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.

Tactile interactions with our environment stimulate afferent fibers within the skin, which deliver information about sensations of pain, texture, itch and other feelings to the brain as a comprehensive sense of self. These tactile interactions can stimulate brain regions involved in interoception and reward processing. This study examined subjective, behavioral, and neural processing as a function of age during stimulation of A-beta (Aβ) and C tactile (CT) afferents using a soft brush stroke task. 16 adolescents (ages 15-17), 22 young adults (ages 20-28), and 20 mature adults (ages 29-55) underwent a simple continuous performance task while periodically anticipating and experiencing a soft touch to the palm or forearm, during functional magnetic resonance imaging (fMRI). fMRI results showed that adolescents displayed greater bilateral posterior insula activation than young and mature adults across all conditions and stimulus types. Adolescents also demonstrated greater bilateral posterior insula activation than young and mature adults specifically in response to the soft touch condition. Adolescents also exhibited greater activation than mature adults in bilateral inferior frontal gyrus and striatum during the soft touch condition. However, mature adults showed greater striatum activation than adolescents and young adults during anticipation. In the left anterior cingulate cortex, mature adults exhibited greater activation than adolescents and young adults when anticipating the upcoming touch. These results support the hypothesis that adolescents show an exaggerated neural response to pleasant stimulation of afferents, which may have profound effects on how they approach or avoid social and risky situations. In particular, heightened interoceptive reactivity to pleasant stimuli might cause adolescents to seek experiences that are associated with pleasant stimulation.

Background

Altered interoception, i.e., processing of stimuli from inside the body, has been considered an important component of drug-taking behavior. However, approaches to examine interoceptive sensitivity in humans have been limited. This study examined the hypothesis that adolescents with substance use disorder show altered interoceptive processing, measured by stimulating mechano-receptive C-fibers (MR-CF) via soft touch.

Methods

Adolescents with substance use disorders (SUD, n=15) and comparison youth (CON, n=17) underwent functional magnetic resonance imaging (fMRI) during anticipation or reception of a positively valenced "Soft Touch" consisting of MR-CF stimulation to the palm or forearm. Visual analog scales (VAS) indexed subjective interoceptive experience (e.g., pleasantness, intensity).

Results

Across all conditions, SUD displayed attenuated left posterior insula activation compared to CON. Greater left anterior insula and right lentiform nucleus activation was evident during the application of soft touch for SUD but not for CON. Whereas for CON, greater left anterior insula activation was associated with higher pleasantness ratings, pleasantness was linked to less anterior insula activation in SUD. Finally, within SUD, attenuated posterior insula activation was related to more recent cannabis use.

Conclusions

SUD adolescents exhibit blunted somatovisceral processing of pleasant stimulation, heightened sensitivity in regions responsible for processing reward value, and altered relationships between interoceptive processing and subjective experience.

Background

Mechano-receptive C-fiber (MR-CF) stimulation via slow stroking of C-fiber rich skin areas can be used to probe the relationship between reward and interoception. Individuals with substance use disorders show impaired reward processing, and dysfunctional interoceptive processing of MR-CF may contribute to this dysfunction. This study predicted that methamphetamine dependent (MD) individuals would exhibit altered responses to MR-CF stimulation in brain regions important for interoception.

Methods

Recently abstinent MD (n=25) and comparison (CTL, n=17) subjects received a pleasant interoceptive stimulus ("Soft Touch" consisting of a slow brush stroke) to the palm or forearm during functional magnetic resonance imaging. Subjects were provided with cues signaling stimulation to examine anticipatory and stimulus-related processing. Subjective responses were measured using visual analog scales (VAS).

Results

Groups were similar on behavioral performance and ratings of the interoceptive stimuli, yet MD exhibited lower anterior insula, dorsal striatum, and thalamus activation than CTL, across anticipation and soft touch conditions. The lower the anterior insula activation, the faster the reaction time across conditions in MD, whereas the opposite pattern was evident in CTL. Striatal activation in MD was greater than CTL during anticipation, but lower during soft touch. Greater striatal attenuation was associated with higher VAS pleasantness ratings of soft touch.

Conclusions

MD expend fewer brain processing resources during soft touch, a form of positively-valenced interoceptive stimuli, in brain areas that are important for both interoception and reward. Future studies will ascertain if sustained abstinence from methamphetamine use can normalize aberrant neural interoceptive processing.

Aims

To understand processes placing individuals at risk for stimulant (amphetamine and cocaine) use disorder.

Design

Longitudinal study.

Setting

University of California, San Diego Department of Psychiatry, CA, USA.

Participants

Occasional stimulant users (OSU; n = 184) underwent a baseline clinical interview and a functional magnetic resonance imaging (fMRI) session. On the basis of a follow-up clinical interview completed 3 years later, OSU (n = 147) were then categorized as problem stimulant users (PSU: n = 36; those who developed stimulant use disorders in the interim) or desisted stimulant users (DSU: n = 74; those who stopped using). OSU who did not meet criteria for PSU or DSU (n = 37) were included in dimensional analyses.

