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      Altered Frontal Cortical Volume and Decision Making in Adolescent Cannabis Users

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          Abstract

          Anticipating future outcomes is central to decision making and a failure to consider long-term consequences may lead to impulsive choices. Adolescence is a vulnerable period during which underdeveloped prefrontal cortical systems may contribute to poor judgment, impulsive choices, and substance abuse. Conversely, substance abuse during this period may alter neural systems involved in decision making and lead to greater impulsivity. Although a broad neural network which supports decision making undergoes extensive change during adolescent development, one region that may be critical is the medial prefrontal cortex. Altered functional integrity of this region may be specifically related to reward perception, substance abuse, and dependence. In the present investigation, we acquired structural magnetic resonance images (MRI), using a 3T Siemens Trio scanner, from 18 cannabis abusing adolescents (CA; 2 female and 16 male subjects; mean age, 17.7 years; range 16–19 years), and 18 healthy controls (HC; 6 female and 12 male subjects; mean age, 17.2 years; range 16–19 years). In order to measure medial orbital prefrontal cortex (moPFC) morphology related to substance abuse and impulsivity, semi-automated cortical reconstruction and volumetric segmentation of MRIs was performed with FreeSurfer. Impulsivity was evaluated with the Barratt Impulsiveness Scale (BIS). Our results indicate that cannabis abusing adolescents have decreased right moPFC volume compared to controls, p = 0.01, d = 0.92, CI 0.95 = 0.21, 1.59. Cannabis abusing adolescents also show decreased future orientation, as indexed by the BIS non-planning subscale, when compared to controls, p = 0.01, d = 0.89, CI 0.95 = 0.23, 1.55. Moreover, total moPFC volume was positively correlated with age of first use r (18) = 0.49, p < 0.03, suggesting that alterations in this region may be related to initiation of cannabis use or that early initiation may lead to reduced moPFC volume.

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          Most cited references49

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          The adolescent brain and age-related behavioral manifestations.

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          To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.
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            The neural basis of drug craving: an incentive-sensitization theory of addiction.

            This paper presents a biopsychological theory of drug addiction, the 'Incentive-Sensitization Theory'. The theory addresses three fundamental questions. The first is: why do addicts crave drugs? That is, what is the psychological and neurobiological basis of drug craving? The second is: why does drug craving persist even after long periods of abstinence? The third is whether 'wanting' drugs (drug craving) is attributable to 'liking' drugs (to the subjective pleasurable effects of drugs)? The theory posits the following. (1) Addictive drugs share the ability to enhance mesotelencephalic dopamine neurotransmission. (2) One psychological function of this neural system is to attribute 'incentive salience' to the perception and mental representation of events associated with activation of the system. Incentive salience is a psychological process that transforms the perception of stimuli, imbuing them with salience, making them attractive, 'wanted', incentive stimuli. (3) In some individuals the repeated use of addictive drugs produces incremental neuroadaptations in this neural system, rendering it increasingly and perhaps permanently, hypersensitive ('sensitized') to drugs and drug-associated stimuli. The sensitization of dopamine systems is gated by associative learning, which causes excessive incentive salience to be attributed to the act of drug taking and to stimuli associated with drug taking. It is specifically the sensitization of incentive salience, therefore, that transforms ordinary 'wanting' into excessive drug craving. (4) It is further proposed that sensitization of the neural systems responsible for incentive salience ('for wanting') can occur independently of changes in neural systems that mediate the subjective pleasurable effects of drugs (drug 'liking') and of neural systems that mediate withdrawal. Thus, sensitization of incentive salience can produce addictive behavior (compulsive drug seeking and drug taking) even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family. We review evidence for this view of addiction and discuss its implications for understanding the psychology and neurobiology of addiction.
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              The neural basis of addiction: a pathology of motivation and choice.

              A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding. Findings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking. While dopamine is critical for acute reward and initiation of addiction, end-stage addiction results primarily from cellular adaptations in anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Pathophysiological plasticity in excitatory transmission reduces the capacity of the prefrontal cortex to initiate behaviors in response to biological rewards and to provide executive control over drug seeking. Simultaneously, the prefrontal cortex is hyperresponsive to stimuli predicting drug availability, resulting in supraphysiological glutamatergic drive in the nucleus accumbens, where excitatory synapses have a reduced capacity to regulate neurotransmission. Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control (choice), and enhancing glutamatergic drive in response to drug-associated stimuli.
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                Author and article information

                Journal
                Front Psychol
                Front. Psychology
                Frontiers in Psychology
                Frontiers Research Foundation
                1664-1078
                28 September 2010
                14 December 2010
                2010
                : 1
                : 225
                Affiliations
                [1] 1simpleThe Brain Institute, University of Utah Salt Lake City, UT, USA
                [2] 2simpleDepartment of Psychiatry, University of Utah School of Medicine Salt Lake City, UT, USA
                Author notes

                Edited by: Reinout W. Wiers, University of Amsterdam, Netherlands

                Reviewed by: Susan F. Tapert, University of California at San Diego, USA; Dick Veltman, Free University, Netherlands

                *Correspondence: Deborah A. Yurgelun-Todd, The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84108, USA. e-mail: deborah.yurgelun-todd@ 123456hsc.utah.edu

                This article was submitted to Frontiers in Psychopathology, a specialty of Frontiers in Psychology.

                Article
                10.3389/fpsyg.2010.00225
                3153830
                21833280
                af733bff-a3a2-4bde-8d16-9b6f9914e526
                Copyright © 2010 Churchwell, Lopez-Larson and Yurgelun-Todd.

                This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 27 August 2010
                : 29 November 2010
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 69, Pages: 8, Words: 6962
                Categories
                Neuroscience
                Original Research

                Clinical Psychology & Psychiatry
                decision making,orbitofrontal,prefrontal,marijuana,impulsivity,adolescence,development,cannabis

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