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Item 501 Maternal PTSD and Child Brain Function During Implicit Emotion Regulation(Cambridge University Press, 2024-04-03) Crum, Kathleen I.; Aloi, Joseph; LeFevre, Katherine; McCormack, Kennedy; Hulvershorn, Leslie; Psychiatry, School of MedicineOBJECTIVES/GOALS: Maternal mental health, such as post-traumatic stress disorder (PTSD), is closely linked to child mental health. PTSD in mothers is associated with their children’s emotional responses. We examined associations between maternal PTSD and child brain function during emotion regulation. METHODS/STUDY POPULATION: Eight children ages 10-12 years, whose mothers had trauma histories, performed the Emotional N-Back task during functional MRI scanning. Mothers and children each reported on their trauma exposure and PTSD symptom severity. BOLD response to fearful faces during the Emotional N-Back was extracted from two specific brain regions of interest, amygdala and anterior cingulate cortex. These regions are involved in emotional response and attentional control, which are processes intrinsic to emotion regulation. An independent samples t-test was conducted on children’s BOLD response to fearful faces, with maternal PTSD symptom severity (high, low) as the independent variable. A parallel analysis was conducted with child PTSD symptom severity (high, low) as the independent variable. RESULTS/ANTICIPATED RESULTS: We found a main effect of maternal PTSD within brain regions of relevance to implicit emotion regulation. Compared to children whose mothers reported low PTSD symptom severity (n=4), children whose mothers reported high PTSD symptom severity (n=4) showed greater responsiveness to fearful faces in anterior cingulate cortex (t=2.04, p=.09,d=1.44) and amygdala (t=2.44, p=.05, d=1.72) at trending significance. A parallel analysis with child PTSD symptom severity showed no differences in brain function by this factor (ps=.55-.61). DISCUSSION/SIGNIFICANCE: Our pilot study is the first, to our knowledge, to examine associations between maternal PTSD and brain function during emotion regulation in their children. This study lays a foundation for future work; our goal is to explore dysfunction in emotion regulation neurocircuitry as one mechanism linking maternal PTSD to their children’s mental health.Item Alcohol Use Disorder and Cannabis Use Disorder Symptomatology in Adolescents and Aggression: Associations With Recruitment of Neural Regions Implicated in Retaliation(Elsevier, 2021) Blair, R. James R.; Bajaj, Sahil; Sherer, Noah; Bashford-Largo, Johannah; Zhang, Ru; Aloi, Joseph; Hammond, Chris; Lukoff, Jennie; Schwartz, Amanda; Elowsky, Jaimie; Tyler, Patrick; Filbey, Francesca M.; Dobbertin, Matthew; Blair, Karina S.; Psychiatry, School of MedicineBackground: Alcohol and cannabis are commonly used by adolescents in the United States. Both alcohol use disorder (AUD) and cannabis use disorder (CUD) have been associated with an increased risk of aggression. One form of aggression seen during retaliation is reactive aggression to social provocation. This study investigated the association between AUD and CUD symptom severity and recruitment of neural regions implicated in retaliation. Methods: In this study, 102 youths aged 13-18 years (67 male; 84 in residential care) completed self-report measures of aggression-related constructs and participated in a retaliation task during functional magnetic resonance imaging to investigate the association between relative severity of AUD/CUD and atypical recruitment of regions implicated in retaliation. Results: AUD Identification Test scores were positively associated with irritability and reactive aggression scores. CUD Identification Test scores were positively associated with callous-unemotional traits and both proactive and reactive aggression scores. In functional magnetic resonance imaging analyses, only AUD Identification Test (not CUD Identification Test) scores were associated with an exaggerated recruitment of regions implicated in retaliation (dorsomedial frontal, anterior insula cortices, caudate, and, to a lesser extent, periaqueductal gray). Conclusions: These data suggest that relative severity of AUD is associated with a disinhibited, exaggerated retaliation response that relates to an increased risk for reactive aggression. Similar findings were not related to severity of CUD.Item Alcohol Use Disorder and Cannabis Use Disorder symptomatology in adolescents is associated with dysfunction in neural processing of future events(Wiley, 2021) Aloi, Joseph; Blair, Karina S.; Meffert, Harma; White, Stuart F.; Hwang, Soonjo; Tyler, Patrick M.; Crum, Kathleen I.; Thornton, Laura C.; Mobley, Alita; Killanin, Abraham D.; Filbey, Francesca M.; Pope, Kayla; Blair, R. James; Psychiatry, School of MedicineTwo of the most commonly used substances by adolescents in the United States are cannabis and alcohol. Cannabis use disorder (CUD) and alcohol use disorder (AUD) are associated with impairments in decision-making processes. One mechanism for impaired decision-making in these individuals is thought to be an inability to adequately represent future events during decision-making. In the current study involving 112 adolescents, we used a comparative optimism task to examine the relationship between relative severity of CUD/AUD (as indexed by the CUD/AUD Identification Tests [CUDIT/AUDIT]) and atypical function within neural systems underlying affect-based neural represenation future events. Greater CUDIT scores were negatively related to responses within subgenual anterior and posterior cingulate cortex when processing high-intensity potential future positive and negative events. There was also a