Department of Psychology

Unexpected events are part of everyday experience. They come in several varieties-action errors, unexpected action outcomes, and unexpected perceptual events-and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events; links the literatures on motor inhibition, performance monitoring, attention, and working memory; and is relevant for understanding clinical symptoms of distractibility and mental inflexibility.

Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence. The capture, sequencing, and analysis of all variants in 16 CHRN genes (CHRNA1-7, 9, 10, CHRNB1-4, CHRND, CHRNG, CHRNE) were performed independently for each subject in each sample. Sequencing reads were aligned to the human reference sequence using BWA prior to variant calling with the Genome Analysis ToolKit (GATK). Low frequency variants (minor allele frequency < 0.05) were analyzed using SKAT-O and C-alpha to examine the distribution of rare variants among cases and controls. In our larger sample, the region containing the CHRNA6/CHRNB3 gene cluster was significantly associated with disease status using both SKAT-O and C-alpha (unadjusted p values <0.05). More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. These data support a role for genetic variants in CHRN genes and antisocial drug behaviors.

Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-related economic impacts. We utilized the longitudinal Adolescent Brain Cognitive Development Study to understand how family- and neighborhood-level socioeconomic disadvantage relate to disease burden, family communication, and preventative responses to the pandemic in over 6,000 youth-caregiver dyads. Data were collected at three timepoints (May-August 2020). Here, we show that both family- and neighborhood-level disadvantage were associated with caregivers' reports of greater family COVID-19 disease burden, less perceived exposure risk, more frequent caregiver-youth conversations about COVID-19 risk/prevention and reassurance, and greater youth preventative behaviors. Families with more socioeconomic disadvantage may be adaptively incorporating more protective strategies to reduce emotional distress and likelihood of COVID-19 infection. The results highlight the importance of caregiver-youth communication and disease-preventative practices for buffering the economic and disease burdens of COVID-19, along with policies and programs that reduce these burdens for families with socioeconomic disadvantage.

Aims: This study explored whether the density of family history (FH) of substance use disorders relates to post-treatment substance use outcomes in adolescents, with the primary aim of determining whether FH exerts a relatively stronger influence on longer-term outcomes. Method: The present investigation examined adolescents (ages 12-18, n= 366) from two independent samples who were treated for alcohol/substance use disorder (ASUD) and re-assessed during the eight years following treatment with identical methodology. Primary substance use outcomes were assessed at 1, 2, 4, 6, and 8 years post-treatment and included total drinks, days using marijuana, and days using other drugs. Results: In hierarchical linear models there were significant FH density × linear time interactions for total drinks (z= 12.75, p< 0.001) and marijuana use days (z= 4.39, p<. 0.001); greater FH density predicted more total drinks and more marijuana use days, with both associations becoming stronger over time. The increasing linkage between FH and other drug use was not significant over time. Conclusions: Findings are consistent with previous research indicating that the risk associated with FH increases over time, especially in relation to quantity/frequency measures of alcohol and marijuana use. By extending these findings to an adolescent clinical sample, the current study highlights that FH density of alcohol and drug dependence is a risk factor for poorer long-term outcomes for adolescent-onset ASUD youth as they transition into adulthood. Future work should explore the mechanisms underlying greater post-treatment substance use for adolescents/young adults with greater FH density.

Three experiments investigate how self-generated explanation influences children's causal learning. Five-year-olds (N = 114) observed data consistent with two hypotheses and were prompted to explain or to report each observation. In Study 1, when making novel generalizations, explainers were more likely to favor the hypothesis that accounted for more observations. In Study 2, explainers favored a hypothesis that was consistent with prior knowledge. Study 3 pitted a hypothesis that accounted for more observations against a hypothesis consistent with prior knowledge. Explainers were more likely to base generalizations on prior knowledge. Findings suggest that attempts to explain drive children to evaluate hypotheses using features of "good" explanations, or those supporting generalizations with broad scope, as informed by children's prior knowledge and observations.

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A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse.

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Externalizing problems (EP), including rule-breaking, aggression, and criminal involvement, are highly prevalent during adolescence, but the adult outcomes of adolescents exhibiting EP are characterized by heterogeneity. Although many youths' EP subside after adolescence, others' persists into adulthood. Characterizing the development of severe EP is essential to prevention and intervention efforts. Multiple predictors of adult antisocial personality disorder (ASPD) and legal outcomes of a large sample (N = 1205) of clinically- or legally-ascertained adolescents (ages 12-19 years) with severe EP were examined. Many psychosocial predictors hypothesized to predict persistence of EP demonstrated zero-order associations with adult outcomes, but accounted for little unique variation after accounting for baseline conduct disorder symptoms (CD) and demographic factors. Baseline measures of intelligence, which explained independent variation in legal outcomes, provided the only consistent exception to this pattern, though future work is needed to parse these effects from those of socioeconomic factors. CD severity during adolescence is a parsimonious index of liability for persistence of EP into adulthood that explains outcome variance above and beyond all other demographic and psychosocial predictors in this sample.

Most studies that focus on understanding how top-down knowledge influences behavior attempt to manipulate either 'attention' or 'expectation' and often use the terms interchangeably. However, having expectations about statistical regularities in the environment and the act of willfully allocating attention to a subset of relevant sensory inputs are logically distinct processes that could, in principle, rely on similar neural mechanisms and influence information processing at the same stages. In support of this framework, several recent studies attempted to isolate expectation from attention, and advanced the idea that expectation and attention both modulate early sensory processing. Here, we argue that there is currently insufficient empirical evidence to support this conclusion, because previous studies have not fully isolated the effects of expectation and attention. Instead, most prior studies manipulated the relevance of different sensory features, and as a result, few existing findings speak directly to the potentially separable influences of expectation and attention on early sensory processing. Indeed, recent studies that attempt to more strictly isolate expectation and attention suggest that expectation has little influence on early sensory responses and primarily influences later 'decisional' stages of information processing.