National Science Foundation (Cognitive Neuroscience) BCS-1461009 (PI: Gluck; Co-PI, Lerner). Neurocognitive Studies of Sleep and the Generalization of Emotion Learning and Threat Detection. 2015-2018

In response to NSF 14-514, we propose an integrated interdisciplinary exploration of the neural substrates of human sleep and its effect on the generalization of emotional learning. The ability to encode emotionally laden memories and exploit them efficiently in novel situations is among the most important learning capabilities of an individual. From correct recognition of facial expressions in emotionally-charged social situations, to discrimination between threatening and safe signals in fight-or-flight scenarios, the way we build on our past emotional experiences to decipher unfamiliar conditions strongly determines our ability to survive and function adaptively. Contemporary research on sleep and memory indicates that sleep plays a key role in the generalization of past experiences to novel situations, a process involving core brain regions such as the hippocampus and prefrontal cortex. However, significant inconsistencies exist between findings regarding the effect of sleep on emotional versus non-emotional memories. Specifically, the contributions of various sleep stages to the generalization of fear, and the neural pathways involved, are poorly understood. To this end, the current project will attempt to elucidate the mechanism involved in the way sleep affects fear generalization and threat detection in humans, addressing the empirical and theoretical gaps by: (1) Employing long-term monitoring of sleep stages prior to, and following, fear learning; (2) Using novel neurocognitive assessments of generalization processes accompanied by functional neuroimaging (fMRI); and (3) Studying computational network models of the hippocampus, prefrontal cortex and amygdala, to simulate and interpret the current experimental findings.

Intellectual Merits

The proposed research will advance our understanding of the role of sleep in both cognitive and affective neuroscience. Building on P.I. Mark Gluck’s prior NSF-supported experimental and computational work on generalization in the hippocampus and cortex, Co-P.I. Itamar Lerner’s NSF-supported studies of the long-term effects of sleep on cognition, and consultants Mathew Walker and Gina Poe’s empirical and theoretical investigations over the last decade on sleep and emotional processing in both humans and rodents, this study will: (1) Bridge the gap between inconsistent findings concerning the effect of sleep on generalization of emotional memory and those concerning generalization of non-emotional memory; (2) Relate individual differences in sleep patterns to individual differences in observed learning and fear generalization behaviors; and (3) Suggest neural pathways and plausible biological learning mechanisms contributing to these phenomena, informed by new brain imaging data.

Broader Impact
Broader Impact of Research.  Elucidating the role of sleep in emotional generalization will contribute to broader knowledge of emotional intelligence as it relates to trait-like sleep patterns, aiding individuals to optimally plan their sleep schedules with benefits to their wellbeing and performance. Moreover, the exploration of these questions is highly relevant to any future developments in the prevention and treatment of anxiety disorders, specifically post-traumatic stress disorder for which sleep irregularities have been emphasized as a key factor,

Training underrepresented minorities. This research takes place at Rutgers University – Newark, ranked the #1 most diverse public university in the nation, enabling the inclusion of significant number of minority students. Gluck trains 8-12 undergraduate interns each semester, the majority of whom are women, minorities or from low-income families, often supported by one of two federally-financed minority training grants at Rutgers University-Newark for which Gluck is a Co-I: an NSF Lewis Stokes Alliance for Minority Participation (LSAMP) grant and an NIH Minority Biomedical Research Support (MBRS) grant. Past success in training undergraduates is exemplified by Stephanie Lazzaro who won both a Goldwater Congressional Science Award and a Fulbright Training Fellowship while working Gluck’s lab.

DARPA RAM-Replay Program. W911NF-16-C-0018. IMPACTS: Improving Memory Performance by Augmenting Consolidation with Transcranial Stimulation. 2016-2018

The objective of the DARPA RAM Replay program is to investigate memory replays with respect to the consolidation of episodic memories and newly learned skills and how these memories are recalled and utilized by humans during subsequent task performance. This will be achieved by quantitatively modeling various parameters associated with human memory replay, and utilizing this model in the development of interventions that assess quality of replays and enable and improve associated memory recall during operationally relevant tasks. 

Press Release from HRL (Prime Contractor):

National Institute of Aging (NIH). R56-AG053961. Pathways to Brain Health for African Americans: A Community-Based Participatory Research Study. 2016-2017

 In 1R56AG053961 - 01 (PI: Gluck) we will study the cognitive, neural, and lifestyle factors associated with cognitive resilience and early cognitive decline in older African Americans. This R56 “Bridge to an R01” will support a first year of research on “Pathways to Brain Health in African Americans: A Community-Based Participatory Research Study” that was submitted in July, 2016, as a 5-year R01 in response to NIA’s PAR-15-349.  African Americans are at elevated risk for age-related cognitive decline and memory loss, having twice the rate of Alzheimer’s disease (AD) compared to that of white Americans. Stress, sleep deprivation, sedentary lifestyles, poor cardiovascular fitness, depressive symptoms, high body mass, and low education are all known risk factors for cognitive decline and AD; their higher rates among African Americans, particularly in low socioeconomic groups, have been well documented in previous epidemiological studies. However, little is known about the relative importance (and interactions) among these different risk factors within African-American communities.

To address these gaps in understanding minority health disparities, we will recruit 120 African Americans, age 65 and above, who will receive an extensive battery of neuropsychological, cognitive, health, fitness, and lifestyle assessments as well as measures of education and verbal fluency. Half (60) will receive functional and structural brain imaging to provide data on the neural correlates of cognitive decline.

