MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early‐life adversity

Abstract

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic.

Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

“…A recent study revealed a widespread and pronounced loss of dendritic spines in MS cortex independent of cortical demyelination and axon loss 2. The latest evidence using combined MRI and histopathology suggests that, in principle, the DTI‐based measures of the cortex can reflect dendrite pathology,46, 47 which is a possible explanation for the widespread changes of DTI‐based measures in the cortex of MS patients 30, 39, 40, 41…”

New insights into early-life stress and behavioral outcomes

“…Third, the type and difficulty of the test that is used to measure behavioral outcomes is important. For example, a rigorous test such as object location memory (OL) might uncover subtle deficits not apparent in a less challenging test, such as object recognition memory (OR) [69]. These caveats are illustrated below.…”

“…For example, in a rigorous and hippocampus-dependent test of OL memory, an overt impairment in spatial memory was found as early as adolescence in LBN rats [69]. A less rigorous memory task for OR found comparable performance in LBN vs. Control adolescent rats.…”

“…A less rigorous memory task for OR found comparable performance in LBN vs. Control adolescent rats. However, an acute-stress “challenge” imposed 24 hours prior to the test led to memory problems only in the LBN rats, thus unmasking a latent cognitive vulnerability [69]. The memory deficits after chronic early-life stress also progressed over the lifespan of LBN rats, so that deficits in OR memory emerged by middle-age [69].…”

“…However, an acute-stress “challenge” imposed 24 hours prior to the test led to memory problems only in the LBN rats, thus unmasking a latent cognitive vulnerability [69]. The memory deficits after chronic early-life stress also progressed over the lifespan of LBN rats, so that deficits in OR memory emerged by middle-age [69]. At this age, hippocampus-dependent memory deficits were also present using the Morris water maze task [54,73].…”