Hostname: page-component-cd4964975-ppllx Total loading time: 0 Render date: 2023-03-31T01:37:40.108Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

Response inhibition in alcohol-dependent patients and patients with depression/anxiety: a functional magnetic resonance imaging study

Published online by Cambridge University Press:  09 September 2013

Z. Sjoerds*
Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands
W. van den Brink
Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands
A. T. F. Beekman
Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
B. W. J. H. Penninx
Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, Leiden University Medical Center, The Netherlands Department of Psychiatry, University Medical Center of Groningen, The Netherlands
D. J. Veltman
Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
*Address for correspondence: Z. Sjoerds, M.Sc., VU University Medical Center, Department of Psychiatry, Van der Boechorststraat 7, MF-A422, 1081 BT Amsterdam, The Netherlands. (Email:



The inability to inhibit certain behaviors is a key feature of impulsivity, which is often present in people with a substance use disorder. However, the findings on impulsivity in people with alcohol dependence (AD) are inconsistent, possibly because of the frequent co-occurrence of depression/anxiety (D/A) and its influence on impulsivity. In the current study, we aimed to distinguish response inhibition impairments in AD from possible response inhibition effects associated with D/A.


AD patients (n = 31) with high D/A co-morbidity were compared to patients with D/A only (n = 18) and healthy controls (HCs; n = 16) using the Stop Signal Task (SST) during functional magnetic resonance imaging (fMRI). Correlation analyses were performed between activated brain areas, behavioral data and addiction and D/A characteristics.


The three groups did not differ on response inhibition performance. However, AD severity, but not D/A severity, was positively associated with decreased response inhibition. During the SST, AD patients showed hyperactivity in the putamen and thalamus compared with D/A patients and HCs. Thalamus activation was negatively associated with AD duration. In addition, AD patients showed hypoactivity in the supplementary motor area (SMA) compared with HCs. SMA activity within HCs was negatively correlated with depressive symptom severity.


In general, AD patients were not more impulsive than D/A patients or HCs but they did reveal inhibition impairments with increasing AD severity. A shift from cortical to subcortical engagement in AD patients during response inhibition may represent an alternative strategy, which decreased with longer drinking history, suggesting the presence of an AD-specific endophenotype.

Original Articles
Copyright © Cambridge University Press 2013 

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.)


