Schuster RM, Hoeppner SS, Evins EA, Gilman JM. Early onset marijuana use is associated with learning inefficiencies. Neuropsychology. 2016;30 (4) :405-15.Abstract
OBJECTIVE: Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. METHOD: Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. RESULTS: Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. CONCLUSIONS: Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record
Gilman JM, Schuster RM, Curran MT, Calderon V, van der Kouwe A, Evins EA. Neural mechanisms of sensitivity to peer information in young adult cannabis users. Cogn Affect Behav Neurosci. 2016;16 (4) :646-61.Abstract
Though social influence is a critical factor in the initiation and maintenance of marijuana use, the neural correlates of influence in those who use marijuana are unknown. In this study, marijuana-using young adults (MJ; n = 20) and controls (CON; n = 23) performed a decision-making task in which they made a perceptual choice after viewing the choices of unknown peers via photographs, while they underwent functional magnetic resonance imaging scans. The MJ and CON groups did not show differences in the overall number of choices that agreed with versus opposed group influence, but only the MJ group showed reaction time slowing when deciding against group choices. Longer reaction times were associated with greater activation of frontal regions. The MJ goup, compared to CON, showed significantly greater activation in the caudate when presented with peer information. Across groups, caudate activation was associated with self-reported susceptibility to influence. These findings indicate that young adults who use MJ may exhibit increased effort when confronted with opposing peer influence, as well as exhibit greater responsivity of the caudate to social information. These results not only better define the neural basis of social decisions, but also suggest that marijuana use is associated with exaggerated neural activity during decision making that involves social information.
Gilman JM, Lee S, Kuster JK, Lee MJ, Kim BW, van der Kouwe A, Blood AJ, Breiter HC. Variable activation in striatal subregions across components of a social influence task in young adult cannabis users. Brain Behav. 2016;6 (5) :e00459.Abstract
INTRODUCTION: Decades of research have demonstrated the importance of social influence in initiation and maintenance of drug use, but little is known about neural mechanisms underlying social influence in young adults who use recreational drugs. METHODS: To better understand whether the neural and/or behavioral response to social influence differs in young adults using illicit drugs, 20 marijuana-using young adults (MJ) aged 18-25, and 20 controls (CON) performed a decision-making task in the context of social influence, while they underwent functional magnetic resonance imaging scans. A priori analyses focused on the nucleus accumbens (NAc), with post hoc analyses in the rest of the striatum. In this task, participants could choose to either follow or go against group influence. RESULTS: When subjects applied social information to response choice selection (independent of following or going against group influence), we observed activation in the middle striatum (caudate), in the MJ group only, that extended ventrally into the NAc. MJ users but not CON showed greater activation in the NAc but not the caudate while making choices congruent with group influence as opposed to choices going against group influence. Activation in the NAc when following social influence was associated with amount of drug use reported. In contrast, during the feedback phase of the task we observed significant NAc activation in both MJ and CON, along with dorsal caudate activation only in MJ participants. This NAc activation did not correlate with drug use. CONCLUSIONS: This study shows that MJ users, but not CON, show differential brain activation across striatal subregions when applying social information to make a decision, following versus going against a group of peers, or receiving positive feedback. The current work suggests that differential neural sensitivity to social influence in regions such as the striatum may contribute to the development and/or maintenance of marijuana use.
Lee S, Lee MJ, Kim BW, Gilman JM, Kuster JK, Blood AJ, Kuhnen CM, Breiter HC. The Commonality of Loss Aversion across Procedures and Stimuli. PLoS One. 2015;10 (9) :e0135216.Abstract
Individuals tend to give losses approximately 2-fold the weight that they give gains. Such approximations of loss aversion (LA) are almost always measured in the stimulus domain of money, rather than objects or pictures. Recent work on preference-based decision-making with a schedule-less keypress task (relative preference theory, RPT) has provided a mathematical formulation for LA similar to that in prospect theory (PT), but makes no parametric assumptions in the computation of LA, uses a variable tied to communication theory (i.e., the Shannon entropy or information), and works readily with non-monetary stimuli. We evaluated if these distinct frameworks described similar LA in healthy subjects, and found that LA during the anticipation phase of the PT-based task correlated significantly with LA related to the RPT-based task. Given the ease with which non-monetary stimuli can be used on the Internet, or in animal studies, these findings open an extensive range of applications for the study of loss aversion. Furthermore, the emergence of methodology that can be used to measure preference for both social stimuli and money brings a common framework to the evaluation of preference in both social psychology and behavioral economics.
