SUMMARY/ABSTRACT
The goal of this proposed research is to examine how cardiorespiratory fitness (CRF) and chronic psychosocial
stress modulate the medial temporal hippocampal (MTH) system in Black emerging adults aged 18 to 25 years
who are exposed to daily psychosocial stress, examined through the lens of racism-rated chronic stress.
Emerging adulthood is a life period of identity exploration that is experienced by the majority of emerging adults
as stressful. Black emerging adults have the added burden of racism-related chronic stress. Chronic stress and
CRF are well-known, opposite modulators of the MTH system, but the neurobiological basis of this modulation
in humans is unknown. Theoretical and animal models point to a shared neurobiological basis for exercise-
and stress-induced modulation of the MTH system: up- vs. downregulation, respectively, of plasticity mecha-
nisms in the hippocampus. These models highlight expression of brain derived neurotrophic factor (BDNF) and
an important role for adult-born, immature neurons in the dentate gyrus (DG) subfield of the hippocampus in a
computational process known as pattern separation (PS). PS is critical for memory formation and implicated in
anxiety and depression. Whether allostatic load, the physiological ‘wear and tear’ response to chronic stress
across multiple biological systems is associated with MTH system function is unclear, but critical to under-
standing the role of the MTH system in mental and brain health. In contrast, greater CRF is associated with
better mental health and MTH system function and structure in young adults. Despite this knowledge it is un-
known how putative markers of MTH plasticity (e.g., serum BDNF, CRF) and allostatic load interact to modu-
late the MTH system in emerging adults. Here, we propose to examine MTH system plasticity by combining
CRF and serum BDNF measurement with measures of racism burden and with DG-CA3 circuit assessments
using high-resolution functional and structural MRI, and performance on mnemonic discrimination tasks de-
signed to tax PS. Our central hypothesis is that racism burden will negatively correlate with MTH system func-
tion and positively with allostatic load, whereas CRF will positively correlate with MTH system function and se-
rum BDNF and negatively with allostatic load in Black emerging adults. We will examine this hypothesis with
three Specific Aims. Aim 1 will examine impact of CRF on the MTH system, serum BDNF, and allostatic load,
and Aim 2 will examine the impact of racism burden, assessed using measures ranging from perceived racial
discrimination to cultural and structural racism, on the MTH system and allostatic load. Aim 3 is exploratory and
will examine the impact of cumulative racism burden and CRF on the MTH system mechanistically via allo-
static load, serum BDNF and mental health using a structural equation modeling approach. A positive outcome
of this research will provide evidence for an interplay between allostatic load and neuroplasticity mechanisms
as opposing mechanisms affecting the MTH system and will fill an important knowledge gap about racism bur-
den as a negative modulator of brain health and MTH plasticity in Black emerging adults.
