Our work examines neural mechanisms of emotion and cognition, and their relationships to mental health and recovery in treatment using a variety of technologies including computational modeling, peripheral psychophysiology, and neuroimaging. We apply insights from this work to understand how individuals change in treatment, with particular emphasis on understanding who will benefit from conventional interventions, and how to better target identified mechanisms using novel mechanistic interventions.

Major Themes and Representative Publications

Understanding the time course of emotional information processing in psychopathology.

Disorders of negative mood are characterized by rumination on the time course of minutes or hours or days, and biases to perceive and attend to emotional information on the order of milliseconds. Together these features yield pathologies in which emotional information is perceived and fixated on with little chance of regulation or moving past it. My research program works to understand why and how emotional information processing in psychopathology is often very fast or very sustained using self-report, behavioral assessment, computational modeling, peripheral psychophysiology, and neuroimaging. I conducted the first psychophysiological and first fMRI studies of sustained emotional information processing in depression. This work has lead to a more nuanced approach to assessing emotional information processing in psychopathology, and a stronger understanding of debilitating negative-thinking phenomena such as rumination, yielding mechanistic targets for intervention.

1. Siegle, G. J., Steinhauer, S.R., Thase, M.E., Stenger, V.A., Carter, C. S., (2002). Can’t shake that feeling: Event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry, 51, 693-707. 
2. Larson, C., Schaefer, H.S., Siegle, G.J., Jackson, C. A. B., Anderle, M.J., Davidson, R.J. (2006). Fear is fast in phobic individuals: Amygdala activation in response to fear-relevant stimuli. Biological Psychiatry. 60, 410-417. PMID:  16919528.
3. Siegle, G.J., Thompson, W., Thase, M.E., Steinhauer, S.R., Carter, C. S., (2007). Increased amygdala and decreased dorso-lateral prefrontal BOLD responses in unipolar depression: Related and independent features. Biological Psychiatry, 61, 198-209. PMID:  17027931.
4. Brandeis, B.O., Siegle, G.J.*, Franzen, P., Soehner, A., Hasler, B., McMakin, D., Young, K., Buysse, D.J. (in press) Subjective and neural reactivity during savoring and rumination. Cognitive, Affective, and Behavioral Neuroscience.

Improving methods for translation from neuroscience to psychophysiology to the clinic

There is a notorious gap between basic neuroscience and interventions in the clinic. A great deal of my work is devoted to paving translational pathways including highlighting breaks in translation, providing translations from neuroimaging to less effortful/costly assessments (e.g., I published the first paper using pupil dilation to identify the expected time course of fMRI reactivity), including validating consumer grade psychophysiology outside non-traditional laboratory environments and making advanced techniques available to the world via publicly available toolkits.

1. Siegle, G. J., Steinhauer, S.R., Stenger, V.A., Konecky, R., Carter, C. S., (2003). Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data. Neuroimage. 20(1), 114-124. PMID:  14527574.
2. Biswal, B. B.,  Mennes, M.,  Zuo, X.,  Gohel, S.,  Kelly, C.,  Smith, S. M.,  Beckmann, C. F.,  Adelstein, J. S.,  Buckner, R. L.,  Colcombe, S.,  Dogonowski, A.,  Ernst, M.,  Fair, D.,  Hampson, M.,  Hoptman, M. J.,  Hyde, J. S.,  Kiviniemi, V. J.,  Kötter, R.,  Li, S.,  Lin, C.,  Lowe, M. J.,  Mackay, C.,  Madden, D. J.,  Madsen, K. H.,  Margulies, D. S.,  Mayberg, H. S.,  McMahon, K.,  Monk, C. S.,  Mostofsky, S. H.,  Nagel, B. J.,  Pekar, J. J.,  Peltier, S. J.,  Petersen, S. E.,  Riedl, V.,  Rombouts, S. A.,  Rypma, B.,  Schlaggar, B. L.,  Seidler, S. S.,  Siegle, G. J.,  Sorg, C.,  Teng, G.,  Veijola, J.,  Villringer, A.,  Walter, M.,  Wang, L.,  Weng, X.,  Whitfield-Gabrieli, S.,  Williamson, P.,  Windischberger, C.,  Zang, Y.,  Zhang, H.,  Castellanos, F. X.,  Milham, M. P., (2010) Towards discovery science of human brain function. Proceedings of the National Academy of Science, 107, 4734-4739. PMID:  20176931.
3. Siegle, G.J., Cramer, A.O.J., van Eck, N. J., Spinhoven, P., Hollon, D., Ormel, J., Strege, M., Bockting, C.H. (2019) Where are the breaks in translation from theory to clinical practice (and back) in addressing depression? An empirical graph-theoretic approach. Psychological Medicine, 49(16), 2681-2691
4. Compere, L., Siegle, G.J.*, Young, K.D. (2021) Importance of test-retest reliability for promoting fMRI based screening and interventions in major depressive disorder. Translational Psychiatry, 11(1), 387, https://doi.org/10.1038/s41398-021-01507-3

Neural basis of disorders of mood and emotion throughout the lifespan

It has long been recognized that emotional information processing styles in psychopathology do not emerge and dissipate in mid-adulthood, but rather, their roots can be seen in childhood, and that they may transform in old age to particularly sinister variants associated with critically important outcomes such as suicide. Thus, I have worked with talented collaborators and students to identify early emotional information processing biases in depressed and anxious youth, and to examine how emotional and cognitive processes may be disrupted in old age.

