73 results on '"Bebko G"'
Search Results
2. Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth
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Bertocci, M A, Bebko, G, Versace, A, Fournier, J C, Iyengar, S, Olino, T, Bonar, L, Almeida, J R C, Perlman, S B, Schirda, C, Travis, M J, Gill, M K, Diwadkar, V A, Forbes, E E, Sunshine, J L, Holland, S K, Kowatch, R A, Birmaher, B, Axelson, D, Horwitz, S M, Frazier, T W, Arnold, L E, Fristad, M A, Youngstrom, E A, Findling, R L, and Phillips, M L
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- 2016
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3. Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder
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Manelis, A., Ladouceur, C. D., Graur, S., Monk, K., Bonar, L. K., Hickey, M. B., Dwojak, A. C., Axelson, D., Goldstein, B. I., Goldstein, T. R., Bebko, G., Bertocci, M. A., Gill, M. K., Birmaher, B., and Phillips, M. L.
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- 2016
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4. Behavioral and emotional dysregulation trajectories marked by prefrontal–amygdala function in symptomatic youth
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Bertocci, M. A., Bebko, G., Olino, T., Fournier, J., Hinze, A. K., Bonar, L., Almeida, J. R. C., Perlman, S. B., Versace, A., Travis, M., Gill, M. K., Demeter, C., Diwadkar, V. A., White, R., Schirda, C., Sunshine, J. L., Arnold, L. E., Holland, S. K., Kowatch, R. A., Birmaher, B., Axelson, D., Youngstrom, E. A., Findling, R. L., Horwitz, S. M., Fristad, M. A., and Phillips, M. L.
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- 2014
5. Abnormal anterior cingulate cortical activity during emotional n-back task performance distinguishes bipolar from unipolar depressed females
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Bertocci, M. A., Bebko, G. M., Mullin, B. C., Langenecker, S. A., Ladouceur, C. D., Almeida, J. R. C., and Phillips, M. L.
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- 2012
6. Predicting anxiety from wholebrain activity patterns to emotional faces in young adults: a machine learning approach
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Portugal, L., Schrouff, J., Stiffler, R., Bertocci, M., Bebko, G., Chase, H., Lockovitch, J., Aslam, H., Graur, S., Greenberg, T., Pereira, M., Oliveira, L., Phillips, M., and Mourão-Miranda, J.
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Adult ,Male ,Brain Mapping ,Adolescent ,Emotions ,Brain ,Regular Article ,Anxiety ,lcsh:Computer applications to medicine. Medical informatics ,Magnetic Resonance Imaging ,lcsh:RC346-429 ,Facial Expression ,Machine Learning ,Young Adult ,Humans ,lcsh:R858-859.7 ,Female ,Facial Recognition ,lcsh:Neurology. Diseases of the nervous system - Abstract
Background: It is becoming increasingly clear that pathophysiological processes underlying psychiatric disorders categories are heterogeneous on many levels, including symptoms, disease course, comorbidity and biological underpinnings. This heterogeneity poses challenges for identifying biological markers associated with dimensions of symptoms and behaviour that could provide targets to guide treatment choice and novel treatment. In response, the research domain criteria (RDoC) (Insel et al., 2010) was developed to advocate a dimensional approach which omits any disease definitions, disorder thresholds, or cut-points for various levels of psychopathology to understanding the pathophysiological processes underlying psychiatry disorders. In the present study we aimed to apply pattern regression analysis to identify brain signatures during dynamic emotional face processing that are predictive of anxiety and depression symptoms in a continuum that ranges from normal to pathological levels, cutting across categorically-defined diagnoses. Methods: The sample was composed of one-hundred and fifty-four young adults (mean age=21.6 and s.d.=2.0, 103 females) consisting of eighty-two young adults seeking treatment for psychological distress that cut across categorically-defined diagnoses and 72 matched healthy young adults. Participants performed a dynamic face task involving fearful, angry and happy faces (and geometric shapes) while undergoing functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Gaussian Process Regression (GPR) implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Predicted and actual clinical scores were compared using Pearson's correlation coefficient (r) and normalized mean squared error (MSE) to evaluate the models' performance. Permutation test was applied to estimate significance levels. Results: GPR identified patterns of neural activity to dynamic emotional face processing predictive of self-report anxiety in the whole sample, which covered a continuum that ranged from healthy to different levels of distress, including subthreshold to fully-syndromal psychiatric diagnoses. Results were significant using two different cross validation strategies (two-fold: r=0.28 (p-value=0.001), MSE=4.47 (p-value=0.001) and five fold r=0.28 (p-value=0.002), MSE=4.62 (p-value=0.003). The contributions of individual regions to the predictive model were very small, demonstrating that predictions were based on the overall pattern rather than on a small combination of regions. Conclusions: These findings represent early evidence that neuroimaging techniques may inform clinical assessment of young adults irrespective of diagnoses by allowing accurate and objective quantitative estimation of psychopathology. Keywords: RDoC, Anxiety, Depression, fMRI, Pattern recognition, Pattern regression analysis, Machine learning, Faces, MVPA
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- 2019
7. Mediation by anxiety of the relationship between amygdala activity during emotion processing and poor quality of life in young adults
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Greenberg, T, primary, Bertocci, M A, additional, Chase, H W, additional, Stiffler, R, additional, Aslam, H A, additional, Graur, S, additional, Bebko, G, additional, Lockovich, J C, additional, and Phillips, M L, additional
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- 2017
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8. A pathway linking reward circuitry, impulsive sensation-seeking and risky decision-making in young adults: identifying neural markers for new interventions
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Chase, H W, primary, Fournier, J C, additional, Bertocci, M A, additional, Greenberg, T, additional, Aslam, H, additional, Stiffler, R, additional, Lockovich, J, additional, Graur, S, additional, Bebko, G, additional, Forbes, E E, additional, and Phillips, M L, additional
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- 2017
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9. Reward-related neural activity and structure predict future substance use in dysregulated youth
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Bertocci, M. A., primary, Bebko, G., additional, Versace, A., additional, Iyengar, S., additional, Bonar, L., additional, Forbes, E. E., additional, Almeida, J. R. C., additional, Perlman, S. B., additional, Schirda, C., additional, Travis, M. J., additional, Gill, M. K., additional, Diwadkar, V. A., additional, Sunshine, J. L., additional, Holland, S. K., additional, Kowatch, R. A., additional, Birmaher, B., additional, Axelson, D. A., additional, Frazier, T. W., additional, Arnold, L. E., additional, Fristad, M. A., additional, Youngstrom, E. A., additional, Horwitz, S. M., additional, Findling, R. L., additional, and Phillips, M. L., additional
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- 2016
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10. Can emotional and behavioral dysregulation in youth be decoded from functional neuroimaging?
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Portugal, LCL, Rosa, MJ, Rao, A, Bebko, G, Bertocci, MA, Hinze, AK, Bonar, L, Almeida, JRC, Perlman, SB, Versace, A, Schirda, C, Travis, M, Gill, MK, Demeter, C, Diwadkar, VA, Ciuffetelli, G, Rodriguez, E, Forbes, EE, Sunshine, JL, Holland, SK, Kowatch, RA, Birmaher, B, Axelson, D, Horwitz, SM, Arnold, EL, Fristad, MA, Youngstrom, EA, Findling, RL, Pereira, M, Oliveira, L, Phillips, ML, Mourao-Miranda, J, Portugal, LCL, Rosa, MJ, Rao, A, Bebko, G, Bertocci, MA, Hinze, AK, Bonar, L, Almeida, JRC, Perlman, SB, Versace, A, Schirda, C, Travis, M, Gill, MK, Demeter, C, Diwadkar, VA, Ciuffetelli, G, Rodriguez, E, Forbes, EE, Sunshine, JL, Holland, SK, Kowatch, RA, Birmaher, B, Axelson, D, Horwitz, SM, Arnold, EL, Fristad, MA, Youngstrom, EA, Findling, RL, Pereira, M, Oliveira, L, Phillips, ML, and Mourao-Miranda, J
- Abstract
Introduction High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points. Methods A sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multisite study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels. Results Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regress
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- 2016
11. Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder
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Manelis, A., primary, Ladouceur, C. D., additional, Graur, S., additional, Monk, K., additional, Bonar, L. K., additional, Hickey, M. B., additional, Dwojak, A. C., additional, Axelson, D., additional, Goldstein, B. I., additional, Goldstein, T. R., additional, Bebko, G., additional, Bertocci, M. A., additional, Gill, M. K., additional, Birmaher, B., additional, and Phillips, M. L., additional
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- 2015
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12. Reward-related neural activity and structure predict future substance use in dysregulated youth.
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Bertocci, M. A., Bebko, G., Versace, A., Iyengar, S., Bonar, L., Forbes, E. E., Almeida, J. R. C., Perlman, S. B., Schirda, C., Travis, M. J., Gill, M. K., Diwadkar, V. A., Sunshine, J. L., Holland, S. K., Kowatch, R. A., Birmaher, B., Axelson, D. A., Frazier, T. W., Arnold, L. E., and Fristad, M. A.
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BRAIN physiology , *CEREBRAL cortex , *SUBSTANCE abuse & psychology , *ANALYSIS of variance , *BIOMARKERS , *EMOTIONS , *LIMBIC system , *MENTAL health , *NEURORADIOLOGY , *REGRESSION analysis , *REWARD (Psychology) - Abstract
Background. Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically unwell youth. Method. LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (S.D. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. Results. Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. Conclusions. These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Abnormal anterior cingulate cortical activity during emotional n-back task performance distinguishes bipolar from unipolar depressed females
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Bertocci, M. A., primary, Bebko, G. M., additional, Mullin, B. C., additional, Langenecker, S. A., additional, Ladouceur, C. D., additional, Almeida, J. R. C., additional, and Phillips, M. L., additional
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- 2011
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14. Lifetime depression and mania/hypomania risk predicted by neural markers in three independent young adult samples during working memory and emotional regulation.
