Cindy Hagan PhD

Affect perception and experience in healthy and clinical populations.

A core aspect of my current and past research concerns the perception and experience of emotion and how these processes go awry in disorders of neurodevelopment such as fragile X syndrome, conduct disorder, depression, and addiction. My doctoral work showed that emotion perception is multimodal, with visual and auditory signals being integrated within the first 250ms in motion-sensitive regions of the brain such as the superior temporal sulcus (Hagan et al., PNAS, 2009; Hagan et al., PLoS One, 2013). Pre- and post-doctoral work examined emotion perception in clinical populations and identified aberrant neural systems involved in emotional control (females with fragile X syndrome: Hagan et al., J Amer Acad Child Adol Psych, 2008; females with conduct disorder: Fairchild, Hagan et al., J Amer Acad Child Adol Psych, 2014), affective salience (males with conduct disorder: Passamonti, Fairchild, Goodyer, Hurford, Hagan et al., Arch Gen Psych, 2010), and threat perception (addiction: Ersche, Hagan et al., Trans Psych, 2015). Alterations in both threat and reward neural systems are proposed to underlie many affective disorders, perhaps partially driven by adversity in early life. Research that I conducted with others in young adults with conduct disorder identified structural and functional anomalies irrespective of whether conduct disorder emerged in childhood or adolescence (Fairchild, Passamonti, Hurford, Hagan et al., Am J Psych, 2011), contrary to theories suggesting divergent pathways of emergence for the two forms of the disorder (Developmental Taxonomic Theory: Moffitt, 1993). These findings informed the development of a human model for threat anticipation and survival optimization (Mobbs, Hagan et al., Front Neurosci, 2015).

Other work in healthy individuals has identified that extraversion is associated with positive affect and increased activity in the mesolimbic reward systems (Mobbs, Hagan et al., PNAS, 2005). Healthy individuals also engage reward systems when an individual accepts the advice that we provide to them and when our advice leads to positive outcomes in this individual’s experience (i.e., reflected glory: Hagan, Mobbs et al., SCAN, 2015).

Understanding depression and the effects of talking therapy treatment.

During my post-doctoral work I worked alongside others to conduct a meta-analysis prior to the corpus of data collection in adolescents with depression. Results from the meta-analysis indicated that aberrant subcortical neural activity in depression is treatment insensitive and thus may represent regions vulnerable to depressive illness in individuals. Contrariwise, frontal regions show treatment sensitivity and could represent biomarker(s) of treatment response (Graham, Salimi-Khorshidi, Hagan et al., J Affect Disord, 2013). Our neuroimaging investigations of a pragmatic effectiveness treatment trial for depression in adolescence supported these findings, indicating initially aberrant responses in the orbitofrontal cortex were normalized following cognitive behavioral therapy (Chuang, Whitaker, Murray, Elliott, Hagan et al., J Affect Disord, 2016). As many of the adolescents involved in this treatment trial were obtaining treatment for their first experience with depression, our observation of no significant group differences in brain structure prior to treatment was unsurprising. Nonetheless, significant group-by-age interactions were observed in the thalamus (associated with severity of depressive symptoms) and the ACC (not associated with severity of depressive symptoms) (Hagan et al., Neuroimage Clin, 2015), suggesting the importance of cortico-striatal-pallidalthalamic/reward-salience models of depressive illness onset. The thalamus could be a multimodal gateway between the autonomic nervous system and the regions of the brain that interpret our experiences as Walter Cannon once proposed.

Examples of my research in depression:
Hagan CC, Graham, JME, Wilkinson PO, Suckling J, Sahakian BJ, Goodyer IM (2015). Neurodevelopment and ages of onset in depressive disorders. Lancet Psychiatry, 2(12): 1112-1116.

Hagan CC, Graham JME, Tait R, Widmer B, van Nieuwenhuizen AO, Ooi C, Whitaker KJ, Simas T, Bullmore ET, Lennox BR, Sahakian BJ, Goodyer IM, Suckling J (2015). Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus. Neuroimage Clin, 7: 391-399.

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Current work

Interoception and transdiagnostic relationship to affective symptoms. Compelling theories link internal body signals with emotions (Two Factor Theory) and emotional decision-making (Somatic Marker Hypothesis), yet there is a notable absence of theory when it comes to how internal body sensations become encoded into episodic memory and subsequently utilized to construct knowledge representations of the external world (i.e., the world is a friendly/hostile place) or generate predictions of future events (akin to the Constructive Episodic Simulation Hypothesis). Embodied Predictive Interoception Coding suggests that alterations in interoceptive memory formation and prediction generation could confer vulnerability to psychiatric disorders. One goal of my work at Caltech is therefore to examine how interoceptive events are featured in memory of past events and imagery for future events in healthy individuals, and how the level of confidence one has in the precision of his/her ability to identify (i.e., metacognitive awareness) internal body signals relates to depressive and anxious symptoms in healthy individuals. My recent NARSAD Junior Investigator Award will allow me to test some of these questions in female patients with​ anorexia nervosa in collaboration with Professor Jamie Feusner at the UCLA Eating Disorders and Body Dysmorphic Disorder Research Program.