1. Conner, O. L., Siegle, G. J.*, Mcfarland, A. M., Silk, J. S., Ladouceur, C. D., Dahl, R. E., Coan, J.A., Ryan, N.D. (2012). Mom – it helps when you’re right here! Attenuation of neural stress markers in anxious youths whose caregivers are present during fMRI. PLoS ONE, 7(12), e50680
2. Dombrovski, A.Y., Szanto, K., Clark, L., Reynolds, C.F., Siegle, G.J.* (2013). Reward signals, attempted suicide, and impulsivity in late-life depression. JAMA Psychiatry, 70(10), 1020-1030.
3. Price, R.B., Siegle, G.J.*, Silk, J.S., Ladouceur, C., McFarland, A., Dahl, R.E., Ryan, N.D. (2014). Looking under the hood of the dot-probe task: an fMRI study in anxious youth. Depression and Anxiety, 31(3), 178-187, DOI: 10.1002/da.22255, PMCID: 3992818. (Winner, Donald Klein Award paper).
4. Butterfield, R.D., Siegle, G.J.*, Lee, K.H., Ladouceur, C.D., Forbes, E.E., Dahl, R.E., Ryan, N.D., Sheeber, L., Silk, J.S. (2019) Parental coping socialization is associated with healthy and anxious early adolescents’ neural and real-world response to threat. Developmental Science, e12812.

Understanding and predicting response to conventional treatments

The assessments of emotional information processing pioneered in our lab have identified mechanisms that are ideally targeted with conventional treatments. Thus, we have used these assessments to examine whether individuals with identified mechanisms recover more reliably than those without them. This work has lead to replicated findings that 1) identified mechanisms of sustained emotional information processing do change in treatment and 2) assessing these mechanisms can reliably predict who recovers in cognitive and drug therapies. Replication by our group and others has suggested that fMRI and peripheral physiological proxies are strong enough predictors to warrant clinical exploration.

1. DeRubeis, R.J., Siegle, G. J., Hollon, S., (2008). Cognitive therapy versus medications for depression: treatment outcomes and neural mechanisms. Nature Neuroscience: Reviews, 9, 788-796. PMID:  18784657.
2. Siegle, G.J., Thompson, W. K., Collier, A., Berman, S. R., Feldmiller, J., Thase, M. E., & Friedman, E. S. (2012). Towards clinically useful neuroimaging in depression treatment: Prognostic Utility of subgenual cingulate activity for determining depression outcome in Cognitive Therapy across studies, scanners, and patient characteristics. Archives of General Psychiatry, 69(9), 913-924. NIHMSID 524641.
3. Siegle, G.J., Steinhauer, S.R., Friedman, E., Thase, M.E. (2011). Remission prognosis for Cognitive Therapy for recurrent depression using the pupil: Utility and neural correlates, Biological Psychiatry, 69, 726-33. PMID:  21447417.
4. Young, K.D.., Friedman, E.S., Collier, A., Berman, S.R., Feldmiller, J., Haggerty, A.E., Thase, M.E., Siegle, G.J.* (2020) Response to SSRI intervention and amygdala activity during self-referential processing in major depressive disorder. NeuroImage: Clinical, 28: 102388, doi: 10.1016/j.nicl.2020.102388, PMCID: PMC7476063, PMID: 32871385

Novel mechanistically targeted treatment development

Identification of cognitive and brain mechanisms of psychopathology has led our group to test a series of novel neurocognitive interventions devoted to cognitive remediation of deficits or abnormalities. My 2007 publication on the potential of bringing cognitive rehabilitation to neural mechanisms of emotional information processing biases has been particularly well regarded, with the intervention proposed in that paper spurring a series of tests, randomized trials, trials involving augmentation by direct stimulation throughout the world.

1. Siegle, G. J.+, Price, R. B.+, Jones, N. P., Ghinassi, F., & Thase, M. E. (2014). You gotta work at it: Pupillary indices of task focus are prognostic for response to a neurocognitive intervention for depression. Clinical Psychological Science.  + These authors contributed equally. 2(4) 455-471.
2. Collier, A., Siegle, G.J.* (2015). Individual differences in response to prediction bias training. Clinical Psychological Science, 3(1), 79-90.
3. Young, K. D., Siegle, G. J.*, Misaki, M., Zotev, V., Phillips, R., Drevets, W. C., & Bodurka, J. (2018). Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder. Neuroimage Clin, 17, 691-703. doi:10.1016/j.nicl.2017.12.004
4. Fani, N., Guelfo, A., La Barrie, D.L., Teer, A.P., Clendinen, C., Karimzadeh, L., Jain, J., Ely, T.D., Powers, A., Bradley, B., Siegle, G.J.* (in press) Neurophysiological changes associated with vibroacoustically augmented breath-focused mindfulness for dissociation: Targeting interoception and attention. Psychological Medicine, doi: 10.1017/S0033291723001277.