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Afriyie-Agyemang Y, Bertocci MA, Iyengar S, Stiffler RS, Bonar LK, Aslam HA, Graur S, Bebko G, Skeba AS, Brady TJ, Benjamin O, Wang Y, Chase HW, and Phillips ML
- Abstract
Objective markers of pathophysiological processes underlying lifetime depression and mania/hypomania risk can provide biologically informed targets for novel interventions to help prevent the onset of affective disorders in individuals with subsyndromal symptoms. Greater activity within and functional connectivity (FC) between the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. Using an emotional n-back paradigm designed to examine WM and ER capacity, we examined in young adults: (1) relationships among activity and FC in these networks and lifetime depression and mania/hypomania risk; (2) the extent to which these relationships were specific to lifetime depression risk versus lifetime mania/hypomania risk; (3) whether findings in a first, Discovery sample n = 101, 63 female, age = 23.85 (2.9) could be replicated in a two independent Test samples of young adults: Test sample 1: n = 90, 60 female, age = 21.7 (2.0); Test sample 2: n = 96, 65 female, age = 21.6 (2.1). The Mood Spectrum Self-Report (MOODS-SR-L) assessed lifetime mania/hypomania risk and depression risk. We showed significant clusters of activity to each contrast in similar locations in the anatomic mask in each Test sample as in the Discovery sample, and, using extracted mean BOLD signal from these clusters as IVs, we showed similar patterns of IV-DV relationships in each Test sample as in the Discovery sample. Specifically, in the Discovery sample, greater DMN activity during WM was associated with greater lifetime depression risk. This finding was specific to depression and replicated in both independent samples (all ps<0.05 qFDR). Greater CEN activity during ER was associated with increased lifetime depression risk and lifetime mania/hypomania risk in all three samples (all ps< 0.05 qFDR). These replicated findings provide promising objective, neural markers to better identify, and guide and monitor early interventions for, depression and mania/hypomania risk in young adults., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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15. Sex differences in neural responses to emotional facial expressions are associated with lifetime depression and mania risk.
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Arora M, Bertocci MA, Schumer MC, Skeba AS, Bebko G, Stiffler RS, Brady TJ, Afriyie-Agyemang Y, Aslam HA, Graur S, Benjamin O, Wang Y, and Phillips ML
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- Humans, Female, Male, Young Adult, Adult, Bipolar Disorder physiopathology, Bipolar Disorder psychology, Bipolar Disorder diagnostic imaging, Depression physiopathology, Depression psychology, Facial Recognition physiology, Brain physiopathology, Brain diagnostic imaging, Sex Factors, Facial Expression, Magnetic Resonance Imaging, Emotions physiology, Mania physiopathology
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Introduction: No studies systematically examined sex differences in neural mechanisms underlying depression and mania/hypomania risk., Method: 80 females and 35 males, n = 115(age21.6±1.90) were scanned using 3TfMRI during an implicit emotional-faces task. We examined neural activation to all emotional faces versus baseline, using an anatomical region-of-interest mask comprising regions supporting emotion and salience processing. Sex was a covariate. Extracted parameter estimates(FWE < 0.05,k > 15), age, IQ and their sex interactions were independent variables(IV) in two penalized regression models: dependent variable either MOODS-SR-lifetime, depressive or manic domain score as measures of mania and depression risk. Subsequent Poisson regression models included the non-zero variables identified in the penalized regression models. We tested each model in 2 independent samples. Test sample-I,n = 108(21.6 ± 2.09 years,males/females = 33/75); Test sample-II,n = 93(23.7 ± 2.9 years,males/females = 31/62)., Results: Poisson regression models yielded significant relationships with depression and mania risk: Positive correlations were found between right fusiform activity and depression(beta = 0.610) and mania(beta = 0.690) risk. There was a significant interaction between sex and right fusiform activity(beta = -0.609) related to depression risk, where females had a positive relationship than; and a significant interaction(beta = 0.743) between sex and left precuneus activity related to mania risk, with a more negative relationship in females than males. All findings were replicated in the test samples(qs < 0.05,FDR)., Limitations: No longitudinal follow-up., Conclusion: Greater visual attention to emotional faces might underlie greater depression and mania risk, and confer greater vulnerability to depression in females, because of heightened visual attention to emotional faces. Females have a more negative relationship between mania risk and left precuneus activity, suggesting heightened empathy might be associated with reduced mania/hypomania risk in females more than males., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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16. Identifying tripartite relationship among cortical thickness, neuroticism, and mood and anxiety disorders.
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Rozovsky R, Bertocci M, Iyengar S, Stiffler RS, Bebko G, Skeba AS, Brady T, Aslam H, and Phillips ML
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- Female, Young Adult, Humans, Adult, Neuroticism, Affect, Emotions, Anxiety psychology, Mood Disorders, Anxiety Disorders psychology, Mania
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The number of young adults seeking help for emotional distress, subsyndromal-syndromal mood/anxiety symptoms, including those associated with neuroticism, is rising and can be an early manifestation of mood/anxiety disorders. Identification of gray matter (GM) thickness alterations and their relationship with neuroticism and mood/anxiety symptoms can aid in earlier diagnosis and prevention of risk for future mood and anxiety disorders. In a transdiagnostic sample of young adults (n = 252;177 females; age 21.7 ± 2), Hypothesis (H) 1:regularized regression followed by multiple regression examined relationships among GM cortical thickness and clinician-rated depression, anxiety, and mania/hypomania; H2:the neuroticism factor and its subfactors as measured by NEO Personality Inventory (NEO-PI-R) were tested as mediators. Analyses revealed positive relationships between left parsopercularis thickness and depression (B = 4.87, p = 0.002), anxiety (B = 4.68, p = 0.002), mania/hypomania (B = 6.08, p ≤ 0.001); negative relationships between left inferior temporal gyrus (ITG) thickness and depression (B = - 5.64, p ≤ 0.001), anxiety (B = - 6.77, p ≤ 0.001), mania/hypomania (B = - 6.47, p ≤ 0.001); and positive relationships between left isthmus cingulate thickness (B = 2.84, p = 0.011), and anxiety. NEO anger/hostility mediated the relationship between left ITG thickness and mania/hypomania; NEO vulnerability mediated the relationship between left ITG thickness and depression. Examining the interrelationships among cortical thickness, neuroticism and mood and anxiety symptoms enriches the potential for identifying markers conferring risk for mood and anxiety disorders and can provide targets for personalized intervention strategies for these disorders., (© 2024. The Author(s).)
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- 2024
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17. Patterns of Neural Network Functional Connectivity Associated With Mania/Hypomania and Depression Risk in 3 Independent Young Adult Samples.
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Schumer MC, Bertocci MA, Aslam HA, Graur S, Bebko G, Stiffler RS, Skeba AS, Brady TJ, Benjamin OE, Wang Y, Chase HW, and Phillips ML
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- Humans, Male, Female, Young Adult, Adult, Depression, Cross-Sectional Studies, Neural Pathways, Magnetic Resonance Imaging, Mania, Bipolar Disorder diagnosis
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Importance: Mania/hypomania is the pathognomonic feature of bipolar disorder (BD). Established, reliable neural markers denoting mania/hypomania risk to help with early risk detection and diagnosis and guide the targeting of pathophysiologically informed interventions are lacking., Objective: To identify patterns of neural responses associated with lifetime mania/hypomania risk, the specificity of such neural responses to mania/hypomania risk vs depression risk, and the extent of replication of findings in 2 independent test samples., Design, Setting, and Participants: This cross-sectional study included 3 independent samples of young adults aged 18 to 30 years without BD or active substance use disorder within the past 3 months who were recruited from the community through advertising. Of 603 approached, 299 were ultimately included and underwent functional magnetic resonance imaging at the University of Pittsburgh, Pittsburgh, Pennsylvania, from July 2014 to May 2023., Main Outcomes and Measures: Activity and functional connectivity to approach-related emotions were examined using a region-of-interest mask supporting emotion processing and emotional regulation. The Mood Spectrum Self-Report assessed lifetime mania/hypomania risk and depression risk. In the discovery sample, elastic net regression models identified neural variables associated with mania/hypomania and depression risk; multivariable regression models identified the extent to which selected variables were significantly associated with each risk measure. Multivariable regression models then determined whether associations in the discovery sample replicated in both test samples., Results: A total of 299 participants were included. The discovery sample included 114 individuals (mean [SD] age, 21.60 [1.91] years; 80 female and 34 male); test sample 1, 103 individuals (mean [SD] age, 21.57 [2.09] years; 30 male and 73 female); and test sample 2, 82 individuals (mean [SD] age, 23.43 [2.86] years; 48 female, 29 male, and 5 nonbinary). Associations between neuroimaging variables and Mood Spectrum Self-Report measures were consistent across all 3 samples. Bilateral amygdala-left amygdala functional connectivity and bilateral ventrolateral prefrontal cortex-right dorsolateral prefrontal cortex functional connectivity were positively associated with mania/hypomania risk: discovery omnibus χ2 = 1671.7 (P < .001); test sample 1 omnibus χ2 = 1790.6 (P < .001); test sample 2 omnibus χ2 = 632.7 (P < .001). Bilateral amygdala-left amygdala functional connectivity and right caudate activity were positively associated and negatively associated with depression risk, respectively: discovery omnibus χ2 = 2566.2 (P < .001); test sample 1 omnibus χ2 = 2935.9 (P < .001); test sample 2 omnibus χ2 = 1004.5 (P < .001)., Conclusions and Relevance: In this study of young adults, greater interamygdala functional connectivity was associated with greater risk of both mania/hypomania and depression. By contrast, greater functional connectivity between ventral attention or salience and central executive networks and greater caudate deactivation were reliably associated with greater risk of mania/hypomania and depression, respectively. These replicated findings indicate promising neural markers distinguishing mania/hypomania-specific risk from depression-specific risk and may provide neural targets to guide and monitor interventions for mania/hypomania and depression in at-risk individuals.
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- 2024
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18. Neurobehavioral Reward and Sleep-Circadian Profiles Predict Present and Next-Year Mania/Hypomania Symptoms.
