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Item Advanced Meditation Alters Resting-State Brain Network Connectivity Correlating With Improved Mindfulness(Frontiers Media, 2021-11) Vishnubhotla, Ramana V.; Radhakrishnan, Rupa; Kveraga, Kestas; Deardorff, Rachael; Ram, Chithra; Pawale, Dhanashri; Wu, Yu-Chien; Renschler, Janelle; Subramaniam, Balachundhar; Sadhasivam, Senthilkumar; Radiology and Imaging Sciences, School of MedicinePurpose: The purpose of this study was to investigate the effect of an intensive 8-day Samyama meditation program on the brain functional connectivity using resting-state functional MRI (rs-fMRI). Methods: Thirteen Samyama program participants (meditators) and 4 controls underwent fMRI brain scans before and after the 8-day residential meditation program. Subjects underwent fMRI with a blood oxygen level dependent (BOLD) contrast at rest and during focused breathing. Changes in network connectivity before and after Samyama program were evaluated. In addition, validated psychological metrics were correlated with changes in functional connectivity. Results: Meditators showed significantly increased network connectivity between the salience network (SN) and default mode network (DMN) after the Samyama program (p < 0.01). Increased connectivity within the SN correlated with an improvement in self-reported mindfulness scores (p < 0.01). Conclusion: Samyama, an intensive silent meditation program, favorably increased the resting-state functional connectivity between the salience and default mode networks. During focused breath watching, meditators had lower intra-network connectivity in specific networks. Furthermore, increased intra-network connectivity correlated with improved self-reported mindfulness after Samyama.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 Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking(Elsevier, 2015-08-30) Weafer, Jessica; Dzemidzic, Mario; Eiler, William J. A. II; Oberlin, Brandon G.; Wang, Yang; Kareken, David A.; Department of Neurology, IU School of MedicineTrait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n = 117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), as well as measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n = 40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems.Item Atypical Cortical Activation during Risky Decision-making in Disruptive Behavior Disordered Youth with Histories of Suicidal Ideation(Elsevier, 2020) Dir, Allyson L.; Allebach, Christian L.; Hummer, Tom A.; Adams, Zachary; Aalsma, Matthew C.; Finn, Peter R.; Nurnberger, John I.; Hulvershorn, Leslie A.; Psychiatry, School of MedicineBackground: Suicidality is a leading cause of death among adolescents. In addition to other psychiatric conditions, youths with attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) are at heightened risk for suicide. Decision-making deficits are a hallmark symptom of ADHD and DBDs and are also implicated in suicidal behavior. We examined behavioral and neural differences in decision making among youths with ADHD and DBDs with (SI+) and without (SI-) histories of suicidal ideation. Methods: The Balloon Analog Risk Task, a risky decision-making task, was completed by 57 youths with ADHD and DBDs (38% SI+) during functional magnetic resonance imaging. Mean stop wager (mean wager at which youths bank money) was the primary measure of risk taking. We conducted whole-brain and region-of-interest analyses in the anterior cingulate cortex and orbitofrontal cortex (OFC) during choice (win vs. inflate) and outcome (inflate vs. explode) contrasts using parametric modulators accounting for probability of balloon explosion. Results: There were no differences between SI+ and SI- youths in Balloon Analog Risk Task performance. SI+ youths showed decreasing activation in the right medial frontal gyrus when choosing inflate as explosion probability increased compared with SI- youths. During explosions, SI- youths showed increasing activation in the left OFC as explosions became more likely. SI+ showed increasing left medial OFC activity in response to inflations as explosion probability increased. Conclusions: SI+ youths may show heightened sensitivity to immediate reward and decreased sensitivity to potential loss as evidenced by medial frontal gyrus activity. OFC findings suggest that SI+ youths may be drawn to reward even when there is high probability of loss.Item Brain Activation