and affective switching) in patients with major depressive disorder (MDD). Obsessive–compulsive disorder (OCD) is also characterized by abnormal reversal learning, and is often co-morbid with MDD. However, neurobiological distinctions between the disorders are unclear. Functional neuroimaging (activation) studies comparing MDD and OCD directly are lacking.

Method

Twenty non-medicated OCD-free patients with MDD, 20 non-medicated MDD-free patients with OCD, and 27 healthy controls performed a self-paced reversal learning task in an event-related design during functional magnetic resonance imaging (fMRI).

Results

Compared with healthy controls, both MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal accuracy. In MDD subjects, mean RTs were correlated with disease severity. Imaging results showed MDD-specific hyperactivity in the anterior insula during punishment processing and in the putamen during reward processing. Moreover, blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal cortex (DLPFC) and the anterior PFC during affective switching showed a linear decrease across controls, MDD and OCD. Finally, the OCD group showed blunted responsiveness of the orbitofrontal (OFC)–striatal loop during reward, and in the OFC and anterior insula during affective switching.

Conclusions

This study shows frontal–striatal and (para)limbic functional abnormalities during reversal learning in MDD, in the context of generic psychomotor slowing. These data converge with currently influential models on the neuropathophysiology of MDD. Moreover, this study reports differential neural patterns in frontal–striatal and paralimbic structures on this task between MDD and OCD, confirming previous findings regarding the neural correlates of deficient reversal learning in OCD.

