Interoception and alcohol: Mechanisms, networks, and implications.

Interoception refers to the perception of the internal state of the body and is increasingly being recognized as an important factor in mental health disorders. Drugs of abuse produce powerful interoceptive states that are upstream of behaviors that drive and influence drug intake, and addiction pathology is impacted by interoceptive processes. The goal of the present review is to discuss interoceptive processes related to alcohol. We will cover physiological responses to alcohol, how interoceptive states can impact drinking, and the recruitment of brain networks as informed by clinical research. We also review the molecular and brain circuitry mechanisms of alcohol interoceptive effects as informed by preclinical studies. Finally, we will discuss emerging treatments with consideration of interoception processes. As our understanding of the role of interoception in drug and alcohol use grows, we suggest that the convergence of information provided by clinical and preclinical studies will be increasingly important. Given the complexity of interoceptive processing and the multitude of brain regions involved, an overarching network-based framework can provide context for how focused manipulations modulate interoceptive processing as a whole. In turn, preclinical studies can systematically determine the roles of individual nodes and their molecular underpinnings in a given network, potentially suggesting new therapeutic targets and directions. As interoceptive processing drives and influences motivation, emotion, and subsequent behavior, consideration of interoception is important for our understanding of processes that drive ongoing drinking and relapse.

Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study.

BACKGROUND: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. METHOD: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. RESULTS: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. CONCLUSION: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.

Putative role of vitamin D in the mechanism of alcoholism and other addictions - a hypothesis.

OBJECTIVE: Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and develop a hypothesis which can direct future research of the possible mechanistic role of vitamin D in the process of addiction. METHODS: Systematic review of the literature found in PubMed and EMBASE followed by narrative review combined with clinical experiences leading to hypotheses for future research. RESULTS: Only five articles were identified about a role of vitamin D in the pathophysiology of addiction. Their results are in line with a possible influence of vitamin D in dopaminergic transmission. The cerebral vitamin D status depends on the functionality of genetic variants of vitamin D receptor and other involved genes. Routine serum calcidiol levels may not adequately reflect cerebral vitamin D status. Uncertainty exists regarding appropriate calcidiol blood levels and proper dosages for affecting the central nervous system (CNS). CONCLUSIONS: The putative pathophysiological role of vitamin D in substance abuse has been insufficiently studied which calls to more studies how to measure cerebral vitamin D status in clinical practice. Research is indicated whether vitamin D supplementation should use higher dosages and aim to reach higher calcidiol serum levels. Measuring dopaminergic functioning within the prefrontal cortex as reflected by neuropsychological tests selected as suitable could be a appropriate proxy for the cerebral vitamin D status when studying the pharmacogenomics of this functionality in patients.

Assessing the Role of Corticothalamic and Thalamo-Accumbens Projections in the Augmentation of Heroin Seeking in Chronically Food-Restricted Rats.

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.SIGNIFICANCE STATEMENT Relapse to heroin use is one of the major obstacles in the treatment of opiate addiction. Triggers for relapse are modulated by environmental challenges such as caloric restriction. Elucidating the brain mechanisms that underlie relapse is critical for evidence-based treatment development. Here we demonstrate a critical role for the input from the paraventricular thalamus (PVT), a hub for cortical, sensory, and limbic information, to the nucleus accumbens shell (an area known to be important for reward and motivation) in the augmentation of heroin seeking in food-restricted rats. Our findings highlight a previously unknown role for the PVT in heroin seeking following a period of abstinence.

Exploring Differences Among Video Gamers With and Without Depression: Contrasting Emotion Regulation and Mindfulness.

