Trauma-associated anterior cingulate connectivity during reward learning predicts affective and anxiety states in late adolescence and young adulthood

• In Event: The consequences of adversity and maltreatment in brain function among adolescents and young adults

Abstract

Introduction. Trauma exposure is common and associated with the development of depression and anxiety. However, not all exposed individuals will develop negative affective symptoms and some adapt positively to trauma exposure. Differentiating mechanisms underlying development of negative affect and resilience following trauma is critical for developing effective interventions. One pathway where trauma could exert its effects on negative affect is through reward learning neural networks. In this study, we examine the relationships among lifetime trauma exposure, reward learning network function, and negative affective states in young adults.

Methods. One hundred eleven young adults ages 18-25 (78F, 33M) self-reported lifetime trauma using the Trauma History Questionnaire (THQ) and emotional states using the Hamilton Anxiety and Depression Rating Scales (HAMA, HDRS), Mood and Anxiety Symptom Questionnaire (MASQ), and Snaith-Hamilton Pleasure Scale (SHAPS). All participants underwent functional magnetic resonance imaging during a monetary reward task. Trauma exposure was regressed against neural activation and reward learning network functional connectivity during reward prediction error (RPE) using SPM12 (punc<0.001). Relationships between trauma-associated neural functioning and affective and anxiety symptoms were examined using multiple linear regression models in SPSS.

Results. 72% of participants reported traumatic events (M = 2.0 ± 1.93 events; range 0–10 events). Number of traumatic events was associated with greater ventral anterior cingulate cortex (vACC) activation, and lower vACC connectivity with regions including the anterior insula (aIns), frontopolar cortex (FPC), and inferior parietal lobule (IPL). the anterior insula, frontopolar, inferior parietal, and temporoparietal regions, during RPE. Lower vACC-IPL connectivity was associated with greater anxiety symptom severity (HAMA: β= -0.58, p=0.05), greater anxious arousal (MASQ-AA: β=−0.04, p=0.05), and greater anhedonia (SHAPS: β=-0.60, p=0.04). Lower vACC-FPC connectivity was associated with greater anxious arousal (β=−0.06, p=0.05). In contrast, lower vACC connectivity with the aIns was associated with lower anxiety symptom severity (HAMA: β=1.21, p=0.02), lower depression symptom severity (HRSD: β=1.29, p=0.03), and lower anhedonic depression severity (MASQ-AD: β=0.11, p=0.04).

Discussion. In a young adult sample, lower trauma-associated vACC connectivity with frontoparietal regions implicated in regulatory and decision-making processes was associated with heightened affective and anxiety symptoms whereas lower vACC connectivity with insular regions implicated in interoception was associated with lower affective and anxiety symptoms. These results implicate two pathways in the impact of trauma on reward-learning networks with resultant higher versus 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 versus resilience against negative affective and anxiety symptoms.

Authors

• Kristen Eckstrand, University of Pittsburgh School of Medicine
  Presenting Author

• Erika E Forbes, University of Pittsburgh
  Non-Presenting Author

• Lindsay C Hanford, Harvard University
  Non-Presenting Author

• Michele A Bertocci, University of Pittsburgh Medical Center
  Non-Presenting Author

• Henry W Chase, University of Pittsburgh Medical Center
  Non-Presenting Author

• Tsafrir Greenberg, University of Pittsburgh Medical Center
  Non-Presenting Author

• Jeanette Lockovich, University of Pittsburgh Medical Center
  Non-Presenting Author

• Ricki Stiffler, University of Pittsburgh Medical Center
  Non-Presenting Author

• Haris Aslam, University of Pittsburgh Medical Center
  Non-Presenting Author

• Simona Graur, University of Pittsburgh Medical Center
  Non-Presenting Author

• Genna Bebko, University of Pittsburgh Medical Center
  Non-Presenting Author

• Mary L Phillips, University of Pittsburgh
  Non-Presenting Author