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Soehner AM, Wallace ML, Edmiston K, Chase HW, Lockovich J, Aslam H, Stiffler R, Graur S, Skeba A, Bebko G, Benjamin OE, Wang Y, and Phillips ML
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- Adult, Humans, Cross-Sectional Studies, Sleep, Reward, Mania, Bipolar Disorder
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Background: Heightened reward sensitivity/impulsivity, related neural activity, and sleep-circadian disruption are important risk factors for bipolar spectrum disorders, the defining feature of which is mania/hypomania. Our goal was to identify neurobehavioral profiles based on reward and sleep-circadian features and examine their specificity to mania/hypomania versus depression vulnerability., Methods: At baseline, a transdiagnostic sample of 324 adults (18-25 years) completed trait measures of reward sensitivity (Behavioral Activation Scale), impulsivity (UPPS-P-Negative Urgency), and a functional magnetic resonance imaging card-guessing reward task (left ventrolateral prefrontal activity to reward expectancy, a neural correlate of reward motivation and impulsivity, was extracted). At baseline, 6-month follow-up, and 12-month follow-up, the Mood Spectrum Self-Report Measure - Lifetime Version assessed lifetime predisposition to subthreshold-syndromal mania/hypomania, depression, and sleep-circadian disturbances (insomnia, sleepiness, reduced sleep need, rhythm disruption). Mixture models derived profiles from baseline reward, impulsivity, and sleep-circadian variables., Results: Three profiles were identified: 1) healthy (no reward or sleep-circadian disruption; n = 162); 2) moderate-risk (moderate reward and sleep-circadian disruption; n = 109); and 3) high-risk (high impulsivity and sleep-circadian disruption; n = 53). At baseline, the high-risk group had significantly higher mania/hypomania scores than the other groups but did not differ from the moderate-risk group in depression scores. Over the follow-up period, the high-risk and moderate-risk groups exhibited elevated mania/hypomania scores, whereas depression scores increased at a faster rate in the healthy group than in the other groups., Conclusions: Cross-sectional and next-year predisposition to mania/hypomania is associated with a combination of heightened reward sensitivity and impulsivity, related reward circuitry activity, and sleep-circadian disturbances. These measures can be used to detect mania/hypomania risk and provide targets to guide and monitor interventions., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2023
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19. Altered patterns of central executive, default mode and salience network activity and connectivity are associated with current and future depression risk in two independent young adult samples.
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Bertocci MA, Afriyie-Agyemang Y, Rozovsky R, Iyengar S, Stiffler R, Aslam HA, Bebko G, and Phillips ML
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- Humans, Young Adult, Adult, Cognition, Magnetic Resonance Imaging methods, Brain, Brain Mapping methods, Neural Pathways, Mania, Depression
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Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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20. Working memory updating in individuals with bipolar and unipolar depression: fMRI study.
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Manelis A, Halchenko YO, Bonar L, Stiffler RS, Satz S, Miceli R, Ladouceur CD, Bebko G, Iyengar S, Swartz HA, and Phillips ML
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- Brain diagnostic imaging, Humans, Magnetic Resonance Imaging, Memory, Short-Term, Bipolar Disorder, Depressive Disorder psychology
- Abstract
Understanding neurobiological characteristics of cognitive dysfunction in distinct psychiatric disorders remains challenging. In this secondary data analysis, we examined neurobiological differences in brain response during working memory updating among individuals with bipolar disorder (BD), those with unipolar depression (UD), and healthy controls (HC). Individuals between 18-45 years of age with BD (n = 100), UD (n = 109), and HC (n = 172) were scanned using fMRI while performing 0-back (easy) and 2-back (difficult) tasks with letters as the stimuli and happy, fearful, or neutral faces as distractors. The 2(n-back) × 3(groups) × 3(distractors) ANCOVA examined reaction time (RT), accuracy, and brain activation during the task. HC showed more accurate and faster responses than individuals with BD and UD. Difficulty-related activation in the prefrontal, posterior parietal, paracingulate cortices, striatal, lateral occipital, precuneus, and thalamic regions differed among groups. Individuals with BD showed significantly lower difficulty-related activation differences in the left lateral occipital and the right paracingulate cortices than those with UD. In individuals with BD, greater difficulty-related worsening in accuracy was associated with smaller activity changes in the right precuneus, while greater difficulty-related slowing in RT was associated with smaller activity changes in the prefrontal, frontal opercular, paracingulate, posterior parietal, and lateral occipital cortices. Measures of current depression and mania did not correlate with the difficulty-related brain activation differences in either group. Our findings suggest that the alterations in the working memory circuitry may be a trait characteristic of reduced working memory capacity in mood disorders. Aberrant patterns of activation in the left lateral occipital and paracingulate cortices may be specific to BD., (© 2022. The Author(s).)
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- 2022
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21. White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder.
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Lima Santos JP, Bertocci M, Bebko G, Goldstein T, Kim T, Iyengar S, Bonar L, Gill M, Merranko J, Yendiki A, Birmaher B, Phillips ML, and Versace A
- Abstract
Diffusion Magnetic Resonance Imaging (dMRI) studies have reported abnormalities in emotion regulation circuits in BD; however, no study has examined the contribution of previous illness on these mechanisms. Using global probabilistic tractography, we aimed to identify neural correlates of previous BD illness and the extent to which these can help predict one-year recurrence of depressive episodes. dMRI data were collected in 70 adults with early-onset BD who were clinically followed for up to 18 years and 39 healthy controls. Higher number of depressive episodes during childhood/adolescence and higher percentage of time with syndromic depression during longitudinal follow-up was associated with lower fractional anisotropy (FA) in focal regions of the forceps minor (left, F = 4.4, p = 0.003; right, F = 3.1, p = 0.021) and anterior cingulum bundle (left, F = 4.7, p = 0.002; right, F = 7.0, p < 0.001). Lower FA in these regions was also associated with higher depressive and anxiety symptoms at scan. Remarkably, those having higher FA in the right cluster of the forceps minor (AOR = 0.43, p = 0.017) and in a cluster of the posterior cingulum bundle (right, AOR = 0.50, p = 0.032) were protected against the recurrence of depressive episodes. Previous depressive symptomatology may cause neurodegenerative effects in the forceps minor that are associated with worsening of BD symptomatology in subsequent years. Abnormalities in the posterior cingulum may also play a role.
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- 2022
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22. White matter predictors of worsening of subthreshold hypomania severity in non-bipolar young adults parallel abnormalities in individuals with bipolar disorder.
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Santos JPL, Versace A, Stiffler RS, Aslam HA, Lockovich JC, Bonar L, Bertocci M, Iyengar S, Bebko G, Skeba A, Gill MK, Monk K, Hickey MB, Birmaher B, and Phillips ML
- Subjects
- Anisotropy, Diffusion Tensor Imaging methods, Humans, Mania, Young Adult, Bipolar Disorder psychology, White Matter diagnostic imaging, White Matter pathology
- Abstract
Background: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals., Methods: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF)., Results: Lower FA in left CB (middle, β = -0.22, P = 0.022; posterior, β = -0.32, P < 0.001), right CB (anterior, β = -0.30, P = 0.003; posterior, β = -0.27, P = 0.005), and right UF (frontal, β = -0.29, P = 0.002; temporal, β = -0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals., Limitations: Relatively short follow-up., Conclusions: White matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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23. Informing the study of suicidal thoughts and behaviors in distressed young adults: The use of a machine learning approach to identify neuroimaging, psychiatric, behavioral, and demographic correlates.
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Oppenheimer CW, Bertocci M, Greenberg T, Chase HW, Stiffler R, Aslam HA, Lockovich J, Graur S, Bebko G, and Phillips ML
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- Adolescent, Adult, Demography, Functional Neuroimaging, Humans, Machine Learning, Young Adult, Suicidal Ideation, Suicide, Attempted psychology
- Abstract
Young adults are at high risk for suicide, yet there is limited ability to predict suicidal thoughts and behaviors. Machine learning approaches are better able to examine a large number of variables simultaneously to identify combinations of factors associated with suicidal thoughts and behaviors. The current study used LASSO regression to investigate extent to which a number of demographic, psychiatric, behavioral, and functional neuroimaging variables are associated with suicidal thoughts and behaviors during young adulthood. 78 treatment seeking young adults (ages 18-25) completed demographic, psychiatric, behavioral, and suicidality measures. Participants also completed an implicit emotion regulation functional neuroimaging paradigm. Report of recent suicidal thoughts and behaviors served as the dependent variable. Five variables were identified by the LASSO regression: Two were demographic variables (age and level of education), two were psychiatric variables (depression and general psychiatric distress), and one was a neuroimaging variable (left amygdala activity during sad faces). Amygdala function was significantly associated with suicidal thoughts and behaviors above and beyond the other factors. Findings inform the study of suicidal thoughts and behaviors among treatment seeking young adults, and also highlight the importance of investigating neurobiological markers., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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24. Differentiating white matter measures that protect against vs. predispose to bipolar disorder and other psychopathology in at-risk youth.
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Rozovsky R, Versace A, Bonar LK, Bertocci M, Ladouceur CD, Fournier J, Monk K, Abdul-Waalee H, Bebko G, Hafeman D, Sakolsky D, Goldstein T, Birmaher B, and Phillips ML
- Subjects
- Adolescent, Anisotropy, Diffusion Tensor Imaging, Humans, Psychopathology, Bipolar Disorder, White Matter diagnostic imaging
- Abstract
Bipolar disorder (BD) is highly heritable. Identifying objective biomarkers reflecting pathophysiological processes predisposing to, versus protecting against BD, can help identify BD risk in offspring of BD parents. We recruited 21 BD participants with a first-degree relative with BD, 25 offspring of BD parents, 27 offspring of comparison parents with non-BD psychiatric disorders, and 32 healthy offspring of healthy parents. In at-risk groups, 23 had non-BD diagnoses and 29, no Axis-I diagnoses(healthy). Five at-risk offspring who developed BD post scan(Converters) were included. Diffusion imaging(dMRI) analysis with tract segmentation identified between-group differences in the microstructure of prefrontal tracts supporting emotional regulation relevant to BD: forceps minor, anterior thalamic radiation(ATR), cingulum bundle(CB), and uncinate fasciculus(UF). BD participants showed lower fractional anisotropy (FA) in the right CB (anterior portion) than other groups (q < 0.05); and in bilateral ATR (posterior portion) versus at-risk groups (q < 0.001). Healthy, but not non-BD, at-risk participants showed significantly higher FA in bilateral ATR clusters than healthy controls (qs < 0.05). At-risk groups showed higher FA in these clusters than BD participants (qs < 0.05). Non-BD versus healthy at-risk participants, and Converters versus offspring of BD parents, showed lower FA in the right ATR cluster (qs < 0.05). Low anterior right CB FA in BD participants versus other groups might result from having BD. High bilateral ATR FA in at-risk groups, and in healthy at-risk participants, versus healthy controls might protect against BD/other psychiatric disorders. Absence of elevated right ATR FA in non-BD versus healthy at-risk participants, and in Converters versus non-converter offspring of BD parents, might lower protection against BD in at-risk groups., (© 2021. The Author(s).)
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- 2021
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25. Trait sensation seeking is associated with heightened beta-band oscillatory dynamics over left ventrolateral prefrontal cortex during reward expectancy.