Video games are a leisure activity with mass appeal for individuals of all ages. However, for some individuals, playing video games may become problematic and addictive, resulting in negative consequences affecting their physical, social, and psychological well-being. Internet gaming disorder (IGD) has estimated prevalence rates of around 3 percent and has been strongly associated with several psychopathologies, including depression. Given that emotion regulation (ER) and mindfulness are fluid constructs that can be enhanced, the potential for intervention and prevention is considerable. Thus, this study sought to, as a first step in determining clinical relevance, explore the differences in ER, mindfulness, and impulsivity among emerging adult gamers who met criteria for IGD, depression, or both IGD and depression (Dep + IGD). A sample of 1,536 gamers (45 percent male, Mage = 20.45 years old) completed an online survey, including an assessment for IGD, depression, difficulties with ER, impulsivity, and mindfulness. Relative to individuals below IGD and depression cutoffs (control), the clinical groups (IGD, depression, and Dep + IGD) reported greater ER difficulties, higher impulsivity, and lower mindfulness. Finally, relative to the IGD + depression group, the other two clinical groups had fewer difficulties with cognitive impulsivity, whereas the depression group reported more difficulties with strategy use. These results suggest that gamers should be considered a heterogeneous group and that comorbid disorders are important considerations when developing targeted treatments for individuals with IGD.

The Controllability Hypothesis: Near-miss effect points to common neurological machinery in posterior parietal cortex for controllable objects and concepts.

In this paper, I postulate that the processing of concepts which are deemed controllable is rooted in neurological machinery located in the posterior parietal cortex specialised for the processing of objects which are immediately actionable because they are within reach. This is demonstrated with reference to the near-miss effect in gambling behaviour, where it is argued that the configurative proximity of the near-miss outcome to the win outcome creates the impression that the win outcome is 'almost within reach' or controllable. The perceived realisability of the desired outcome increases subjective reward probability and the associated expected action value, which impacts decision-making and behaviour. When extended to substance addiction, this novel hypothesis adds fresh insight into understanding the motivational effects associated with cue exposure and opportunity for drug-taking. Moreover, by postulating that a perception of control can be generated to minimise unpleasant affective states, it can also reconcile contrasting models of decision-making and provide a neurological explanation for the efficacy of mindfulness-based techniques in treating addictions. With reference to the previously hypothesised link between the self and control, these ideas can provide an explanation for the increased subjective value of self-associated concepts in the 'endowment effect', as well as a neurological correlate for the concept of the 'narrative self'. This paper therefore provides an innovative and unifying perspective for the study and treatment of behavioural and substance addictions as well as contributing to our neurological understanding of philosophical approaches to the self.

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction.

Rats trained to perform a version of the rat gambling task (rGT) in which salient audiovisual cues accompany reward delivery, similar to commercial gambling products, show greater preference for risky options. Given previous demonstrations that probabilistic reinforcement schedules can enhance psychostimulant-induced increases in accumbal DA and locomotor activity, we theorized that performing this cued task could perpetuate a proaddiction phenotype. Significantly more rats developed a preference for the risky options in the cued versus uncued rGT at baseline, and this bias was further exacerbated by cocaine self-administration, whereas the choice pattern of optimal decision-makers was unaffected. The addition of reward-paired cues therefore increased the proportion of rats exhibiting a maladaptive cognitive response to cocaine self-administration. Risky choice was not associated with responding for conditioned reinforcement or a marker of goal/sign-tracking, suggesting that reward-concurrent cues precipitate maladaptive choice via a unique mechanism unrelated to simple approach toward, or responding for, conditioned stimuli. Although "protected" from any resulting decision-making impairment, optimal decision-makers trained on the cued rGT nevertheless self-administered more cocaine than those trained on the uncued task. Collectively, these data suggest that repeated engagement with heavily cued probabilistic reward schedules can drive addiction vulnerability through multiple behavioral mechanisms. Rats trained on the cued rGT also exhibited blunted locomotor sensitization and lower basal accumbal DA levels, yet greater cocaine-induced increases in accumbal DA efflux. Gambling in the presence of salient cues may therefore result in an adaptive downregulation of the mesolimbic DA system, rendering individuals more sensitive to the deleterious effects of taking cocaine.SIGNIFICANCE STATEMENT Impaired cost/benefit decision making, exemplified by preference for the risky, disadvantageous options on the Iowa Gambling Task, is associated with greater risk of relapse and treatment failure in substance use disorder. Understanding factors that enhance preference for risk may help elucidate the neurobiological mechanisms underlying maladaptive decision making in addiction, thereby improving treatment outcomes. Problem gambling is also highly comorbid with substance use disorder, and many commercial gambling products incorporate salient win-paired cues. Here we show that adding reward-concurrent cues to a rat analog of the IGT precipitates a hypodopaminergic state, characterized by blunted accumbal DA efflux and attenuated locomotor sensitization, which may contribute to the enhanced responsivity to uncertain rewards or the reinforcing effects of cocaine we observed.

Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction.

It is important to find new treatments for addiction due to high relapse rates despite current interventions and due to expansion of the field with non-substance related addictive behaviors. Neuromodulation may provide a new type of treatment for addiction since it can directly target abnormalities in neurocircuits. We review literature on five neuromodulation techniques investigated for efficacy in substance related and behavioral addictions: transcranial direct current stimulation (tDCS), (repetitive) transcranial magnetic stimulation (rTMS), EEG, fMRI neurofeedback and deep brain stimulation (DBS) and additionally report on effects of these interventions on addiction-related cognitive processes. While rTMS and tDCS, mostly applied at the dorsolateral prefrontal cortex, show reductions in immediate craving for various addictive substances, placebo-responses are high and long-term outcomes are understudied. The lack in well-designed EEG-neurofeedback studies despite decades of investigation impedes conclusions about its efficacy. Studies investigating fMRI neurofeedback are new and show initial promising effects on craving, but future trials are needed to investigate long-term and behavioral effects. Case studies report prolonged abstinence of opioids or alcohol with ventral striatal DBS but difficulties with patient inclusion may hinder larger, controlled trials. DBS in neuropsychiatric patients modulates brain circuits involved in reward processing, extinction and negative-reinforcement that are also relevant for addiction. To establish the potential of neuromodulation for addiction, more randomized controlled trials are needed that also investigate treatment duration required for long-term abstinence and potential synergy with other addiction interventions. Finally, future advancement may be expected from tailoring neuromodulation techniques to specific patient (neurocognitive) profiles.

Automatic detection advantage of network information among Internet addicts: behavioral and ERP evidence.

Converging evidence has proved the attentional bias of Internet addicts (IAs) on network information. However, previous studies have neither explained how characteristics of network information are detected by IAs with priority nor proved whether this advantage is in line with the unconscious and automatic process. To answer the two questions, this study aims to investigate whether IAs prioritize automatic detection of network information from the behavior and cognitive neuroscience aspects. 15 severe IAs and 15 matching healthy controls were selected using Internet Addiction Test (IAT). Dot-probe task with mask was used in the behavioral experiment, while deviant-standard reverse oddball paradigm was used in the event-related potential (ERP) experiment to induce mismatch negativity (MMN). In the dot-probe task, when the probe location appeared on the Internet-related picture's position, the IAs had significantly shorter reaction time than do the controls; in the ERP experiment, when Internet-related picture appeared, MMN was significantly induced in the IAs relative to the controls. Both experiments show that IAs can automatically detect network information.

The interplay among stress, frustration tolerance, mindfulness, and social support in Internet gaming disorder symptoms among Chinese working adults.

INTRODUCTION: Internet gaming disorder (IGD) is a growing mental health threat across age groups, but existing literature regarding IGD mainly focuses on student populations. Empirical investigation of the risk and protective factors in adult populations is warranted. This study aimed to fill the research gap by examining whether stress and 3 positive psychology factors (ie, frustration tolerance, mindfulness, and social support) are associated with IGD symptoms in working adults. It was also the first attempt to test the buffering effects of these positive psychology factors on the relationship between stress and IGD vulnerability. METHOD: This cross-sectional study was conducted in Shenzhen, China. We recruited 327 full-time working Chinese adults (mean age = 31.93 years), who had online gaming experience and voluntarily completed an anonymous questionnaire with DSM-5 criteria to measure their IGD symptoms. RESULTS: Internet gaming disorder symptoms were positively correlated with stress and negatively correlated with the 3 positive psychology factors, among which mindfulness emerged as the most salient protective factor. Moreover, mindfulness, but not frustration tolerance and social support, was found to significantly alleviate the relationship between stress and IGD. DISCUSSION: Our findings provide supportive evidence for the protective and moderating roles of positive psychology variables against IGD among Chinese working adults. Workplace-based prevention programs may take the identified factors into account to help promote individuals' personal resources to mitigate development of IGD.

