Eric D. Claus

Anatomy of a Decision: Striato-Orbitofrontal Interactions in Reinforcement Learning, Decision Making, and Reversal

The authors explore the division of labor between the basal ganglia-dopamine (BG-DA) system and the orbitofrontal cortex (OFC) in decision making. They show that a primitive neural network model of the BG-DA system slowly learns to make decisions on the basis of the relative probability of rewards but is not as sensitive to (a) recency or (b) the value of specific rewards. An augmented model that explores BG-OFC interactions is more successful at estimating the true expected value of decisions and is faster at switching behavior when reinforcement contingencies change. In the augmented model, OFC areas exert top-down control on the BG and premotor areas by representing reinforcement magnitudes in working memory. The model successfully captures patterns of behavior resulting from OFC damage in decision making, reversal learning, and devaluation paradigms and makes additional predictions for the underlying source of these deficits.

Age differences in affective decision making as indexed by performance on the Iowa Gambling Task.

Contemporary perspectives on age differences in risk taking, informed by advances in developmental neuroscience, have emphasized the need to examine the ways in which emotional and cognitive factors interact to influence decision making. In the present study, a diverse sample of 901 individuals between the ages of 10 and 30 were administered a modified version of the Iowa Gambling Task, which is designed to measure affective decision making. Results indicate that approach behaviors (operationalized as the tendency to play increasingly from the advantageous decks over the course of the task) display an inverted U-shape relation to age, peaking in mid- to late adolescence. In contrast, avoidance behaviors (operationalized as the tendency to refrain from playing from the disadvantageous decks) increase linearly with age, with adults avoiding disadvantageous decks at higher rates than both preadolescents and adolescents. The finding that adolescents, compared to adults, are relatively more approach oriented in response to positive feedback and less avoidant in response to negative feedback is consistent with recent studies of brain development, as well as epidemiological data on various types of risky behavior, and may have important practical implications for the prevention of adolescent risk taking.

Prefrontal Cortex Activity is Reduced in Gambling and Nongambling Substance Users During Decision-Making

Objective: Poor decision‐making is a hallmark of addiction, whether to substances or activities. Performance on a widely used test of decision‐making, the Iowa Gambling Task (IGT), can discriminate controls from persons with ventral medial frontal lesions, substance‐dependence, and pathological gambling. Positron emission tomography (PET) studies indicate that substance‐dependent individuals show altered prefrontal activity on the task. Here we adapted the IGT to an fMRI setting to test the hypothesis that defects in ventral medial and prefrontal processing are associated with impaired decisions that involve risk but may differ depending on whether substance dependence is comorbid with gambling problems. Method: 18 controls, 14 substance‐dependent individuals (SD), and 16 SD with gambling problems (SDPG) underwent fMRI while performing a modified version of the IGT. Result: Group differences were observed in ventral medial frontal, right frontopolar, and superior frontal cortex during decision‐making. Controls showed the greatest activity, followed by SDPG, followed by SD. Conclusion: Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision‐making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance‐dependent individuals. Hum Brain Mapp, 2007.

Exposure to the Taste of Alcohol Elicits Activation of the Mesocorticolimbic Neurocircuitry

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

Differential neural response to alcohol priming and alcohol taste cues is associated with DRD4 VNTR and OPRM1 genotypes.