Keywords

Functional MRImajor depressive disorderobsessive–compulsive disorderorbitofrontal cortexreversal learning
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 9 , September 2009 , pp. 1503 - 1518
Copyright
Copyright © 2009 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, GE, Crutcher, MD, DeLong, MR (1990). Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, ‘prefrontal’ and ‘limbic’ functions. Progress in Brain Research 85, 119–146.Google Scholar
Anand, A, Li, Y, Wang, Y, Wu, J, Gao, S, Bukhari, L, Mathews, VP, Kalnin, A, Lowe, MJ (2005). Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biological Psychiatry 57, 1079–1088.Google Scholar
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Beck, AT (1963). Thinking and depression. I. Idiosyncratic content and cognitive disorders. Archives of General Psychiatry 9, 36–45.Google Scholar
Beck, AT, Ward, CH, Mendeson, M, Mock, J, Arbough, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 53–63.Google Scholar
Bremner, JD, Vythilingam, M, Vermetten, E, Charney, DS (2007). Effects of antidepressant treatment on neural correlates of emotional and neutral declarative verbal memory in depression. Journal of Affective Disorders 101, 99–111.Google Scholar
Bremner, JD, Vythilingam, M, Vermetten, E, Vaccarino, V, Charney, DS (2004). Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. American Journal of Psychiatry 161, 637–645.Google Scholar
Budhani, S, Marsh, AA, Pine, DS, Blair, RJR (2006). Neural correlates of response reversal: considering acquisition. NeuroImage 34, 1754–1765.Google Scholar
Chamberlain, SR, Blackwell, AD, Fineberg, NA, Robbins, TW, Sahakian, BJ (2005). The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioral inhibition as candidate endophenotypic markers. Neuroscience and Biobehavioral Reviews 293, 399–419.Google Scholar
Chamberlain, SR, Müller, U, Blackwell, AD, Clark, L, Robbins, TW, Sahakian, BJ (2006). Neurochemical modulation of response inhibition and probabilistic learning in humans. Science 311, 861–863.Google Scholar
Chamberlain, SR, Sahakian, BJ (2006). The neuropsychology of mood disorders. Current Psychiatry Reports 8, 458–463.CrossRefGoogle ScholarPubMed
Clark, L, Cools, R, Robbins, TW (2004). The neuropsychology of ventral prefrontal cortex: decision-making and reversal learning. Brain and Cognition 55, 41–53.CrossRefGoogle ScholarPubMed
Cools, R, Clark, L, Owen, AM, Robbins, TW (2002). Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. Journal of Neuroscience 22, 4563–4567.Google Scholar
Deichmann, R, Gottfried, JA, Hutton, C, Turner, R (2003). Optimized EPI for fMRI studies of the orbitofrontal cortex. NeuroImage 19, 430–441.CrossRefGoogle ScholarPubMed
Dias, R, Robbins, TW, Roberts, AC (1996). Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380, 69–72.CrossRefGoogle ScholarPubMed
Dolan, RJ, Bench, CJ, Liddle, PF, Friston, KJ, Frith, CD, Grasby, PM, Frackowiak, RSJ (1993). Dorsolateral prefrontal cortex dysfunction in the major psychoses: symptom or disease specificity? Journal of Neurology, Neurosurgery and Psychiatry 56, 1290–1294.CrossRefGoogle ScholarPubMed
Drevets, WC (2000). Neuroimaging studies of mood disorders. Biological Psychiatry 48, 813–829.CrossRefGoogle ScholarPubMed
Edmonstone, Y, Austin, MP, Prentice, N, Dougall, N, Freeman, CPL, Ebmeier, KP, Goodwin, GM (1994). Uptake of 99mTc-exametazime shown by single photon emission computed tomography in obsessive-compulsive disorder compared with major depression and normal controls. Acta Psychiatrica Scandinavica 90, 298–303.Google Scholar
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, 975–989.Google Scholar
Epstein, J, Pan, H, Kocsis, JH, Yang, Y, Butler, T, Chusid, J, Hochberg, H, Murrough, J, Strohmayer, E, Stern, E, Silbersweig, DA (2006). Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. American Journal of Psychiatry 163, 1784–1790.Google Scholar
Evers, EAT, 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, 1138–1147.CrossRefGoogle ScholarPubMed
Fellows, LF, Farah, MJ (2003). Ventromedial frontal cortex mediates affective shifting in humans: evidence from a reversal learning paradigm. Brain 126, 1830–1837.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1996). Structured Clinical Interview for DSM-IV Axis I Disorders–Patient Edition (SCID-1/P, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute: New York.Google Scholar
Frank, E, Prien, RF, Jarrett, RB, Keller, MB, Kupfer, DJ, Lavori, PW, Rush, AJ, Weissman, MM (1991). Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Archives of General Psychiatry 48, 851–855.CrossRefGoogle ScholarPubMed
