Convergence of Aberrant Electrophysiological Correlates of Salience, Affective Processing and Stress Reactivity in Patients with Schizophrenia

Patients with schizophrenia exhibit debilitating deficits in attention and affective processing, which are often resistant to treatment and associated with poor functional outcomes. Attentional and affective processing relies on a distributed neural network of fronto-limbic circuits, which enable cognitive control and affective processing, and assist in their interaction to regulate emotional responses. Despite evidence of intact affective valence processing, schizophrenia patients are often unable to employ cognitive change strategies to reduce attentional capture by emotionally salient stimuli, or modulate neurophysiological responses to aversive stimuli. Aberrant neurophysiological correlates of orienting to task-relevant emotional stimuli are also present in unaffected first-degree relatives of schizophrenia patients, suggesting they may represent vulnerability markers. However, less is known about the attentional processing of emotionally salient, task-irrelevant information in these groups, which is examined in Experiment 1 (Chapter 2). Results suggest that despite intact novelty detection, schizophrenia patients and relatives shared deficiencies in attentional processing of emotionally salient information. First-degree relatives exhibited a unique enhancement of the electrophysiological correlate underlying salience evaluation, possibly indicating a compensatory engagement of neural circuitry. While fronto-limbic circuits are fundamental for affective processing and its modulation by higher order cognitive control, this network also plays a critical role in stress regulation, and is disproportionally affected by the deleterious effects of stress. To understand the efficiency and resilience of fronto-limbic circuitry in adapting and recovering from stress exposure in schizophrenia, Experiment 2 (Chapter 3) investigated the effect of an acute experimental psychosocial stressor on neurophysiological indices of fronto-limbic-mediated emotional regulation processes. Results suggest that stress exposure modified electrophysiological correlates of affective processing in patients and controls. Furthermore, patients demonstrated aberrant fronto-limbic oscillatory indices of affective processing, as indicated by exaggerated neural excitability and inefficient frontal cognitive control, and maladaptive stress function. This imbalance between heightened neural responsivity and inefficient frontal regulation may reflect an atypical arousal state that may in turn interfere with fronto-limbic processing and promote symptomatology. Elucidating the neurophysiological correlates underlying salience detection, affective processing, and their modification by stress, will be crucial for identifying vulnerability markers, and for developing innovative treatment strategies targeting the fronto-limbic circuitry to relieve psychopathology.Doctor of Philosoph