White matter integrity of right frontostriatal circuit predicts internet addiction severity among internet gamers.

Excessive use of the internet, which is a typical scenario of self-control failure, could lead to potential consequences such as anxiety, depression, and diminished academic performance. However, the underlying neuropsychological mechanisms remain poorly understood. This study aims to investigate the structural basis of self-control and internet addiction. In a cohort of 96 internet gamers, we examined the relationships among grey matter volume and white matter integrity within the frontostriatal circuits and internet addiction severity, as well as self-control measures. The results showed a significant and negative correlation between dACC grey matter volume and internet addiction severity (p < 0.001), but not with self-control. Subsequent tractography from the dACC to the bilateral ventral striatum (VS) was conducted. The fractional anisotropy (FA) and radial diffusivity of dACC-right VS pathway was negatively (p = 0.011) and positively (p = 0.020) correlated with internet addiction severity, respectively, and the FA was also positively correlated with self-control (p = 0.036). These associations were not observed for the dACC-left VS pathway. Further mediation analysis demonstrated a significant complete mediation effect of self-control on the relationship between FA of the dACC-right VS pathway and internet addiction severity. Our findings suggest that the dACC-right VS pathway is a critical neural substrate for both internet addiction and self-control. Deficits in this pathway may lead to impaired self-regulation over internet usage, exacerbating the severity of internet addiction.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

A brief child-friendly reward task reliably activates the ventral striatum in two samples of socioeconomically diverse youth.

Adolescence is a period of increased risk-taking behavior, thought to be driven, in part, by heightened reward sensitivity. One challenge of studying reward processing in the field of developmental neuroscience is finding a task that activates reward circuitry, and is short, not too complex, and engaging for youth of a wide variety of ages and socioeconomic backgrounds. In the present study, we tested a brief child-friendly reward task for activating reward circuitry in two independent samples of youth ages 7-19 years old enriched for poverty (study 1: n = 464; study 2: n = 27). The reward task robustly activated the ventral striatum, with activation decreasing from early to mid-adolescence and increasing from mid- to late adolescence in response to reward. This response did not vary by gender, pubertal development, or income-to-needs ratio, making the task applicable for a wide variety of populations. Additionally, ventral striatum activation to the task did not differ between youth who did and did not expect to receive a prize at the end of the task, indicating that an outcome of points alone may be enough to engage reward circuitry. Thus, this reward task is effective for studying reward processing in youth from different socioeconomic backgrounds.

Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.

Deep Brain Stimulation of the Nucleus Accumbens, Ventral Striatum, or Internal Capsule Targets for Medication-Resistant Obsessive-Compulsive Disorder: A Multicenter Study.

BACKGROUND: Deep brain stimulation of the nucleus accumbens, ventral striatum, or internal capsule region has shown a 45%-60% response rate in adults with severe treatment-refractory obsessive-compulsive disorder, regardless of which target is used. We sought to improve the effectiveness of deep brain stimulation by placing the electrode along a trajectory including these 3 targets, enabling a change of stimulation site depending on the patient's response. METHODS: This study used the medical records of 14 patients from 4 different Spanish institutions: 7 from the Hospital Universitario La Princesa, 3 from the Hospital Universitario Central de Asturias, 2 from Hospital Universitario Fundación Jiménez Díaz, and 2 from Hospital Universitari Son Espases. All patients were operated on under the same protocol. Qualitative and quantitative data were collected. RESULTS: Of 14 patients, 11 showed significant improvement in obsessive-compulsive disorder symptoms, as evident in a reduction ≥35% in Yale-Brown Obsessive Compulsive Scale scores following stimulation relative to preoperative scores. Seven patients responded to stimulation at the nucleus accumbens (the first area we set for stimulation), whereas 4 patients needed to have the active contact switched to the internal capsule to benefit from stimulation. CONCLUSIONS: Deep brain stimulation of the nucleus accumbens, internal capsule, and ventral striatum significantly benefited our cohort of patients with medication-resistant obsessive-compulsive disorder. Electrode insertion through the 3 main targets might confer additional therapeutic efficacy.

Dorsal and ventral striatal functional connectivity shifts play a potential role in internet gaming disorder.

