Addiction related alteration in resting-state brain connectivity

It is widely accepted that addictive drug use is related to abnormal functional organization in the user's brain. The present study aimed to identify this type of abnormality within the brain networks implicated in addiction by resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI). With fMRI data acquired during resting state from 14 chronic heroin users (12 of whom were being treated with methadone) and 13 non-addicted controls, we investigated the addiction related alteration in functional connectivity between the regions in the circuits implicated in addiction with seed-based correlation analysis. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens and ventral/rostral anterior cingulate cortex (ACC), between nucleus accumbens and orbital frontal cortex (OFC), and between amygdala and OFC and reduced functional connectivity between prefrontal cortex and OFC and between prefrontal cortex and ACC. These observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state.

[1]  Yu-Shin Ding,et al.  Behavioral / Systems / Cognitive Activation of Orbital and Medial Prefrontal Cortex by Methylphenidate in Cocaine-Addicted Subjects But Not in Controls : Relevance to Addiction , 2005 .

[2]  E. Nestler.  Is there a common molecular pathway for addiction? , 2005, Nature Neuroscience.

[3]  Yu-Shin Ding,et al.  Expectation Enhances the Regional Brain Metabolic and the Reinforcing Effects of Stimulants in Cocaine Abusers , 2003, The Journal of Neuroscience.

[4]  J S Fowler,et al.  Addiction changes orbitofrontal gyrus function: involvement in response inhibition , 2001, Neuroreport.

[5]  Baoci Shan,et al.  Disrupted White Matter Integrity in Heroin Dependence: A Controlled Study Utilizing Diffusion Tensor Imaging , 2008, The American journal of drug and alcohol abuse.

[6]  N. Volkow,et al.  Drug addiction: the neurobiology of disrupted self-control. , 2006, Trends in molecular medicine.

[7]  A. Bechara.  Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective , 2005, Nature Neuroscience.

[8]  Kuncheng Li,et al.  Altered functional connectivity in early Alzheimer's disease: A resting‐state fMRI study , 2007, Human brain mapping.

[9]  John Listerud,et al.  Prelude to Passion: Limbic Activation by “Unseen” Drug and Sexual Cues , 2008, PloS one.

[10]  P. Kalivas,et al.  Brain circuitry and the reinstatement of cocaine-seeking behavior , 2003, Psychopharmacology.

[11]  Sheng He,et al.  Masked smoking‐related images modulate brain activity in smokers , 2009, Human brain mapping.

[12]  Brian Knutson,et al.  Splitting the Difference , 2007, Annals of the New York Academy of Sciences.

[13]  Chun-Ming Xie,et al.  Dynamic neural responses to cue‐reactivity paradigms in heroin‐dependent users: An fMRI study , 2009, Human brain mapping.

[14]  J. O'Doherty,et al.  What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies , 2007, The Journal of Neuroscience.

[15]  H. Curran,et al.  Additional methadone increases craving for heroin: a double-blind, placebo-controlled study of chronic opiate users receiving methadone substitution treatment. , 1999, Addiction.

[16]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[17]  N. Volkow,et al.  The neural basis of addiction: a pathology of motivation and choice. , 2005, The American journal of psychiatry.

[18]  M. Greicius.  Resting-state functional connectivity in neuropsychiatric disorders , 2008, Current opinion in neurology.

[19]  Daniel S. Margulies,et al.  Functional connectivity of the human amygdala using resting state fMRI , 2009, NeuroImage.

[20]  P. Kalivas,et al.  Drug Addiction as a Pathology of Staged Neuroplasticity , 2008, Neuropsychopharmacology.

[21]  Peter A. Bandettini,et al.  Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI , 2006, NeuroImage.

[22]  M. Kringelbach.  The human orbitofrontal cortex: linking reward to hedonic experience , 2005, Nature Reviews Neuroscience.

[23]  Daniel S. Margulies,et al.  Mapping the functional connectivity of anterior cingulate cortex , 2007, NeuroImage.

