Daniel J. Fridberg

The impact of processing load on emotion

This event-related fMRI study examined the impact of processing load on the BOLD response to emotional expressions. Participants were presented with composite stimuli consisting of neutral and fearful faces upon which semi-transparent words were superimposed. This manipulation held stimulus-driven features constant across multiple levels of processing load. Participants made either (1) gender discriminations based on the face; (2) case judgments based on the words; or (3) syllable number judgments based on the words. A significant main effect for processing load was revealed in prefrontal cortex, parietal cortex, visual processing areas, and amygdala. Critically, enhanced activity in the amygdala and medial prefrontal cortex seen during gender discriminations was significantly reduced during the linguistic task conditions. A connectivity analysis conducted to investigate theories of cognitive modulation of emotion showed that activity in dorsolateral prefrontal cortex was inversely related to activity in the ventromedial prefrontal cortex. Together, the data suggest that the processing of task-irrelevant emotional information, like neutral information, is subject to the effects of processing load and is under top-down control.

Neural Substrates of Reward Magnitude, Probability, and Risk During a Wheel of Fortune Decision-Making Task

Economic decision-making involves the weighting of magnitude and probability of potential gains/losses. While previous work has examined the neural systems involved in decision-making, there is a need to understand how the parameters associated with decision-making (e.g., magnitude of expected reward, probability of expected reward and risk) modulate activation within these neural systems. In the current fMRI study, we modified the monetary wheel of fortune (WOF) task [Ernst, M., Nelson, E.E., McClure, E.B., Monk, C.S., Munson, S., Eshel, N., et al. (2004). Choice selection and reward anticipation: an fMRI study. Neuropsychologia 42(12), 1585-1597.] to examine in 25 healthy young adults the neural responses to selections of different reward magnitudes, probabilities, or risks. Selection of high, relative to low, reward magnitude increased activity in insula, amygdala, middle and posterior cingulate cortex, and basal ganglia. Selection of low-probability, as opposed to high-probability reward, increased activity in anterior cingulate cortex, as did selection of risky, relative to safe reward. In summary, decision-making that did not involve conflict, as in the magnitude contrast, recruited structures known to support the coding of reward values, and those that integrate motivational and perceptual information for behavioral responses. In contrast, decision-making under conflict, as in the probability and risk contrasts, engaged the dorsal anterior cingulate cortex whose role in conflict monitoring is well established. However, decision-making under conflict failed to activate the structures that track reward values per se. Thus, the presence of conflict in decision-making seemed to significantly alter the pattern of neural responses to simple rewards. In addition, this paradigm further clarifies the functional specialization of the cingulate cortex in processes of decision-making.

Temporal Discounting of Rewards in Patients With Bipolar Disorder and Schizophrenia

Patients with bipolar disorder (BD) and schizophrenia (SZ) often show decision-making deficits in everyday circumstances. A failure to appropriately weigh immediate versus future consequences of choices may contribute to these deficits. We used the delay discounting task in individuals with BD or SZ to investigate their temporal decision making. Twenty-two individuals with BD, 21 individuals with SZ, and 30 healthy individuals completed the delay discounting task along with neuropsychological measures of working memory and cognitive function. Both BD and SZ groups discounted delayed rewards more steeply than did the healthy group even after controlling for current substance use, age, gender, and employment. Hierarchical multiple regression analyses showed that discounting rate was associated with both diagnostic group and working memory or intelligence scores. In each group, working memory or intelligence scores negatively correlated with discounting rate. The results suggest that (a) both BD and SZ groups value smaller, immediate rewards more than larger, delayed rewards compared with the healthy group and (b) working memory or intelligence is related to temporal decision making in individuals with BD or SZ as well as in healthy individuals.

Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans

Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Δ9-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous Δ9-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory ‘oddball’ P300 task). Δ9-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Δ9-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Δ9-THC induced psychotomimetic effects, perceptual alterations, and subjective ‘high’ in a dose-dependent manner. Δ9-THC -induced reductions in P3b amplitude correlated with Δ9-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ9-THC, there were no dose-related effects of Δ9-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Δ9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing.