Animal models suggest transitions from non-addictive to addictive behavioral engagement are associated with ventral-to-dorsal striatal shifts. However, few studies have examined such features in humans, especially in internet gaming disorder (IGD), a proposed behavioral addiction. We recruited 418 subjects (174 with IGD; 244 with recreational game use (RGU)). Resting-state fMRI data were collected and functional connectivity analyses were performed based on ventral and dorsal striatal seeds. Correlations and follow-up spectrum dynamic causal model (spDCM) analyses were performed to examine relationships between the ventral/dorsal striatum and middle frontal gyrus (MFG). Longitudinal data were also analysed to investigate changes over time. IGD relative to RGU subjects showed lower ventral-striatum-to-MFG (mostly involving supplementary motor area (SMA)) and higher dorsal-striatum-to-MFG functional connectivity. spDCM revealed that left dorsal-striatum-to-MFG connectivity was correlated with IGD severity. Longitudinal data within IGD and RGU groups found greater dorsal striatal connectivity with the MFG in IGD versus RGU subjects. These findings suggest similar ventral-to-dorsal striatal shifts may operate in IGD and traditional addictions.

Reinforcement Learning Disruptions in Individuals With Depression and Sensitivity to Symptom Change Following Cognitive Behavioral Therapy.

Importance: Major depressive disorder is prevalent and impairing. Parsing neurocomputational substrates of reinforcement learning in individuals with depression may facilitate a mechanistic understanding of the disorder and suggest new cognitive therapeutic targets. Objective: To determine associations among computational model-derived reinforcement learning parameters, depression symptoms, and symptom changes after treatment. Design, Setting, and Participants: In this mixed cross-sectional-cohort study, individuals performed reward and loss variants of a probabilistic learning task during functional magnetic resonance imaging at baseline and follow-up. A volunteer sample with and without a depression diagnosis was recruited from the community. Participants were assessed from July 2011 to February 2017, and data were analyzed from May 2017 to May 2021. Main Outcomes and Measures: Computational model-based analyses of participants' choices assessed a priori hypotheses about associations between components of reward-based and loss-based learning with depression symptoms. Changes in both learning parameters and symptoms were then assessed in a subset of participants who received cognitive behavioral therapy (CBT). Results: Of 101 included adults, 69 (68.3%) were female, and the mean (SD) age was 34.4 (11.2) years. A total of 69 participants with a depression diagnosis and 32 participants without a depression diagnosis were included at baseline; 48 participants (28 with depression who received CBT and 20 without depression) were included at follow-up (mean [SD] of 115.1 [15.6] days). Computational model-based analyses of behavioral choices and neural data identified associations of learning with symptoms during reward learning and loss learning, respectively. During reward learning only, anhedonia (and not negative affect or arousal) was associated with model-derived learning parameters (learning rate: posterior mean regression ß = -0.14; 95% credible interval [CrI], -0.12 to -0.03; outcome sensitivity: posterior mean regression ß = 0.18; 95% CrI, 0.02 to 0.37) and neural learning signals (moderation of association between striatal prediction error and expected value signals: t97 = -2.10; P = .04). During loss learning only, negative affect (and not anhedonia or arousal) was associated with learning parameters (outcome shift: posterior mean regression ß = -0.11; 95% CrI, -0.20 to -0.01) and disrupted neural encoding of learning signals (association with subgenual anterior cingulate prediction error signals: r = -0.28; P = .005). Symptom improvement following CBT was associated with normalization of learning parameters that were disrupted at baseline (reward learning rate: posterior mean regression ß = 0.15; 90% CrI, 0.001 to 0.41; loss outcome shift: posterior mean regression ß = 0.42; 90% CrI, 0.09 to 0.77). Conclusions and Relevance: In this study, the mapping of reinforcement learning components to symptoms of major depression revealed mechanistic features associated with these symptoms and points to possible learning-based therapeutic processes and targets.

Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders.