Achenbach, TM (1966). The classification of children's psychiatric symptoms: a factor-analytic study. Psychological Monographs 80, 137.CrossRefGoogle ScholarPubMed
Aron, AR (2011). From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses. Biological Psychiatry 69, e55e68.CrossRefGoogle ScholarPubMed
Aron, AR, Poldrack, RA (2006). Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. Journal of Neuroscience 26, 24242433.CrossRefGoogle ScholarPubMed
Babor, TF, Hofmann, M, DelBoca, FK, Hesselbrock, V, Meyer, RE, Dolinsky, ZS, Rounsaville, B (1992). Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. Archives of General Psychiatry 49, 599608.CrossRefGoogle ScholarPubMed
Babor, TF, Kranzler, HR, Lauerman, RJ (1989). Early detection of harmful alcohol consumption: comparison of clinical, laboratory, and self-report screening procedures. Addictive Behaviors 14, 139157.CrossRefGoogle ScholarPubMed
Baler, RD, Volkow, ND (2006). Drug addiction: the neurobiology of disrupted self-control. Trends in Molecular Medicine 12, 559566.CrossRefGoogle ScholarPubMed
Beck, AT, Epstein, N, Brown, G, Steer, RA (1988). An inventory for measuring clinical anxiety: psychometric properties. Journal of Consulting and Clinical Psychology 56, 893897.CrossRefGoogle ScholarPubMed
Bellani, M, Hatch, JP, Nicoletti, MA, Ertola, AE, Zunta-Soares, G, Swann, AC, Brambilla, P, Soares, JC (2012). Does anxiety increase impulsivity in patients with bipolar disorder or major depressive disorder? Journal of Psychiatric Research 46, 616621.CrossRefGoogle ScholarPubMed
Bobb, DS Jr., Adinoff, B, Laken, SJ, McClintock, SM, Rubia, K, Huang, HW, Husain, MM, Mapes, KS, Tamminga, C, Cullum, CM, Gopinath, K, Trivedi, MH, Kozel, FA (2012). Neural correlates of successful response inhibition in unmedicated patients with late-life depression. American Journal of Geriatric Psychiatry 20, 10571069.CrossRefGoogle ScholarPubMed
Boschloo, L, Vogelzangs, N, Smit, JH, van den Brink, W, Veltman, DJ, Beekman, ATF, Penninx, BWJH (2011). Comorbidity and risk indicators for alcohol use disorders among persons with anxiety and/or depressive disorders. Findings from the Netherlands Study of Depression and Anxiety (NESDA). Journal of Affective Disorders 131, 233242.CrossRefGoogle Scholar
Brett, M, Anton, J-L, Valabreque, R, Poline, J-B (2002). Region of interest analysis using an SPM toolbox [Abstract]. Presented at the 8th International Conference on Functional Mapping of the Human Brain, 2–6 June 2002, Sendai, Japan. Available on CD-ROM in Neuroimage 16, no. 2, Abstract 497 ( Scholar
Broos, N, Schmaal, L, Wiskerke, J, Kostelijk, L, Lam, T, Stoop, N, Weierink, L, Ham, J, de Geus, EJ, Schoffelmeer, AN, van den Brink, W, Veltman, DJ, de Vries, TJ, Pattij, T, Goudriaan, AE (2012). The relationship between impulsive choice and impulsive action: a cross-species translational study. PLoS One 7, e36781.CrossRefGoogle ScholarPubMed
Cai, W, Leung, HC (2011). Rule-guided executive control of response inhibition: functional topography of the inferior frontal cortex. PLoS One 6, e20840.CrossRefGoogle ScholarPubMed
Cloninger, CR, Bohman, M, Sigvardsson, S (1981). Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Archives of General Psychiatry 38, 861868.CrossRefGoogle ScholarPubMed
de Graaf, R, Bijl, RV, Smit, F, Vollebergh, WAM, Spijker, J (2002). Risk factors for 12-month comorbidity of mood, anxiety, and substance use disorders: findings from the Netherlands Mental Health Survey and Incidence Study. American Journal of Psychiatry 159, 620629.CrossRefGoogle ScholarPubMed
Deichmann, R, Gottfried, JA, Hutton, C, Turner, R (2003). Optimized EPI for fMRI studies of the orbitofrontal cortex. NeuroImage 19, 430441.CrossRefGoogle ScholarPubMed
de Jong, R, Coles, MG, Logan, GD, Gratton, G (1990). In search of the point of no return: the control of response processes. Journal of Experimental Psychology. Human Perception and Performance 16, 164182.CrossRefGoogle ScholarPubMed
de Ruiter, MB, Oosterlaan, J, Veltman, DJ, van den Brink, W, Goudriaan, AE (2012). Similar hyporesponsiveness of the dorsomedial prefrontal cortex in problem gamblers and heavy smokers during an inhibitory control task. Drug and Alcohol Dependence 121, 8189.CrossRefGoogle ScholarPubMed