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Coffman BA, Torrence N, Murphy T, Bebko G, Graur S, Chase HW, Salisbury DF, and Phillips ML
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- Adolescent, Electroencephalography, Female, Humans, Prefrontal Cortex, Sensation, Young Adult, Cerebral Cortex, Reward
- Abstract
Background: Sensation Seeking, the proclivity toward novel and stimulating experiences, is associated with greater left ventrolateral prefrontal cortex (vlPFC) activity during uncertain reward expectancy. Here, we examined relationships between sensation seeking and vlPFC oscillatory dynamics using electroencephalography (EEG)., Methods: In 26 adolescents/young adults (16 female; 22.3 ± 1.7yrs), EEG was measured during uncertain reward expectancy. Event-related spectral perturbations (ERSP) from 15-80 Hz (beta/gamma bands) were compared as a function of uncertain reward expected value and assessed for relationships with feedback-related negativity (FRN) response to outcome feedback and response tendency measures of risk for BD., Results: Event-related synchronization (ERS) between 15-25 Hz (beta) over left vlPFC was sensitive to the expected value of uncertain reward (rho=0.46; p = 0.048), and correlated with sensation seeking (r = 0.49, p < 0.01) and feedback-related negativity (FRN), where greater beta ERS was related to larger FRN (r = -0.39, p = 0.047). FRN was also related to behavioral inhibition (r = 0.49, p < 0.01)., Limitations: It is unknown whether results may extrapolate to clinical populations, given the healthy sample used here. Further, although we have confidence that the beta-band signal we measure in this study arises from left prefrontal cortex, we largely infer a left vlPFC source., Conclusions: These findings highlight the role of left vlPFC in evaluation of immediate rewards. We now provide a link between reward expectancy-related left vlPFC activity and the well-characterized FRN, with a known role in attentive processing. These findings can guide treatment development for mania/hypomania at-risk individuals, including transcranial alternating current stimulation., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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26. A specific neural substrate predicting current and future impulsivity in young adults.
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Steele JS, Bertocci M, Eckstrand K, Chase HW, Stiffler R, Aslam H, Lockovich J, Bebko G, and Phillips ML
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- Emotions, Fear, Humans, Impulsive Behavior, Neural Pathways, Prefrontal Cortex, Young Adult, Amygdala, Magnetic Resonance Imaging
- Abstract
Impulsivity (rash action with deleterious outcomes) is common to many psychiatric disorders. While some studies indicate altered amygdala and prefrontal cortical (PFC) activity associated with impulsivity, it remains unclear whether these patterns of neural activity are specific to impulsivity or common to a range of affective and anxiety symptoms. To elucidate neural markers specific to impulsivity, we aimed to differentiate patterns of amygdala-PFC activity and functional connectivity associated with impulsivity from those associated with affective and anxiety symptoms, and identify measures of this circuitry predicting future worsening of impulsivity. Using a face emotion processing task that reliably activates amygdala-PFC circuitry, neural activity and connectivity were assessed in a transdiagnostically-recruited sample of young adults, including healthy (N = 47) and treatment-seeking individuals (N = 67). Relationships were examined between neural measures and impulsivity, anhedonia, and affective and anxiety symptoms at baseline (N = 114), and at 6 months post scan (N = 30). Impulsivity, particularly negative urgency and lack of perseverance, was related to greater amygdala activity (beta = 0.82, p = 0.003; beta = 0.68, p = 0.004; respectively) and lower amygdala-medial PFC functional connectivity (voxels = 60, t
peak = 4.45, pFWE = 0.017; voxels = 335, tpeak = 5.26, pFWE = 0.001; respectively) to facial fear. Left vlPFC, but not amygdala, activity to facial anger was inversely associated with mania/hypomania (beta = -2.08, p = 0.018). Impulsivity 6 months later was predicted by amygdala activity to facial sadness (beta = 0.50, p = 0.017). There were no other significant relationships between neural activity and 6-month anhedonia, affective, and anxiety symptoms. Our findings are the first to associate amygdala-PFC activity and functional connectivity with impulsivity in a large, transdiagnostic sample, providing neural targets for future interventions to reduce predisposition to impulsivity and related future mental health problems in young adults., (© 2021. The Author(s).)- Published
- 2021
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27. Trauma Affects Prospective Relationships Between Reward-Related Ventral Striatal and Amygdala Activation and 1-Year Future Hypo/Mania Trajectories.
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Eckstrand KL, Forbes EE, Bertocci MA, Chase HW, Greenberg T, Lockovich J, Stiffler R, Aslam HA, Graur S, Bebko G, and Phillips ML
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- Adolescent, Adult, Amygdala, Female, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Reward, Young Adult, Mania, Ventral Striatum diagnostic imaging
- Abstract
Background: Trauma exposure is associated with a more severe, persistent course of affective and anxiety symptoms. Markers of reward neural circuitry function, specifically activation to reward prediction error (RPE), are impacted by trauma and predict the future course of affective symptoms. This study's purpose was to determine how lifetime trauma exposure influences relationships between reward neural circuitry function and the course of future affective and anxiety symptoms in a naturalistic, transdiagnostic observational context., Methods: A total of 59 young adults aged 18-25 (48 female and 11 male participants, mean ± SD = 21.5 ± 2.0 years) experiencing psychological distress completed the study. Participants were evaluated at baseline, 6, and 12 months. At baseline, the participants reported lifetime trauma events and completed a monetary reward functional magnetic resonance imaging task. Affective and anxiety symptoms were reported at each visit, and trajectories were calculated using MPlus. Neural activation during RPE and other phases of reward processing were determined using SPM8. Trauma and reward neural activation were entered as predictors of symptom trajectories., Results: Trauma exposure moderated prospective relationships between left ventral striatum (β = -1.29, p = .02) and right amygdala (β = 0.58, p = .04) activation to RPE and future hypo/mania severity trajectory: the interaction between greater trauma and greater left ventral striatum activation to RPE was associated with a shallower increase in hypo/mania severity, whereas the interaction between greater trauma and greater right amygdala activation to RPE was associated with increasing hypo/mania severity., Conclusions: Trauma exposure affects prospective relationships between markers of reward circuitry function and affective symptom trajectories. Evaluating trauma exposure is thus crucial in naturalistic and treatment studies aiming to identify neural predictors of future affective symptom course., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2021
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28. Depression and anxiety mediate the relationship between frontotemporal white matter integrity and quality of life in distressed young adults.
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Greenberg T, Bertocci MA, Versace A, Lima Santos JP, Chase HW, Siffler R, Aslam HA, Graur S, Bebko G, Lockovich JC, and Phillips ML
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- Adolescent, Adult, Anisotropy, Anxiety diagnostic imaging, Brain, Depression diagnostic imaging, Diffusion Tensor Imaging, Emotions, Humans, Young Adult, Quality of Life, White Matter diagnostic imaging
- Abstract
Depression and anxiety have been linked to poor quality of life (QoL) - one's subjective perception of relationships, physical health, daily functioning, general sense of well-being and life satisfaction. Elucidating abnormal white matter microstructure associated with mood and other symptoms and QoL is important to facilitate treatment. Ninety-six young adults (18-25 years old) seeking help for psychological distress, irrespective of presence or absence of psychiatric diagnosis completed diffusion weighted and anatomical scans, clinical and behavioral measures, and QoL assessment. We examined relationships between diffusion imaging properties in major white matter tracts involved in emotion processing and regulation, symptoms, and QoL. Depression and general distress levels fully mediated the relationship between fractional anisotropy (FA), an indirect index of fiber collinearity, and radial diffusivity (RD), an index sensitive to axonal/myelin damage, in right uncinate fasciculus and QoL. The relationship between reduced FA (and increased RD) in right uncinate fasciculus and poor QoL was explained by greater severity of depression and general distress. These findings underscore the role of white matter microstructure in right uncinate fasciculus in relation to depressive and general distress symptoms and, in turn, QoL. Importantly, they suggest that measures of white matter microstructure in this tract can be used as putative objective markers of emotion dysregulation, to inform and monitor the impact of interventions to reduce affective symptoms and improve QoL in young adults., (Copyright © 2020. Published by Elsevier Ltd.)
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- 2021
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29. White Matter Correlates of Suicidality in Adults With Bipolar Disorder Who Have Been Prospectively Characterized Since Childhood.
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Lima Santos JP, Brent D, Bertocci M, Mailliard S, Bebko G, Goldstein T, Kim T, Iyengar S, Hafeman D, Fenster-Ehrlich VC, Skeba A, Bonar L, Abdul-Waalee H, Gill M, Merranko J, Birmaher B, Phillips ML, and Versace A
- Subjects
- Adolescent, Adult, Child, Humans, Suicidal Ideation, Suicide, Attempted, Bipolar Disorder, Suicide, White Matter diagnostic imaging
- Abstract
Background: Prevention of suicide in individuals with early-onset bipolar disorder (BD) remains a challenge. Diffusion magnetic resonance imaging studies in BD have identified neural correlates of emotional dysregulation implicated in BD and suicide. Using diffusion magnetic resonance imaging, we sought to identify neural signatures of suicide attempts in adults with childhood-onset BD who have been clinically followed for up to 19 years as part of the COBY (Course and Outcome of Bipolar Youth) study., Methods: Diffusion magnetic resonance imaging data were collected in 68 adults with BD: 20 in the suicide attempter (SA
+ ) group and 48 in the non-suicide attempter (SA- ) group. Multivariate analysis of covariance was used to identify the effect of group (SA+ , SA- ) on mean fractional anisotropy (indirect index of fiber collinearity) in key white matter tracts of emotional regulation. The effect of suicidal ideation and other clinical factors was further explored. False discovery rate was used to account for multiple comparison. Forty healthy control subjects were included., Results: Analyses revealed a main effect of group on fractional anisotropy (F5,59 = 3.0, p = .017). Specifically, the SA+ group showed lower fractional anisotropy than the SA- and healthy control groups in the middle portion of the forceps minor (FMIN) (F1,63 = 8.5, p = .010) and in the anterior (F1,63 = 7.8, p = .010) and posterior (F1,63 = 8.7, p = .006) portion of the right cingulum bundle (CB). Abnormalities in the FMIN, but not CB, were also associated with suicidal ideation (F1,64 = 10.6, p = .002) and levels of emotional distress at scan., Conclusions: FMIN and CB abnormalities have been associated with emotional dysregulation in BD. Our findings suggest that the FMIN may represent a generic marker of suicidal ideation and, more broadly, emotional distress, while CB may represent a specific marker of attempted suicide., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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30. Emotional regulation neural circuitry abnormalities in adult bipolar disorder: dissociating effects of long-term depression history from relationships with present symptoms.