Fu, CHY, Williams, SCR, Cleare, AJ, Brammer, MJ, Walsh, ND, Kim, J, Andrew, CM, Pich, EM, Williams, PM, Reed, LJ, Mitterschiffthaler, MT, Suckling, J, Bullmore, ET (2004). Attenuation of the neural response to sad faces in major depression by antidepressant treatment. A prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry 61, 877–889.Google Scholar
Garavan, H, Ross, TJ, Murphy, K, Roche, RAP, Stein, EA (2002). Dissociable executive functions in the dynamic control of behavior: inhibition, error detection, and correction. NeuroImage 17, 1820–1829.Google Scholar
Genovese, CR, Lazar, NA, Nichols, T (2002). Thresholding of statistical maps in functional neuroimaging using the false discovery rate. NeuroImage 15, 870–878.Google Scholar
Goodman, WK, Price, LH, Rasmussen, SA, Mazure, C, Fleischmann, RL, Hill, CL, Heninger, GR, Charney, DS (1989). The Yale–Brown Obsessive Compulsive Scale. I: Development, use, and reliability. Archives of General Psychiatry 46, 1006–1011.CrossRefGoogle ScholarPubMed
Hamilton, M (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 50–55.CrossRefGoogle ScholarPubMed
Hamilton, M (1967). Development of a rating scale of primary depressive illness. British Journal of Social and Clinical Psychology 6, 278–296.CrossRefGoogle ScholarPubMed
Haruno, M, Kawato, M (2006). Different neural correlates of reward expectation and reward expectation error in the putamen and caudate nucleus during stimulus-action-reward association learning. Journal of Neurophysiology 95, 948–959.CrossRefGoogle ScholarPubMed
Henriques, JB, Glowacki, JM, Davidson, RJ (1994). Reward fails to alter response bias in depression. Journal of Abnormal Psychology 103, 460–466.Google Scholar
Jans, LAW, Riedel, WJ, Markus, CR, Blokland, A (2007). Serotonergic vulnerability and depression: assumptions, experimental evidence and implications. Molecular Psychiatry 12, 522–543.CrossRefGoogle ScholarPubMed
Joel, D, Zohar, O, Afek, M, Hermesh, H, Lerner, L, Kuperman, R, Gross-Isseroff, R, Weizman, A, Inzelberg, R (2005). Impaired procedural learning in obsessive-compulsive disorder and Parkinson's disease, but not in major depressive disorder. Behavioural Brain Research 157, 253–263.CrossRefGoogle ScholarPubMed
Kalb, R, Dorner, M, Kalb, S (2006). Opposite effects of depression and antidepressants on processing speed and error rate. Progress in Neuro-Psychopharmacology and Biological Psychiatry 30, 244–250.CrossRefGoogle ScholarPubMed
Keedwell, PA, Andrew, C, Williams, SCR, Brammer, MJ, Phillips, ML (2005). A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biological Psychiatry 58, 495–503.CrossRefGoogle ScholarPubMed
Kennedy, SH, Evans, KR, Krüger, S, Mayberg, SH, Meyer, JH, McCann, S, Arifuzzman, AI, Houle, S, Vaccarino, FJ (2001). Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. American Journal of Psychiatry 158, 899–905.Google Scholar
Kumari, V, Mitterschiffthaler, MT, Teasdale, JD, Malhi, GS, Brown, RG, Giampietro, V, Brammer, MJ, Poon, L, Simmons, A, Williams, SCR, Checkley, SA, Sharma, T (2003). Neural abnormalities during cognitive generation of affect in treatment-resistant depression. Biological Psychiatry 54, 777–791.Google Scholar
Levine, J, Cole, DP, Roy, Chengappa KN, Gershon, S (2001). Anxiety disorders and major depression, together or apart. Depression and Anxiety 14, 94–104.CrossRefGoogle ScholarPubMed
Mann, JJ, Malone, KM, Diehl, DJ, Perel, J, Cooper, TB, Mintun, MA (1996). Demonstration in vivo of reduced serotonin responsivity in the brain of untreated depressed patients. American Journal of Psychiatry 153, 174–182.Google Scholar
Mayberg, HS (1997). Limbic-cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry and Clinical Neurosciences 9, 471–481.Google ScholarPubMed
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, 193–207.CrossRefGoogle ScholarPubMed
Mayberg, HS, Lewis, PJ, Regenold, W, Wagner, HN Jr. (1994). Paralimbic hypoperfusion in unipolar depression. Journal of Nuclear Medicine 35, 929–934.Google ScholarPubMed
Mitterschiffthaler, MT, Ettinger, U, Mehta, MA, Mataix-Cols, D, Williams, SCR (2006). Applications of functional magnetic resonance imaging in psychiatry. Journal of Magnetic Resonance Imaging 23, 851–861.CrossRefGoogle ScholarPubMed
Mitterschiffthaler, MT, Kumari, V, Malhi, GS, Brown, RG, Giampietro, VP, Brammer, MJ, Suckling, J, Poon, L, Simmons, A, Andrew, C, Sharma, T (2003). Neural response to pleasant stimuli in anhedonia: an fMRI study. Neuroreport 14, 177–182.Google Scholar
Montgomery, SA, Asberg, M (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382–389.Google Scholar
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, 455–467.Google Scholar
