Background

Although the interaction of brain volume with amphetamine-type stimulants (ATS) and cocaine has been investigated in chronically dependent individuals, little is known about structural differences that might exist in individuals who consume ATS and cocaine occasionally but are not dependent on these drugs.

Methods

Regional brain volumes in 165 college aged occasional users of ATS (namely: amphetamine, methamphetamine, methylphenidate, and 3,4-methylenedioxymethamphetamine; MDMA) and cocaine were compared by voxel-based morphometry with 48 ATS/cocaine-naive controls.

Results

Grey matter volume was significantly higher in the left ventral anterior putamen of occasional users, and lower in the right dorsolateral cerebellum and right inferior parietal cortex. A regression in users alone on lifetime consumption of combined ATS (namely: amphetamine, methamphetamine, methylphenidate and MDMA) and cocaine use revealed that individuals who used more ATS/cocaine had greater volume in the right ventromedial frontal cortex. A second regression on lifetime consumption of ATS with cocaine as a covariate revealed that individuals with a greater history of ATS use alone had more grey matter volume in the left mid-insula. Interestingly, structural changes in the ventromedial prefrontal cortex, insula and striatum have been consistently observed in volumetric studies of chronic ATS and cocaine dependence.

Conclusion

The present results suggest that these three brain regions may play a role in stimulant use even in early occasional users.

Frustration is common in adolescence and often interferes with executive functioning, particularly reward-based decision-making, and yet very little is known about how incidental frustrating events (independent of task-based feedback) disrupt the neural circuitry of reward processing in this important age group. While undergoing functional magnetic resonance imaging (fMRI), 45 healthy adolescents played a card game in which they had to guess between two options to earn points, in low- and high-stake conditions. Functioning of button presses through which they made decisions was intermittently blocked, thereby increasing frustration potential. Neural deactivation of the precuneus, a Default Mode Network region, was observed during obstructed action blocks across stake conditions, but less so on high- relative to low-stake trials. Moreover, less deactivation in goal-directed reward processing regions (i.e., caudate), frontoparietal "task control" regions, and interoceptive processing regions (i.e., somatosensory cortex, thalamus) were observed on high-stake relative to low-stake trials. These findings are consistent with less disruption of goal-directed reward seeking during blocked action efficacy in high-stake conditions among healthy adolescents. These results provide a roadmap of neural systems critical to the processing of frustrating events during reward-based decision-making in youths and could help to characterize how frustration regulation is altered in a range of pediatric psychopathologies.

Cocaine-dependent individuals show altered brain activation during decision making. It is unclear, however, whether these activation differences are related to relapse vulnerability. This study tested the hypothesis that brain-activation patterns during reinforcement learning are linked to relapse 1 year later in individuals entering treatment for cocaine dependence. Subjects performed a Paper-Scissors-Rock task during functional magnetic resonance imaging (fMRI). A year later, we examined whether subjects had remained abstinent (n=15) or relapsed (n=15). Although the groups did not differ on demographic characteristics, behavioral performance, or lifetime substance use, abstinent patients reported greater motivation to win than relapsed patients. The fMRI results indicated that compared with abstinent individuals, relapsed users exhibited lower activation in (1) bilateral inferior frontal gyrus and striatum during decision making more generally; and (2) bilateral middle frontal gyrus and anterior insula during reward contingency learning in particular. Moreover, whereas abstinent patients exhibited greater left middle frontal and striatal activation to wins than losses, relapsed users did not demonstrate modulation in these regions as a function of outcome valence. Thus, individuals at high risk for relapse relative to those who are able to abstain allocate fewer neural resources to action-outcome contingency formation and decision making, as well as having less motivation to win on a laboratory-based task.

Background and aims

Individuals with methamphetamine dependence (MD) exhibit dysfunction in brain regions involved in goal maintenance and reward processing when compared with healthy individuals. We examined whether these characteristics also reflect relapse vulnerability within a sample of MD patients.

Design

Longitudinal, with functional magnetic resonance imaging (fMRI) and clinical interview data collected at baseline and relapse status collected at 1-year follow-up interview.

Setting

Keck Imaging Center, University of California San Diego, USA.

Participants

MD patients (n = 60) enrolled into an in-patient drug treatment program at baseline. MD participants remaining abstinent at 1-year follow-up (abstinent MD group; n = 42) were compared with MD participants who relapsed within this period (relapsed MD group; n = 18).

Measurements

Behavioral and neural responses to a reinforcement learning (paper-scissors-rock) paradigm recorded during an fMRI session at time of treatment.

Findings

The relapsed MD group exhibited greater bilateral inferior frontal gyrus (IFG) and right striatal activation than the abstinent MD group during the learning of reward contingencies (Cohen's d range: 0.60-0.83). In contrast, the relapsed MD group displayed lower bilateral striatum, bilateral insula, left IFG and left anterior cingulate activation than the abstinent MD group (Cohen's d range: 0.90-1.23) in response to winning, tying and losing feedback.

Conclusions

Methamphetamine-dependent individuals who achieve abstinence and then relapse show greater inferior frontal gyrus activation during learning, and relatively attenuated striatal, insular and frontal activation in response to feedback, compared with methamphetamine-dependent people who remain abstinent.

HIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV - associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies.

Graph theory analysis of structural brain networks derived from diffusion tensor imaging (DTI) has become a popular analytical method in neuroscience, enabling advanced investigations of neurological and psychiatric disorders. The purpose of this study was to investigate (1) the effects of edge weighting schemes and (2) the effects of varying interscan periods on graph metrics within the adolescent brain. We compared a binary (B) network definition with three weighting schemes: fractional anisotropy (FA), streamline count, and streamline count with density and length correction (SDL). Two commonly used global and two local graph metrics were examined. The analysis was conducted with two groups of adolescent volunteers who received DTI scans either 12 weeks apart (16.62 ± 1.10 years) or within the same scanning session (30 min apart) (16.65 ± 1.14 years). The intraclass correlation coefficient was used to assess test-retest reliability and the coefficient of variation (CV) was used to assess precision. On average, each edge scheme produced reliable results at both time intervals. Weighted measures outperformed binary measures, with SDL weights producing the most reliable metrics. All edge schemes except FA displayed high CV values, leaving FA as the only edge scheme that consistently showed high precision while also producing reliable results. Overall findings suggest that FA weights are more suited for DTI connectome studies in adolescents.