ABSTRACT
The hippocampus is one of the most phylogenetically preserved structures in the mammalian brain. Engaged in a host of diverse cognitive processes, there has been increasing interest in understanding how the hippocampus dynamically supports these functions. One of the lingering questions is how to reconcile the seemingly disparate cytoarchitectonic organization, which favors a dorsal-ventral layering, with the neurofunctional topography, which has strong support for longitudinal axis (anterior-posterior) and medial-lateral orientation. More recently, meta-analytically driven (e.g., big data) approaches have been employed, however, the question remains whether they are sensitive to important task-specific features such as context, cognitive processes recruited, or the type of stimulus being presented. Here, we used hierarchical clustering on functional magnetic resonance imaging (fMRI) data acquired from healthy individuals at 7T using a battery of tasks that engage the hippocampus to determine whether stimulus or task features influence cluster profiles in the left and right hippocampus. Our data suggest that resting state clustering appears to favor the cytoarchitectonic organization, while task-based clustering favors the neurofunctional clustering. Furthermore, encoding tasks were more sensitive to stimulus type than were recognition tasks. Interestingly, a face-name paired associate task had nearly identical clustering profiles for both the encoding and recognition conditions of the task, which were qualitatively morphometrically different than simple encoding of words or faces. Finally, corroborating previous research, the left hippocampus had more stable cluster profiles compared to the right hippocampus. Together, our data suggest that task-based and resting state cluster profiles are different and may account for the disparity or inconsistency in results across studies.
ABSTRACT
Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men-an advantage that has been termed "memory reserve." Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might differ by sex in AD. This study employed group independent component analysis (ICA) to analyze resting state fMRI data from 158 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with baseline diagnoses of normal cognition or early mild cognitive impairment (eMCI). pDMN and aDMN were defined on a subject-specific basis; prefrontal areas were selected from the Brodmann atlas (BA 6, 44, 8, and 9). Moderation regression analyses examined whether sex and amyloid PET positivity (A+/-) moderated effects of apolipoprotein ε4 (APOE ε4) on connectivity between left PFC, aDMN, and pDMN; and between aDMN and pDMN. Significant analyses were followed up with partial correlations assessing relationship of connectivity to verbal memory on the Rey Auditory Verbal Learning Test (RAVLT), and with preliminary analyses within NC and eMCI groups separately. Results showed no sex moderation of effects of A+ and APOE ε4 on left prefrontal/DMN connectivity in the full sample. However, sex significantly moderated impact of A+ and APOE ε4 on connectivity between aDMN and pDMN (p < 0.01). Women with an APOE allele (ε4+) and A+ showed greater aDMN/pDMN connectivity than their ε4- counterparts. No significant results were observed in men. Subgroup analyses suggested the aDMN/pDMN finding was true for those with NC, not eMCI. Partial correlations controlling for age and education showed increased aDMN/pDMN connectivity related to better verbal learning in women (p < 0.01) and not men (p = 0.18). In women at risk for AD or in early symptomatic stages who also have evidence of amyloid burden, stronger aDMN/pDMN connectivity may support verbal learning.
ABSTRACT
Chronic traumatic encephalopathy (CTE) is associated with pathological changes, yet detecting these changes during life has proven elusive. Positron emission tomography (PET) offers the potential for identifying such pathology. Few studies have been completed to date and their approaches and results have been diverse. It was the objective of this review to systematically examine relevant research using ligands for PET that bind to identified pathology in CTE. We focused on identification of patterns of binding and addressing gaps in knowledge of PET imaging for CTE. A comprehensive literature search was conducted. Data used were published on or before May 22, 2017. As the extant literature is limited, any peer-reviewed article assessing military, contact sports athletes, or professional fighters was considered for inclusion. The main outcomes were regional binding to brain regions identified through control comparisons or through clinical metrics (e.g., standardized uptake volume ratios). A total of 1207 papers were identified for review, of which six met inclusion criteria. Meta-analyses were planned but were deemed inappropriate given the small number of studies identified. Methodological concerns in these initial papers included small sample sizes, lack of a control comparison, use of nonstandard statistical procedures to quantify data, and interpretation of potentially off-target binding areas. Across studies, the hippocampi, amygdalae, and midbrain had reasonably consistent increased uptake. Evidence for increased uptake in cortical regions was less consistent. The evidence suggests that the field of PET imaging in those at risk for CTE remains nascent. As the field evolves to include more stringent studies, ligands for PET may prove an important tool in identifying CTE in vivo.