Murphy, FC, Sahakian, BJ, Rubinsztein, JS, Michael, A, Rogers, RD, Robbins, TW, Paykel, ES (1999). Emotional bias and inhibitory control processes in mania and depression. Psychological Medicine 29, 1307–1321.Google Scholar
Murphy, FC, Smith, KA, Cowen, PJ, Robbins, TW, Sahakian, BJ (2002). The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacology 163, 42–53.CrossRefGoogle ScholarPubMed
Must, A, Szabó, Z, Bódi, N, Szász, A, Janka, Z, Kéri, S (2006). Sensitivity to reward and punishment and the prefrontal cortex in major depression. Journal of Affective Disorders 90, 209–215.CrossRefGoogle ScholarPubMed
Ninan, PT, Berger, J (2001). Symptomatic and syndromal anxiety and depression. Depression and Anxiety 14, 79–85.Google Scholar
Okada, G, Okamoto, Y, Morinobu, S, Yamawaki, S, Yokota, N (2003). Attenuated left prefrontal activation during a verbal fluency task in patients with depression. Neuropsychobiology 47, 21–26.Google Scholar
Overbeek, T, Schruers, K, Vermetten, E, Griez, E (2002). Comorbidity of obsessive-compulsive disorder and depression: prevalence, symptom severity, and treatment effect. Journal of Clinical Psychiatry 63, 1106–1112.Google Scholar
Phillips, ML, Drevets, WC, Rauch, SL, Lane, R (2003). Neurobiology of emotion perception. II: Implications for major psychiatric disorders. Biological Psychiatry 54, 515–528.Google Scholar
Purcell, R, Maruff, P, Kyrios, M, Pantelis, C (1998). Neuropsychological deficits in obsessive-compulsive disorder. A comparison with unipolar depression, panic disorder, and normal controls. Archives of General Psychiatry 55, 415–423.Google Scholar
Remijnse, PL, Nielen, MMA, Uylings, HBM, Veltman, DJ (2005 a). Neural correlates of a reversal learning task with an affectively neutral baseline: an event-related fMRI study. NeuroImage 26, 609–618.Google Scholar
Remijnse, PL, Nielen, MMA, van Balkom, AJLM, Cath, DC, van Oppen, P, Uylings, HBM, Veltman, DJ (2006). Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder. Archives of General Psychiatry 63, 1225–1236.CrossRefGoogle ScholarPubMed
Remijnse, PL, van den Heuvel, OA, Veltman, DJ (2005 b). Neuroimaging in obsessive-compulsive disorder. Current Medical Imaging Reviews 1, 331–351.CrossRefGoogle Scholar
Rogers, RD, Blackshaw, AJ, Middleton, HC, Matthews, K, Hawtin, K, Crowley, C, Hopwood, A, Wallace, C, Deakin, JFW, Sahakian, BJ, Robbins, TW (1999). Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology 146, 482–491.CrossRefGoogle ScholarPubMed
Rogers, MA, Kasai, K, Koji, M, Fukuda, R, Iwanami, A, Nakagome, K, Fukuda, M, Kato, N (2004). Executive and prefrontal dysfunction in unipolar depression: a review of neuropsychological and imaging evidence. Neuroscience Research 50, 1–11.Google Scholar
Rolls, ET (1999). The functions of the orbitofrontal cortex. Neurocase 5, 301–312.Google Scholar
Roth, RM, Baribeau, J, Milovan, DL, O'Connor, K (2004). Speed and accuracy on tests of executive function in obsessive-compulsive disorder. Brain and Cognition 54, 263–265.Google Scholar
Sanavio, E (1988). Obsessions and compulsions: the Padua Inventory. Behaviour Research and Therapy 26, 169–177.CrossRefGoogle ScholarPubMed
Saxena, S, Brody, AL, Ho, ML, Alborzian, S, Ho, MK, Maidment, KM, Huang, SC, Wu, HM, Au, SC, Baxter, LR Jr. (2001). Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently. Biological Psychiatry 50, 159–170.Google Scholar
Siegle, GJ, Thompson, W, Carter, CS, Steinhauer, SR, Thase, ME (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198–209.Google Scholar
Smith, AB, Taylor, E, Brammer, M, Rubia, K (2004). Neural correlates of switching set as measured in fast, event-related functional magnetic resonance imaging. Human Brain Mapping 21, 247–256.Google Scholar
Smith, KA, Fairburn, CG, Cowen, PJ (1997). Relapse of depression after rapid depletion of tryptophan. Lancet 349, 915–919.Google Scholar
Surguladze, S, Brammer, MJ, Keedwell, P, Giampietro, V, Young, AW, Travis, MJ, Williams, SCR, Phillips, ML (2005). A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry 57, 201–209.Google Scholar
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, 1118–1126.Google Scholar
van Oppen, P, Hoekstra, RJ, Emmelkamp, PM (1995). The structure of obsessive-compulsive symptoms. Behaviour Research and Therapy 331, 15–23.CrossRefGoogle Scholar
Zimmerman, M, Posternak, MA, Chelminski, I (2004). Derivation of a definition of remission on the Montgomery–Asberg depression rating scale corresponding to the definition of remission on the Hamilton rating scale for depression. Journal of Psychiatric Research 38, 577–582.Google Scholar