Center on Longevity Seed Grants

The Center provides awards of up to $50,000 to faculty researchers across the Stanford campus. Projects are selected through a competitive process open to all faculty, and proposals have encompassed a wide range of solutions to improve life at all ages. Seed grants are intended to back new areas of study that might not be funded through traditional sources. The Center’s goal is that these studies will then win support from external sponsors or have tangible impacts in the private or public sector.

Seed grants are also available through the Center’s NIH-funded Scientific Research Network on Decision Neuroscience and Aging grant, and are awarded to faculty from peer institutions who are engaged in research in this important area.

SCIENTIFIC RESEARCH NETWORK ON DECISION NEUROSCIENCE AND AGING SEED GRANTS, 2014

FEEDBACK-BASED LEARNING IN AGING: SPECIFIC CONTRIBUTIONS OF STRAITAL AND HIPPOCAMPAL SYSTEMS
Nichole Lighthall – Post-Doctoral Fellow, Center for Cognitive Neuroscience, Duke University
Roberto Cabeza – Professor of Psychology and Neuroscience, Duke University
Scott Huettel – Associate Professor of Psychology and Neuroscience, Duke University
René San Martín – Universidad Diego Portales

Learning plays a central role in decision making across the life span, and appears to mediate age differences in specific decision making domains including risk taking. These age differences may result from decline in brain regions that represent feedback-based learning signals. The striatum is commonly implicated in feedback-based learning, but a growing number of studies indicate that feedback learning is also dependent on the hippocampus. Age-related change to these brain regions may explain age differences in feedback-based learning and decision making, as the striatum and hippocampus both decline in normal aging. However, age differences may be more pronounced with greater reliance on the hippocampus, as behavioral research strongly suggests greater decline in hippocampal versus striatal functions. The proposed study will investigate age differences in striatal- and hippocampal-supported feedback learning using functional magnetic resonance imaging (fMRI). The study will utilize a feedback-based learning task that includes different levels of delay between choice and outcome. A recent fMRI experiment with younger adults, found that adding a delay between choice and outcome resulted in a shift in learning signals from the striatum to the hippocampus.Our research will expand on these findings in two ways. First, by directly comparing neural correlates of feedback-based learning in younger and older adults. And second, by adding post-learning behavioral tasks that will shed light on the relationship between learning signals in the brain and decision outcomes. Specifically, the current study will determine whether neural correlates of feedback-based learning predict inter-individual differences in cue preferences, accuracy of explicit outcome-probability estimates, and choice behavior (willingness-to-pay).

THE ROLE OF OXYTOCIN IN PROSOCIAL DECISION MAKING IN AGING ACROSS HUMANS AND MONKEYS
Steve Chang – Assistant Professor of Psychology, Yale University
Natalie Ebner – Assistant Professor, Department of Psychology, University of Florida

In social environments, humans are routinely faced with decisions concerning self and others that directly determine the nature of their social interactions. The nine-amino acid neuropeptide OT has been proposed to centrally mediate various social processes, such as pair-bonding in monogamous voles, social memory formation in mice, prosocial behavior in monkeys, mother-infant affiliation in humans, as well as modulate more complex behaviors such as trust formation in humans. Across species, it is important to note that although most OT-mediated behaviors are categorically prosocial, OT sometimes controls neural signals that trigger antisocial actions as well depending on individuals, gender, and social contexts. Thus, it is critical to view the peptide as a neuromodulator either amplifying or attenuating neural circuit operations primed by context-specific factors. Recently, we have shown that increasing OT level in the brain via OT inhalation (confirmed by cerebrospinal fluid draws) enhances both prosocial decision preference as well as self reinforcement in rhesus macaques depending on decision context. In this proposal, we will extend our paradigm to examine the neuroendocrinological basis of prosocial decision making in aging. Critically, we will apply a parallel platform across humans and monkeys to establish a new cross-species collaboration aimed at supplementing our understanding of the neural basis of decision making across the adult lifespan with the strength of neurobiological investigations in animals.