Measurements

fMRI blood oxygen level-dependent (BOLD) contrast percentage signal change from baseline collected during a Paper-Scissors-Rock task was examined during three decision-making conditions, those resulting in: (1) wins, (2) ties and (3) losses. These data were used as dependent variables in categorical analyses comparing PSU and DSU, as well as dimensional analyses including interim drug use as predictors, controlling for baseline drug use.

Findings

PSU exhibited lower anterior cingulate, middle insula, superior temporal, inferior parietal, precuneus and cerebellum activation than DSU across all three conditions (significant brain clusters required > 19 neighboring voxels to exceed F_(1,108)  = 5.58, P < 0.01 two-tailed; all Cohen's d > 0.83). Higher interim marijuana use was linked to lower pre-central and superior temporal activation during choices resulting in wins (> 19 neighboring voxels to exceed t = 2.61, P < 0.01 two-tailed; R² change > 0.11).

Conclusions

Individuals who transition from stimulant use to stimulant use disorder appear to show alterations in neural processing of stimulus valuation and outcome monitoring, patterns also evident in chronic stimulant use disorder. Attenuated anterior cingulate and insular processing may constitute a high-risk neural processing profile, which could be used to calculate risk scores for individuals experimenting with stimulants.

Aims

Altered interoception, how the brain processes afferents from the body, may contribute to the urge to take drugs, and subsequently, the development of addiction. Although chronic stimulant dependent individuals exhibit attenuated brain responses to pleasant interoceptive stimuli, it is unclear whether this deficit exists early-on in the process of transition to stimulant addiction.

Methods

To this end, we compared problem stimulant users (PSU; n=18), desisted stimulant users (DSU; n=15), and stimulant naïve comparison subjects (CTL; n=15) during functional magnetic resonance imaging (fMRI) while they anticipated and experienced pleasant soft touch (slow brushstroke to the palm and forearm).

Results

Groups did not differ in behavioral performance or visual analog scale ratings of soft touch stimuli. fMRI results indicated that PSU exhibited greater right anterior insula, left inferior frontal gyrus, and right superior frontal gyrus activation than DSU and CTL during the anticipation and experience of soft touch. Moreover, during the experience of soft touch, PSU demonstrated higher bilateral precentral gyrus/middle insula and right posterior temporal gyrus activation than DSU and CTL.

Conclusions

In contrast to chronic stimulant dependence, individuals who have recently developed stimulant use disorders show exaggerated neural processing of pleasant interoceptive stimuli. Thus, increased processing of body-relevant information signaling pleasant touch in those individuals who develop problem use may be a predictive interoceptive biomarker. However, future investigations will need to determine whether the combination of probing pleasant interoception using neuroimaging is sufficiently sensitive and specific to help identify individuals at high risk for future problem use.

Background

Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use.

Methods

Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use.

Results

Categorical results indicated that relative to those who desisted from stimulant use, problem stimulant users 1) made riskier decisions after winning feedback; 2) exhibited lower frontal, insular, and striatal BOLD responses to win/loss feedback after making risky decisions; and 3) displayed lower thalamic but greater temporo-occipital BOLD responses to risky losses than to risky wins. In comparison, dimensional results indicated that lower BOLD signals to risky choices than to safe choices in frontal, striatal, and additional regions predicted greater marijuana use at follow-up.

Conclusions

Taken together, blunted frontostriatal signals during risky choices may quantify vulnerability to future marijuana consumption, whereas blunted frontostriatal signals to risky outcomes mark risk for future stimulant use disorder. These behavioral and neural processing measures may prove to be useful for identifying ultra-high risk individuals prior to onset of problem drug use.

There is some evidence that neuroimaging can be used to predict relapse among abstinent methamphetamine-dependent (MD) individuals. However, it remains unclear what cognitive and neural processes contribute to relapse. This investigation examined whether insula activation during risk-taking decisions-a process shown to be disrupted in MD-is able to predict susceptibility for relapse. Sixty-eight MD enrolled in a treatment program during early abstinence completed a risk-taking task during functional magnetic resonance imaging. Sixty-three of the sixty-eight individuals were followed up 1 year after the study. Of these, 18 MD reported relapse. The 45 abstinent MD showed patterns of insula activation during risky decisions that resembled those found in prior studies of healthy controls, consisting of lower insula activation during safe decisions paired with higher activation during risky decisions. In contrast, the 18 relapsed MD showed similar insula activation during safe and risky decisions. An increase in one standard deviation in the difference in insula activation between risky and safe choices was associated with a 0.34 odds ratio for relapse at any given time. A median split of insula activation (difference between risky and safe) showed that individuals in the bottom half were two times more likely to relapse. In addition, a model that included several other brain regions increased prediction accuracy compared with insula-based model alone. These results suggest that failure to differentially activate the insula as a function of risk is a part of an altered risk-processing network associated with an increased susceptibility to relapse.

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.