Clinical trial NCT03896529: Neurobiological Mechanisms of Aging and Stress on Prospective Navigation
Official title: Neurobiological Mechanisms of Aging and Stress on Prospective Navigation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Anxiety
Memory Impairment
Keywords: Aging
Spatial Memory
Stress
fMRI
Lead sponsor: Georgia Institute of Technology
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-04-01
Enrollment: 85
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Behavioral (Psychological stress manipulation). Between-subjects design. Participants will be assigned to either a stress-manipulated or control (no stress induced) group.
Primary purpose: BASIC_SCIENCE

Brief summary: Two hallmarks of both healthy aging and age-related disease are 1) memory and navigational deficits, particularly in orienting towards goal locations and planning how to navigate to them, and 2) increased susceptibility to stress and altered regulation of the stress response. However, there are marked individual differences in these age-related changes. The investigators' proposal will help characterize factors that contribute to this variability.

Participants will be pseudorandomly assigned to stress-manipulated or control groups. The investigators will give both groups a novel immersive navigation task, validated by the PI in healthy young adults. This paradigm gives participants the opportunity to either (a) flexibly draw on spatial memory in order to plan efficient routes to goal locations, or (b) fall back on inefficient, but cognitively less-demanding, stimulus-response associations (i.e., habits). Using neuroimaging and behavioral measures, the investigators' protocol will test whether experimentally-induced stress leads individuals to bring fewer details about future locations to mind when route planning, and whether such restricted prospective thought ultimately biases participants towards relatively inflexible, habitual actions.

Detailed description: Two hallmarks of both healthy aging and age-related disease are 1) memory and navigational deficits, particularly in orienting towards goal locations and planning how to navigate to them, and 2) increased susceptibility to stress and altered regulation of the stress response. However, there are marked individual differences in these age-related changes. The investigators' proposal will help characterize factors that contribute to this variability.

The investigators propose a study that utilizes cutting-edge imaging and virtual reality techniques to characterize the neural mechanisms of prospective (future goal-directed) navigational planning in aging. The investigators will use multi-voxel pattern analyses (MVPA) to obtain neural indices of memory-guided navigational planning. The investigators will then examine the mechanisms through which stress limits the ability of individuals to flexibly navigate to future goals. A critical aim will be to evaluate the neural bases for individual differences in navigational planning and the stress response, providing novel insight into convergent neurocognitive traits that underlie different degrees of age-related cognitive decline. The investigators predict that impaired prospective planning is associated with individual differences in (a) susceptibility to exogenous, experimentally-induced stress, and (b) stress-disrupted functioning of memory and attention and cognitive control networks necessary for mental simulation.

The investigators' proposal combines a novel immersive navigation paradigm, validated by the PI in healthy young adults, and an established between-subjects exogenous manipulation of psychological stress (see Research Strategy). This paradigm gives participants the opportunity to either (a) flexibly draw on spatial memory in order to plan efficient routes to goal locations, or (b) fall back on inefficient, but cognitively less-demanding, stimulus-response associations (i.e., habits). Participants will be pseudorandomly assigned to stress-manipulated or control groups, with an initial prospective random assignment of subject IDs being adjusted as recruitment progresses in order to enforce approximately equivalent age distributions in the two groups (and thus limit confounds in subsequent group comparisons). Salivary cortisol (stress hormone) assays (de-identified) will help validate the stress difference between groups. Leveraging MVPA, and trait questionnaires, the investigators' study will test whether experimentally-induced stress leads individuals to bring fewer details about future locations to mind when route planning, and whether such restricted prospective thought ultimately biases participants towards relatively inflexible, habitual actions.

Aging is associated with differences in the degree to which people rely on "map-like" spatial memory vs. procedural motor responses to traverse environments. Thus the investigators' investigation of the effects of stress on habitual vs. prospective spatial memory-guided navigation is embedded within the context of age-related differences in spatial memory processing in the investigators' target population. The investigators will further employ an endogenous navigational strategy identification task, enabling us to 1) establish a link between endogenous navigation strategy preferences and performance on the investigators' prospective navigation task, and 2) study how endogenous navigational strategy preferences interact with induced stress to affect the investigators' neural and behavioral outcome measures indexing efficient, prospective spatial cognition.

Eligibility criteria: Inclusion Criteria:

* adults 65-80
* U.S. citizens or permanent residents
* who speak fluent English
* willing to come to Georgia Tech to participate in group testing sessions.

Exclusion Criteria:

* Individuals will be carefully screened using IRB-approved procedures for safety contraindications to MRI and electrical shock stimulation
* (e.g., metal or electrical implants, heart arrhythmia, or medication affecting the cardiovascular system \[e.g. beta-blockers\]).

The purpose of this study is to investigate mechanisms of normally functioning memory, and memory-related changes in healthy aging. Thus, any confounding factors that may influence cognition, other than age, will be exclusionary. Potential participants that endorse any of the following conditions will be excluded from the study:

* Epilepsy
* Dementia
* Parkinson's disease
* history of stroke or seizure
* psychiatric disorders
* untreated depression or emotional conditions
* Attention Deficit Disorder
* Multiple Sclerosis
* uncontrolled hyper- or hypo-tension
* untreated Diabetes
* Sickle Cell Anemia
* regularly use illegal or psychoactive drugs (e.g., cocaine, alcohol abuse, etc).
* Additionally, individuals scoring \< 3 on WAIS-R forward span, \< 2 on WAIS-R backward span, and failing to name more than 2 vegetable names will be excluded from the study. These exclusions will insure that persons with mild cognitive impairment or typical indications of clinical dementia will be not participate in the research.

Primary outcomes:
measure: Behavioral probability of taking a shortcut between control and treatment groups
timeFrame: Approximately 1.5 years
measure: fMRI activation level between control and treatment groups
timeFrame: Approximately 1.5 years
measure: Neural memory representation reactivation between control and treatment groups
timeFrame: Approximately 1.5 years
Secondary outcomes:
measure: Relationship between fMRI activity level and behavioral probability of taking a shortcut.
timeFrame: Approximately 1.5 years
measure: 2. Salivary cortisol (stress hormone) response difference between stress and control participant groups.
timeFrame: Approximately 1.5 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Center for Advance Brain Imaging
state: Georgia
Study officials:
affiliation: Georgia Institute of Technology
name: Thackery I Brown, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: