April C. May

Striatum and insula dysfunction during reinforcement learning differentiates abstinent and relapsed methamphetamine-dependent individuals

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 (Cohens 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 (Cohens 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.

Young Adults at Risk for Stimulant Dependence Show Reward Dysfunction During Reinforcement-Based Decision Making

BACKGROUND While stimulant-dependent individuals continue to make risky decisions, in spite of poor outcomes, much less is known about decision-making characteristics of occasional stimulant users (OSU) at risk for developing stimulant dependence. This study examines whether OSU exhibit inefficient learning and execution of reinforced decision-outcome contingencies. METHODS Occasional stimulant users (n = 161) and stimulant-naïve comparison subjects (CTL) (n = 48) performed a Paper Scissors Rock task during functional magnetic resonance imaging. Selecting a particular option was associated with a predetermined probability of winning, which was altered repeatedly to examine neural and behavioral characteristics of reinforced contingencies. RESULTS Occasional stimulant users displayed greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL during late trials when contingencies were familiar (as opposed to being learned) in the presence of comparable behavioral performance in both groups. Follow-up analyses demonstrated that during late trials: 1) OSU with high cannabis use displayed greater activation in these brain regions than CTL, whereas OSU with low cannabis use did not differ from the other two groups; and 2) OSU preferring cocaine exhibited greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL and also displayed higher activation in the former two regions than OSU who preferred prescription stimulants. CONCLUSIONS Occasional stimulant users exhibit inefficient resource allocation during the execution of reinforced contingencies that may be a result of additive effects of cocaine and cannabis use. A critical next step is to establish whether this inefficiency predicts transition to stimulant dependence.

The effect of age on neural processing of pleasant soft touch stimuli

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.

You are the danger: attenuated insula response in methamphetamine users during aversive interoceptive decision-making.

BACKGROUND Drug dependent individuals often make drug-taking decisions when they do not feel well. Yet, few studies have examined the influence of an aversive state on decision-making related neural processing. METHODS We investigate brain activation to decision-making during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Recently abstinent inpatients with methamphetamine use disorder (METH; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (ER; 20%=reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI. RESULTS METH exhibited higher trait anxiety in conjunction with lower anterior insula (AI) and inferior frontal gyrus (IFG) activation than CTL across trials. METH also showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of ER. For the crucial ER by interoception interaction, METH displayed lower ACC activation to punishment/loss than CTL during breathing load. Within METH, lower trait anxiety was linked to AI/IFG attenuation across trials. CONCLUSIONS AI/IFG attenuations in METH are suggestive of an executive functioning deficit, particularly in users with low anxiety, reflecting reduced resources allocated to choice selection. In contrast, PI/ACC reductions in METH appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activation of brain areas that are important for regulating when one does not feel well may be the neural basis for poor decision-making by METH.

A pilot study investigating changes in neural processing after mindfulness training in elite athletes

The ability to pay close attention to the present moment can be a crucial factor for performing well in a competitive situation. Training mindfulness is one approach to potentially improve elite athletes’ ability to focus their attention on the present moment. However, virtually nothing is known about whether these types of interventions alter neural systems that are important for optimal performance. This pilot study examined whether an intervention aimed at improving mindfulness [Mindful Performance Enhancement, Awareness and Knowledge (mPEAK)] changes neural activation patterns during an interoceptive challenge. Participants completed a task involving anticipation and experience of loaded breathing during functional magnetic resonance imaging recording. There were five main results following mPEAK training: (1) elite athletes self-reported higher levels of interoceptive awareness and mindfulness and lower levels of alexithymia; (2) greater insula and anterior cingulate cortex (ACC) activation during anticipation and post-breathing load conditions; (3) increased ACC activation during the anticipation condition was associated with increased scores on the describing subscale of the Five Facet Mindfulness Questionnaire; (4) increased insula activation during the post-load condition was associated with decreases in the Toronto Alexithymia Scale identifying feelings subscale; (5) decreased resting state functional connectivity between the PCC and the right medial frontal cortex and the ACC. Taken together, this pilot study suggests that mPEAK training may lead to increased attention to bodily signals and greater neural processing during the anticipation and recovery from interoceptive perturbations. This association between attention to and processing of interoceptive afferents may result in greater adaptation during stressful situations in elite athletes.