All participants will complete the Rutgers Generalization Tasks, innovative cognitive assessments developed by the Co-I (Myers) and PI (Gluck) and derived from their prior neuro-computational models of the entorhinal cortex, a brain region disrupted in the earliest stages of prodromal AD. In previous publications, Gluck, Myers, and colleagues have shown that performance on generalizationthe ability to apply previously learned rules to novel task demands and new stimuli—correlates with hippocampal volume in non-demented elderly, and, when combined with clinical diagnoses or standardized assessments, better aids in the prediction of progression to amnestic mild cognitive impairment (aMCI) and AD than when standardized measures are used alone.

Furthermore, unpublished data collected through the PI's recent NIA R03 shows that healthy and asymptomatic gene carriers of autosomal dominant early-onset Familial Alzheimer’s Disease perform worse on generalization as compared to matched non-carriers from the same families, despite both groups showing equal levels of initial learning and retention. From this, we hypothesize that deficits in generalization will correlate with cognitive decline and neural changes in those with prodromal late-onset AD. These Rutgers Generalization Tasks may be especially useful in diverse populations, as they are based on non-verbal animal conditioning paradigms, and thus may be less sensitive to variations in education and verbal fluency.

Institutional distrust is a major barrier to research involving African Americans. Our innovative strategies for recruitment build on the trust we have established from a decade of community engagement serving over 5000 African-American seniors from Greater Newark through the Rutgers University-Newark African-American Brain Health Initiative: A University-Community Partnership (AABHI), co-directed by the PI. A recent five-year grant from the NJ Department of Health has expanded our community programs and outreach capabilities, especially in federally-assisted low-income housing. This past year alone, in partnership with NJ Office of Minority and Multicultural Health, we recruited over 1000 older African Americans who attended our events and participated in a health and lifestyle research survey.

Aim 1: CROSS-SECTIONAL CORRELATIONAL ANALYSES: We will evaluate (1) how variations in physical fitness and physical activity are correlated with cognitive function, medial temporal lobe structure, activity, and connectivity, and (2) how the influence of these variables is mediated by other factors including education, social support, and genetics, with the goal of examining the relative contributions of, and especially the interactions between, all these risk-and-resilience-factors in mediating the likelihood of cognitive decline in elderly African Americans. Predictions: Low levels of physical activity, and cardiovascular fitness will be correlated with (a) poorer performance on the Rutgers Generalization Tasks, (b) reduced hippocampal volume; particularly DG/CA3 volume loss, (c) reduced entorhinal cortical thickness, (d) reduced intra-hippocampal (DG/CA3 – CA1 and CA1 – Subiculum) as well as entorhinal-hippocampal (EC – DG/CA3 and EC – CA1) microcircuit connectivity.

Aim 2: BRIDGE TO RESUBMISSION OF R01 AG053961: Although longitudinal aims are not feasible within the one-year time frame of the R56, all 120 of the current participants will be consented to be contacted for re-testing two years later, pending R01 support. As such, we anticipate that the revised R01 will include an additional 120 individuals already enrolled for subsequent longitudinal follow-up. The R01 resubmission will be further strengthened by implementing, in the R56 period, several changes in the protocol and methods suggested by the reviewers, including bringing our brain imaging methods and analyses in line with those used at the UC-Irvine ADRC.

NJ Department of Health (with federal funding from US Department of Health & Human Services). Improving Mental Health and Physical Activity in Older African Americans. 2015-2020

OBJECTIVES: We will implement and evaluate interventions for older African Americans living in lower-income urban neighborhoods of Greater Newark (our “geographical hotspot”) to reduce health disparities in mental health and physical activity.

PROGRAM PLAN: Through partnerships with both community-based (CBO) and church/faith-based organizations (FBO), our team will conduct an initial Health Disparities Profile of 1000 older (55 and above) African American residents of Greater Newark to assess (a) major indicators of mental health status (both emotional and cognitive), (b) mental and brain health awareness and knowledge, and (c) physical activity. While most participants will have these health indicators assessed through self-report surveys only, a subset of 100 will be selected for in-depth objective assessments including both: (a) investigator or clinician-administered emotional and cognitive instruments, and (b) week-long 24/7 mobile monitoring of physical activity and movement using wrist-band accelerometers and pedometers. Additional assessment of potential social determinants or correlates of health disparities will also be collected. The results will be compared to existing data from within and beyond New Jersey to provide rigorous baseline data on health disparities. Our primary community interventionswill involve partnerships with leading black churches in lower-income neighborhoods of Greater Newark to offer a two-tiered intervention integrated with their health and aging ministries, including:

(#1) Community education and awareness programs to promote knowledge, attitude, and practice changes regarding mental health and physical activity, including large university-based community-educational events, smaller church-based events, and broader distribution of culturally-sensitive print materials on mental health and physical activity specifically written for lower-income African Americans.

(#2) Church-based exercise programs for older adults build on prior evidence-based studies indicating that physical activity that includes aerobic exercise, balance training, and sensory-motor skill learning can provide immediate improvement in both emotional and cognitive health in older adults, as well as reduce future risk for Alzheimer’s disease and Major Depressive Disorder. The exercise programs are designed to be culturally relevant and appealing to our targeted population while also ensuring the greatest possible cardiorespiratory and cognitive benefits. African American adults between the ages of 55 and 90 years, who are overweight and lead a largely sedentary life, will be invited to participate in a 20-week aerobic dance exercise intervention program. Participants will undergo assessment before and after the exercise intervention to measure cardiovascular fitness, lifestyle behaviors, cognition, and mood. We predict significant improvements in cognition, especially reasoning, learning, and memory, which are known to decline with age and especially with the onset of Alzheimer’s disease. The exercise program is also expected to lead to improvements in mood (fewer depressive symptoms).