Patterns during Visual Scene Encoding and Recognition fMRI Tasks in Early Phase Psychosis(Office of the Vice Chancellor for Research, 2015-04-17) Ayoubi, Nawead Z.; Mehdiyoun, Nicole F.; Yung, Matthew G.; Hummer, Tom; Francis, Michael M.; Breier, AlanSchizophrenia is a chronic and disabling illness that is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning. Cognitive dysfunction is a core facet of schizophrenia with deficits occurring in areas of abstraction, attention, language, and memory. Episodic memory (EM) is a cognitive domain that has been shown to be impaired in schizophrenia. EM combines event-specific autobiographical experiences and information regarding the context in which events took place. Patients with schizophrenia may exhibit broad impairments in EM, with deficits occurring during encoding and retrieval with both visual and verbal tasks. There are a number of inconsistencies in the EM fMRI literature and indicating a need for first episode psychosis (FEP) versus chronic phase schizophrenia research. FEP have fewer and less severe medical comorbidities, shorter durations of antipsychotic treatment exposure, and lower severity of illness, all of which can impact data interpretation. In this study, brain activation patterns were assessed during performance of visual scene encoding and recognition fMRI tasks in FEP patients and healthy control subjects. It is hypothesized that FEP patients would demonstrate decreased activation during encoding and recognition in the main areas that mediate EM function, namely the hippocampus, prefrontal, and parietal cortices. Within the FEP group correlations can be determined by comparing brain activation patterns with cognition (Brief Assessment of Cognition in Schizophrenia [BACS]) and symptom (Positive and Negative Syndrome Scale [PANSS]) outcome measures. Results indicate that during the encoding task FEP exhibited significantly lower activation in the hippocampus and fusiform gyrus when compared to controls. During the recognition task FEP showed a significantly weaker cortical response in the posterior cingulate cortex, the precuneus, and the left middle temporal cortex when compared to controls. These results demonstrate a pattern of alteration in hippocampal, parietal, and temporal activity during EM processes in FEP. Altered hippocampal response in FEP may reflect dysfunctional binding mechanisms and less efficient encoding.Item Brain Responses to Sugar: Implications for Alcohol Use Disorder and Obesity(2024-05) Alessi, Jonathan P.; Yoder, Karmen K.; Kareken, David A.; Džemidžić, Mario; Considine, Robert V.; Harezlak, JaroslawObesity and alcohol use may together account for 640,000 adult deaths each year in the United States. In both cases, overconsumption drives untoward effects. Alcohol use and obesity also both relate to sweet liking, as sugar consumption is consistently linked to weight gain and intense sweet liking has been linked to an inherited risk for alcohol use disorder (AUD). However, the neural underpinnings of these associations are largely unknown. Thus, we used sugar-sweetened water administration during functional magnetic resonance imaging (fMRI) to probe these relationships in two studies. In the first, we tested the relationship between a known AUD risk factor, subjective response to alcohol, and the brain response to both sucrose and monetary reward in 140 young adults. We found a significant positive correlation between the enjoyable component of subjective responses to a standardized intravenous alcohol exposure and activation to high-concentration sucrose (but not monetary reward) in the right dorsal anterior insula and the supplementary motor area, supporting a role for these regions in AUD risk. In the second study, we investigated the neural mechanisms of sweet liking decreases following bariatric surgery, the most effective obesity treatment. Here, we evaluated the change in brain activation to sucrose in 24 women before (BMI 47.0 + 6.9 kg/m2) and 21 women after (BMI 37.6 + 6.5 kg/m2) bariatric surgery and compared the pre- and post-surgical activation patterns to those of 21 normal to overweight (BMI 23.5 + 2.5 kg/m2) control participants. Brain activation did not differ between controls and surgery participants at either time point. However, activation to sucrose in reward, but not sensory, regions decreased significantly after surgery, consistent with reduced drive to consume sweet