Cannabis users differ from non-users on measures of personality and schizotypy

Accumulating evidence indicates that cannabis use may be a risk factor for schizophrenia (SZ), and chronic cannabis users score higher than non-users on measures of schizotypal personality traits. The purpose of the present study was to investigate the relations between normal personality, schizotypy, and cannabis use. Sixty-two chronic cannabis users and 45 cannabis-naïve controls completed a measure of normal personality, the NEO-Five Factor Inventory (NEO-FFI), and two measures of schizotypy, the schizotypal personality questionnaire (SPQ) and perceptual aberration scale (PAS). Substance use was assessed using the SCID I alcohol/drug module and a locally developed drug use questionnaire. On the NEO-FFI, users scored higher than controls on openness, but lower on agreeableness and conscientiousness, and endorsed greater schizotypy on the SPQ and PAS. Higher neuroticism predicted greater schizotypy in both groups, and, higher Extraversion predicted lower negative-syndrome schizotypy among users. Finally, duration of cannabis use was positively correlated with scores on the SPQ and PAS among users, suggesting a relation between overall cannabis use chronicity and schizotypy. These data show that cannabis users differ from non-users on dimensions of normal personality and schizotypy, and provide further evidence that cannabis use is associated with increased levels of psychosis-related personality traits.

Brain-derived neurotrophic factor (BDNF) and neurocognitive deficits in people with schizophrenia: A meta-analysis

Studies suggest that the BDNF Val66Met (rs6265) polymorphism is associated with the incidence of schizophrenia and neurocognitive functioning. These associations appear to be however somewhat mixed. We conducted two separate meta-analyses to investigate (1) the association between the Val66Met polymorphism and neurocognition in people with schizophrenia and (2) the association between peripheral expression of BDNF and neurocognitive phenotypes. For the first aim, we identified 12 studies and 67 comparisons of Met allele carriers and Val homozygotes. These comparisons included 1890 people with schizophrenia (men=1465, women=553), of whom 972 were Met allele carriers and 918 were Val homozygotes. For the second aim, we identified five studies and 25 correlations of peripheral BDNF and neurocognitive scores. The meta-analysis for the second aim included 414 people with schizophrenia (men=292, women=170). First, we found non-significant difference between the genotype groups on most neurocognitive domains. Second, correlations between peripheral BDNF and neurocognitive phenotypes were minimal but we obtained significant effects for the reasoning and problem-solving domains; thus, higher levels of BDNF expression corresponded to better performance on reasoning/problem-solving tasks. The meta-analyses did not robustly establish an association between BDNF Val66Met polymorphism and neurocognition in schizophrenia.

Passive exposure to electronic cigarette (e-cigarette) use increases desire for combustible and e-cigarettes in young adult smokers

Background Passive exposure to combustible cigarette use has been shown to act as a cue to increase smoking urge. Given the resemblance of e-cigarettes and other electronic nicotine delivery systems (ENDS) to combustible cigarettes, we examined whether these devices could also act as a cue to increase smoking desire and urges in those passively exposed. Methods Young adult daily smokers (age 18–35 years; N=60) completed subjective ratings before and after exposure to a study confederate drinking bottled water (control cue) and then smoking either a combustible or e-cigarette (active cue). Smoking desire and urge ratings were measured with visual analogue scale items for desire for a regular and an e-cigarette and the Brief Questionnaire of Smoking Urges. Results Passive exposure to both the e-cigarette and combustible cigarette cue significantly increased observers’ ratings of desire and urge to smoke a regular cigarette (all ps<0.05). Exposure to the e-cigarette cue but not the regular cigarette cue also increased desire to smoke an e-cigarette (p<0.01). Conclusions The results provide the first evidence in a controlled setting that electronic cigarette exposure may evoke smoking urges in young adult daily smokers. With replication, these findings may have relevance for ENDS regulation and policy.