Importance: Eating disorders are severe psychiatric disorders; however, disease models that cross subtypes and integrate behavior and neurobiologic factors are lacking. Objective: To assess brain response during unexpected receipt or omission of a salient sweet stimulus across a large sample of individuals with eating disorders and healthy controls and test for evidence of whether this brain response is associated with the ventral striatal-hypothalamic circuitry, which has been associated with food intake control, and whether salient stimulus response and eating disorder related behaviors are associated. Design, Setting, and Participants: In this cross-sectional functional brain imaging study, young adults across the eating disorder spectrum were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classic conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error. Dynamic effective connectivity during expected sweet taste receipt was studied to investigate hierarchical brain activation between food intake relevant brain regions. The study was conducted from June 2014 to November 2019. Data were analyzed from December 2019 to February 2020. Main Outcomes and Measures: Prediction error brain reward response across insula and striatum; dynamic effective connectivity between hypothalamus and ventral striatum; and demographic and behavior variables and their correlations with prediction error brain response and connectivity edge coefficients. Results: Of 317 female participants (197 with eating disorders and 120 healthy controls), the mean (SD) age was 23.8 (5.6) years and mean (SD) body mass index was 20.8 (5.4). Prediction error response was elevated in participants with anorexia nervosa (Wilks λ, 0.843; P = .001) and in participants with eating disorders inversely correlated with body mass index (left nucleus accumbens: r = -0.291; 95% CI, -0.413 to -0.167; P < .001; right dorsal anterior insula: r = -0.228; 95% CI, -0.366 to -0.089; P = .001), eating disorder inventory-3 binge eating tendency (left nucleus accumbens: r = -0.207; 95% CI, -0.333 to -0.073; P = .004; right dorsal anterior insula: r = -0.220; 95% CI, -0.354 to -0.073; P = .002), and trait anxiety (left nucleus accumbens: r = -0.148; 95% CI, -0.288 to -0.003; P = .04; right dorsal anterior insula: r = -0.221; 95% CI, -0.357 to -0.076; P = .002). Ventral striatal to hypothalamus directed connectivity was positively correlated with ventral striatal prediction error in eating disorders (r = 0.189; 95% CI, 0.045-0.324; P = .01) and negatively correlated with feeling out of control after eating (right side: r = -0.328; 95% CI, -0.480 to -0.164; P < .001; left side: r = -0.297; 95% CI, -0.439 to -0.142; P = .001). Conclusions and Relevance: The results of this cross-sectional imaging study support that body mass index modulates prediction error and food intake control circuitry in the brain. Once altered, this circuitry may reinforce eating disorder behaviors when paired with behavioral traits associated with overeating or undereating.

Reward-Related Responses and Tonic Craving in Cocaine Addiction: An Imaging Study of the Monetary Incentive Delay Task.

BACKGROUND: Cocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses were mixed, and few studies have examined whether reward responses relate to tonic cocaine craving. METHODS: We combined functional magnetic resonance imaging and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines, and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine-dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use. RESULTS: The VS showed higher activation to large as compared with small or no wins, but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses. CONCLUSIONS: The results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving, and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug-seeking behavior in addicted individuals.

Impact of the KCNQ2/3 Channel Opener Ezogabine on Reward Circuit Activity and Clinical Symptoms in Depression: Results From a Randomized Controlled Trial.

OBJECTIVE: Preclinical studies point to the KCNQ2/3 potassium channel as a novel target for the treatment of depression and anhedonia, a reduced ability to experience pleasure. The authors conducted the first randomized placebo-controlled trial testing the effect of the KCNQ2/3 positive modulator ezogabine on reward circuit activity and clinical outcomes in patients with depression. METHODS: Depressed individuals (N=45) with elevated levels of anhedonia were assigned to a 5-week treatment period with ezogabine (900 mg/day; N=21) or placebo (N=24). Participants underwent functional MRI during a reward flanker task at baseline and following treatment. Clinical measures of depression and anhedonia were collected at weekly visits. The primary endpoint was the change from baseline to week 5 in ventral striatum activation during reward anticipation. Secondary endpoints included depression and anhedonia severity as measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Snaith-Hamilton Pleasure Scale (SHAPS), respectively. RESULTS: The study did not meet its primary neuroimaging endpoint. Participants in the ezogabine group showed a numerical increase in ventral striatum response to reward anticipation following treatment compared with participants in the placebo group from baseline to week 5. Compared with placebo, ezogabine was associated with a significantly larger improvement in MADRS and SHAPS scores and other clinical endpoints. Ezogabine was well tolerated, and no serious adverse events occurred. CONCLUSIONS: The study did not meet its primary neuroimaging endpoint, although the effect of treatment was significant on several secondary clinical endpoints. In aggregate, the findings may suggest that future studies of the KCNQ2/3 channel as a novel treatment target for depression and anhedonia are warranted.

