Real-time fMRI for insular cortex brain state-triggered experience sampling

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PROJECT SUMMARY/ABSTRACT For many patients suffering from psychiatric illness, the primary source of daily-life distress is inner experiences that often seem to occur ‘on their own’ (self-generated experiences). These uncontrollable experiences can take various forms, including rumination, worry, hallucination or delusional thinking. Given the severe global burden of mental illness, and the high prevalence of patients who are resistant to current treatments, there is a pressing need to develop new therapies designed to directly target the brain’s systems that produce maladaptive self-generated experiences. As a precursor to therapy development, significant progress must be made in our fundamental understanding of how the brain gives rise to self-generated experiences. To address this need, we will develop a new approach called “real-time functional MRI (fMRI)- triggered experience-sampling” to efficiently sample spontaneous neural events (of a predefined type) and to map those events to specific qualities of self-generated experiences. Within 32 healthy adults, we will use online (real-time) fMRI analysis to detect brain activations and trigger the appearance of visual rating scales so that participants can report their experiences immediately after the occurrence of a neural event of interest. This approach aims to maximize how informative the data are on each trial and to offer rigorous investigation of the psychological significance of specific neural events. We will develop and validate our approach with a focus on real-time fMRI analysis of the dorsal anterior insular cortex (daIC), a brain region implicated in salience detection that is consistently identified as having aberrant structure, function, and connectivity in psychiatric illness at a transdiagnostic level. Our Aim 1 is to determine whether spontaneous daIC activation events are time-locked to instances of salient, high-arousal self-generated experience. We will sample self- generated experiences both during instances of daIC activation and during baseline (intermediate daIC activity) events. We hypothesize that daIC activation, relative to baseline events, will be time-locked to self- generated experiences with higher subjective ratings of arousal and vividness (regardless of affective valence). We will further test whether relationships between the daIC and self-generated experiences are mediated by autonomic arousal, as assessed based on pupil dilation and activation within the locus coeruleus (a subcortical generator of arousal-related neuromodulation). Our Aim 2 is to determine whether specific qualities of self- generated experience depend on coupling between the daIC and whole-brain activity. We will examine whether different instances of daIC activation co-occur with multiple, distinct whole-brain co-activation patterns. We will further test whether distinct daIC co-activation patterns are associated with fluctuations in affect (positive vs. negative experiences). If successful, our protocols can later be applied in patients with psychiatric illness and to potentially guide the development of interventions (e.g., neurostimulation) that aim to target the neural processes that produce self-generated experiences that are core to mental illness.