Viswanathan V, Lee S, Gilman JM, Kim BW, Lee N, Chamberlain L, Livengood SL, Raman K, Lee MJ, Kuster J, et al. Age-related striatal BOLD changes without changes in behavioral loss aversion. Front Hum Neurosci. 2015;9 :176.Abstract
Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task.
Smith MJ, Cobia DJ, Reilly JL, Gilman JM, Roberts AG, Alpert KI, Wang L, Breiter HC, Csernansky JG. Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects. Hippocampus. 2015;25 (9) :1042-51.Abstract
Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis.
Gilman JM, Treadway MT, Curran MT, Calderon V, Evins EA. Effect of social influence on effort-allocation for monetary rewards. PLoS One. 2015;10 (5) :e0126656.Abstract
Though decades of research have shown that people are highly influenced by peers, few studies have directly assessed how the value of social conformity is weighed against other types of costs and benefits. Using an effort-based decision-making paradigm with a novel social influence manipulation, we measured how social influence affected individuals' decisions to allocate effort for monetary rewards during trials with either high or low probability of receiving a reward. We found that information about the effort-allocation of peers modulated participant choices, specifically during conditions of low probability of obtaining a reward. This suggests that peer influence affects effort-based choices to obtain rewards especially under conditions of risk. This study provides evidence that people value social conformity in addition to other costs and benefits when allocating effort, and suggests that neuroeconomic studies that assess trade-offs between effort and reward should consider social environment as a factor that can influence decision-making.
Gilman JM, Calderon V, Curran MT, Evins EA. Young adult cannabis users report greater propensity for risk-taking only in non-monetary domains. Drug Alcohol Depend. 2015;147 :26-31.Abstract
BACKGROUND: Though substance use is often associated with elevated risk-taking in real-world scenarios, many risk-taking tasks in experimental psychology using financial gambles fail to find significant differences between individuals with substance use disorders and healthy controls. We assessed whether participants using marijuana would show a greater propensity for risk-taking in distinct domains including, but not limited to, financial risk-taking. METHODS: In the current study, we assessed risk-taking in young adult (age 18-25) regular marijuana users and in non-using control participants using a domain-specific risk-taking self-report scale (DOSPERT) encompassing five domains of risk-taking (social, financial, recreational, health/safety, and ethical). We also measured behavioral risk-taking using a laboratory monetary risk-taking task. RESULTS: Marijuana users and controls reported significant differences on the social, health/safety, and ethical risk-taking scales, but no differences in the propensity to take recreational or financial risks. Complementing the self-report finding, there were no differences between marijuana users and controls in their performance on the laboratory risk-taking task. CONCLUSIONS: These findings suggest that financial risk-taking may be less sensitive than other domains of risk-taking in assessing differences in risky behavior between those who use marijuana and those who do not. In order to more consistently determine whether increased risk-taking is a factor in substance use, it may be necessary to use both monetary risk-taking tasks and complementary assessments of non-monetary-based risk-taking measures.
Gilman JM, Smith AR, Bjork JM, Ramchandani VA, Momenan R, Hommer DW. Cumulative gains enhance striatal response to reward opportunities in alcohol-dependent patients. Addict Biol. 2015;20 (3) :580-93.Abstract
Substance use disorder is characterized by a transition from volitional to compulsive responding for drug reward. A possible explanation for this transition may be that alcohol-dependent patients (ADP) show a general propensity for a history of rewarded instrumental responses, and these rewarded responses may boost the activation of motivational neurocircuitry for additional reward. Brain imaging studies of decision-making have demonstrated that ADP relative to controls (CON) often show altered neural activation in response to anticipating and receiving rewards, but the majority of studies have not investigated how past performance affects activation. A potential exists for ADP to show increased sensitivity to reward as a function of reward delivery history. In the current study, we used functional magnetic resonance imaging to investigate the neural correlates of risky decision-making in ADP (n = 18) and CON (n = 18) while they played a two-choice monetary risk-taking game. In addition to investigating general neural recruitment by risky decision-making, we also modeled each participant's running total of monetary earnings in order to determine areas of activation that correlated with cumulative reward. We found that ADP and CON showed few differences in behavior or in mesolimbic activation by choice for, and receipt of, risky gains. However, when including a cumulative-earnings covariate, ADP exhibited heightened striatal activation that correlated with total earnings during the choice event in the task. The heightened contextual sensitivity of striatal responses to cumulative earnings in ADP may represent a general neurobiological affective substrate for development of automatized instrumental behavior.
