Stacey M. Schaefer, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): This research will examine both the neural circuitry of emotion regulation and the impact of individual differences in the experience of emotion on emotion regulatory processes. Objectives include (1) identifying the role of regions hypothesized to be a part of the circuitry underlying emotion regulation (e.g. the amygdala and regions within prefrontal codex), (2) characterizing the interaction between these regions during voluntary emotion regulation, and (3) relating individual differences in the expedence of emotion and activity within this circuitry. Event-related fMRI of neurologically intact volunteers and patients with focal frontal brain damage will be performed during the voluntary modulation of an emotional response to affective pictures. Self-report and psychophysiological data will be collected during fMRI scanning to confirm and measure the degree to which the emotion regulation manipulation is successful. Dispositional affect levels and degree of emotion differentiation (the parsing of emotional experience into discrete specific emotion terms) will be assessed using a 14-day diary protocol with handheld computers after completion of the fMRI procedure. Individual differences in awareness of emotional responses (indexed by self-report compared to psychophysiological measures) will also be assessed via a backward-masking paradigm involving subliminal presentation of affective stimuli. Analysis of the relation between emotion differentiation, emotional awareness, and ability to regulate emotion will test whether knowing exactly how one feels is associated with greater ability to modulate that feeling in a goal-appropriate manner. [unreadable] [unreadable]

Project Summary Despite the high rates of depression, anxiety, and dysregulated emotion characterized by agitation, irritation, and mood swings in Alzheimer's Disease (AD), few studies have asked how emotional responses may change with the development of AD. Recent work has shown prolonged emotional responses in AD patients' self-report that persist even after memory for the emotional provocation has decayed, and an impaired ability to regulate facial responses to a loud startling noise when instructed to do so. Whether differences in the reactivity to and regulation of emotion are observed over the course of the development of the disease as memory and cognition start to fail remains unknown. Similarly, whether potential differences in the time course of emotion relate to changes in emotional memory biases or to tau and amyloid deposition in brain regions important for emotion are important but unmapped domains of emotion processing. This proposal will use objective measures of emotional responding - facial electromyography (facEMG) and functional magnetic resonance imaging (fMRI) - to measure the temporal dynamics of negative and positive emotional responses in 100 individuals with preclinical AD. Preclinical AD will have been previously confirmed with tau and amyloid positron emission tomography (PET) obtained in a Wisconsin Registry for Alzheimer's Prevention (WRAP) substudy under a separately funded protocol. In this proposal, processes occurring directly in response to emotional stimuli (emotional reactivity) will be differentiated from processes occurring after offset of the stimuli (emotional recovery) in both facEMG and fMRI measures. These data will be combined with the extant longitudinal cognitive and imaging data from the WRAP study and compared to normative data previously collected in our laboratory from the Midlife in the US (MIDUS) study using the identical procedures and methods as this protocol. FacEMG and fMRI measures of emotional reactivity to and recovery from negative and positive stimuli will be examined in relation to (i) tau and amyloid deposition in emotion regulation brain circuitry (e.g. the amygdala, hippocampus, anterior cingulate cortex, and other regions of prefrontal cortex), (ii) longitudinal cognitive and executive function changes, (iii) later memory for the emotional stimuli, and (iv) compared with normative emotional reactivity and recovery data from the MIDUS study. In all analyses we will explore age and gender interactions. We predict that individuals with preclinical AD will exhibit impaired emotion regulation, which will be proportional to the pathological protein burden and cognitive and memory changes. Because impaired emotion regulation may exacerbate and prolong stress responses which have been linked to neurodegeneration such as occurs in AD, gaining a better understanding of emotional processes in preclinical AD is critical for development of target interventions that may prove useful for slowing and/or preventing the progression to full clinical onset as well as guide treatment and care decisions.

Project Summary/Abstract This proposal seeks five years of additional funding to examine in depth the structural and functional neural, behavioral, and cognitive correlates of three fundamental dimensions of the time course of emotion: a) the rapidity with which an individual recovers from negative affect, b) the duration with which positive affect persists, and c) the change (e.g. habituation) in affective responses across repeated stimuli presentations. These three important features of affective chronometry have received very little attention, and their neural bases and psychological correlates are not well understood. The proposed research will be carried out in a set of six inter-related aims. The measures described for each will be obtained in the same 350 participants between the ages of 25-45 years, and include facial EMG measures of corrugator and zygomatic activity and fMRI activity recorded in response to affective picture presentations. From these measures, metrics of individual differences in recovery from negative affect, persistence of positive affect, and change across repeated stimulations will be derived. We will investigate the impact of these affective chronometric measures on subsequent memory for the stimuli. The Trier Social Stress Test will also be used to assess affective chronometry through the lens of stress reactivity, quantified via the rise and fall of stress hormones in saliva and perceived stress. Outside the laboratory, we will obtain day reconstructions and ecological momentary assessment, or experience sampling, in the context of a simple probabilistic reward and punishment task that involves winning or losing money. From these measures, we can examine the temporal dynamics of affective responses in the field. All participants will complete questionnaires and undergo clinical diagnostic interviews to assess for mental health symptomatology and trait affect, as well as a cognitive battery assessing executive function and attentional flexibility. Collectively, this incredibly rich dataset will allow us to systematically characterize the import of these affective chronometric measures for varied domains including emotional memory, stress reactivity, mental health, cognition, daily emotional experiences, and reward responsivity, while elucidating the critical functional and structural brain substrates underlying these relationships. Overall, we predict that faster recovery from negative affect, greater persistence of positive affect, and less response change across repeated occurrences of positive incentives will be adaptive, associated with well-being and fewer depressive symptoms, and instantiated in circuits that involve both lateral and medial prefrontal- amygdala connectivity and lateral and medial prefrontal-ventral striatal connectivity. Support for these predictions would provide strong evidence that affective chronometry is a critical factor to include in the RDoC negative and positive valence system domains.