Massimiliano de Zambotti, Ph.D. - US grants

Despite a sizeable literature on emotional speech and speech under stress, little is understood about how features in continuous speech vary with subtle and real-world-relevant changes in physiological state within any particular speaker. This EArly Grant for Exploratory Research relates speech features to direct measures of physiological activation, rather than to categorical hand-annotated labels of emotion or state. The study collects and analyzes a corpus of speech and autonomic nervous system (ANS) sensor data to discover what changes occur in speech features when a person is exposed to different activation-relevant emotional, cognitive, stress-related conditions. The broader significance and impact is discovery of cues in speech that can be used to estimate changes in a speaker's physiological activation level when no sensors are available. Applications include health care (monitoring physical, mental, cognitive states), education and learning (monitoring engagement), social interaction (monitoring activation level), and law enforcement/intelligence (monitoring behavioral changes of high interest individuals).

In Phase 1 (Corpus Collection), the project creates a 40-subject corpus of time-aligned speech and physiological signals. Activation is measured using state-of-the-art methods to extract cardiovascular (ECG), blood pressure, respiration rate, and skin conductance signals. Each subject participates in five conditions: (1) neutral baseline; (2) emotional (description of emotionally salient pictures); (3) stressed (speaking task incentivized for accuracy and completion time); (4) cognitive load (speaking task with a visual distractor, incentivized for task completion and distractor task accuracy); and (5) computer-directed speech (task requiring perfect recognition from a speech recognizer). In Phase 2 (Analysis), sensor output is post-processed to calibrate the signals and look for changes. These changes are then compared to a range of automatically extracted features (based on acoustics, prosody, discourse patterns, and disfluency patterns) from the time-aligned speech. Analyses and machine learning experiments then examine which speech feature changes correlate with changes in sensor output, both within and across speakers. Results shed light on how information from natural continuous speech can be used to estimate changes in a speaker?s physiological activation level in ongoing, subtle and everyday contexts.

PROJECT SUMMARY/ABSTRACT Chronic and acute consumption of alcohol are associated with alterations in autonomic nervous system (ANS) activity. Acute alcohol consumption leads to an immediate increase in heart rate and blood pressure and a reduction in vagal tone. Chronic heavy drinking in the context of Alcohol Use Disorder (AUD), is also associated with tonically elevated heart rate even when sober. Acute alcohol intoxication and AUD are also associated with dramatically disturbed sleep with common findings including increased wakefulness and likelihood of brief arousals throughout the night in AUD and in the second half of the night following drinking prior to sleep. Sleep should be a cardio-protective state with lower heart rate (HR) and blood pressure (BP) than wakefulness. Sleep disturbance is a known risk factor for the development of cardiovascular disease (CVD) with sleep deprivation and common sleep disorders being associated with increased cardiovascular morbidity and mortality. Indeed it has been argued that sleep disturbance may be the most important, potentially modifiable, cardiovascular risk factor. NIAAA has established guidelines that indicate that up to four drinks per day (maximum of fourteen drinks per week) for men and three drinks per day (maximum of seven drinks per week) for women are considered as low risk, yet little is known of the impact of this level of drinking on sleep and ANS function. This exploratory/developmental grant proposal will evaluate sleep, sleep EEG and state of the art measures of ANS and CV function during sleep under sober, and recommended safe drinking conditions.