BACKGROUNDnStudies suggest that polymorphisms in the D4 dopamine receptor (DRD4) and opioid receptor, mu 1 (OPRM1) genes are involved in differential response to the effects of alcohol and to alcohol cues. However, to date, the mechanisms that underlie these differences remain largely unknown.nnnMETHODSnUsing functional magnetic resonance imaging, hemodynamic response in mesocorticolimbic structures after exposure to alcohol tastes was contrasted with a control taste and compared between DRD4 variable number of tandem repeats (VNTR) genotypes and OPRM1 A118G genotypes. Additionally, the effects of a priming dose of alcohol on this response were examined.nnnRESULTSnThe results indicated that DRD4 VNTR >7 repeat individuals (DRD4.L) had significantly greater response to alcohol cues in the orbitofrontal cortex, anterior cingulate gyrus, and striatum compared with individuals with <7 repeats (DRD4.S) prior to a priming dose of alcohol (p < 0.05), but not after a priming dose. In the OPRM1 comparisons, results showed that individuals with at least 1 copy of the OPRM1 + 118 G allele had greater hemodynamic response in mesocorticolimbic areas both before and after priming compared with those who were homozygous for the OPRM1 + 118 A allele. For the DRD4.L and OPRM1 + 118 G groups, brain response in the striatum was highly correlated with measures of alcohol use and behavior such that greater activity corresponded with greater frequency and quantity of alcohol use.nnnCONCLUSIONSnThe DRD4 VNTR and OPRM1 A118G polymorphisms are associated with functional neural changes in mesocorticolimbic structures after exposure to alcohol cues. This provides evidence for the contributions of the DRD4 and OPRM1 genes in modulating neural activity in structures that are involved in the motivation to drink.

Reducing Susceptibility Artifacts in fMRI Using Volume- Selective z-Shim Compensation

Susceptibility‐induced magnetic field gradients (SFGs) can result in severe signal loss in the orbitofrontal cortex (OFC) in gradient‐echo‐based functional MRI (fMRI) studies. Although conventional z‐shim techniques can effectively recover the MRI signal in this region, the substantial penalty in imaging time hampers their use in routine fMRI studies. A modified z‐shim technique with high imaging efficiency is presented in this study. In this technique, z‐shim compensations are applied only to a selective volume where the susceptibility artifact is severe. The results of an fMRI study (N = 6) demonstrate the feasibility of detecting the OFC activation with z‐shim in whole‐brain fMRI studies at a temporal resolution of 2 s. Magn Reson Med 57:396–404, 2007.

Insula and Orbitofrontal Cortical Morphology in Substance Dependence Is Modulated by Sex

BACKGROUND AND PURPOSE: Frontolimbic circuits are involved in learning and decision-making processes thought to be affected in substance-dependent individuals. We investigated frontolimbic cortical morphometry in substance-dependent men and women and determined whether morphometric measurements correlated with decision-making performance. MATERIALS AND METHODS: Twenty-eight abstinent SDI (17 men/11 women) were compared with 28 controls (13 men/15 women). Cortical thicknesses and volumes were computed by using FreeSurfer. After controlling for age and intracranial volume, group and sex effects were analyzed in 3 a priori regions of interest: the insula, orbitofrontal cortex, and anterior cingulate cortex by using analysis of covariance. A secondary whole-brain analysis was conducted to verify region-of-interest results and to explore potential differences in other brain regions. RESULTS: Region-of-interest analyses revealed a main effect of group on the left insula cortex, which was thinner in SDI compared with controls (P = .02). There was a group by sex interaction on bilateral insula volume (left, P = .02; right, P = .001) and right insula cortical thickness (P = .007). Compared with same-sex controls, female SDI had smaller insulae, whereas male SDI had larger insulae. Neither ACC nor OFC significantly differed across group. Performance on a decision-making task was better in controls than SDI and correlated with OFC measurements in the controls. CONCLUSIONS: SDI and controls differed in insula morphology, and those differences were modulated by sex. No group differences in OFC were observed, but OFC measurements correlated with negative-reinforcement learning in controls. These preliminary results are consistent with a hypothesis that frontolimbic pathways may be involved in behaviors related to substance dependence.

White matter integrity is associated with alcohol cue reactivity in heavy drinkers

Neuroimaging studies have shown that white matter damage accompanies excessive alcohol use, but the functional correlates of alcohol‐related white matter disruption remain unknown. This study applied tract‐based spatial statistics (TBSS) to diffusion tensor imaging (DTI) data from 332 heavy drinkers (mean age = 31.2 ± 9.4; 31% female) to obtain averaged fractional anisotropy (FA) values of 18 white matter tracts. Statistical analyses examined correlations of FA values with blood‐oxygenation‐level‐dependent (BOLD) response to an alcohol taste cue, measured with functional magnetic resonance imaging (fMRI). FA values of nine white matter tracts (anterior corona radiata, body of corpus callosum, cingulate gyrus, external capsule, fornix, inferior frontooccipital fasciculus, posterior corona radiata, retrolenticular limb of internal capsule, and superior longitudinal fasciculus) were significantly, negatively correlated with BOLD activation in medial frontal gyrus, parahippocampal gyrus, fusiform gyrus, cingulum, thalamus, caudate, putamen, insula, and cerebellum. The inverse relation between white matter integrity and functional activation during the alcohol taste cue provides support for the hypothesis that lower white matter integrity in frontoparietal and corticolimbic networks is a factor in loss of control over alcohol consumption.