SCIENTIFIC RESEARCH NETWORK ON DECISION NEUROSCIENCE AND AGING SEED GRANTS, 2013

OXYTOCIN AND SOCIAL DECISION MAKING IN AGING
Natalie Ebner – Assistant Professor, Department of Psychology, University of Florida
Ronald Cohen – Professor of Aging and Geriatric Research, University of Florida
David Feifel – Professor, Department of Psychiatry, UCSD

Determining whether an unfamiliar person is trustworthy and approachable are crucial decisions humans routinely face in their social environments. Older compared to young adults show increased interpersonal trust, rendering them more susceptible to trusting ill-intending people and scams, seriously compromising emotional and physical health and social life. This age-related increase in trust may be due to older adults’ decreased ability to accurately read other people’s social and emotional cues; it may also be due to age-related alterations in brain function associated with trust-related decision making and/or specific peptides/hormones that directly affect prosociality. The neuropeptide oxytocin has been shown to elevate interpersonal trust. However, nothing is known about age-related changes in the oxytocin system in the context of trust-related decision making. Following a standardized, double-blind procedure, participants in this research study will self-administer synthetic oxytocin (or placebo) intra-nasally before engaging in an economic trust game, a food trust game, and a facial trustworthiness task, while undergoing fMRI. The findings will advance basic science in clarifying neuroendocrine and behavioral relationships in the context of trust and decision making in aging. In addition, information gained from this project will have the potential to inform interventions targeted at social and emotional dysfunction in the elderly with the long-term goal to help older adults make better decisions in social contexts and reduce social stress and anxiety.

ACUTE STRESS AND AGE-RELATED DIFFERENCES IN REWARD PROCESSING AND EXECUTIVE FUNCTION
Anthony Porcelli – Assistant Professor of Psychology, Marquette University; Assistant Adjunct Professor of the CTSI, Medical College of Wisconsin
Kristy Nielson – Professor of Psychology, Marquette University; Associate Adjunct Professor of Neurology, Medical College of Wisconsin
April Harkins – Assistant Professor in Clinical Lab Science, Marquette University

Aging is associated with cognitive declines across multiple functional domains, at the extreme end converting to dementia or neurodegenerative disorders such as Alzheimer’s Disease. Even “healthy aging” is associated with declines in memory and executive functioning (EF), which are essential to independent living. EF is a broad construct composed of multiple neurocognitive functions including, but not limited to, working memory, attention, response selection and inhibition, and mental set formation/maintenance, and depends on the integrity of fronto-striatal circuitry. While much research has been conducted along these lines with memory, some aspects of EF such as decision-making are only beginning to be examined. This research project will study the relationship between acute stress and age-related differences in reward processing and executive function. The project will tap new directions in clarifying age-related cognitive decline, focusing on fundamental cognitive processes that are highly susceptible to decline. The project has the potential to reveal as yet undiscovered harbingers of cognitive decline that can also give rise to early interventions to address those declines.


FINANCIAL FRAUD RESEARCH CENTER SEED GRANT, 2012

The Financial Fraud Research Center, a joint initiative of the Stanford Center on Longevity and the FINRA Investor Education Foundation, is pleased to announce the recipients of it its first $50,000 seed grant. Stanford researchers, led by Ian Gotlib, David Starr Jordan Professor of Psychology, will investigate the role of emotion on responses to fraudulent advertising.

THE EFFECTS OF POSITIVE AND NEGATIVE AROUSAL ON THE SUSCEPTIBILITY OF OLDER ADULTS TO FALSE ADVERTISING
Ian H. Gotlib, PhD – Professor, Department of Psychology
Katharina Kircanski, PhD – Postdoctoral Fellow, Department of Psychology
Nanna Notthoff, MA – Doctoral Student, Department of Psychology

Perpetrators of fraud often report attempting to evoke strong emotions, such as excitement or anger, in potential victims as a way of impairing their decision-making ability. Although excitement and anger are distinct emotions, they share a state of high arousal, assessed with self report and psychophysiological measurement. Ian Gotlib, Professor of Psychology, and his team are using their seed grant to conduct a laboratory study with older adults in which they are examining the immediate effects of positive and negative high-arousal states on responses to fraudulent advertisements, compared with a low-arousal control condition. Findings from this study will allow these investigators to examine the differential impact of positive and negative mood states and levels of arousal on susceptibility to fraudulent advertisements and will help in the design of fraud prevention programs.


