Patrick D. Worhunsky

Meditation experience is associated with differences in default mode network activity and connectivity

Many philosophical and contemplative traditions teach that “living in the moment” increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default-mode network (medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta‐analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.

Pretreatment Brain Activation During Stroop Task Is Associated with Outcomes in Cocaine-Dependent Patients

BACKGROUND Cognitive behavioral and related therapies for cocaine dependence may exert their effects, in part, by enhancing cognitive control over drug use behavior. No prior studies have systematically examined the neural correlates of cognitive control as related to treatment outcomes for cocaine dependence. METHODS Twenty treatment-seeking cocaine-dependent individuals performed a Stroop color-word interference task while undergoing functional magnetic resonance imaging (fMRI) prior to initiating treatment. The primary outcome measures were percent of urine drug screens negative for cocaine, percent days abstinent, and treatment retention. Correlations between regional brain activation during Stroop task performance and treatment outcome measures were analyzed. RESULTS During Stroop performance, individuals activated brain regions similar to those reported in nonaddicted individuals, including the anterior cingulate cortex, dorsolateral prefrontal cortex, parietal lobule, insula, and striatum. Activations at treatment onset correlated differentially with specific outcomes: longer duration of self-reported abstinence correlated with activation of ventromedial prefrontal cortex, left posterior cingulate cortex, and right striatum; percent drug-free urine screens correlated with striatal activation; and treatment retention correlated with diminished activation of dorsolateral prefrontal cortex. A modest correlation between Stroop effect and treatment retention was found. CONCLUSIONS The functions of specific brain regions underlying cognitive control relate differentially to discrete outcomes for the treatment of cocaine dependence. These findings implicate neurocircuitry underlying cognitive control in behavioral treatment outcome and provide insight into the mechanisms of behavioral therapies for cocaine dependence. They also suggest neural activation patterns during cognitive control tasks are more sensitive predictors of treatment response than behavioral measures.

Diminished frontostriatal activity during processing of monetary rewards and losses in pathological gambling.

BACKGROUND Mesocorticolimbic neurocircuitry and impulsivity have both been implicated in pathological gambling (PG) and in reward processing. However, the neural underpinnings of specific phases of reward and loss processing in PG and their relationships to impulsivity remain only partially understood. The present functional magnetic resonance imaging study examined brain activity associated with different phases of reward and loss processing in PG. Given an inverse relationship between ventral striatal recruitment during anticipation of monetary rewards and impulsivity in alcohol dependence, the current study explored whether a similar association might also be present in PG. METHODS Fourteen adults with PG and 14 control comparison participants performed the Monetary Incentive Delay Task to identify brain activation changes associated with reward/loss prospect, reward/loss anticipation, and reward/loss notification. Impulsivity was assessed separately using the Barratt Impulsiveness Scale. RESULTS Relative to the control comparison group, the PG group exhibited significantly reduced activity in the ventromedial prefrontal cortex, insula, and ventral striatum during several phases, including the prospect and anticipation phases of both gains and losses. Activity in the ventral striatum correlated inversely with levels of impulsivity in PG participants, consistent with prior findings in alcohol dependence. CONCLUSIONS Relatively decreased activity in corticostriatal neurocircuitry during multiple phases of reward processing suggests consistent alterations in neurocircuitry underlying incentive valuation and loss prediction. Together with findings in alcohol dependence, these results suggest that impulsive tendencies in addictions may be reflected in diminished ventral striatal activations to reward anticipation and may represent targets for treatment development in addictions.

An Initial Study of Neural Responses to Monetary Incentives as Related to Treatment Outcome in Cocaine Dependence

BACKGROUND Although cocaine dependence (CD) involves abnormalities in drug-related, reward-based decision making, it is not well understood whether these abnormalities generalize to nondrug-related cues and rewards and how neural functions underlying reward processing in cocaine abusers relate to treatment outcome. METHODS Twenty CD patients before treatment and 20 matched healthy control (HC) subjects participated in functional magnetic resonance imaging while performing a monetary incentive delay task. Outcomes through 8 weeks were assessed via percent cocaine-negative urine toxicology, self-reported cocaine abstinence, and treatment retention. RESULTS Among the whole sample, anticipation of working for monetary reward (i.e., reward anticipation) was associated with activation in the ventral striatum (VS), medial frontal gyrus, thalamus, right subcallosal gyrus, right insula, and left amygdala. Cocaine dependence compared with HC participants exhibited greater activation during notification of rewarding outcome (i.e., reward receipt) in left and right VS, right caudate, and right insula. In CD participants during reward anticipation, activation in left and right thalamus and right caudate correlated negatively with percent cocaine-negative urine toxicology, activation in thalamus bilaterally correlated negatively with self-reported abstinence measures, and activation in left amygdala and parahippocampal gyrus correlated negatively with treatment retention. During reward notification, activation in right thalamus, right VS, and left culmen correlated negatively with abstinence and with urine toxicology. CONCLUSIONS These findings suggest that in treatment-seeking CD participants, corticolimbic reward circuitry is relatively overactivated during monetary incentive delay task performance and specific regional activations related to reward processing may predict aspects of treatment outcome and represent important targets for treatment development in CD.