[24]  J. Allman,et al.  The Anterior Cingulate Cortex , 2001, Annals of the New York Academy of Sciences.

[25]  Rita Z. Goldstein,et al.  Thalamo-cortical dysfunction in cocaine abusers: Implications in attention and perception , 2007, Psychiatry Research: Neuroimaging.

[26]  Chunshui Yu,et al.  Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia , 2008, Schizophrenia Research.

[27]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[28]  R. Elliott,et al.  Hedonic and informational functions of the human orbitofrontal cortex. , 2010, Cerebral cortex.

[29]  T. Robbins,et al.  Drug Addiction and the Memory Systems of the Brain , 2008, Annals of the New York Academy of Sciences.

[30]  Nora D. Volkow,et al.  Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex , 2004, Neuropsychologia.

[31]  S. Hyman,et al.  Neural mechanisms of addiction: the role of reward-related learning and memory. , 2006, Annual review of neuroscience.

[32]  G. Glover,et al.  Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus , 2007, Biological Psychiatry.

[33]  David J. Nutt,et al.  Functional connectivity analysis of the neural circuits of opiate craving: “more” rather than “different”? , 2003, NeuroImage.

[34]  Kosha Ruparel,et al.  Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues. , 2008, The American journal of psychiatry.

[35]  N. Volkow,et al.  Drug addiction: the neurobiology of behaviour gone awry , 2004, Nature Reviews Neuroscience.

[36]  J. O'Doherty,et al.  Lights, Camembert, Action! The Role of Human Orbitofrontal Cortex in Encoding Stimuli, Rewards, and Choices , 2007, Annals of the New York Academy of Sciences.

[37]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[38]  Hugh Garavan,et al.  The Role of Cognitive Control in Cocaine Dependence , 2007, Neuropsychology Review.

[39]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[40]  M. Connock,et al.  Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. , 2007, Health technology assessment.

[41]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[42]  H. Gu,et al.  Association of nicotine addiction and nicotine's actions with separate cingulate cortex functional circuits. , 2009, Archives of general psychiatry.

[43]  P. Falkai,et al.  Functional neuroimaging of reward processing and decision-making: A review of aberrant motivational and affective processing in addiction and mood disorders , 2008, Brain Research Reviews.

[44]  T. Paus,et al.  Functional coactivation map of the human brain. , 2008, Cerebral cortex.

[45]  D. Auer.  Spontaneous low-frequency blood oxygenation level-dependent fluctuations and functional connectivity analysis of the 'resting' brain. , 2008, Magnetic resonance imaging.

[46]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

[47]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[48]  E. Rolls,et al.  Abstract reward and punishment representations in the human orbitofrontal cortex , 2001, Nature Neuroscience.

[49]  Chunshui Yu,et al.  Whole brain functional connectivity in the early blind. , 2007, Brain : a journal of neurology.

[50]  Ruben C. Gur,et al.  Anger and depression in cocaine addiction: association with the orbitofrontal cortex , 2005, Psychiatry Research: Neuroimaging.

[51]  J Talairach,et al.  Stereotaxic exploration in frontal epilepsy. , 1992, Advances in neurology.

[52]  J. Swanson,et al.  Dopamine in drug abuse and addiction: results from imaging studies and treatment implications , 2004, Molecular Psychiatry.

[53]  J. O'Doherty,et al.  Reward representations and reward-related learning in the human brain: insights from neuroimaging , 2004, Current Opinion in Neurobiology.

[54]  E. Stein,et al.  Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. , 2000, The American journal of psychiatry.

[55]  J S Fowler,et al.  Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. , 2000, Cerebral cortex.

[56]  Rita Z. Goldstein,et al.  Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. , 2002, The American journal of psychiatry.

[57]  E. Rolls,et al.  The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology , 2004, Progress in Neurobiology.

[58]  Dimitris Samaras,et al.  Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? , 2007, The American journal of psychiatry.

[59]  Monique Ernst,et al.  Prefrontal cortical dysfunction in abstinent cocaine abusers. , 2004, The Journal of neuropsychiatry and clinical neurosciences.