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Bertocci MA, Bergman J, Santos JPL, Iyengar S, Bonar L, Gill MK, Abdul-Waalee H, Bebko G, Stiffler R, Lockovich J, Aslam H, Ladouceur C, Merranko J, Diler R, Birmaher B, Versace A, and Phillips ML
- Subjects
- Adolescent, Adult, Child, Emotions, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Prefrontal Cortex, Prospective Studies, Bipolar Disorder psychology, Depression, Emotional Regulation
- Abstract
Bipolar disorder (BD) is common and debilitating and confounding effects of depression history on neural activity in BD are unknown. We aimed to dissociate neural activity reflecting past depression-load vs. present symptom severity using the Course and Outcome of Bipolar Youth (COBY), a prospective longitudinal cohort study of pediatric-onset BD. In n = 54 COBY (18-32 years), we modeled depression scores over time (up to 17.5 years) using a standardized autoregressive moving average (ARMA) model, followed by k-means cluster analysis. N = 36 healthy participants (HC, 20-36 years) were included. Using two factorial analyses, we parsed the impact of ARMA-defined past depression-load on neural activity from the impact of current symptoms on neural activity (p < 0.001, k > 30) and examined relationships with past and present symptoms (ps FDR-corrected). ARMA identified three COBY groups based on past depression-load. ARMA-defined COBY participants with the greatest past depression-load vs. other groups showed greater activity in right temporoparietal junction, thalamus, insula, premotor cortex, left fusiform gyrus, bilateral precuneus and cerebellum. In contrast, BD-COBY participants vs. HC showed greater activity in left hippocampus, dorsolateral prefrontal cortex, and right somatosensory cortex, plus the above thalamus, premotor cortex and cerebellum; activity positively correlated with present symptom severity in most regions. Past depression-load was related to social cognition and salience perception network activity, potentially reflecting heightened attention to socially relevant distracters, while present symptoms were associated with emotion processing and reappraisal network activity, potentially reflecting abnormal emotional experience and regulation. Differentiating aberrant neural activity related to long-term depression vs. present affective symptoms can help target interventions to networks associated with pathophysiological processes, rather than long-term illness effects.
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- 2020
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31. Assessing Relationships Among Impulsive Sensation Seeking, Reward Circuitry Activity, and Risk for Psychopathology: A Functional Magnetic Resonance Imaging Replication and Extension Study.
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Edmiston EK, Fournier JC, Chase HW, Bertocci MA, Greenberg T, Aslam HA, Lockovich J, Graur S, Bebko G, Forbes EE, Stiffler R, and Phillips ML
- Subjects
- Female, Humans, Impulsive Behavior, Magnetic Resonance Imaging, Male, Sensation, Young Adult, Bipolar Disorder, Reward
- Abstract
Background: High trait impulsive sensation seeking (ISS), the tendency to engage in behavior without forethought and to seek out new or extreme experiences, is a transdiagnostic risk factor for externalizing and mood disorders, particularly bipolar disorder. We published a positive association between trait ISS and reward expectancy-related activity in the left ventrolateral prefrontal cortex (L vlPFC) and the ventral striatum. We aimed to replicate this finding and extend it by testing for mediation effects of ISS on relationships between reward expectancy-related activity and measures denoting hypomania., Methods: A transdiagnostic sample of 127 adults, 18 to 25 years of age, completed a card-guessing functional magnetic resonance imaging task as well as measures of ISS (inattention, motor impulsivity, fun seeking, positive and negative urgency) and the Moods Spectrum as a measure of hypomania. An original sample of 98 was included for confirmatory and mediation analyses., Results: We replicated a positive relationship between reward expectancy-related L vlPFC activity and negative urgency, an ISS component (β = .28, t = 2.44, p = .0169). We combined these data with the original sample, confirming this finding (β = .27, t = 2.41, p = .0184). Negative urgency statistically mediated the relationship between reward expectancy-related L vlPFC activity and Moods Spectrum factors associated with hypomania. No other associations between ISS measures and reward expectancy-related activity were replicated., Conclusions: We replicated findings showing that reward expectancy-related L vlPFC activity is a biomarker for negative urgency, the tendency to react with frustration during distressing conditions. Negative urgency also statistically mediated the relationship between L vlPFC activity and measures indicative of hypomanic symptoms., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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32. The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.
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Hanford LC, Eckstrand K, Manelis A, Hafeman DM, Merranko J, Ladouceur CD, Graur S, McCaffrey A, Monk K, Bonar LK, Hickey MB, Goldstein TR, Goldstein BI, Axelson D, Bebko G, Bertocci MA, Gill MK, Birmaher B, and Phillips ML
- Subjects
- Adolescent, Bipolar Disorder etiology, Child, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Adverse Childhood Experiences statistics & numerical data, Bipolar Disorder physiopathology, Emotions, Genetic Predisposition to Disease, Neural Pathways, Reward, Stress, Psychological complications
- Abstract
A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Risk calculator score was used to assess risk for developing BD in the next 5 years. Environmental risk was tabulated using the Stressful Life Events Schedule (SLES). Emotion and reward processing networks were investigated for genetic and/or environment interactions. Interaction effects were found between risk calculator scores, negative SLES score and activity in right amygdala and bilateral fusiform gyri during the emotion processing task, as well as activity in the fronto-, striatal, and parietal regions during the reward processing task. Our findings are preliminary; however, they support the unique and interactive contributions of both familial and environmental risk factors on emotion and reward processing within OBP. They also identify potential neural targets to guide development of interventions for youth at greatest risk for psychiatric disorders., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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33. Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication.
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Bertocci MA, Hanford L, Manelis A, Iyengar S, Youngstrom EA, Gill MK, Monk K, Versace A, Bonar L, Bebko G, Ladouceur CD, Perlman SB, Diler R, Horwitz SM, Arnold LE, Hafeman D, Travis MJ, Kowatch R, Holland SK, Fristad MA, Findling RL, Birmaher B, and Phillips ML
- Subjects
- Adolescent, Adult, Anxiety physiopathology, Anxiety Disorders physiopathology, Biomarkers, Bipolar Disorder physiopathology, Cerebral Cortex physiopathology, Depression physiopathology, Depressive Disorder, Major physiopathology, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Parietal Lobe physiopathology, Prognosis, Psychiatric Status Rating Scales, Risk Factors, Temporal Lobe physiopathology, Young Adult, Bipolar Disorder diagnosis, Bipolar Disorder metabolism, Neural Pathways physiopathology
- Abstract
We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.
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- 2019
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34. Unstable wakefulness during resting-state fMRI and its associations with network connectivity and affective psychopathology in young adults.
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Soehner AM, Chase HW, Bertocci MA, Greenberg T, Stiffler R, Lockovich JC, Aslam HA, Graur S, Bebko G, and Phillips ML
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- Brain physiopathology, Brain Mapping, Female, Humans, Male, Nerve Net diagnostic imaging, Nerve Net physiopathology, Principal Component Analysis, Psychopathology, Rest, Sleep, Sleep Wake Disorders physiopathology, Young Adult, Magnetic Resonance Imaging methods, Mood Disorders physiopathology, Sleep Wake Disorders psychology, Wakefulness physiology
- Abstract
Background: Drifts between wakefulness and sleep are common during resting state functional MRI (rsfMRI). Among healthy adults, within-scanner sleep can impact functional connectivity of default mode (DMN), task-positive (TPN), and thalamo-cortical networks. Because dysfunctional arousal states (i.e., sleepiness, sleep disturbance) are common in affective disorders, individuals with affective psychopathology may be more prone to unstable wakefulness during rsfMRI, hampering the estimation of clinically meaningful functional connectivity biomarkers., Methods: A transdiagnostic sample of 150 young adults (68 psychologically distressed; 82 psychiatrically healthy) completed rsfMRI and reported whether they experienced within-scanner sleep. Symptom scales were reduced into depression/anxiety and mania proneness dimensions using principal component analysis. We evaluated associations between within-scanner sleep, clinical status, and functional connectivity of the DMN, TPN, and thalamus., Results: Within-scanner sleep during rsfMRI was reported by 44% of participants (n = 66) but was unrelated to psychiatric diagnoses or mood symptom severity (p-values > 0.05). Across all participants, self-reported within-scanner sleep was associated with connectivity signatures akin to objectively-assessed sleep, including lower within-DMN connectivity, lower DMN-TPN anti-correlation, and altered thalamo-cortical connectivity (p < 0.05, corrected). Among participants reporting sustained wakefulness (n = 84), depression/anxiety severity positively associated with averaged DMN-TPN connectivity and mania proneness negatively associated with averaged thalamus-DMN connectivity (p-values < 0.05). Both relationships were attenuated and became non-significant when participants reporting within-scanner sleep were included (p-values > 0.05)., Limitations: Subjective report of within-scanner sleep., Conclusions: Findings implicate within-scanner sleep as a source of variance in network connectivity; careful monitoring and correction for within-scanner sleep may enhance our ability to characterize network signatures underlying affective psychopathology., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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35. Anhedonia Reduction and the Association Between Left Ventral Striatal Reward Response and 6-Month Improvement in Life Satisfaction Among Young Adults.