foods. Together, these studies highlight the utility of quantifying brain responses to sweet taste as a method to understand the mechanisms underlying overconsumptive behavior.Item Childhood neglect is associated with alterations in neural prediction error signaling and the response to novelty(Cambridge University Press, 2024-10-24) Aloi, Joseph; Crum, Kathleen I.; Blair, Karina S.; Zhang, Ru; Bashford-Largo, Johannah; Bajaj, Sahil; Hwang, Soonjo; Averbeck, Bruno B.; Tottenham, Nim; Dobbertin, Matthew; Blair, R. James R.; Psychiatry, School of MedicineBackground: One in eight children experience early life stress (ELS), which increases risk for psychopathology. ELS, particularly neglect, has been associated with reduced responsivity to reward. However, little work has investigated the computational specifics of this disrupted reward response - particularly with respect to the neural response to Reward Prediction Errors (RPE) - a critical signal for successful instrumental learning - and the extent to which they are augmented to novel stimuli. The goal of the current study was to investigate the associations of abuse and neglect, and neural representation of RPE to novel and non-novel stimuli. Methods: One hundred and seventy-eight participants (aged 10-18, M = 14.9, s.d. = 2.38) engaged in the Novelty task while undergoing functional magnetic resonance imaging. In this task, participants learn to choose novel or non-novel stimuli to win monetary rewards varying from $0 to $0.30 per trial. Levels of abuse and neglect were measured using the Childhood Trauma Questionnaire. Results: Adolescents exposed to high levels of neglect showed reduced RPE-modulated blood oxygenation level dependent response within medial and lateral frontal cortices particularly when exploring novel stimuli (p < 0.05, corrected for multiple comparisons) relative to adolescents exposed to lower levels of neglect. Conclusions: These data expand on previous work by indicating that neglect, but not abuse, is associated with impairments in neural RPE representation within medial and lateral frontal cortices. However, there was no association between neglect and behavioral impairments on the Novelty task, suggesting that these neural differences do not necessarily translate into behavioral differences within the context of the Novelty task.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 Effect of Electro-Acupuncture and Moxibustion on Brain Connectivity in Patients with Crohn’s Disease: A Resting-State fMRI Study(Frontiers Media, 2017-11-17) Bao, Chunhui; Wang, Di; Liu, Peng; Shi, Yin; Jin, Xiaoming; Wu, Luyi; Zeng, Xiaoqing; Zhang, Jianye; Liu, Huirong; Wu, Huangan; Anatomy and Cell Biology, School of MedicineAcupuncture and moxibustion have been shown to be effective in treating Crohn’s disease (CD), but their therapeutic mechanisms remain unclear. Here we compared brain responses to either electro-acupuncture or moxibustion treatment in CD patients experiencing remission. A total of 65 patients were randomly divided into an electro-acupuncture group (n = 32) or a moxibustion group (n = 33), and treated for 12 weeks. Eighteen patients in the electro-acupuncture group and 20 patients in the moxibustion group underwent resting-state functional magnetic resonance imaging at baseline and after treatment. Seed-based analysis was used to compare the resting-state functional connectivity (rsFC) between bilateral hippocampus and other brain regions before and after the treatments, as well as between the two groups. The CD activity index (CDAI) and inflammatory bowel disease questionnaire (IBDQ) were used to evaluate disease severity and patient quality of life. Electro-acupuncture and moxibustion both significantly reduced CDAI values and increased IBDQ scores. In the electro-acupuncture group, the rsFC values between bilateral hippocampus and anterior middle cingulate cortex (MCC) and insula were significantly increased, and the changes were negatively correlated with the CDAI scores. In the moxibustion group, the rsFC values between bilateral hippocampus and precuneus as well as inferior parietal lobe (IPC) were significantly elevated, and the changes were negatively correlated with the CDAI scores. We conclude that the therapeutic effects of electro-acupuncture and moxibustion on CD may involve the differently modulating brain homeostatic afferent processing network and default mode network (DMN), respectively.