SCIENTIFIC RESEARCH NETWORK ON DECISION NEUROSCIENCE AND AGING SEED GRANTS, 2012

NEURAL MECHANISMS OF VALUE-DIRECTED REMEMBERING IN YOUNGER AND OLDER ADULTS
Michael Cohen – PhD student in Psychology, UCLA
Alan Castel – Assistant Professor of Cognitive Psychology, UCLA
Jesse Rissman – Assistant Professor of Cognitive Psychology, UCLA
Barbara Knowlton – Professor of Behavioral Neuroscience, UCLA
Aimee Drolet – Professor of Marketing, UCLA

The ability to use memory effectively requires one to focus on more important to-be-remembered information at theexpense of less important information. Previous studies have shown that, at least in certain contexts, older adults are able to successfully prioritize the encoding of valuable information. Still, relatively little is known about the cognitive and neural mechanisms that underlie the ways in which high-value items are processed differently from less valuable items, particularly in healthy older adults. In this research project, an fMRI study will adapt Castel et al.’s behavioral paradigm to characterize neural correlates of value-directed remembering in young and older adults. In addition, to provide a stronger connection between the laboratory measure of value-incentivized remembering and real-world economic outcomes, the project will relate individual differences in selectivity on the word memory task with more traditional measures of economic decision-making.

FINANCIAL DECISION MAKING AT RETIREMENT
Vinod Venkatraman – Assistant Professor of Marketing, Temple University
John Payne – Professor of Business, Law, and Psychology, Duke University

This project examines complex decisions like annuities and ducumulation of retirement investments in older adults using a multi-methodological approach that involves behavioral, eye tracking, and neuroscience experiments. A major emphasis will be on the development and validation of decision-making tasks that represent the complexities of real-world decisions and yet are suitable for experimentation using all three methodologies. This research will be carried out in two phases. The first will be an exploratory phase where the researchers will design and validate complex decision-making tasks that are suitable for laboratory evaluation using eye-tracking and fMRI. In phase 2, the researchers will obtain pilot data about the effects of aging on decision preferences in this task.

Blau and Santiago's third generation implantable pump

Blau and Santiago’s third generation implantable pump


CENTER ON LONGEVITY SEED GRANTS, 2007-2011

DRUG DELIVERY MICROPUMP FOR MUSCLE STEM CELL DELIVERY
Helen Blau – Donald E. and Delia B. Baxter Professor of Pharmacology and Professor of Chemical and Systems Biology, Stanford University
Juan Santiago – Associate Professor of Mechanical Engineering, Stanford University

Faculty Affiliates Blau and Santiago combined their expertise and a Center on Longevity seed grant to investigate how frequent, tiny doses of stem cell regulator molecules might help older muscles heal more quickly. The study led them to develop a novel, miniature implantable micropump that can deliver doses as small as 100 nanoliters. The device was successfully tested in laboratory mice. The work led to two patent applications and more than $750,000 in follow-on funding from other sources.

A lab assistant demonstrates system

A lab assistant demonstrates system

STEP BY STEP FALL PREVENTION
Tom Andriacchi – Professor of Mechanical Engineering and of Orthopaedic Surgery, Stanford University

Fall related injuries are a serious problem for older adults. A study in the New England Journal of Medicine reports that more than one in three adults over 65 experience a fall every year and that falls are the leading cause of injury- related death in older adults. At the Stanford Biomotion Lab, Faculty Affiliate Tom Andriacchi and his team have approached this problem with technology- based solutions. Previous research has shown that falls are often preceded by development of a “gait asymmetry,” in which stride length and pace are not identical for both legs. Using seed grant funding from the Stanford Center on Longevity, the team developed a system that measures gait symmetry and provides biofeedback through a series of sounds. In the future, this system could be used to create an evaluation and rehabilitation program for patients who develop asymmetry as a result of various health conditions.