particularly marked negative relationship between CUD symptoms and blood oxygen level-dependent (BOLD) responses within visual and premotor cortices to high-intensity, negatively valenced potential future events. However, AUD symptom severity was not associated with dysfunction within these brain regions. These data indicate that relative risk/severity of CUD is associated with reduced responsiveness to future high-intensity events. This may impair decision-making where future significant consequences should guide response choice.Item Altered amygdala-cortical connectivity in individuals with Cannabis use disorder(Sage, 2021) Aloi, Joseph; McCusker, Marie C.; Lew, Brandon J.; Schantell, Mikki; Eastman, Jacob A.; Frenzel, Michaela R.; Wilson, Tony W.; Psychiatry, School of MedicineBackground: Cannabis is one of the most commonly used substances in the United States. Prior literature using task-based functional magnetic resonance imaging (fMRI) has identified that individuals with Cannabis use disorder (CUD) show impairments in emotion processing circuitry. However, whether the functional networks involving these regions are also altered in CUD remains poorly understood. Aims: Investigate changes in resting-state functional connectivity (rsFC) in regions related to emotional processing in CUD. Methods: Sixty-two participants completed resting-state fMRI, including 21 with CUD, 20 with histories of illicit substance use but no current CUD diagnosis, and 21 with no history of illicit substance use. Whole-brain seed-based connectivity analyses were performed and one-way analyses of covariance (ANCOVAs) were conducted to detect group differences in the bilateral amygdalae, hippocampi, and the anterior and posterior cingulate cortices. Results: The CUD group exhibited significant reductions in rsFC between the amygdala and the cuneus, paracentral lobule, and supplementary motor area, and between the cingulate cortices and the occipital and temporal lobes. There were no significant group differences in hippocampal functional connectivity. In addition, CUD symptom counts based on the Structured Clinical Interview for DSM-5 (SCID) and the Cannabis Use Disorders Identification Test (CUDIT) significantly correlated with multiple connectivity metrics. Conclusion: These data expand on emerging literature indicating that CUD is associated with dysfunction in the neural circuits underlying emotion processing. Dysfunction in emotion processing circuits may play a role in the behavioral impairments seen in emotion processing tasks in individuals with CUD, and the severity of CUD symptoms appears to be directly related to the degree of dysfunction in these circuits.Item Correction: Neural correlates of automatic emotion regulation and their association with suicidal ideation in adolescents during the first 90-days of residential care(Springer Nature, 2024-02-19) Dobbertin, Matthew; Blair, Karina S.; Aloi, Joseph; Bajaj, Sahil; Bashford-Largo, Johannah; Mathur, Avantika; Zhang, Ru; Carollo, Erin; Schwartz, Amanda; Elowsky, Jaimie; Ringle, J. L.; Tyler, Patrick; Blair, R. James; Psychiatry, School of MedicineCorrection to: Translational Psychiatry 10.1038/s41398-023-02723-9, published online 23 January 2024 In this article, the affiliation details for Author Sahil Bajaj were incorrectly given as “Department of Cancer Systems Imaging, MD Anderson Center, South Campus Research Bldg, Houston, TX, USA” but should have been “Department of Cancer Systems Imaging, MD Anderson Cancer Center, Houston, TX, USA” The original article has been corrected.Item Dysfunction in differential reward-punishment responsiveness in conduct disorder relates to severity of callous-unemotional traits but not irritability(Cambridge University Press, 2023) Zhang, Ru; Aloi, Joseph; Bajaj, Sahil; Bashford-Largo, Johannah; Lukoff, Jennie; Schwartz, Amanda; Elowsky, Jamie; Dobbertin, Matthew; Blair, Karina S.; Blair, R. James R.; Psychiatry, School of MedicineBackground: Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD. Methods: The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment. Results: Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices. Conclusions: The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.Item Evaluating Instrumental Learning and Striatal-cortical Functional Connectivity in Adolescent Alcohol and Cannabis Use(Wiley, 2023) Hubbard, Nicholas A.; Miller, Kevin B.; Aloi, Joseph; Bajaj, Sahil; Wakabayashi, Ken T.; Blair, R. James R.; Psychiatry, School of MedicineAdolescence is a vulnerable time for the acquisition of substance use disorders, potentially relating to ongoing development of neural circuits supporting instrumental learning. Striatal-cortical circuits undergo dynamic changes during instrumental learning and are implicated in contemporary addiction theory. Human studies have not yet investigated these dynamic changes in relation to adolescent substance use. Here, functional magnetic resonance imaging was used while 135 adolescents without (AUD-CUDLow ) and with significant alcohol (AUDHigh ) or cannabis use disorder symptoms (CUDHigh ) performed an instrumental learning task. We assessed how cumulative experience with instrumental cues altered cue selection preferences and functional connectivity strength between reward-sensitive striatal and cortical regions. Adolescents in AUDHigh and CUDHigh groups were slower in learning to select optimal instrumental cues relative to AUD-CUDLow adolescents. The relatively fast learning observed for AUD-CUDLow adolescents coincided with stronger functional connectivity between striatal and frontoparietal regions during early relative to later periods of task experience, whereas the slower learning for the CUDHigh group