Effects of Equine-Assisted Activities and Therapies on the Affective Network of Adolescents with Internet Gaming Disorder.

OBJECTIVES: Internet gaming disorder (IGD) has been suggested to be a mental health disorder. Attachment and emotional status in IGD patients are important for understanding the etiology and progression of IGD because both parameters are considered to be associated with the affective network. Equine-assisted activities and therapies (EAAT) have been reported to improve emotional status and attachment in subjects. We hypothesized that EAAT would improve attachment in IGD adolescents with insecure attachment issues and increase functional connectivity (FC) within the affective network. DESIGN: Subjects completed a demographic questionnaire, the Korean Experiences in Close Relationships Scale Revised version (K-ECRS), the Child Depression Inventory, Young's Internet Addiction Scale, the Korean Attention-Deficit Hyperactivity Disorder Rating Scale, and resting-state functional magnetic resonance imaging at baseline at the end of EAAT. SUBJECTS: Fifteen IGD adolescents with insecure attachment issues and 15 healthy comparison adolescents with secure attachment agreed to participate in this study. RESULTS: After 7 days of EAAT, K-ECRS avoidance and anxiety scores improved in all adolescents. K-ECRS avoidance scores of the IGD group showed marked improvement compared with those of the healthy group. In all participants, FC from the left amygdala to the left parahippocampal gyrus, left medial frontal gyrus, and left inferior frontal gyrus, as well as from the right amygdala to the left caudate, right claustrum, and left inferior frontal gyrus increased. In IGD adolescents, FC from the left amygdala to the left frontal orbital gyrus, as well as from the right amygdala to the right corpus callosum also increased. CONCLUSION: These findings suggested that EAAT improves attachment, which could lead to a decrease in the severity of IGD symptoms in IGD patients with insecure attachment issues. In addition, EAAT increases FC within the affective network, which was associated with attachment not only in healthy adolescents but also in adolescents with IGD.

Mindfulness-based treatment of addiction: current state of the field and envisioning the next wave of research.

Contemporary advances in addiction neuroscience have paralleled increasing interest in the ancient mental training practice of mindfulness meditation as a potential therapy for addiction. In the past decade, mindfulness-based interventions (MBIs) have been studied as a treatment for an array addictive behaviors, including drinking, smoking, opioid misuse, and use of illicit substances like cocaine and heroin. This article reviews current research evaluating MBIs as a treatment for addiction, with a focus on findings pertaining to clinical outcomes and biobehavioral mechanisms. Studies indicate that MBIs reduce substance misuse and craving by modulating cognitive, affective, and psychophysiological processes integral to self-regulation and reward processing. This integrative review provides the basis for manifold recommendations regarding the next wave of research needed to firmly establish the efficacy of MBIs and elucidate the mechanistic pathways by which these therapies ameliorate addiction. Issues pertaining to MBI treatment optimization and sequencing, dissemination and implementation, dose-response relationships, and research rigor and reproducibility are discussed.

Physical Therapy.

Physical therapy has the evidence-based science knowledge to address a wide range of physical and psychological problems of addiction. Neuromodulation techniques are becoming more and more important in the treatment of addiction. Here, the efficacy of different neuromodulation techniques in addiction, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), is critically evaluated. Other physical therapy methods including Biofeedback, Physical Activity and Acupuncture are also presented.

Traditional Chinese Medicine (TCM) Therapy.

Traditional Chinese Medicine(TCM) has been utilized in China for more than 2,000 years, and it has been practiced in treatment of substance addiction and non-substance addictions. TCM have efficacy in the rehabilitation of abnormal physical problems induced by chronic drug use, including improving immune function, increasing working memory, and protecting against neurological disorders. Given that TCM is potentially effective in the prevention of relapse, it has been suggested that TCM may be the ideal choice in the future for the treatment of opiate addiction. This review examines the significance of effective Chinese herbs and prescriptions for Drug Addiction, Alcohol addiction and food addiction.

Nutrition Support Therapy.