Sleep apnea may indirectly have a link to dementia through insulin resistance

Sleep apnea may indirectly have a link to dementia through insulin resistance

SLEEP APNEA, INSULIN RESISTANCE, AND DEMENTIA
Ruth O’Hara
– Associate Professor of Psychiatry & Behavioral Science, Stanford University

Researchers struggle to explain the causes of dementia, a condition that afflicts an estimated 3 of every 20 Americans over 65. Ruth O’Hara explored a correlation between sleep apnea (where breathing pauses during sleep) and dementia. With her seed grant, O’Hara and her team hypothesized that both sleep apnea and dementia are linked to insulin resistance. Their findings support the theory that sleep apnea contributes to cognitive impairment indirectly, by increasing insulin resistance—which several studies link to dementia. By providing a clearer understanding of the actual roots of cognitive impairment, this research will contribute to a conclusive, long-term study that could suggest specific ways of reducing risk for dementia.

A time series of infra--red thermography images taken at 1 minute intervals show hand temperature rising (as indicated by the lighter colors)

A time series of infra–red thermography images taken at 1 minute intervals show hand temperature rising (as indicated by the lighter colors)

THE MIND-BODY LINKAGES OF TAI CHI
Jessica Rose – Associate Professor of Orthopaedic Surgery, Stanford University
Gary Glover – Professor of Radiology, Stanford University
Scott Atlas – Professor of Radiology and Senior Fellow at the FSI and the Hoover Institution, Stanford University

Faculty Affiliates Rose, Glover, and Atlas used their seed grant to develop a joint Stanford University-Lucile Packard Children’s Hospital study that examined the ability of tai chi masters to control normally autonomous functions through concentration. In the study, three tai chi masters were asked to “focus their chi” on their hands. They were able to raise the temperature of the hands 2° C – something normally thought to be outside the sphere of conscious control. Further, the masters exhibited the ability to isolate the effect to one side of the body. Brain images were recorded during the testing and documented exceptionally well developed neural pathways within these masters. Studying the brains and physiological responses of tai chi masters may shed light on medical concerns as wide-ranging as pain management, musculoskeletal conditions, and chronic circulatory disorders.

 

MRI scan

MRI scan

THE EFFECTS OF “WHITE MATTER” IN THE BRAIN
Michael Greicius
– Assistant Professor of Neurology and Neurological Sciences, Stanford University

Affiliate Mike Greicius used his Center on Longevity seed grant to explore a hypothesized series of connections between white matter lesions (or “hyperintensities”) in the brain and behavioral impairments. These lesions are small areas of altered brain tissue that appear in MRI scans and are more frequently noticed in the brains of older individuals. Greicius’ hypothesis suggests that white matter lesions may lead to disrupted structural connectivity within the brain along what are known as neural “tracks.” These disruptions could then lead to functional deficits, in turn contributing to behavioral impairments. Such declines in function are what many people commonly associate with old age. With his seed grant, Greicius demonstrated a compelling correlation between white matter and cognitive abilities within a small sample of subjects and developed better methods for tracking hyperintensities. These findings suggest a more comprehensive study is warranted.

Knowledge of personal costs had a large affect on support for reforms, but some types of reforms still were favored by a majority.

Faculty Affiliates Kessler and Brady investigated how knowledge of the personal cost of healthcare reform affects consumers’ decisions to support specific reforms

HEALTH CARE REFORM – PUBLIC SUPPORT AND PERSONAL COSTS
Daniel Kessler
– David S. and Ann M. Barlow Professor and Senior Fellow at the Hoover Institution, and Professor, by Courtesy on Health Research Policy and Law, Stanford University
David Brady – Bowen H. & Janice Arthur McCoy Professor in Leadership Values; Professor of Political Science; Senior Fellow, the Hoover Institution, Stanford University

Access to healthcare has been a hot topic in the news, but does the public understand what health care access means for their personal finances? Faculty Affiliates Kessler and Brady investigated how knowledge of the personal cost of healthcare reform affects consumers’ decisions to support specific reforms. Kessler and Brady designed a survey that incorporated the respondents’ income level into a calculation that estimated the cost of reforms to that individual – described as an increase to their income tax. As a result, participants with higher income levels were asked to pay more for the reforms than lower income respondents, which is likely how actual reforms would be implemented. The results indicated that the public’s view of healthcare reform may be more nuanced than portrayed in the news. Knowledge of personal costs had a large affect on support for reforms, but some types of reforms still were favored by a majority.