How Stress “Gets Under the Skin.” Considerable evidence indicates that early-life adversity increases risk for emotional and physical health problems across the lifespan. This phenomenon raises an important question for scientists and clinicians alike. How does adversity get under the skin of a developing child to confer vulnerability to a heterogeneous set of mental and physical illnesses? Working with IPR health psychologists Greg Miller and Edith Chen, Nusslock is investigating these questions. He and Miller developed a neuroimmune network (NIN) model that argues that life adversity amplifies crosstalk between peripheral inflammation and brain systems subserving both negative and positive emotions. When dysregulated, this crosstalk results in chronic low-grade inflammation and neuroplastic changes in the brain that elevate risk for illness. Nusslock is currently testing the central tenets of this model across multiple projects examining the relationship between neuroimmune signaling and both mental and physical health. He is also interested in identifying neural and psychosocial processes that can help protect people from the health consequences of stress and adversity, and the influence of policies and interventions on these profiles of resilience.
The Neuroscience of Emotion and Decision Making. Nusslock uses behavioral techniques, neurophysiology, and both structural and functional brain imaging to investigate how the brain generates approach (such as reward) and avoidance (such as threat or fear) emotional states. He is particularly interested in how emotional brain systems modulate our everyday decisions. The Rational Choice Perspective in Economics argues that humans make consistent decisions to maximize preferences. Economists, cognitive scientists, and psychologists have started to refine this perspective by proposing a model of Bounded Rationality, which argues that humans may deviate from rational decision making in predictable ways. Nusslock uses neuroscientific methods to try to model these deviations in rationality. Specifically, he examines whether variation in brain systems involved in processing reward and threat predict the likelihood that someone will make optimal versus suboptimal choices both in the laboratory and in naturalistic settings.
The Neuroscience of Mental Illness. Nusslock translates his research on the basic mechanics of emotion in the brain to investigate emotional disorders such as depression, anxiety, and mania. This work, funded by the National Institutes of Health, focuses on abnormalities in brain systems involved in processing rewards and threats in the environment. Epidemiological research indicates it can take up to ten years for individuals with a serious psychiatric disorder to receive an accurate diagnosis, which delays treatment and worsens the course of illness. A goal of Nusslock’s research program is to develop “brain stress tests” to facilitate more accurate and timely diagnoses of psychiatric illness. The logic of this vision is similar to a cardiac-stress test for detecting risk for heart disease. In addition to facilitating diagnosis, understanding the biological mechanisms of psychiatric risk can inform our understanding of the causes and consequences of mental illness, provide targets for intervention and prevention programs, and provide metrics to measure the efficacy of social policy programs aimed at maximizing mental health and minimizing mental illness.
Leve, L.D., Kanamori, M., Humphreys, K.L., Jaffee, R., Nusslock, R., Oro, V., and Hyde, L.W. In press. The Promise and Challenges of Integrating Biological and Prevention Sciences: A Community-Engaged Model for the Next Generation of Translational Research. Prevention Science.
Miller, G.E., A. L. Carroll, C. C. Armstrong, M. G. Craske, R. E. Zinbarg, S. Y. Bookheimer, I. K. Y. Chat, M. Vinograd, K. S. Young, and R. Nusslock. 2024. Major stress in early childhood strengthens the association between peripheral inflammatory activity and corticostriatal responsivity to reward. Brain, Behavior, and Immunity 117: 215-23.
Nusslock, R., L. B. Alloy, G. H. Brody, and G.E. Miller. 2024. Neuroimmune network model of depression: A developmental perspective. Journal of Child Psychology and Psychiatry 65: 538-567.
Anderson, Z., K. Damme, A. Carroll, I. Chat, K. Young, M. Craske, S. Bookheimer, R. Zinbarg, and R. Nusslock. 2023. Association between reward-related functional connectivity and tri-level mood and anxiety symptoms. NeuroImage: Clinical 37:103335.
Craske, M., M. Herzallah, R. Nusslock, and V. Patel. 2023. From neural circuits to communities: An integrative multidisciplinary roadmap for global mental health. Nature Mental Health 1: 12–24.
Kraus, B., R. Zinbarg, R. M. Braga, R. Nusslock, V. A. Mittal, and C. Gratton. 2023. Insights from Personalized Models of Brain and Behavior for Identifying Biomarkers in Psychiatry. Neuroscience & Biobehavioral Reviews 152:105259.
Nusslock, R. and M. Farah. 2022. The affective neuroscience of poverty. Journal of Cognitive Neuroscience 34(10): 1806–09.
White, S., R. Nusslock, G. Miller. 2022. Low socioeconomic status is associated with greater neural responses to both rewards and losses. Journal of Cognitive Neuroscience 34(10): 1939–51.
Bart, C., R. Nusslock, T. Ng, M. Titone, A. Carroll, K. Damme, C. Young, C. Armstrong, J. Chein, and L. Alloy. 2021. Decreased reward-related brain function prospectively predicts increased substance use. Journal of Abnormal Psychology 130(8): 886–98.
Miller, G., E. Chen, E. Finegood, P. Lam, R. Weissman-Tsukamoto, A. Leigh, L. Hoffer, A. Carroll, G. Brody, T. Parrish, and R. Nusslock. 2021. Resting-state functional connectivity of the central executive network moderates the relationship between neighborhood violence and pro-inflammatory phenotype in children. Biological Psychiatry 90(3): 165–72.
Miller, G., S. White, E. Chen, and R. Nusslock. 2020. Association of inflammatory activity with larger neural responses to threat and reward among children living in poverty. American Journal of Psychiatry 178(4): 313–20.
Damme, K., L. Alloy, C. Young, N. Kelley, J. Chein, T. Ng, M. Titone, C. Black, and R. Nusslock. 2020. Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion-based subsegmentation and a high-risk design. Human Brain Mapping 41(12): 3358–69.
Nusslock, R., G. Brody, C. Armstrong, A. Carroll, L. Sweet, T. Yu, A. Barton, E. Hallowell, E. Chen, J. Higgins, T. Parrish, L. Wang, and G. Miller. 2019. Higher peripheral inflammatory signaling associated with lower resting state functional brain connectivity in emotion regulation and central executive networks. Biological Psychiatry 86:153–62.
Brody, G., T. Yu, R. Nusslock, A. Barton, G. Miller, E. Chen, and L. Sweet. 2019. Effect of supportive parenting on the relationship between adolescent poverty and resting state functional brain connectivity during adulthood. Psychological Science 30:1040–49.
Miller, G., E. Chen, C. Armstrong, A. Carroll, S. Ozturk, K. Rydland, G. Brody, T. Parrish, and R. Nusslock. 2018. Functional connectivity in central executive network protects youth against cardiometabolic risks linked with neighborhood violence. Proceedings of the National Academy of Sciences 115:12063–68.