Diener, C, Kuehner, C, Brusniak, W, Ubl, B, Wessa, M, Flor, H (2012). A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression. NeuroImage 61, 677685.CrossRefGoogle ScholarPubMed
Dom, G, D'haene, P, Hulstijn, W, Sabbe, B (2006). Impulsivity in abstinent early- and late-onset alcoholics: differences in self-report measures and a discounting task. Addiction 101, 5059.CrossRefGoogle Scholar
Etkin, A, Prater, KE, Hoeft, F, Menon, V, Schatzberg, AF (2010). Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. American Journal of Psychiatry 167, 545554.CrossRefGoogle ScholarPubMed
Eugene, F, Joormann, J, Cooney, RE, Atlas, LY, Gotlib, IH (2010). Neural correlates of inhibitory deficits in depression. Psychiatry Research 181, 3035.CrossRefGoogle ScholarPubMed
Evenden, JL (1999). Varieties of impulsivity. Psychopharmacology 146, 348361.CrossRefGoogle ScholarPubMed
Everitt, BJ, Belin, D, Economidou, D, Pelloux, Y, Dalley, JW, Robbins, TW (2008). Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 363, 31253135.CrossRefGoogle ScholarPubMed
Everitt, BJ, Robbins, TW (2005). Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neuroscience 8, 14811489.CrossRefGoogle ScholarPubMed
Forman, SD, Dougherty, GG, Casey, BJ, Siegle, GJ, Braver, TS, Barch, DM, Stenger, VA, Wick-Hull, C, Pisarov, LA, Lorensen, E (2004). Opiate addicts lack error-dependent activation of rostral anterior cingulate. Biological Psychiatry 55, 531537.CrossRefGoogle ScholarPubMed
Fox, PT, Lancaster, JL (1994). Neuroscience on the net. Science 266, 994996.CrossRefGoogle ScholarPubMed
Friston, KJ, Holmes, AP, Poline, JB, Grasby, PJ, Williams, SC, Frackowiak, RS, Turner, R (1995). Analysis of fMRI time-series revisited. NeuroImage 2, 4553.CrossRefGoogle ScholarPubMed
Fu, LP, Bi, GH, Zou, ZT, Wang, Y, Ye, EM, Ma, L, Ming, Fan, Yang, Z (2008). Impaired response inhibition function in abstinent heroin dependents: an fMRI study. Neuroscience Letters 438, 322326.CrossRefGoogle ScholarPubMed
Goldstein, RZ, Volkow, ND (2002). Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. American Journal of Psychiatry 159, 16421652.CrossRefGoogle ScholarPubMed
Gray, JA, McNaughton, N (2000). The Neuropsychology of Anxiety, An Enquiry into the Function of the Septo-Hippocampal System. Oxford University Press: New York.Google Scholar
Heatherton, TF, Kozlowski, LT, Frecker, RC, Fagerstrom, KO (1991). The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. British Journal of Addiction 86, 11191127.CrossRefGoogle ScholarPubMed
Heslenfeld, DJ, Oosterlaan, J (2003). Where does the brain stop? Brain areas involved in the inhibition of behavior. Journal of Psychophysiology 17, 138.Google Scholar
Hester, R, Garavan, H (2004). Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity. Journal of Neuroscience 24, 1101711022.CrossRefGoogle ScholarPubMed
Hur, JW, Kim, YK (2009). Comparison of clinical features and personality dimensions between patients with major depressive disorder and normal control. Psychiatry Investigation 6, 150155.CrossRefGoogle ScholarPubMed
Jakubczyk, A, Klimkiewicz, A, Topolewska-Wochowska, A, Serafin, P, Sadowska-Mazuryk, J, Pupek-Pyziol, J, Brower, KJ, Wojnar, M (2012). Relationships of impulsiveness and depressive symptoms in alcohol dependence. Journal of Affective Disorders 136, 841847.CrossRefGoogle ScholarPubMed
Jentsch, JD, Taylor, JR (1999). Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 146, 373390.CrossRefGoogle ScholarPubMed
Joormann, J, Dkane, M, Gotlib, IH (2006). Adaptive and maladaptive components of rumination? Diagnostic specificity and relation to depressive biases. Behavior Therapy 37, 269280.CrossRefGoogle ScholarPubMed
Joormann, J, Gotlib, IH (2010). Emotion regulation in depression: relation to cognitive inhibition. Cognition and Emotion 24, 281298.CrossRefGoogle ScholarPubMed
Karch, S, Jager, L, Karamatskos, E, Graz, C, Stammel, A, Flatz, W, Lutz, J, Holtschmidt-Taschner, B, Genius, J, Leicht, G, Pogarell, O, Born, C, Moller, HJ, Hegerl, U, Reiser, M, Soyka, M, Mulert, C (2008). Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses. Journal of Psychiatric Research 42, 734745.CrossRefGoogle ScholarPubMed
Katz, R, De Sanctis, P, Mahoney, JR, Sehatpour, P, Murphy, CF, Gomez-Ramirez, M, Alexopoulos, GS, Foxe, JJ (2010). Cognitive control in late-life depression: response inhibition deficits and dysfunction of the anterior cingulate cortex. American Journal of Geriatric Psychiatry 18, 10171025.CrossRefGoogle ScholarPubMed
Kaufman, JN, Ross, TJ, Stein, EA, Garavan, H (2003). Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging. Journal of Neuroscience 23, 78397843.Google ScholarPubMed
Kirby, KN, Petry, NM (2004). Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls. Addiction 99, 461471.CrossRefGoogle ScholarPubMed
Krueger, RF (1999). The structure of common mental disorders. Archives of General Psychiatry 56, 921926.CrossRefGoogle ScholarPubMed
Lambert, C, Zrinzo, L, Nagy, Z, Lutti, A, Hariz, M, Foltynie, T, Draganski, B, Ashburner, J, Frackowiak, R (2012). Confirmation of functional zones within the human subthalamic nucleus: patterns of connectivity and sub-parcellation using diffusion weighted imaging. NeuroImage 60, 8394.CrossRefGoogle Scholar
Lau, MA, Christensen, BK, Hawley, LL, Gemar, MS, Segal, ZV (2007). Inhibitory deficits for negative information in persons with major depressive disorder. Psychological Medicine 37, 12491259.CrossRefGoogle ScholarPubMed
Lawrence, AJ, Luty, J, Bogdan, NA, Sahakian, BJ, Clark, L (2009). Impulsivity and response inhibition in alcohol dependence and problem gambling. Psychopharmacology 207, 163172.CrossRefGoogle ScholarPubMed
Li, CS, Huang, C, Constable, RT, Sinha, R (2006). Imaging response inhibition in a stop-signal task: neural correlates independent of signal monitoring and post-response processing. Journal of Neuroscience 26, 186192.Google Scholar
Li, CS, Huang, C, Yan, P, Bhagwagar, Z, Milivojevic, V, Sinha, R (2008 a). Neural correlates of impulse control during stop signal inhibition in cocaine-dependent men. Neuropsychopharmacology 33, 17981806.CrossRefGoogle ScholarPubMed
Li, CS, Luo, X, Yan, P, Bergquist, K, Sinha, R (2009). Altered impulse control in alcohol dependence: neural measures of stop signal performance. Alcoholism: Clinical and Experimental Research 33, 740750.CrossRefGoogle ScholarPubMed
Li, CS, Yan, P, Sinha, R, Lee, TW (2008 b). Subcortical processes of motor response inhibition during a stop signal task. NeuroImage 41, 13521363.Google ScholarPubMed
Liddle, PF, Kiehl, KA, Smith, AM (2001). Event-related fMRI study of response inhibition. Human Brain Mapping 12, 100109.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
Lipszyc, J, Schachar, R (2010). Inhibitory control and psychopathology: a meta-analysis of studies using the stop signal task. Journal of the International Neuropsychological Society: JINS 16, 10641076.CrossRefGoogle ScholarPubMed
Logan, GD (1994). On the ability to inhibit thought and action: a user's guide to the stop signal paradigm. In Inhibitory Processes in Attention, Memory and Language (ed. Dagenbach, D. and Carr, T. H.), pp. 189239. Academic Press: San Diego, CA.Google Scholar
Lubman, DI, Yucel, M, Pantelis, C (2004). Addiction, a condition of compulsive behaviour? Neuroimaging and neuropsychological evidence of inhibitory dysregulation. Addiction 99, 14911502.CrossRefGoogle ScholarPubMed
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.CrossRefGoogle ScholarPubMed
Matthews, S, Simmons, A, Strigo, I, Gianaros, P, Yang, T, Paulus, M (2009). Inhibition-related activity in subgenual cingulate is associated with symptom severity in major depression. Psychiatry Research 172, 16.CrossRefGoogle ScholarPubMed
Nambu, A, Tokuno, H, Takada, M (2002). Functional significance of the cortico-subthalamo-pallidal ‘hyperdirect’ pathway. Neuroscience Research 43, 111117.CrossRefGoogle ScholarPubMed
Ngo, HTT, Street, HL, Hulse, GK (2011). Is there a relationship between impulsivity and depression in adults? A research synthesis. Current Psychiatry Reviews 7, 281297.CrossRefGoogle Scholar
Nielsen, FA, Hansen, LK (2002). Automatic anatomical labeling of Talairach coordinates and generation of volumes of interest via the BrainMap database. Neuroimage 16(2). Available on CD-ROM ( Presented at the 8th International Conference on Functional Mapping of the Human Brain, 2–6 June 2002, Sendai, Japan.Google Scholar
