The period following a first episode of schizophrenia (SZ) is considered a critical window for treating cognitive impairment, and cognitive training (CT) interventions have shown promising efficacy. Cognitive impairment in SZ is associated with widespread alterations in functional neural network connectivity. However, research has not identified consistent associations between specific connectivity measures and individual domains of cognitive impairment. Furthermore, few studies have examined whether CT works by promoting normalization of neural networks (i.e., reduction of pre-existing disturbances) and/or by fostering compensatory network processes. In the present studies, we used graph-theory connectivity analysis to evaluate properties of intrinsic functional network organization and their relationship to cognitive function in first-episode SZ before and after CT. Using resting-state fMRI data from 45 young adults with SZ and 32 healthy comparison participants (HC), we tested for group differences in graph properties of the ‘task-positive’ cingulo-opercular (CON) and frontoparietal (FPN) networks and the whole-brain network, as well as their relationship with global and domain-specific measures of cognitive function prior to CT. SZ and HC did not differ substantially on measures of network organization, and across groups, generalized cognitive performance was positively associated with centrality of a node in right dorsal anterior cingulate cortex (dACC). Cognitive function in SZ was more positively associated with whole-brain functional segregation than in HC. In SZ, cognitive performance appeared to be decoupled from bilateral dACC node centrality, though effects were non-significant after correcting for multiple comparisons. Next, using longitudinal data from 17 SZ who completed a six-month course of CT and 20 HC who received no intervention, we tested for network normalization and compensation following CT. Although effects were non-significant after correcting for multiple comparisons, we found preliminary evidence of compensation in SZ following CT. Centrality of a node in right dACC decreased after CT, and this decrease corresponded with gains in processing speed. Reduced centrality of two other nodes in right dACC following CT was associated with gains in working memory and generalized cognitive performance. Results illuminate a potential role for compensation in cognitive recovery from SZ and may contribute to increased precision of future CT interventions.

Individuals with depression and anxiety have difficulty inhibiting their response to emotional information. Depression has been related to more attentional bias to negative information as well as less attentional bias to positive information. Anxiety has been associated with more attentional bias to high arousal, negative (or threat-related) stimuli. Independent of depression and anxiety symptoms, stress across the lifespan has also been linked to alterations in emotion inhibition along with increased risk for the development of internalizing psychopathology in adulthood. Three studies were conducted in order to identify behavioral and neural correlates of a novel emotion inhibition task, and evaluate a potential mechanistic pathway linking stress exposure to psychopathology via alterations to emotion inhibition. To better characterize the role that distracting emotional contexts plays in disruption of inhibitory control, the Image-Color-Word Stroop (IMCWS) task was developed. Participants (N=133) completed the IMCWS as well as questionnaires assessing life stress, resilience, depression, and anxiety. EEG data were collected on a subset of participants (N = 72) during completion of the IMCWS task. The inclusion of emotionally valenced, high-arousal scenes resulted in longer reaction times during high-conflict conditions of the superimposed color-word Stroop, indicating that the IMCWS task successfully enhanced the automatic recruitment of emotion processing to be inhibited. Further, the IMCWS was found to alter event-related potential (ERP) components commonly associated with allocation of attention and emotion processing (e.g., N250, P300) and inhibitory control processes (N450), suggesting that emotion inhibition during the IMCWS involved increased early attentional allocation to emotional contexts followed by increased recruitment of inhibitory control mechanisms. Current life stress (CLS) was found to be predictive of anhedonic depression, and both were associated with alterations in emotion inhibition. Whereas CLS was associated with more biased attention and, therefore, reduced emotion inhibition during the presentation of negative-valence context images, anhedonic depression was found to be related to less biased attention (i.e., increased emotion inhibition) during the presentation of positive-valence context images. Emotion inhibition was not found to play a mechanistic role in the pathway from CLS to anhedonic depression. Rather, results suggest distinct, yet complementary impacts of CLS and anhedonic depression on emotion inhibition function. Given the comorbidity of CLS and depression, CLS should be considered in future studies of emotion regulation and cognitive control disruptions in depression.

Cardiac vagal tone (CVT) reflects the contribution of the parasympathetic nervous system to cardiac regulation and is hypothesized to contribute to the regulation of inflammation and expression of psychopathology. CVT may play an important role in sleep disturbance and insomnia treatment. Through a series of four studies, this dissertation interrogated the associations between CVT, inflammation, and clinical symptoms in sleep disturbed samples and evaluated possible roles for CVT in insomnia intervention. Studies 1 and 2 proposed a specific model: chronic sleep disturbance reduces CVT with downstream effects on inflammation and clinical symptoms. Studies 1 and 2 then evaluated cross-sectional associations between these variables and tested exploratory mediation models in two samples with poor sleep quality: 106 older adults with insomnia and 39 patients with first episode schizophrenia. Overall, results did not support the mediation models in either sample. However, findings revealed novel associations between CVT and cellular inflammatory processes in older adults and extended a negative association between CVT and systemic inflammation to schizophrenia, consistent with the cholinergic anti-inflammatory pathway. Studies 3 and 4 then evaluated possible roles for CVT in a randomized controlled trial which compared active behavioral treatments (Cognitive Behavioral Therapy for Insomnia and Tai Chi Chih) to sleep education in older adults with insomnia. Study 3 revealed that active behavioral interventions led to improvements in insomnia and clinical symptoms without up-regulating CVT, indicating that CVT is unlikely to be a mechanism supporting insomnia recovery. Study 4 then determined whether individual differences in CVT at pre-treatment moderated the effects of active behavioral interventions on key trial outcomes. Results showed that CVT did not moderate treatment effects. Null findings from Studies 3 and 4 underscore the need for further identification and evaluation of candidate mechanisms and moderators to maximize existing behavioral treatments for insomnia. Taken together, present results add to the mixed literature on CVT. Findings simultaneously challenge the assumption that CVT is a reliable correlate of clinical state and extend prior research on the role of the anti-inflammatory pathway in two unique samples with poor sleep quality.