coincided with the opposite pattern. The AUDHigh group not only exhibited slower learning but also produced more instrumental choice errors relative to AUD-CUDLow adolescents. For the AUDHigh group, Bayesian analyses evidenced moderate support for no experience-related changes in striatal-frontoparietal connectivity strength during the task. Findings suggest that adolescent cannabis use is related to slowed instrumental learning and delays in peak functional connectivity strength between the striatal-frontoparietal regions that support this learning, whereas adolescent alcohol use may be more closely linked to broader impairments in instrumental learning and a general depression of the neural circuits supporting it.Item Family history of substance use disorder and parental impulsivity are differentially associated with neural responses during risky decision-making(Frontiers Media, 2023-06-21) Aloi, Joseph; Kwon, Elizabeth; Hummer, Tom A.; Crum, Kathleen I.; Shah, Nikhil; Pratt, Lauren; Aalsma, Matthew C.; Finn, Peter; Nurnberger, John; Hulvershorn, Leslie A.; Psychiatry, School of MedicineBackground: Risky decision-making is associated with the development of substance use behaviors during adolescence. Although prior work has investigated risky decision-making in adolescents at familial high risk for developing substance use disorders (SUDs), little research has controlled for the presence of co-morbid externalizing disorders (EDs). Additionally, few studies have investigated the role of parental impulsivity in offspring neurobiology associated with risky decision-making. Methods: One-hundred twenty-five children (28 healthy controls, 47 psychiatric controls with EDs without a familial history of SUD, and 50 high-risk children with co-morbid EDs with a familial history of SUD) participated in the Balloon Analog Risk Task while undergoing functional magnetic resonance imaging. Impulsivity for parents and children was measured using the UPPS-P Impulsive Behavior Scale. Results: We found that individuals in the psychiatric control group showed greater activation, as chances of balloon explosion increased, while making choices, relative to the healthy control and high-risk groups in the rostral anterior cingulate cortex (rACC) and lateral orbitofrontal cortex (lOFC). We also found a positive association between greater activation and parental impulsivity in these regions. However, within rACC, this relationship was moderated by group, such that there was a positive relationship between activation and parental impulsivity in the HC group, but an inverse relationship in the HR group. Conclusions: These findings suggest that there are key differences in the neurobiology underlying risky decision-making in individuals with EDs with and without a familial history of SUD. The current findings build on existing models of neurobiological factors influencing addiction risk by integrating parental factors. This work paves the way for more precise risk models in which to test preventive interventions.Item Individual associations of adolescent alcohol use disorder versus cannabis use disorder symptoms in neural prediction error signaling and the response to novelty(Elsevier, 2021-04) Aloi, Joseph; Crum, Kathleen I.; Blair, Karina S.; Zhang, Ru; Bashford-Largo, Johannah; Bajaj, Sahil; Schwartz, Amanda; Carollo, Erin; Hwang, Soonjo; Leiker, Emily; Filbey, Francesca M.; Averbeck, Bruno B.; Dobbertin, Matthew; Blair, R. James R.; Psychiatry, School of MedicineTwo of the most commonly used illegal substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with poorer decision-making in adolescents. In adolescents, level of AUD symptomatology has been negatively associated with striatal reward responsivity. However, little work has explored the relationship with striatal reward prediction error (RPE) representation and the extent to which any augmentation of RPE by novel stimuli is impacted. One-hundred fifty-one adolescents participated in the Novelty Task while undergoing functional magnetic resonance imaging (fMRI). In this task, participants learn to choose novel or non-novel stimuli to gain monetary reward. Level of AUD symptomatology was negatively associated with both optimal decision-making and BOLD response modulation by RPE within striatum and regions of prefrontal cortex. The neural alterations in RPE representation were particularly pronounced when participants were exploring novel stimuli. Level of CUD symptomatology moderated the relationship between novelty propensity and RPE representation within inferior parietal lobule and dorsomedial prefrontal cortex. These data expand on an emerging literature investigating individual associations of AUD symptomatology levels versus CUD symptomatology levels and RPE representation during reinforcement processing and provide insight on the role of neuro-computational processes underlying reinforcement learning/decision-making in adolescents.Item Latent profiles of substance use, early life stress, and attention/externalizing problems and their association with neural correlates of reinforcement learning in adolescents(Cambridge University Press, 2023) Crum, Kathleen I.; Aloi, Joseph; Blair, Karina S.; Bashford-Largo, Johannah; Bajaj, Sahil; Zhang, Ru; Hwang, Soonjo; Schwartz, Amanda; Elowsky, Jaimie; Filbey, Francesca M.; Dobbertin, Matthew; Blair, R. James; Psychiatry, School of MedicineBackground: Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other. Methods: In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13-18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations. Results: In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons). Conclusions: Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.