Neuroticism and reward-related ventral striatum activity: Probing vulnerability to stress-related depression.

Elevated neuroticism may confer vulnerability to the depressogenic effects of stressful life events (SLEs). However, the mechanisms underlying this susceptibility remain poorly understood. Accumulating evidence suggests that stress-related disruptions in neural reward processing might undergird links between stress and depression. Using data from the Saint Louis Personality and Aging Network (SPAN) study and Duke Neurogenetics Study (DNS), we examined whether neuroticism moderates links between stressful life events (SLE) and depression as well as SLEs and ventral striatum (VS) response to reward. In the longitudinal SPAN sample (n = 971 older adults), SLEs prospectively predicted future depressive symptoms, especially among those reporting elevated neuroticism, even after accounting for prior depressive symptoms and previous SLE exposure (NxSLE interaction: p = .016, ΔR² = 0.003). Cross-sectional analyses of the DNS, a young adult college sample with neuroimaging data, replicated this interaction (n = 1,343: NxSLE interaction: p = .019, ΔR² = 0.003) and provided evidence that neuroticism moderates the association between SLEs and reward-related VS response (n = 1,195, NxSLE: p = .017, ΔR² = 0.0048). Blunted left VS response to reward was associated with a lifetime depression diagnosis, r = -0.07, p = .02, but not current depressive symptoms, r = -0.003, p = .93. These data suggest that neuroticism may promote vulnerability to stress-related depression and that sensitivity to stress-related reductions in VS response may be a potential neural mechanism underlying vulnerability to clinically significant depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Reduced frontostriatal response to expected value and reward prediction error in remitted monozygotic twins with mood disorders and their unaffected high-risk co-twins.

BACKGROUND: Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders. METHODS: In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25). RESULTS: Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions. CONCLUSION: Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders.

Clinical and Neural Correlates of Reward and Relief Drinking.

BACKGROUND: Alcohol use disorder (AUD) is heterogenous. One approach to parsing this heterogeneity is to phenotype individuals by their underlying motivation to drink, specifically drinking for reward (i.e., positive reinforcement) or for relief (i.e., negative reinforcement/normalizing). Reward- versus relief-motivated behavior is thought to be associated with a shift from ventral to dorsal striatal (DS) signaling. The present study examined whether reward and relief drinking were differentially associated with other clinical characteristics and with alcohol cue-elicited activation of the ventral and dorsal striatum. METHODS: Non-treatment-seeking heavy drinkers (N = 184; 61 female, 123 male) completed the UCLA Reward, Relief, Habit Drinking Scale (RRHDS) and the Reasons for Heavy Drinking Questionnaire (RHDQ), to categorize drinking motivation. Measures of alcohol use, alcohol problems, mood, and craving were also collected. A subset of participants (N = 45; 17 female, 28 male) also completed a functional neuroimaging alcohol cue reactivity task. RESULTS: RRHDS-designated relief/habit drinkers scored lower than reward drinkers on the RHDQ Reinforcement subscale (p = 0.04) and higher on the RHDQ Normalizing subscale (p = 0.004). Relief/habit drinkers also demonstrated greater AUD severity on a host of clinical measures. Relief/habit drinkers displayed higher cue-elicited DS activation compared with reward drinkers (p = 0.04), while ventral striatal cue-elicited activation did not significantly differ between groups. CONCLUSIONS: Our findings support and extend the differentiation of reward from relief/habit-motivated drinking and suggest that differences in DS response to conditioned alcohol cues may underlie this distinction. Elucidating neurobiological and clinical differences between these subtypes may facilitate treatment matching and precision medicine for AUD.

Looking into a Deluded Brain through a Neuroimaging Lens.

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer's, and Parkinson's disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain.

Investigation of brain functional connectivity to assess cognitive control over cue-processing in Alcohol Use Disorder.