PROJECT SUMMARY/ABSTRACT Insomnia is highly prevalent in adolescence, particularly in post-pubertal girls and tends to persist over time. Insomnia is considered a hyperarousal disorder, in which abnormally elevated levels of cognitive and physiological activation, particularly evident at bed-time, prevent individuals from falling asleep and having a restorative night?s sleep. Hyperarousal is a major pathophysiological mechanism linking insomnia with poor mental and physical health, including cardiovascular (CV) disease. We and others have shown evidence of autonomic nervous system (ANS) dysfunction such as hyperactivation of the sympathetic branch of the ANS ? a major etiological factor in CV disease ? in young and midlife adults, both before and during sleep. It is unknown if ANS hyperarousal is evident in adolescents with insomnia. The biological basis for an emerging sex difference in insomnia prevalence in adolescence is unknown. Our pilot data reveal intriguing evidence of sex-differences in basic and stress-dependent ANS modulation during sleep in adolescents with girls showing a greater ANS response to stress. These data suggest the existence of a predisposing and stress-dependent ANS vulnerability in female adolescents, a potential pathway to develop insomnia. This proposal takes a novel approach to investigating the manifestation of physiological ANS and CV hyperarousal in adolescents with insomnia by experimentally manipulating the pre-sleep arousal state via stress-induced ANS up-regulation and relaxation-driven ANS down-regulation. In addition, the proposal focuses on sex differences in ANS and CV responses to pre-sleep ANS manipulation, potentially addressing the question of why female sex is a major risk factor for insomnia. We aim to test 110 male and female high-school students (16-18y) with and without DSM-5 Insomnia Disorder, during a regular in-lab polysomnographic night (baseline) and under experimental pre-sleep stress (psychosocial stressor) and pre-sleep relaxation (Virtual reality ANS bio-feedback) intervention nights, using state-of-the-art, noninvasive, beat-to-beat ANS and CV measures, including blood pressure, to assess nocturnal ANS and CV function in adolescents with insomnia (Aim 1); the impact of pre-sleep ANS arousal levels on nocturnal ANS and CV function, and sleep in adolescents with and without insomnia, considering possible sex differences (Aim 2), and the extent to which nocturnal ANS and CV function mediate the effect of pre-sleep arousal levels on objective and perceived sleep quality (Aim 3). This proposal has the potential to elucidate pathophysiological ANS hyperarousal underlying Insomnia Disorder in adolescence, including potential reasons for the vulnerability to insomnia in girls, leading to better recognition and potentially new treatment strategies of this disorder targeted at the state of ANS hyperarousal in the pre-sleep period.

PROJECT SUMMARY / ABSTRACT During young adulthood, drinking dramatically increases, with binge-level drinking peaking at age 22 and nearly half of individuals reporting binge-level alcohol use. Frequent binge alcohol use during the protracted neuromaturation spanning into the mid-20s may result in greater brain and cognitive effects than similar alcohol use in later adulthood. In response to RFA-AA-17-003, this application proposes a Research Project Site of the National Consortium on Alcohol and Neurodevelopment in Adolescence second phase (NCANDA-2) to determine the predictors and effects of heavy adolescent alcohol use in adolescence and young adulthood. To achieve this, the SRI site of NCANDA-2 will continue to follow a cohort of 169 San Francisco Bay Area (n=831 across all 5 sites) participants (ages 12-21 at baseline first visit) to acquire the necessary data to advance our understanding of adolescent development and the effects of alcohol use during adolescence on the adult brain. NCANDA-2 will use multimodal neuroimaging, cognitive testing, behavioral assessment, biospecimen collection, and multimodal assessments in the natural environment. The examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence and young adulthood, are involved in psychological regulation, respond to rewards, and appear vulnerable to neurotoxic effects of alcohol. In addition, the SRI will collaborate with the University of Pittsburgh NCANDA site to study sleep-related predictors and effects of alcohol use in a subgroup of adolescents. Behavioral and electrophysiological measures will be made on overnight visits, including electroencephalography, auditory evoked slow-wave potentials during sleep (K-complexes), and heart rate variability measures of autonomic function during sleep. Sleep-brain structural relationships will also be investigated. SRI will also collaborate with the UCSD site to collect the Stroop task in the fMRI environment to evaluate changes in the cognitive control system for youth who increase drinking versus those who do not. Sex differences in development, alcohol use patterns and history, impact of alcohol use on the brain, and sex- differentiating psychosocial factors (e.g., depression symptoms) will be considered in analyses. With the additional longitudinal data provided by this renewal, we will determine the effects of alcohol exposure on the developmental trajectory of the human brain, and identify preexisting psychobiological vulnerabilities and resiliencies that may alter adolescents' and young adults' risk for alcohol or other substance use disorder and other mental health and developmental outcomes.