- Author
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Eckstrand KL, Forbes EE, Bertocci MA, Chase HW, Greenberg T, Lockovich J, Stiffler R, Aslam HA, Graur S, Bebko G, and Phillips ML
- Subjects
- Adolescent, Adult, Amygdala diagnostic imaging, Amygdala physiopathology, Behavioral Symptoms diagnostic imaging, Biomarkers, Female, Follow-Up Studies, Gyrus Cinguli diagnostic imaging, Gyrus Cinguli physiopathology, Humans, Male, Psychological Distress, Severity of Illness Index, Ventral Striatum diagnostic imaging, Young Adult, Anhedonia physiology, Behavioral Symptoms physiopathology, Personal Satisfaction, Psychosocial Functioning, Reward, Ventral Striatum physiopathology
- Abstract
Importance: Anhedonia is a symptom of multiple psychiatric conditions in young adults that is associated with poorer mental health and psychosocial function and abnormal ventral striatum reward processing. Aberrant function of neural reward circuitry is well documented in anhedonia and other psychiatric disorders. Longitudinal studies to identify potential biomarkers associated with a reduction in anhedonia are necessary for the development of novel treatment targets., Objective: To identify neural reward-processing factors associated with improved psychiatric symptoms and psychosocial function in a naturalistic, observational context., Design, Setting, and Participants: A longitudinal cohort follow-up study was conducted from March 1, 2014, to June 5, 2018, at the University of Pittsburgh Medical Center after baseline functional magnetic resonance imaging in 52 participants between the ages of 18 and 25 years who were experiencing psychological distress., Main Outcomes and Measures: Participants were evaluated at baseline and 6 months. At baseline, participants underwent functional magnetic resonance imaging during a card-guessing monetary reward task. Participants completed measures of affective symptoms and psychosocial function at each visit. Neural activation during reward prediction error (RPE), a measure of reward learning, was determined using Statistical Parametric Mapping software. Neural reward regions with significant RPE activation were entered as regions associated with future symptoms in multiple linear regression models., Results: A total of 52 young adults (42 women and 10 men; mean [SD] age, 21.4 [2.2] years) completed the study. Greater RPE activation in the left ventral striatum was associated with a decrease in anhedonia symptoms during a 6-month period (β = -6.152; 95% CI, -11.870 to -0.433; P = .04). The decrease in anhedonia between baseline and 6 months mediated the association between left ventral striatum activation to RPE and improvement in life satisfaction between baseline and 6 months (total [c path] association: β = 0.245; P = .01; direct [c' path] association: β = 0.133; P = .16; and indirect [ab path] association: 95% CI, 0.026-0.262). Results were not associated with psychotropic medication use., Conclusions and Relevance: Greater left ventral striatum responsiveness to RPE may serve as a biomarker or potential target for novel treatments to improve the severity of anhedonia, overall mental health, and psychosocial function.
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- 2019
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36. Trauma-associated anterior cingulate connectivity during reward learning predicts affective and anxiety states in young adults.
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Eckstrand KL, Hanford LC, Bertocci MA, Chase HW, Greenberg T, Lockovich J, Stiffler R, Aslam HA, Graur S, Bebko G, Forbes EE, and Phillips ML
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- Adolescent, Adult, Affective Symptoms diagnostic imaging, Anxiety diagnostic imaging, Cerebral Cortex diagnostic imaging, Connectome, Female, Gyrus Cinguli diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Nerve Net diagnostic imaging, Psychological Trauma diagnostic imaging, Young Adult, Affective Symptoms physiopathology, Anxiety physiopathology, Brain Mapping, Cerebral Cortex physiopathology, Gyrus Cinguli physiopathology, Nerve Net physiopathology, Psychological Trauma physiopathology, Reward
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Background: Trauma exposure is associated with development of depression and anxiety; yet, some individuals are resilient to these trauma-associated effects. Differentiating mechanisms underlying development of negative affect and resilience following trauma is critical for developing effective interventions. One pathway through which trauma could exert its effects on negative affect is reward-learning networks. In this study, we examined relationships among lifetime trauma, reward-learning network function, and emotional states in young adults., Methods: One hundred eleven young adults self-reported trauma and emotional states and underwent functional magnetic resonance imaging during a monetary reward task. Trauma-associated neural activation and functional connectivity were analyzed during reward prediction error (RPE). Relationships between trauma-associated neural functioning and affective and anxiety symptoms were examined., Results: Number of traumatic events was associated with greater ventral anterior cingulate cortex (vACC) activation, and lower vACC connectivity with the right insula, frontopolar, inferior parietal, and temporoparietal regions, during RPE. Lower trauma-associated vACC connectivity with frontoparietal regions implicated in regulatory and decision-making processes was associated with heightened affective and anxiety symptoms; lower vACC connectivity with insular regions implicated in interoception was associated with lower affective and anxiety symptoms., Conclusions: In a young adult sample, two pathways linked the impact of trauma on reward-learning networks with higher v. lower negative affective and anxiety symptoms. The disconnection between vACC and regions implicated in decision-making and self-referential processes may reflect aberrant regulatory but appropriate self-focused mechanisms, respectively, conferring risk for v. resilience against negative affective and anxiety symptoms.
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- 2019
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37. Predicting Bipolar Disorder Risk Factors in Distressed Young Adults From Patterns of Brain Activation to Reward: A Machine Learning Approach.
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de Oliveira L, Portugal LCL, Pereira M, Chase HW, Bertocci M, Stiffler R, Greenberg T, Bebko G, Lockovich J, Aslam H, Mourao-Miranda J, and Phillips ML
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- Adolescent, Adult, Brain Mapping, Female, Humans, Machine Learning, Magnetic Resonance Imaging, Male, Multivariate Analysis, Risk Factors, Severity of Illness Index, Young Adult, Bipolar Disorder diagnostic imaging, Bipolar Disorder physiopathology, Brain diagnostic imaging, Brain physiopathology, Reward
- Abstract
Background: The aim of this study was to apply multivariate pattern recognition to predict the severity of behavioral traits and symptoms associated with risk for bipolar spectrum disorder from patterns of whole-brain activation during reward expectancy to facilitate the identification of individual-level neural biomarkers of bipolar disorder risk., Methods: We acquired functional neuroimaging data from two independent samples of transdiagnostically recruited adults (18-25 years of age; n = 56, mean age 21.9 ± 2.2 years, 42 women; n = 36, mean age 21.2 ± 2.2 years, 24 women) during reward expectancy task performance. Pattern recognition model performance in each sample was measured using correlation and mean squared error between actual and whole-brain activation-predicted scores on behavioral traits and symptoms., Results: In the first sample, the model significantly predicted severity of a specific hypo/mania-related symptom, heightened energy, measured by the energy manic subdomain of the Mood Spectrum Structured Interviews (r = .42, p = .001; mean squared error = 9.93, p = .001). The region with the highest contribution to the model was the left ventrolateral prefrontal cortex. Results were confirmed in the second sample (r = .33, p = .01; mean squared error = 8.61, p = .01), in which the severity of this symptom was predicted using a bilateral ventrolateral prefrontal cortical mask (r = .33, p = .009, mean squared error = 9.37, p = .04)., Conclusions: The severity of a specific hypo/mania-related symptom was predicted from patterns of whole-brain activation in two independent samples. Given that emerging manic symptoms predispose to bipolar disorders, these findings could provide neural biomarkers to aid early identification of individual-level bipolar disorder risk in young adults., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2019
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38. Decreased functional connectivity in the fronto-parietal network in children with mood disorders compared to children with dyslexia during rest: An fMRI study.
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Horowitz-Kraus T, Woodburn M, Rajagopal A, Versace AL, Kowatch RA, Bertocci MA, Bebko G, Almeida JRC, Perlman SB, Travis MJ, Gill MK, Bonar L, Schirda C, Diwadkar VA, Sunshine JL, Birmaher B, Axelson D, Gerry Taylor H, Horwitz SM, Frazier T, Eugene Arnold L, Fristad MA, Youngstrom EA, Findling RL, Phillips ML, and Holland SK
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- Adolescent, Brain Mapping, Child, Dyslexia physiopathology, Executive Function physiology, Female, Frontal Lobe physiopathology, Functional Neuroimaging, Humans, Magnetic Resonance Imaging, Male, Mood Disorders physiopathology, Nerve Net physiopathology, Neuropsychological Tests, Parietal Lobe physiopathology, Reading, Dyslexia diagnostic imaging, Frontal Lobe diagnostic imaging, Mood Disorders diagnostic imaging, Nerve Net diagnostic imaging, Parietal Lobe diagnostic imaging
- Abstract
Background: The DSM-5 separates the diagnostic criteria for mood and behavioral disorders. Both types of disorders share neurocognitive deficits of executive function and reading difficulties in childhood. Children with dyslexia also have executive function deficits, revealing a role of executive function circuitry in reading. The aim of the current study is to determine whether there is a significant relationship of functional connectivity within the fronto-parietal and cingulo-opercular cognitive control networks to reading measures for children with mood disorders, behavioral disorders, dyslexia, and healthy controls (HC)., Method: Behavioral reading measures of phonological awareness, decoding, and orthography were collected. Resting state fMRI data were collected, preprocessed, and then analyzed for functional connectivity. Differences in the reading measures were tested for significance among the groups. Global efficiency (GE) measures were also tested for correlation with reading measures in 40 children with various disorders and 17 HCs., Results: Significant differences were found between the four groups on all reading measures. Relative to HCs and children with mood disorders or behavior disorders, children with dyslexia as a primary diagnosis scored significantly lower on all three reading measures. Children with mood disorders scored significantly lower than controls on a test of phonological awareness. Phonological awareness deficits correlated with reduced resting state functional connectivity MRI (rsfcMRI) in the cingulo-opercular network for children with dyslexia. A significant difference was also found in fronto-parietal global efficiency in children with mood disorders relative to the other three groups. We also found a significant difference in cingulo-opercular global efficiency in children with mood disorders relative to the Dyslexia and Control groups. However, none of these differences correlate significantly with reading measures., Conclusions/significance: Reading difficulties involve abnormalities in different cognitive control networks in children with dyslexia compared to children with mood disorders. Findings of the current study suggest increased functional connectivity of one cognitive control network may compensate for reduced functional connectivity in the other network in children with mood disorders. These findings provide guidance to clinical professionals for design of interventions tailored for children suffering from reading difficulties originating from different pathologies.
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- 2018
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39. Using machine learning and surface reconstruction to accurately differentiate different trajectories of mood and energy dysregulation in youth.