Stoeckel LE, Garrison KA, Ghosh S, Wighton P, Hanlon CA, Gilman JM, Greer S, Turk-Browne NB, deBettencourt MT, Scheinost D, et al. Optimizing real time fMRI neurofeedback for therapeutic discovery and development. Neuroimage Clin. 2014;5 :245-55.Abstract
While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain-behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.
Gilman JM, Curran MT, Calderon V, Stoeckel LE, Evins EA. Impulsive social influence increases impulsive choices on a temporal discounting task in young adults. PLoS One. 2014;9 (7) :e101570.Abstract
Adolescents and young adults who affiliate with friends who engage in impulsive behavior are more likely to engage in impulsive behaviors themselves, and those who associate with prosocial (i.e. more prudent, future oriented) peers are more likely to engage in prosocial behavior. However, it is difficult to disentangle the contribution of peer influence vs. peer selection (i.e., whether individuals choose friends with similar traits) when interpreting social behaviors. In this study, we combined a novel social manipulation with a well-validated delay discounting task assessing impulsive behavior to create a social influence delay discounting task, in which participants were exposed to both impulsive (smaller, sooner or SS payment) and non-impulsive (larger, later or LL payment) choices from their peers. Young adults in this sample, n = 51, aged 18-25 had a higher rate of SS choices after exposure to impulsive peer influence than after exposure to non-impulsive peer influence. Interestingly, in highly susceptible individuals, the rate of non-impulsive choices did not increase after exposure to non-impulsive influence. There was a positive correlation between self-reported suggestibility and degree of peer influence on SS choices. These results suggest that, in young adults, SS choices appear to be influenced by the choices of same-aged peers, especially for individuals who are highly susceptible to influence.
Gilman JM, Kuster JK, Lee S, Lee MJ, Kim BW, Makris N, van der Kouwe A, Blood AJ, Breiter HC. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014;34 (16) :5529-38.Abstract
Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.
Bjork JM, Gilman JM. The effects of acute alcohol administration on the human brain: insights from neuroimaging. Neuropharmacology. 2014;84 :101-10.Abstract
Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.
Rio DE, Rawlings RR, Woltz LA, Gilman J, Hommer DW. Development of the complex general linear model in the fourier domain: application to FMRI multiple input-output evoked responses for single subjects. Comput Math Methods Med. 2013;2013 :645043.Abstract
A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.
Hendler RA, Ramchandani VA, Gilman J, Hommer DW. Stimulant and sedative effects of alcohol. Curr Top Behav Neurosci. 2013;13 :489-509.Abstract
Alcohol produces both stimulant and sedating effects in humans. These two seemingly opposite effects are central to the understanding of much of the literature on alcohol use and misuse. In this chapter we review studies that describe and attempt to measure various aspects of alcohol's subjective, autonomic, motor, cognitive and behavioral effects from the perspective of stimulation and sedation. Although subjective sedative and stimulatory effects can be measured, it is not entirely clear if all motor, cognitive and behavioral effects can be unambiguously assigned to either one or the other category. Increased heart rate and aggression seem strongly associated with stimulation, but motor slowing and cognitive impairment can also show a similar time course to stimulation, making their relation to sedation problematic. There is good agreement that alcohol's ability to induce striatal dopamine release is the mechanism underlying alcohol's stimulatory effects; however, the change in brain function underlying sedation is less well understood. In general, stimulatory effects are thought to be more rewarding than sedative effects, but this may not be true for anxiolytic effects which seem more closely related to sedation than stimulation. The two major theories of how response to alcohol predicts risk for alcoholism both postulate that individuals at high risk for alcohol use disorders have a reduced sedative response to alcohol compared to individuals not at high risk. In addition one theory proposes that alcoholism risk is also associated with a larger stimulatory response to alcohol.