Cocaine dependent individuals with attenuated striatal activation during reinforcement learning are more susceptible 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.

When the brain does not adequately feel the body: Links between low resilience and interoception

This study examined neural processes of resilience during aversive interoceptive processing. Forty-six individuals were divided into three groups of resilience Low (LowRes), high (HighRes), and normal (NormRes), based on the Connor-Davidson Resilience Scale (2003). Participants then completed a task involving anticipation and experience of loaded breathing during functional magnetic resonance imaging (fMRI) recording. Compared to HighRes and NormRes groups, LowRes self-reported lower levels of interoceptive awareness and demonstrated higher insular and thalamic activation across anticipation and breathing load conditions. Thus, individuals with lower resilience show reduced attention to bodily signals but greater neural processing to aversive bodily perturbations. In low resilient individuals, this mismatch between attention to and processing of interoceptive afferents may result in poor adaptation in stressful situations.

Hyperactivation to pleasant interoceptive stimuli characterizes the transition to stimulant addiction.

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.

Deployment and Post-Deployment Experiences in OEF/OIF Veterans: Relationship to Gray Matter Volume

Background Combat-related PTSD has been associated with reduced gray matter volume in regions of the prefrontal and temporal cortex, hippocampus, insula, and amygdala. However, the relationship between gray matter volume and specific deployment and post-deployment experiences has not been investigated. The aim of this study was to delineate how such experiences may contribute to structural brain changes for combat veterans. Methods Operation Iraqi Freedom/Operation Enduring Freedom veterans (N = 32) completed magnetic resonance imaging, the Deployment Risk and Resilience Inventory, Alcohol Use Disorders Identification Test, and Clinical Administered PTSD Scale. Voxel-wise Huber robust multiple regressions were used to quantify the relationship between gray matter volume and deployment experiences (combat experiences, military social support) and post-deployment symptoms (PTSD, alcohol use). Results There was an interaction between severity of combat experiences and military social support for orbitofrontal gyrus gray matter volume. Specifically, individuals with more orbitofrontal gyrus gray matter volume reported less combat experiences and higher unit support. Individuals with more severe PTSD symptoms showed reduced gray matter volume within a large temporal region (inferior temporal and parahippocampal gyrus). Conclusions The identified association between unit support and orbitofrontal gyrus volume supports two potential resilience mechanisms to be delineated with future longitudinal studies. First, individuals with larger orbitofrontal gyrus may engage in greater quality of social interactions and thus experience combat as less stressful. Second, individuals who experience greater unit support may preserve a larger orbitofrontal gyrus, serving to “protect” them from aversive consequences of combat.

Altered frontocingulate activation during aversive interoceptive processing in young adults transitioning to problem stimulant use.

Problems associated with stimulant use have been linked to frontocingulate, insular, and thalamic dysfunction during decision making and alterations in interoceptive processing. However, little is known about how interoception and decision making interact and contribute to dysfunctions that promote the transition from recreational drug use to abuse or dependence. Here, we investigate brain activation in response to reward, punishment, and uncertainty during an aversive interoceptive challenge in current and former stimulant (cocaine and amphetamine) users using functional magnetic resonance imaging (fMRI). Young adults previously identified as recreational users (n = 184) were followed up 3 years later. Of these, 18 individuals progressed to problem stimulant use (PSU), whereas 15 desisted stimulant use (DSU). PSU, DSU, and 14 healthy comparison subjects (CTL) performed a two-choice prediction task at three fixed error rates (20% = reward, 50% = uncertainty, 80% = punishment) during which they anticipated and experienced episodes of inspiratory breathing load. Although groups did not differ in insula activation or subjective breathing load ratings, PSU exhibited lower right inferior frontal gyrus (IFG) and bilateral anterior cingulate (ACC) activation than DSU and CTL during aversive interoceptive processing as well as lower right IFG in response to decision making involving uncertainty. However, PSU exhibited greater bilateral IFG activation than DSU and CTL while making choices within the context of punishing feedback, and both PSU and DSU showed lower thalamic activation during breathing load than CTL. Findings suggest that frontocingulate attenuation, reflecting reduced resources devoted to goal maintenance and action selection in the presence of uncertainty and interoceptive perturbations, may be a biomarker for susceptibility to PSU.