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Versace A, Sharma V, Bertocci MA, Bebko G, Iyengar S, Dwojak A, Bonar L, Perlman SB, Schirda C, Travis M, Gill MK, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Frazier TW, Arnold LE, Fristad MA, Youngstrom EA, Horwitz SM, Findling RL, and Phillips ML
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- Adolescent, Affect, Bipolar Disorder pathology, Bipolar Disorder physiopathology, Case-Control Studies, Cerebral Cortex pathology, Cerebral Cortex physiopathology, Child, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging statistics & numerical data, Male, Neuroimaging statistics & numerical data, Parahippocampal Gyrus diagnostic imaging, Parahippocampal Gyrus pathology, Parahippocampal Gyrus physiopathology, Parietal Lobe diagnostic imaging, Parietal Lobe pathology, Parietal Lobe physiopathology, Prefrontal Cortex pathology, Prefrontal Cortex physiopathology, Temporal Lobe pathology, Temporal Lobe physiopathology, Bipolar Disorder diagnostic imaging, Cerebral Cortex diagnostic imaging, Image Interpretation, Computer-Assisted, Machine Learning, Prefrontal Cortex diagnostic imaging, Temporal Lobe diagnostic imaging
- Abstract
Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the role of neuroimaging measures in classifying individual subjects by specific symptom trajectory. Cortical thickness measures were extracted in sixty-eight anatomical regions covering the entire brain in 115 participants from the Longitudinal Assessment of Manic Symptoms (LAMS) study and 31 healthy comparison youth (12.5 y/o;-Male/Female = 15/16;-IQ = 104;-Right/Left handedness = 24/5). Using a combination of trajectories analyses, surface reconstruction, and machine learning techniques, the present study aims to identify the extent to which measures of cortical thickness can accurately distinguish youth with higher (n = 18) from those with lower (n = 34) trajectories of manic-like behaviors in a large sample of LAMS youth (n = 115; 13.6 y/o; M/F = 68/47, IQ = 100.1, R/L = 108/7). Machine learning analyses revealed that widespread cortical thickening in portions of the left dorsolateral prefrontal cortex, right inferior and middle temporal gyrus, bilateral precuneus, and bilateral paracentral gyri and cortical thinning in portions of the right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, and right parahippocampal gyrus accurately differentiate (Area Under Curve = 0.89;p = 0.03) youth with different (higher vs lower) trajectories of positive mood and energy dysregulation over a period up to 5years, as measured by the Parent General Behavior Inventory-10 Item Mania Scale. Our findings suggest that specific patterns of cortical thickness may reflect transdiagnostic neural mechanisms associated with different temporal trajectories of positive mood and energy dysregulation in youth. This approach has potential to identify patterns of neural markers of future clinical course.
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- 2017
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40. Reading related white matter structures in adolescents are influenced more by dysregulation of emotion than behavior.
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Horowitz-Kraus T, Holland SK, Versace AL, Bertocci MA, Bebko G, Almeida JRC, Perlman SB, Travis MJ, Gill MK, Bonar L, Schirda C, Sunshine JL, Birmaher B, Taylor G, Diwadkar VA, Horwitz SM, Axelson D, Frazier T, Arnold EL, Fristad MA, Youngstrom EA, Findling RL, and Phillips ML
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- Adolescent, Child, Child Behavior Disorders complications, Comprehension physiology, Diffusion Tensor Imaging, Dyslexia etiology, Dyslexia pathology, Female, Humans, Male, Mood Disorders complications, Neural Pathways pathology, Neuroimaging methods, Child Behavior Disorders pathology, Mood Disorders pathology, Reading, White Matter pathology
- Abstract
Mood disorders and behavioral are broad psychiatric diagnostic categories that have different symptoms and neurobiological mechanisms, but share some neurocognitive similarities, one of which is an elevated risk for reading deficit. Our aim was to determine the influence of mood versus behavioral dysregulation on reading ability and neural correlates supporting these skills in youth, using diffusion tensor imaging in 11- to 17-year-old children and youths with mood disorders or behavioral disorders and age-matched healthy controls. The three groups differed only in phonological processing and passage comprehension. Youth with mood disorders scored higher on the phonological test but had lower comprehension scores than children with behavioral disorders and controls; control participants scored the highest. Correlations between fractional anisotropy and phonological processing in the left Arcuate Fasciculus showed a significant difference between groups and were strongest in behavioral disorders, intermediate in mood disorders, and lowest in controls. Correlations between these measures in the left Inferior Longitudinal Fasciculus were significantly greater than in controls for mood but not for behavioral disorders. Youth with mood disorders share a deficit in the executive-limbic pathway (Arcuate Fasciculus) with behavioral-disordered youth, suggesting reduced capacity for engaging frontal regions for phonological processing or passage comprehension tasks and increased reliance on the ventral tract (e.g., the Inferior Longitudinal Fasciculus). The low passage comprehension scores in mood disorder may result from engaging the left hemisphere. Neural pathways for reading differ mainly in executive-limbic circuitry. This new insight may aid clinicians in providing appropriate intervention for each disorder.
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- 2017
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41. Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth.
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Bertocci MA, Bebko G, Dwojak A, Iyengar S, Ladouceur CD, Fournier JC, Versace A, Perlman SB, Almeida JRC, Travis MJ, Gill MK, Bonar L, Schirda C, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Frazier T, Arnold LE, Fristad MA, Youngstrom EA, Findling RL, and Phillips ML
- Abstract
Background: Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort., Methods: Forty-one youth completed two study visits (mean=21.3 months). Elastic-net regression (Multiple response Gaussian family) identified emotional regulation neural circuitry that changed in association with changes in depression, mania, anxiety, affect lability, and positive mood and energy dysregulation, accounting for clinical and demographic variables., Results: Non-zero coefficients between change in the above symptom measures and change in activity over the inter-scan interval were identified in right amygdala and left ventrolateral prefrontal cortex. Differing patterns of neural activity change were associated with changes in each of the above symptoms over time. Specifically, from Scan1 to Scan2, worsening affective lability and depression severity were associated with increased right amygdala and left ventrolateral prefrontal cortical activity. Worsening anxiety and positive mood and energy dysregulation were associated with decreased right amygdala and increased left ventrolateral prefrontal cortical activity. Worsening mania was associated with increased right amygdala and decreased left ventrolateral prefrontal cortical activity. These changes in neural activity between scans accounted for 13.6% of the variance; that is 25% of the total explained variance (39.6%) in these measures., Conclusions: Distinct neural mechanisms underlie changes in different mood and anxiety symptoms overtime.
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- 2017
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42. Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders.
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Hafeman D, Bebko G, Bertocci MA, Fournier JC, Chase HW, Bonar L, Perlman SB, Travis M, Gill MK, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold LE, Fristad MA, Frazier TW, Youngstrom EA, Findling RL, and Phillips ML
- Subjects
- Adolescent, Amygdala diagnostic imaging, Attention Deficit Disorder with Hyperactivity physiopathology, Bipolar Disorder physiopathology, Bipolar Disorder psychology, Case-Control Studies, Child, Diagnosis, Differential, Facial Expression, Female, Gyrus Cinguli diagnostic imaging, Gyrus Cinguli physiopathology, Humans, Longitudinal Studies, Male, Prefrontal Cortex diagnostic imaging, Psychophysiology, Amygdala physiopathology, Attention Deficit Disorder with Hyperactivity diagnosis, Bipolar Disorder diagnosis, Emotions physiology, Magnetic Resonance Imaging, Prefrontal Cortex physiopathology
- Abstract
Objective: Both bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task., Methods: We scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex., Results: FxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions
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- 2017
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43. Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.
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Soehner AM, Bertocci MA, Manelis A, Bebko G, Ladouceur CD, Graur S, Monk K, Bonar LK, Hickey MB, Axelson D, Goldstein BI, Goldstein TR, Birmaher B, and Phillips ML
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- Adolescent, Case-Control Studies, Cerebral Cortex physiopathology, Child, Connectome, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net physiopathology, Affect physiology, Bipolar Disorder physiopathology, Brain physiopathology, Child of Impaired Parents psychology, Mood Disorders physiopathology, Neural Pathways physiopathology, Reward, Sleep physiology
- Abstract
Background: Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP., Methods: Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed., Results: Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group
⁎ sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only., Limitations: Cross-sectional design and small sample size., Conclusions: Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration., (Copyright © 2016 Elsevier B.V. All rights reserved.)- Published
- 2016
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44. Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?
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Portugal LC, Rosa MJ, Rao A, Bebko G, Bertocci MA, Hinze AK, Bonar L, Almeida JR, Perlman SB, Versace A, Schirda C, Travis M, Gill MK, Demeter C, Diwadkar VA, Ciuffetelli G, Rodriguez E, Forbes EE, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold EL, Fristad MA, Youngstrom EA, Findling RL, Pereira M, Oliveira L, Phillips ML, and Mourao-Miranda J
- Subjects
- Adolescent, Affective Symptoms drug therapy, Affective Symptoms pathology, Affective Symptoms physiopathology, Behavior Rating Scale, Bipolar Disorder psychology, Cerebellum pathology, Cerebellum physiopathology, Cerebral Cortex pathology, Cerebral Cortex physiopathology, Cohort Studies, Confounding Factors, Epidemiologic, Female, Follow-Up Studies, Games, Experimental, Humans, Limbic System pathology, Limbic System physiopathology, Male, Mental Disorders drug therapy, Mental Disorders pathology, Mental Disorders physiopathology, Psychotropic Drugs pharmacology, Psychotropic Drugs therapeutic use, Symptom Assessment, Adolescent Behavior, Affective Symptoms diagnosis, Brain Mapping, Magnetic Resonance Imaging, Mental Disorders diagnosis, Pattern Recognition, Automated, Psychology, Adolescent, Reward
- Abstract
Introduction: High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points., Methods: A sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels., Results: Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model included cerebellum, sensory-motor and fronto-limbic areas., Conclusions: The combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points.
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- 2016
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45. Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder.
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Manelis A, Ladouceur CD, Graur S, Monk K, Bonar LK, Hickey MB, Dwojak AC, Axelson D, Goldstein BI, Goldstein TR, Bebko G, Bertocci MA, Hafeman DM, Gill MK, Birmaher B, and Phillips ML
- Subjects
- Adolescent, Amygdala pathology, Brain Mapping, Child, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Oxygen blood, Parents, Pattern Recognition, Visual, Photic Stimulation, Prefrontal Cortex pathology, Psychiatric Status Rating Scales, Amygdala blood supply, Bipolar Disorder pathology, Child of Impaired Parents psychology, Facial Expression, Neural Pathways blood supply, Prefrontal Cortex blood supply
- Abstract
This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
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46. White matter structure in youth with behavioral and emotional dysregulation disorders: a probabilistic tractographic study.
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Versace A, Acuff H, Bertocci MA, Bebko G, Almeida JR, Perlman SB, Leemans A, Schirda C, Aslam H, Dwojak A, Bonar L, Travis M, Gill MK, Demeter C, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Frazier TW, Arnold LE, Fristad MA, Youngstrom EA, Findling RL, and Phillips ML
- Subjects
- Adolescent, Affective Symptoms complications, Anisotropy, Behavioral Symptoms complications, Case-Control Studies, Diffusion Tensor Imaging, Female, Humans, Male, Affective Symptoms pathology, Behavioral Symptoms pathology, Brain pathology, Gyrus Cinguli pathology, White Matter pathology
- Abstract
Importance: Psychiatric disorders in youth characterized by behavioral and emotional dysregulation are often comorbid and difficult to distinguish. An alternative approach to conceptualizing these disorders is to move toward a diagnostic system based on underlying pathophysiologic processes that may cut across conventionally defined diagnoses. Neuroimaging techniques have potentials for the identification of these processes., Objective: To determine whether diffusion imaging, a neuroimaging technique examining white matter (WM) structure, can identify neural correlates of emotional dysregulation in a sample of youth with different psychiatric disorders characterized by behavioral and emotional dysregulation., Design, Setting, and Participants: Using global probabilistic tractography, we examined relationships between WM structure in key tracts in emotional regulation circuitry (ie, cingulum, uncinate fasciculus, and forceps minor) and (1) broader diagnostic categories of behavioral and emotional dysregulation disorders (DDs) and (2) symptom dimensions cutting across conventional diagnoses in 120 youth with behavioral and/or emotional DDs, a referred sample of the Longitudinal Assessment of Manic Symptoms (LAM) study. Thirty age- and sex-matched typically developing youth (control participants) were included. Multivariate multiple regression models were used. The study was conducted from July 1, 2010, to February 28, 2014., Main Outcomes and Measures: Fractional anisotropy as well as axial and radial diffusivity were estimated and imported into a well-established statistical package. We hypothesized that (1) youth with emotional DDs and those with both behavioral and emotional DDs would show significantly lower fractional anisotropy compared with youth with behavioral DDs in these WM tracts and (2) that there would be significant inverse relationships between dimensional measures of affective symptom severity and fractional anisotropy in these tracts across all participants., Results: Multivariate multiple regression analyses revealed decreased fractional anisotropy and decreased axial diffusivity within the uncinate fasciculus in youth with emotional DDs vs those with behavioral DDs, those with both DDs, and the controls (F6,160 = 2.4; P = .032; all pairwise comparisons, P < .002). In the same model, greater severity of manic symptoms was positively associated with higher fractional anisotropy across all affected youth (F3,85 = 2.8; P = .044)., Conclusions and Relevance: These findings suggest that abnormal uncinate fasciculus and cingulum WM structure may underlie emotional, but not behavioral, dysregulation in pediatric psychiatric disorders and that a different neural mechanism may exist for comorbid emotional and behavioral DDs.
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- 2015
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47. Decreased amygdala-insula resting state connectivity in behaviorally and emotionally dysregulated youth.
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Bebko G, Bertocci M, Chase H, Dwojak A, Bonar L, Almeida J, Perlman SB, Versace A, Schirda C, Travis M, Gill MK, Demeter C, Diwadkar V, Sunshine J, Holland S, Kowatch R, Birmaher B, Axelson D, Horwitz S, Frazier T, Arnold LE, Fristad M, Youngstrom E, Findling R, and Phillips ML
- Subjects
- Adolescent, Anxiety physiopathology, Anxiety Disorders physiopathology, Attention Deficit and Disruptive Behavior Disorders physiopathology, Case-Control Studies, Depression physiopathology, Depressive Disorder physiopathology, Female, Functional Neuroimaging methods, Humans, Longitudinal Studies, Male, Personality Inventory, Young Adult, Amygdala physiopathology, Bipolar Disorder physiopathology, Emotions physiology, Magnetic Resonance Imaging methods
- Abstract
The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
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- 2015
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48. Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication.
- Author
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Hafeman DM, Bebko G, Bertocci MA, Fournier JC, Bonar L, Perlman SB, Travis M, Gill MK, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold LE, Fristad MA, Frazier TW, Youngstrom EA, Findling RL, Drevets W, and Phillips ML
- Subjects
- Adolescent, Amygdala blood supply, Amygdala physiopathology, Bipolar Disorder drug therapy, Bipolar Disorder pathology, Brain Mapping, Case-Control Studies, Child, Emotions drug effects, Face, Facial Expression, Female, Frontal Lobe blood supply, Functional Laterality, Humans, Image Processing, Computer-Assisted, Linear Models, Magnetic Resonance Imaging, Male, Oxygen blood, Pattern Recognition, Visual, Photic Stimulation, Antipsychotic Agents therapeutic use, Bipolar Disorder physiopathology, Emotions physiology, Frontal Lobe drug effects, Frontal Lobe physiopathology
- Abstract
Previous neuroimaging studies of youth with bipolar disorder (BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n = 59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes. Whole brain analysis was used to identify clusters that showed differential activation to emotion vs. shapes across group. To assess pair-wise comparisons and potential confounders, mean activation data were extracted only from clusters within regions previously implicated in emotion regulation (including amygdala and ventral prefrontal regions). A cluster in the right inferior frontal gyrus (IFG) showed group differences to emotion vs. shapes (159 voxels, corrected p < .05). Within this cluster, U-BD youth showed decreased activation relative to HC (p = .007) and non-BD (p = .004) youth. M-BD also showed decreased activation in this cluster relative to HC and non-BD youth, but these differences were attenuated. Results were specific to negative emotions, and not found with happy faces. IFG findings were not explained by other medications (e.g. stimulants) or diagnoses. Compared to both HC and a non-BD sample, U-BD is associated with abnormally decreased right IFG activation to negative emotions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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49. Parsing dimensional vs diagnostic category-related patterns of reward circuitry function in behaviorally and emotionally dysregulated youth in the Longitudinal Assessment of Manic Symptoms study.
- Author
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Bebko G, Bertocci MA, Fournier JC, Hinze AK, Bonar L, Almeida JR, Perlman SB, Versace A, Schirda C, Travis M, Gill MK, Demeter C, Diwadkar VA, Ciuffetelli G, Rodriguez E, Olino T, Forbes E, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold LE, Fristad MA, Youngstrom EA, Findling RL, and Phillips ML
- Subjects
- Adolescent, Attention Deficit and Disruptive Behavior Disorders physiopathology, Brain physiology, Case-Control Studies, Child, Female, Functional Neuroimaging, Gyrus Cinguli physiology, Gyrus Cinguli physiopathology, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Prefrontal Cortex physiology, Prefrontal Cortex physiopathology, Psychiatric Status Rating Scales, Affective Symptoms physiopathology, Bipolar Disorder physiopathology, Brain physiopathology, Child Behavior Disorders physiopathology, Reward
- Abstract
Importance: Pediatric disorders characterized by behavioral and emotional dysregulation pose diagnostic and treatment challenges because of high comorbidity, suggesting that they may be better conceptualized dimensionally rather than categorically. Identifying neuroimaging measures associated with behavioral and emotional dysregulation in youth may inform understanding of underlying dimensional vs disorder-specific pathophysiologic features., Objective: To identify, in a large cohort of behaviorally and emotionally dysregulated youth, neuroimaging measures that (1) are associated with behavioral and emotional dysregulation pathologic dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory 10-Item Mania Scale [PGBI-10M], mania, depression, and anxiety) or (2) differentiate diagnostic categories (bipolar spectrum disorders, attention-deficit/hyperactivity disorder, anxiety, and disruptive behavior disorders)., Design, Setting, and Participants: A multisite neuroimaging study was conducted from February 1, 2011, to April 15, 2012, at 3 academic medical centers: University Hospitals Case Medical Center, Cincinnati Children's Hospital Medical Center, and University of Pittsburgh Medical Center. Participants included a referred sample of behaviorally and emotionally dysregulated youth from the Longitudinal Assessment of Manic Symptoms (LAMS) study (n = 85) and healthy youth (n = 20)., Main Outcomes and Measures: Region-of-interest analyses examined relationships among prefrontal-ventral striatal reward circuitry during a reward paradigm (win, loss, and control conditions), symptom dimensions, and diagnostic categories., Results: Regardless of diagnosis, higher PGBI-10M scores were associated with greater left middle prefrontal cortical activity (r = 0.28) and anxiety with greater right dorsal anterior cingulate cortical (r = 0.27) activity to win. The 20 highest (t = 2.75) and 20 lowest (t = 2.42) PGBI-10M-scoring youth showed significantly greater left middle prefrontal cortical activity to win compared with 20 healthy youth. Disruptive behavior disorders were associated with lower left ventrolateral prefrontal cortex activity to win (t = 2.68) (all P < .05, corrected)., Conclusions and Relevance: Greater PGBI-10M-related left middle prefrontal cortical activity and anxiety-related right dorsal anterior cingulate cortical activity to win may reflect heightened reward sensitivity and greater attention to reward in behaviorally and emotionally dysregulated youth regardless of diagnosis. Reduced left ventrolateral prefrontal cortex activity to win may reflect reward insensitivity in youth with disruptive behavior disorders. Despite a distinct reward-related neurophysiologic feature in disruptive behavior disorders, findings generally support a dimensional approach to studying neural mechanisms in behaviorally and emotionally dysregulated youth.
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- 2014
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50. Emotional face processing in pediatric bipolar disorder: evidence for functional impairments in the fusiform gyrus.
- Author
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Perlman SB, Fournier JC, Bebko G, Bertocci MA, Hinze AK, Bonar L, Almeida JR, Versace A, Schirda C, Travis M, Gill MK, Demeter C, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold LE, Fristad MA, Youngstrom EA, Findling RL, and Phillips ML
- Subjects
- Adolescent, Child, Female, Functional Neuroimaging, Humans, Magnetic Resonance Imaging, Male, Multicenter Studies as Topic, Occipital Lobe physiopathology, Temporal Lobe physiopathology, Bipolar Disorder physiopathology, Cerebral Cortex physiopathology, Emotions physiology, Face, Facial Expression
- Abstract
Objective: Pediatric bipolar disorder involves poor social functioning, but the neural mechanisms underlying these deficits are not well understood. Previous neuroimaging studies have found deficits in emotional face processing localized to emotional brain regions. However, few studies have examined dysfunction in other regions of the face processing circuit. This study assessed hypoactivation in key face processing regions of the brain in pediatric bipolar disorder., Method: Youth with a bipolar spectrum diagnosis (n = 20) were matched to a nonbipolar clinical group (n = 20), with similar demographics and comorbid diagnoses, and a healthy control group (n = 20). Youth participated in a functional magnetic resonance imaging (fMRI) scanning which employed a task-irrelevant emotion processing design in which processing of facial emotions was not germane to task performance., Results: Hypoactivation, isolated to the fusiform gyrus, was found when viewing animated, emerging facial expressions of happiness, sadness, fearfulness, and especially anger in pediatric bipolar participants relative to matched clinical and healthy control groups., Conclusions: The results of the study imply that differences exist in visual regions of the brain's face processing system and are not solely isolated to emotional brain regions such as the amygdala. Findings are discussed in relation to facial emotion recognition and fusiform gyrus deficits previously reported in the autism literature. Behavioral interventions targeting attention to facial stimuli might be explored as possible treatments for bipolar disorder in youth., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
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