Alcohol Use Disorder has been associated with impairments of functional connectivity between neural networks underlying reward processing and cognitive control. Evidence for aberrant functional connectivity between the striatum, insula, and frontal cortex in alcohol users exists at rest, but not during cue-exposure. In this study, we investigated functional connectivity changes during a cue-reactivity task across different subgroups of alcohol consumers. Ninety-six participants (ranging from light social to heavy social drinkers and nonabstinent dependent to abstinent dependent drinkers) were examined. A functional magnetic resonance imaging cue-reactivity paradigm was administered, during which alcohol-related and neutral stimuli were presented. Applying psychophysiological interaction analyses, we found: (a) Abstinent alcohol-dependent patients compared with non-abstinent dependent drinkers showed a greater increase of functional connectivity of the ventral striatum and anterior insula with the anterior cingulate cortex and dorsolateral prefrontal cortex during the presentation of alcohol cues compared with neutral cues. (b) Subjective craving correlated positively with functional connectivity change between the posterior insula and the medial orbitofrontal cortex and negatively with functional connectivity change between the ventral striatum and the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex. (c) Compulsivity of alcohol use correlated positively with functional connectivity change between the dorsolateral prefrontal cortex and the ventral striatum, anterior insula, and posterior insula. Results suggest increased cognitive control over cue-processing in abstinent alcohol-dependent patients, compensating high levels of cue-provoked craving and compulsive use. Clinical trial registration details: ClinicalTrials.gov ID: NCT00926900.

Association of Inflammatory Activity With Larger Neural Responses to Threat and Reward Among Children Living in Poverty.

OBJECTIVE: Children exposed to severe, chronic stress are vulnerable to mental and physical health problems across the lifespan. To explain how these problems develop, the neuroimmune network hypothesis suggests that early-life stress initiates a positive feedback loop between peripheral inflammatory cells and networked brain regions involved in threat and reward processing. The authors sought to test this hypothesis by studying a sample of urban children from diverse socioeconomic backgrounds. METHODS: The authors examined the basic predictions of the neuroimmune network hypothesis in 207 children (mean age=13.9 years, 63% female; 33% Black; 30% Hispanic), focusing on poverty as a stressor. The children had fasting blood drawn to quantify five inflammatory biomarkers-C-reactive protein, tumor necrosis factor-α, and interleukins-6, -8, and -10-which were averaged to form a composite score. Children also completed two functional MRI tasks, which measured amygdala responsivity to angry facial expressions and ventral striatum responsivity to monetary rewards. RESULTS: Poverty status and neural responsivity interacted statistically to predict inflammation. Among children living in poverty, amygdala threat responsivity was positively associated with inflammation, and the same was true for ventral striatum responsivity to reward. As children's socioeconomic conditions improved, these brain-immune associations became weaker. In sensitivity analyses, these patterns were robust to alternative measures of socioeconomic status and were independent of age, sex, racial and ethnic identity, and pubertal status. The associations were also condition specific; no interactions were apparent for amygdala responsivity to neutral faces, or striatal responsivity to monetary losses. CONCLUSIONS: These findings suggest that childhood poverty is associated with accentuated neural-immune signaling, consistent with the neuroimmune network hypothesis.

The Neural Processes Interlinking Social Isolation, Social Support, and Problem Alcohol Use.

BACKGROUND: Subjective feeling of social isolation, as can be measured by perceived burdensomeness (PB), is a major risk factor for alcohol misuse. Heightened PB is associated with elevated stress response and diminished cognitive control, both of which contribute to problem drinking. Here, we sought to identify the neural substrates underlying the relationship between PB and alcohol misuse. METHODS: We employed resting-state functional magnetic resonance imaging data collected from 61 problem drinkers to characterize the functional connectivity of the hypothalamus and ventral striatum (VS) in relation to PB. We specifically examined whether the connectivities of the hypothalamus and VS were differentially influenced by PB to produce contrasting effects on alcohol use. Finally, we evaluated how individual differences in social support modulate the inter-relationships of social isolation, neural connectivity, and the severity of problem drinking. RESULTS: Whole-brain multiple regressions show a positive relationship between PB and hypothalamic connectivity with the hippocampus and an inverse pattern for VS connectivity with the middle frontal gyrus. Difference in strength between the 2 connectivities predicted the severity of problem drinking, suggesting an imbalance involving elevated hypothalamic and diminished prefrontal cortical modulation in socially isolated problem drinkers. A path analysis further revealed that the lack of social support was associated with a bias toward low prefrontal connectivity, which in turn increased PB and facilitated problem drinking. CONCLUSIONS: Altered hypothalamus and VS connectivity may underlie problem drinking induced by social isolation. The current findings also highlight the important role of social support as a potential protective factor against alcohol misuse.

Reduced frontostriatal functional connectivity and associations with severity of Internet gaming disorder.