Verbal memory intrusions in schizophrenia: Associations with self-reflectivity, symptomatology, and neurocognition

Verbal memory deficits commonly observed among patients with schizophrenia include the tendency to commit intrusion errors (i.e., the incorrect recall of task-irrelevant material). Intrusion errors have been linked to deficits in self-monitoring, increased positive and disorganized symptoms, and poor executive functioning in these individuals, but such associations are inconsistent across studies. Accordingly, the purpose of the present study was to investigate further these relations in patients with schizophrenia. Seventy-nine patients with schizophrenia-spectrum disorders were grouped according to their number of intrusions on a verbal recall task (no intrusions, n=54; two or more intrusions, n=25) and compared on measures of metacognitive self-reflectivity (i.e., the ability to reason about ones own mental states), positive and disorganized symptomatology, and executive functioning. After controlling for overall verbal memory performance, the intrusion group exhibited less self-reflectivity and more disorganized symptoms and performed more poorly on neurocognitive measures sensitive to executive dysfunction, relative to the no-intrusion group. Hierarchical logistic regression controlling for overall verbal memory performance indicated that only self-reflectivity and disorganized symptoms significantly predicted group membership. These data suggest that verbal memory intrusions are linked to deficits in the ability to identify, organize, and reason about ones own thoughts in patients with schizophrenia.

Resting state functional magnetic resonance imaging reveals distinct brain activity in heavy cannabis users - a multi-voxel pattern analysis.

Chronic cannabis use can cause cognitive, perceptual and personality alterations, which are believed to be associated with regional brain changes and possible changes in connectivity between functional regions. This study aims to identify the changes from resting state functional magnetic resonance imaging scans. A two-level multi-voxel pattern analysis was proposed to classify male cannabis users from normal controls. The first level analysis works on a voxel basis and identifies clusters for the input of a second level analysis, which works on the functional connectivity between these regions. We found distinct clusters for male cannabis users in the middle frontal gyrus, precentral gyrus, superior frontal gyrus, posterior cingulate cortex, cerebellum and some other regions. Based on the functional connectivity of these clusters, a high overall accuracy rate of 84–88% in classification accuracy was achieved. High correlations were also found between the overall classification accuracy and Barrett Barrett Impulsiveness Scale factor scores of attention and motor. Our result suggests regional differences in the brains of male cannabis users that span from the cerebellum to the prefrontal cortex, which are associated with differences in functional connectivity.

Effects of working memory load, a history of conduct disorder, and sex on decision making in substance dependent individuals

BACKGROUND Substance dependence and antisocial psychopathology, such as a history of childhood conduct disorder (HCCD), are associated with impulsive or disadvantageous decision making and reduced working memory capacity (WMC). Reducing WMC via a working memory load increases disadvantageous decision making in healthy adults, but no previous studies have examined this effect in young adults with substance dependence and HCCD. METHOD Young adults with substance dependence (SubDep; n=158, 71 female), substance dependence and HCCD (SubDep+HCCD; n=72, 24 female), and control participants (n=152, 84 female) completed a test of decision making (the Iowa Gambling Task; IGT) with or without a concurrent working memory load intended to tax WMC. Outcomes were (i) net advantageous decisions on the IGT, and (ii) preferences for infrequent- versus frequent-punishment decks. RESULTS SubDep+HCCD men made fewer advantageous decisions on the IGT than control men without a load, but there were no group differences among women in that condition. Load was associated with fewer advantageous decisions for SubDep+HCCD women and control men, but not for men or women in the other groups. Participants showed greater preference for infrequent-punishment, advantageous decks under load as well. CONCLUSIONS There are gender differences in the effects of substance dependence, HCCD, and working memory load on decision making on the IGT. Decision making by control men and SubDep+HCCD women suffered the most under load. Load increases preferences for less-frequent punishments, similar to a delay discounting effect. Future research should clarify the cognitive and neural mechanisms underlying these effects.