Neural correlates of response inhibition in current and former smokers.

&NA; Loss of behavioral control is a hallmark of addiction. Individual differences in basic cognitive processes such as response inhibition may be important for interrupting automatic behaviors associated with smoking and supporting prolonged abstinence. To examine how response inhibition and error monitoring processes differ as a function of smoking status, current smokers, former smokers and never smokers (N = 126) completed a simple Go/No‐Go task while undergoing functional magnetic resonance imaging. All groups performed similarly on the task and similarly engaged the inferior frontal gyrus and dorsal anterior cingulate cortex, regions traditionally associated with response inhibition and error monitoring, respectively. During response inhibition (i.e., Correct Rejects > Hits contrast), overall group differences emerged in the recruitment of the cerebellum, while individual group differences in error monitoring (False Alarms > Hits contrast) were seen for regions of the parietal lobe and thalamus (current smokers > former smokers), as well as regions of the bilateral cerebellum, parahippocampal gyrus and superior parietal lobe (i.e., ever smokers > never smokers). We discuss how our results replicate two previous large‐sample studies that used the same Go/No‐Go task and review these data in terms of network models of inhibitory and error monitoring abnormalities in addiction. HIGHLIGHTSResponse inhibition in current, former and never smokers was behaviorally similar, but differed in the neural recruitment of the cerebellum.Despite similar task performance across groups, errors differentially activated regions involved in attention and motor control.Regions other than the IFG and dACC should be considered when investigating response inhibition in addiction, especially in older populations.Discussion emphasizes the role of compensatory processes and promotes a connectivity approach to neural processes in addiction.

An Examination of Behavioral and Neuronal Effects of Comorbid Traumatic Brain Injury and Alcohol Use

BACKGROUNDnChronic alcohol use disorders (AUDs) and traumatic brain injury (TBI) are highly comorbid and share commonly affected neuronal substrates (i.e., prefrontal cortex, limbic system, and cerebellum). However, no studies have examined how combined physical trauma and heavy drinking affect neurocircuitry relative to heavy drinking alone.nnnMETHODSnThe current study investigated whether comorbid AUDs and mild or moderate TBI (AUDs+TBI) would negatively affect maladaptive drinking behaviors (nxa0= 90 AUDs+TBI; nxa0= 62 AUDs) as well as brain structure (i.e., increased atrophy; nxa0= 62 AUDs+TBI; nxa0= 44 AUDs) and function (i.e., activation during gustatory cue reactivity; nxa0= 55 AUDs+TBI; nxa0= 37 AUDs) relative to AUDs alone.nnnRESULTSnParticipants reported a much higher incidence of trauma (59.2%) compared with the general population. There were no differences in demographic and clinical measures between groups, suggesting that they were well matched. Although maladaptive drinking behaviors tended to be worse for the AUDs+TBI group, effect sizes were small and not statistically significant. Increased alcohol-cue reactivity was observed in bilateral anterior insula and orbitofrontal cortex, anterior cingulate cortex, medial prefrontal cortex, posterior cingulate cortex, dorsal striatum, thalamus, brainstem, and cerebellum across both groups relative to a carefully matched appetitive control. However, there were no significant differences in structural integrity or functional activation between AUDs+TBI and AUDs participants, even when controlling for AUD severity.nnnCONCLUSIONSnCurrent results indicate that a combined history of mild or moderate TBI was not sufficient to alter drinking behaviors and/or underlying neurocircuitry at detectable levels relative to heavy drinking alone. Future studies should examine the potential long-term effects of combined alcohol and trauma on brain functioning.