Individuals Family History Positive for Alcoholism Show Functional Magnetic Resonance Imaging Differences in Reward Sensitivity That Are Related to Impulsivity Factors

BACKGROUND Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. METHODS We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. RESULTS During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. CONCLUSIONS Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.

Monetary Reward Processing in Obese Individuals With and Without Binge Eating Disorder

BACKGROUND An important step in obesity research involves identifying neurobiological underpinnings of nonfood reward processing unique to specific subgroups of obese individuals. METHODS Nineteen obese individuals seeking treatment for binge eating disorder (BED) were compared with 19 non-BED obese individuals (OB) and 19 lean control subjects (LC) while performing a monetary reward/loss task that parses anticipatory and outcome components during functional magnetic resonance imaging. Differences in regional activation were investigated in BED, OB, and LC groups during reward/loss prospect, anticipation, and notification. RESULTS Relative to the LC group, the OB group demonstrated increased ventral striatal and ventromedial prefrontal cortex activity during anticipatory phases. In contrast, the BED group relative to the OB group demonstrated diminished bilateral ventral striatal activity during anticipatory reward/loss processing. No differences were observed between the BED and LC groups in the ventral striatum. CONCLUSIONS Heterogeneity exists among obese individuals with respect to the neural correlates of reward/loss processing. Neural differences in separable groups with obesity suggest that multiple, varying interventions might be important in optimizing prevention and treatment strategies for obesity.

Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity

An important endeavor involves increasing our understanding of biobehavioral processes underlying different types of obesity. The current study investigated the neural correlates of cognitive control (involving conflict monitoring and response inhibition) in obese individuals with binge eating disorder (BED) as compared to BMI‐matched non‐BED obese (OB) individuals and lean comparison (LC) participants. Alterations in cognitive control may contribute to differences in behavioral control over eating behaviors in BED and obesity.

A preliminary study of the neural effects of behavioral therapy for substance use disorders

BACKGROUND The mechanisms by which behavioral therapies for substance use disorders (SUDs) exert their effects and the components of treatment that contribute most to substance use outcome remain unclear. Disruptions to aspects of impulse control and attention have been hypothesized to contribute to the development and maintenance of addiction; moreover, alterations in these processes may underlie responses to treatment. METHODS Individuals participating in a randomized clinical trial evaluating computer-assisted cognitive behavioral therapy (CBT) for substance abuse participated in fMRI Stroop before and after treatment. A non-substance-using comparison group performed the same task under test-retest conditions. RESULTS The patient group demonstrated decreased Stroop-related BOLD signal in regions including the anterior cingulate, inferior frontal gyrus and midbrain at post-treatment relative to pre-treatment, and displayed a greater decrease in the subthalamic nucleus and surrounding regions compared to healthy controls following test-retest. CONCLUSIONS Behavioral therapies may be associated with reduction in substance use and effects on neural systems involved in cognitive control, impulsivity, motivation and attention.

White Matter Integrity is Associated with Treatment Outcome Measures in Cocaine Dependence

Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users’ abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine dependence. Diffusion tensor imaging (DTI) was used to assess the white matter (WM) of 16 treatment-seeking cocaine-dependent patients before 8 weeks of therapy. The measures for treatment outcome were longest self-reported duration of continuous cocaine abstinence, percent of urine screens negative for cocaine, and duration (weeks) of treatment retention. Correlations between treatment outcome measures and DTI parameters (fractional anisotropy (FA), longitudinal eigenvalue (λ1), perpendicular eigenvalue (λT), and mean diffusivity (MD)) were analyzed. Longest self-reported abstinence from cocaine and percent of cocaine-negative urine samples during treatment positively correlated with FA values and negatively correlated with λ1, λT, and MD values across extensive brain regions including the corpus callosum, frontal, parietal, temporal, and occipital lobes, and cerebellum. The findings of an association between better WM integrity at treatment onset and longer abstinence suggest that strategies for improving WM integrity warrant consideration in developing new interventions for cocaine dependence.