Cognitive, functional, and structural brain factors involving frontal executive and striatal reward networks have been implicated in Internet gaming disorder (IGD). However, frontostriatal network connectivity and its association with addiction severity are poorly understood in IGD. Resting-state fMRI data from 337 subjects (130 with IGD, 207 with recreational game use [RGU]) were collected. Striatal-cortical communications were measured with resting-state functional connectivity (FC) using coherent spontaneous fluctuations in the blood-oxygenation-level-dependent fMRI signal. Correlations were calculated between FC measures and IGD-related assessments (addiction severity and craving scores). Decreased FC was predominantly observed in IGD subjects, with IGD subjects showing decreased FC between the putamen and superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and the ventral striatum and IFG, superior temporal gyrus, and MFG. Disorder severity and craving scores were negatively correlated with FC between striatal and frontal brain regions. Associations between diminished FC in corticostriatal circuitry and clinical features (IGD craving, severity) suggest potential therapeutic targets for neuromodulation treatments. The extent to which frontostriatal circuits involving executive control over reward processes may be altered to treat IGD warrants additional study.

Association of Prefrontal-Striatal Functional Pathology With Alcohol Abstinence Days at Treatment Initiation and Heavy Drinking After Treatment Initiation.

OBJECTIVE: Alcohol use disorder (AUD) is associated with neuroadaptations in brain stress and reward circuits. It is not known whether such neuroadaptations are affected by number of days of alcohol abstinence and whether they influence heavy drinking during the early treatment phase. The authors used a novel functional MRI (fMRI) approach to assess brain responses during sustained exposure to standardized visual stimuli of stressful, alcohol cue, and neutral control images combined with prospective assessment of drinking outcomes during early outpatient treatment, in two related studies. METHODS: In study 1, 44 treatment-entering patients with AUD and 43 demographically matched healthy control subjects participated in the fMRI experiment to identify dysfunctional responses associated with chronic alcohol abuse. In study 2, 69 treatment-entering patients with AUD were assessed for whether fMRI responses at treatment initiation were influenced by alcohol abstinence and were prospectively predictive of early heavy drinking outcomes. RESULTS: Relative to control subjects, patients with AUD showed significant hyperreactivity in the ventromedial prefrontal cortex (vmPFC) in response to neutral images, but significant hypoactivation in the vmPFC and ventral striatum in response to stress images and to alcohol cues relative to response to neutral images. In study 2, this specific prefrontal-ventral striatal dysfunction was associated with fewer days of alcohol abstinence and also predicted greater number heavy drinking days during the subsequent 2 weeks of treatment engagement. CONCLUSIONS: Number of days of alcohol abstinence at treatment initiation significantly affected functional disruption of the prefrontal-striatal responses to stress images and to alcohol cues in patients with AUD, and the severity of this disruption in turn predicted greater heavy drinking during early treatment. Treatments that target this functional prefrontal-striatal pathology could improve early treatment outcomes in AUD.

Altered core networks of brain connectivity and personality traits in internet gaming disorder.

BACKGROUND AND AIMS: Although the Internet has provided convenience and efficiency in many areas of everyday life, problems stemming from Internet use have also been identified, such as Internet gaming disorder (IGD). Internet addiction, which includes IGD, can be viewed as a behavioral addiction or impulse control disorder. This study investigated the altered functional and effective connectivity of the core brain networks in individuals with IGD compared to healthy controls (HCs). METHODS: Forty-five adults with IGD and 45 HCs were included in this study. To examine the brain networks related to personality traits that influence problematic online gaming, the left and right central executive network (CEN) and the salience network (SN) were included in the analysis. Also, to examine changes in major brain network topographies, we analyzed the default mode network (DMN). RESULTS: IGD participants showed lower functional connectivity between the dorsal lateral prefrontal cortex (DLPFC) and other regions in the CEN than HC participants during resting state. Also, IGD participants revealed reduced functional connectivity between the dorsal anterior cingulate cortex and other regions in the SN and lower functional connectivity in the medial prefrontal cortex of the anterior DMN. Notably, in IGD individuals but not HC individuals, there was a positive correlation between IGD severity and effective connectivity and a positive correlation between reward sensitivity and effective connectivity within the ventral striatum of the SN. CONCLUSIONS: Problematic online gaming was associated with neurofunctional alterations, impairing the capacity of core brain networks.