Gilman JM, Smith AR, Ramchandani VA, Momenan R, Hommer DW. The effect of intravenous alcohol on the neural correlates of risky decision making in healthy social drinkers. Addict Biol. 2012;17 (2) :465-78.Abstract
Alcohol is thought to contribute to an increase in risk-taking behavior, but the neural correlates underlying this effect are not well understood. In this study, participants were given intravenous alcohol or placebo while undergoing functional magnetic resonance imaging (fMRI) and playing a risk-taking game. The game allowed us to examine the neural response to choosing a safe or risky option, anticipating outcome and receiving feedback. We found that alcohol increased risk-taking behavior, particularly among participants who experienced more stimulating effects of alcohol. fMRI scans demonstrated that alcohol increased activation in the striatum to risky compared with safe choices and dampened the neural response to notification of both winning and losing throughout the caudate, thalamus and insula. This study suggests that alcohol may increase risk-taking behavior by both activating brain regions involved in reward when a decision is made, and dampening the response to negative and positive feedback.
Gilman JM, Ramchandani VA, Crouss T, Hommer DW. Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacology. 2012;37 (2) :467-77.Abstract
Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We performed a double-blind, placebo-controlled, randomized crossover alcohol challenge study comparing functional magnetic resonance imaging and subjective response to intravenously administered 6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo between HDs and social drinkers (SDs). During the imaging, we presented emotional cues in order to measure how emotion modulated the effects of alcohol on the brain's reward circuitry. We found that, at equivalent blood alcohol concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol significantly activated the nucleus accumbens in SDs, but not in HDs. Self-reported ratings of intoxication correlated with striatal activation, suggesting that activation may reflect subjective experience of intoxication. Fearful faces significantly activated the amygdala in the SDs only, and this activation was attenuated by alcohol. This study shows that HDs not only experience reduced subjective effects of alcohol, but also demonstrate a blunted response to alcohol in the brain's reward system. Our findings indicate that reduced subjective and neural response to alcohol in HDs may be suggestive of either the development of tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's effects.
Hommer DW, Bjork JM, Gilman JM. Imaging brain response to reward in addictive disorders. Ann N Y Acad Sci. 2011;1216 :50-61.Abstract
We compare the evidence from human neuroimaging studies for and against two of the major hypotheses of how alterations in the brain's reward system underlie addiction. One of these, the impulsivity hypothesis, proposes that addiction is characterized by excessive sensitivity to reward combined with a failure of inhibition. The other, the reward-deficiency hypothesis, proposes that addicted individuals have a reduced response to nondrug rewards that leads them to seek drugs in preference to more socially acceptable goals. Positron emission tomographic (PET) studies of dopamine receptor density and dopamine release strongly support the reward-deficiency hypothesis, while the more recent and numerous functional magnetic resonance imaging (fMRI) studies of goal-directed behavior provide both support and contradiction for each of the hypotheses. Differences in the time scale on which PET and fMRI make measurements probably account for differences in results, at least in part. It is likely that aspects of brain function described by both the impulsivity and reward-deficiency hypotheses contribute to the pathophysiology of addiction.
Gilman JM, Davis MB, Hommer DW. Greater activation in left hemisphere language-related regions during simple judgment tasks among substance-dependent patients in treatment for alcoholism. Alcohol Clin Exp Res. 2010;34 (2) :331-41.Abstract
BACKGROUND: Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive-type tasks. In this study, we compared brain activations of alcohol-dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. METHODS: We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. RESULTS: There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. CONCLUSIONS: Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision-making tasks.
Ciccocioppo R, Gehlert DR, Ryabinin A, Kaur S, Cippitelli A, Thorsell A, Lê AD, Hipskind PA, Hamdouchi C, Lu J, et al. Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond. Alcohol. 2009;43 (7) :491-8.Abstract
This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin 1 receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism.