Abstract
Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field.
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Acknowledgements
Dr Fineberg has consulted for Lundbeck, Glaxo-Smith Kline, Servier, and Bristol Myers Squibb; has received research support from Lundbeck, Glaxo-SmithKline, Astra Zeneca, Wellcome; has received honoraria and support to lecture at scientific meetings from Janssen, Jazz, Lundbeck, Servier, Astra Zeneca, Wyeth. Dr Potenza consults for and has advised to Boehringer Ingelheim; has consulted for and has financial interests in Somaxon; has received research support from the National Institutes of Health, Veteran's Administration, Mohegan Sun Casino, the National Center for Responsible Gambling and the Institute for Research on Gambling Disorders, and Glaxo-SmithKline, Forest Laboratories, Ortho-McNeil and Oy-Control/Biotie pharmaceuticals; has participated in surveys, mailings, or telephone consultations related to drug addiction, ICDs or other health topics; has consulted for law offices and the federal public defender's office in issues related to ICDs and drug addiction; has performed grant reviews for the National Institutes of Health and other agencies; has given academic lectures in grand rounds, CME events, and other clinical or scientific venues; has guest-edited sections of journals; has generated books or book chapters for publishers of mental health texts; and provides clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program. Dr Chamberlain consults for Cambridge Cognition, Shire, and P1Vital. Dr Menzies has received financial compensation resulting from the transfer of a technology not relating to the subject matter of this article between Cambridge Enterprise Limited, University of Cambridge, Cambridge, UK, and Cypress Bioscience, Inc, San Diego. Dr Bechara receives royalties from PAR, Inc. Dr Sahakian holds shares in CeNeS; has consulted for Cambridge Cognition, Novartis, Shire, GlaxoSmithKline, and Lilly; and has received honoraria for grand rounds in psychiatry at Massachusetts General Hospital (CME credits) and for speaking at the International Conference on Cognitive Dysfunction in Schizophrenia and Mood Disorders (2007). Dr Robbins consults for Cambridge Cognition, E. Lilly, GlaxoSmithKline, and Allon Therapeutics. Dr Bullmore is an employee of GlaxoSmithKline (50%) and the University of Cambridge (50%) and a shareholder in GlaxoSmithKline. Dr Bullmore has received financial compensation resulting from the transfer of a technology not relating to the subject matter of this article between Cambridge Enterprise Limited, University of Cambridge, Cambridge, UK, and Cypress Bioscience, Inc, San Diego. Dr Hollander has consulted to Somaxon, Neuropharm, Transcept, and Nastech. Dr Hollander has consulted to law offices and testified in the Mirapex Product Liability case. He has received research support from the National Institutes of Health, Orphan Products Division of the Food and Drug Administration, National Alliance for Research in Schizophrenia and Affective Disorders, Autism Speaks, the Seaver Foundation, and Solvay, Oy Contral, and Somaxon. This work was supported in part by a Wellcome Trust Programme Grant (076274/Z/04/Z) to Dr Robbins, Dr Sahakian, BJ Everitt, and AC Roberts. The Behavioural and Clinical Neuroscience Institute is supported by a joint award from the Medical Research Council (MRC) and Wellcome Trust (G001354). Supported by the National Alliance for Research on Schizophrenia and Depression (RG37920 Distinguished Investigator Award to Dr Bullmore), the Harnett Fund and James Baird Fund (University of Cambridge) and the University of Cambridge School of Clinical Medicine, (MB/PhD studentship to Dr Menzies), and the Medical Research Council (MB/PhD studentship to Dr Chamberlain). Dr Bechara receives grant support from the National Institutes on Health (NIDA R01 DA023051, DA11779, DA12487, and DA1670), (NINDS P01 NS019632), and the National Science Foundation (NSF IIS 04-42586). Dr Potenza receives grant support from the National Institutes of Health (R01 s DA019039, DA020908, DA015757, DA020709; R37 DA15969; RL1 AA017539; P50 s DA09241, AA12870, AA015632), the VA (VISN1 MIRECC and REAP), and Women's Health Research at Yale. Dr Robbins consults for pfizer, Dr Menzies has received honoraria for presenting at the 8th Annual conference on Research of psychopathology and for work on the UK Government Foresight Project on mental capital and wellbeing.
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Fineberg, N., Potenza, M., Chamberlain, S. et al. Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review. Neuropsychopharmacol 35, 591–604 (2010). https://doi.org/10.1038/npp.2009.185
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