Noel, X, Van der Linden, M, Brevers, D, Campanella, S, Verbanck, P, Hanak, C, Kornreich, C, Verbruggen, F (2012). Separating intentional inhibition of prepotent responses and resistance to proactive interference in alcohol-dependent individuals. Drug and Alcohol Dependence 128, 200205.CrossRefGoogle ScholarPubMed
Patton, JH, Stanford, MS, Barratt, ES (1995). Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology 51, 768774.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Peluso, MAM, Hatch, JP, Glahn, DC, Monkul, ES, Sanches, M, Najt, P, Bowden, CL, Barratt, ES, Soares, JC (2007). Trait impulsivity in patients with mood disorders. Journal of Affective Disorders 100, 227231.CrossRefGoogle ScholarPubMed
Penninx, BWJH, Beekman, ATF, Smit, JH, Zitman, FG, Nolen, WA, Spinhoven, P, Cuijpers, P, de Jong, PJ, van Marwijk, HWJ, Assendelft, WJJ, van der Meer, K, Verhaak, P, Wensing, M, de Graaf, R, Hoogendijk, WJ, Ormel, J, van Dyck, R (2008). The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods. International Journal of Methods in Psychiatric Research 17, 121140.CrossRefGoogle ScholarPubMed
Perry, JL, Carroll, ME (2008). The role of impulsive behavior in drug abuse. Psychopharmacology 200, 126.CrossRefGoogle ScholarPubMed
Robins, LN, Wing, J, Wittchen, HU, Helzer, JE, Babor, TF, Burke, J, Farmer, A, Jablenski, A, Pickens, R, Regier, DA, Sartorius, N, Towle, LH (1988). The Composite International Diagnostic Interview. An epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Archives of General Psychiatry 45, 10691077.CrossRefGoogle ScholarPubMed
Robinson, TE, Berridge, KC (2003). Addiction. Annual Review of Psychology 54, 2553.CrossRefGoogle ScholarPubMed
Rubia, K, Smith, AB, Brammer, MJ, Taylor, E (2003). Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection. NeuroImage 20, 351358.CrossRefGoogle ScholarPubMed
Rush, AJ, Gullion, CM, Basco, MR, Jarrett, RB, Trivedi, MH (1996). The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychological Medicine 26, 477486.CrossRefGoogle ScholarPubMed
Schmaal, L, Joos, L, Koeleman, M, Veltman, DJ, van den Brink, W, Goudriaan, AE (2012). Effects of modafinil on neural correlates of response inhibition in alcohol-dependent patients. Biological Psychiatry 73, 211218.CrossRefGoogle ScholarPubMed
Spielberger, CD, Gorsuch, RL, Lushene, RE (1970). STAI Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press: Palo Alto, CA.Google Scholar
Sullivan, JT, Sykora, K, Schneiderman, J, Naranjo, CA, Sellers, EM (1989). Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). British Journal of Addiction 84, 13531357.CrossRefGoogle Scholar
Tricomi, E, Balleine, BW, O'Doherty, JP (2009). A specific role for posterior dorsolateral striatum in human habit learning. European Journal of Neuroscience 29, 22252232.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273289.CrossRefGoogle ScholarPubMed
Vandermeeren, R, Hebbrecht, M (2012). The dual process model of addiction. Towards an integrated model? [in Dutch] Tijdschrift voor Psychiatrie 54, 731740.Google Scholar
van Holst, RJ, Schilt, T (2011). Drug-related decrease in neuropsychological functions of abstinent drug users. Current Drug Abuse Reviews 4, 4256.CrossRefGoogle ScholarPubMed
van Strien, JW (1992). Classification of left- and right-handed research participants [in Dutch]. Nederlands Tijdschrift voor de Psychologie 47, 8892.Google Scholar
Worsley, KJ, Marrett, S, Neelin, P, Vandal, AC, Friston, KJ, Evans, AC (1996). A unified statistical approach for determining significant signals in images of cerebral activation. Human Brain Mapping 4, 5873.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Yang, TT, Simmons, AN, Matthews, SC, Tapert, SF, Frank, GK, Bischoff-Grethe, A, Lansing, AE, Wu, J, Brown, GG, Paulus, MP (2009). Depressed adolescents demonstrate greater subgenual anterior cingulate activity. Neuroreport 20, 440444.CrossRefGoogle ScholarPubMed
Zandbelt, BB, Vink, M (2010). On the role of the striatum in response inhibition. PLoS One 5, e13848.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Sjoerds Supplementary Material

Supplementary Methods

Download Sjoerds Supplementary Material(PDF)
PDF 292 KB