Article

Decision Making, Impulse Control and Loss of Willpower to Resist Drugs: A Neurocognitive Perspective

Institute for the Neurological Study of Emotion and Creativity, Department of Psychology, University of Southern California, Los Angeles, California 90089-2520, USA.
Nature Neuroscience (Impact Factor: 16.1). 12/2005; 8(11):1458-63. DOI: 10.1038/nn1584
Source: PubMed

ABSTRACT

Here I argue that addicted people become unable to make drug-use choices on the basis of long-term outcome, and I propose a neural framework that explains this myopia for future consequences. I suggest that addiction is the product of an imbalance between two separate, but interacting, neural systems that control decision making: an impulsive, amygdala system for signaling pain or pleasure of immediate prospects, and a reflective, prefrontal cortex system for signaling pain or pleasure of future prospects. After an individual learns social rules, the reflective system controls the impulsive system via several mechanisms. However, this control is not absolute; hyperactivity within the impulsive system can override the reflective system. I propose that drugs can trigger bottom-up, involuntary signals originating from the amygdala that modulate, bias or even hijack the goal-driven cognitive resources that are needed for the normal operation of the reflective system and for exercising the willpower to resist drugs.

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    • "This hyperactivity can lead to severe impulsivity and diminished cognitive control. Behaviorally , this would manifest as high trait impulsivity and decreased avoidance (Bechara 2005). At the neuroanatomical level, it would be caused by reduced availability of midbrain dopaminergic receptors, leading to enhanced dopamine release following rewarding stimuli (Buckholtz et al. 2010). "
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    ABSTRACT: Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction.
    Full-text · Article · Jan 2016 · Addiction Biology
    • "The circuit broadly consists of a reflective system located in the medial prefrontal cortex and a reactive system located in the striatum. The reactive system is sensitive to reward and generates impulses following dopaminergic stimulation of the NAc whereas the reflective system operates glutamatergic control over impulses generated in the striatum (Bechara 2005; Faure et al. 2010; Kalivas and Volkow 2005). All drugs of abuse increase dopamine transmission in the NAc (Nestler 2005) which is essential for acute drug reward (Dagher and Robbins 2009; Kalivas and Volkow 2011; Volkow et al. 2011) and may be very relevant for progressively shaping drug use into drug seeking behavior (Kalivas 2009) by reducing inhibitory control over the reactive system (D'Amour-Horvat and Leyton 2014). "
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    ABSTRACT: The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.
    No preview · Article · Dec 2015 · Brain Imaging and Behavior
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    • "It has been widely reported that chronic stimulant use is related to dysregulation of DLPFC function, impulsive behavior, and inhibitory control deficits [4] [23] [30]. Because DLPFC dysfunction is related to increased anti-saccade error rates in patients with neurological disorders, including Huntington's, Parkinson's, Schizophrenia, and Alzheimer's [7,8,77], similar impairments in anti-saccade performance might be expected in CD patients. "

    Full-text · Article · Nov 2015
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