In most addictions, serious nutritional deficiencies of major proteins, fats, vitamins and minerals exist which prevent their capability to digest carbohydrates efficiently. This review aims to point out some treatment approaches in nutrition management for alcohol addiction, drug addiction, food addiction, Internet addiction and sex addiction, according to existing literatures.

The effect of crack cocaine addiction and age on the microstructure and morphology of the human striatum and thalamus using shape analysis and fast diffusion kurtosis imaging.

The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction (CA), showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging (MRI) have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack CA compared to matched healthy controls (HCs), while investigating the effect of age and years of cocaine consumption. We did not find significant differences in volume and mean kurtosis (MKT) between groups. However, we found significant contraction of nucleus accumbens in CA compared to HCs. We also found significant age-related changes in volume and MKT of CA in striatum and thalamus that are different to those seen in normal aging. Interestingly, we found different effects and contributions of age and years of consumption in volume, displacement and MKT changes, suggesting that each measure provides different but complementing information about morphological brain changes, and that not all changes are related to the toxicity or the addiction to the drug. Our findings suggest that the use of finer methods and sequences provides complementing information about morphological and microstructural changes in CA, and that brain alterations in CA are related cocaine use and age differently.

Effect of electro-acupuncture combined with psychological intervention on mental symptoms and P50 of auditory evoked potential in patients with internet addiction disorder.

OBJECTIVE: To observe the therapeutic effects of electro-acupuncture (EA) combined with psychological intervention on the symptom of somzatization or obsession and mental symptom of depression or anxiety and P50 of Auditory Evoked Potential (AEP) on internet addiction disorder (IAD). METHODS: One hundred and twenty cases of IAD ere randomly divided into an EA group, a psycho- intervention (PI) group and a comprehensive therapy (EA plus PI) group. Patients in the EA group were treated with EA. Patients in the PI group were treated with cognition and behavior therapy. Patients in the EA plus PI group were treated with electro-acupuncture plus psychological intervention. Scores of IAD, scores of the symptom checklist 90 (SCL-90), latency and amplitude of P50 of AEP were measured before and after treatment. RESULTS: The scores of IAD after treatment significantly decreased in all groups (P < 0.05), and the scores of IAD in the EA plus PI group were significantly lower than those in the other two groups (P < 0.05). The scores of SCL-90 assembled and each factor after treatment in the EA plus PI group significantly decreased (P < 0.05). After treatment in the EA plus PI group, the amplitude distance of S1P50 and S2P50 (S1-S2) significantly increased (P < 0.05). CONCLUSION: EA combined with PI could relieve the mental symptoms of IAD patients, and the mechanism is possibly related to the increase of cerebrum sense perception gating function.

Cigarette Smoke Extract: A Preclinical Model of Tobacco Dependence.

Animal models are used to study many human diseases, one of which is tobacco addiction. Most preclinical models use nicotine alone, although there are >7000 constituents present in tobacco smoke. The clinical literature suggests that cigarettes have a strong addictive potential, which is not paralleled in preclinical studies using nicotine alone. In order to address the gap between clinical and preclinical literature on tobacco dependence, cigarette smoke extracts containing tobacco constituents have been developed. This unit describes a procedure for producing an aqueous cigarette smoke extract (CSE) which animals readily self-administer. In addition, we describe how to make the apparatus for producing CSE and how to analyze the solution for nicotine content. © 2016 by John Wiley & Sons, Inc.

Face it, don't Facebook it: Impacts of Social Media Addiction on Mindfulness, Coping Strategies and the Consequence on Emotional Exhaustion.

Addiction to social media has now become a problem that societies are concerned with. The aim of the present study is to investigate the impacts that social media addiction has on mindfulness and choice of coping strategy, as well as to explore the consequences on emotional exhaustion. The survey data were collected from 211 employees in 13 enterprises in Thailand. Results from partial least square structural equation modelling revealed that people who are highly addicted to social media tended to have lower mindfulness and tended to use emotion-focused coping to deal with stress. Lack of mindfulness and the decision to use emotion-coping strategy are also subsequently associated with higher emotional exhaustion. Copyright © 2015 John Wiley & Sons, Ltd.

White matter connectivity and Internet gaming disorder.

Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play.