Increased fMRI activity correlations in autobiographical memory versus resting states.

Autobiographical memory retrieval is associated with activity of a distributed network that is similar to the default-mode network (DMN) identified via activity correlations measured during rest. We tested whether activity correlations could be used to identify the autobiographical network during extended bouts of retrieval. Global-correlativity analysis identified regions with activity correlation differences between autobiographical-retrieval and resting states. Increased correlations were identified for retrieval versus resting states within a distributed network that included regions prototypical for autobiographical memory. This network segregated into two subnetworks comprised of regions related to memory versus cognitive control, suggesting greater functional segregation during autobiographical retrieval than rest. DMN regions were important drivers of these effects, with increased correlations between DMN and non-DMN regions and segregation of the DMN into distinct subnetworks during retrieval. Thus, the autobiographical network can be robustly identified via activity correlations and retrieval is associated with network functional organization distinct from rest.

Stimulating the hippocampal posterior-medial network enhances task-dependent connectivity and memory.

Successful episodic memory involves dynamic increases in activity across distributed hippocampal networks, including the posterior-medial (PMN) and the anterior-temporal (ATN) networks. We tested whether this up-regulation of functional connectivity during memory processing can be enhanced within hippocampal networks by noninvasive stimulation, and whether such task-dependent connectivity enhancement predicts memory improvement. Participants received stimulation targeting the PMN or an out-of-network control location. We compared the effects of stimulation on fMRI connectivity during an autobiographical retrieval task versus during rest within the PMN and the ATN. PMN-targeted stimulation significantly increased connectivity during autobiographical retrieval versus rest within the PMN. This effect was not observed in the ATN, or in either network following control stimulation. Task-dependent increases in connectivity within the medial temporal lobe predicted improved performance of a separate episodic memory test. It is therefore possible to enhance the task-dependent regulation of hippocampal network connectivity that supports memory processing using noninvasive stimulation.

In vivo hippocampal subfield shape related to TDP-43, amyloid beta, and tau pathologies.

Despite advances in the development of biomarkers for Alzheimer's disease (AD), accurate ante-mortem diagnosis remains challenging because a variety of neuropathologic disease states can coexist and contribute to the AD dementia syndrome. Here, we report a neuroimaging study correlating hippocampal deformity with regional AD and transactive response DNA-binding protein of 43 kDA pathology burden. We used hippocampal shape analysis of ante-mortem T1-weighted structural magnetic resonance imaging images of 42 participants from two longitudinal cohort studies conducted by the Rush Alzheimer's Disease Center. Surfaces were generated for the whole hippocampus and zones approximating the underlying subfields using a previously developed automated image-segmentation pipeline. Multiple linear regression models were constructed to correlate the shape with pathology measures while accounting for covariates, with relationships mapped out onto hippocampal surface locations. A significant relationship existed between higher paired helical filaments-tau burden and inward hippocampal shape deformity in zones approximating CA1 and subiculum which persisted after accounting for coexisting pathologies. No significant patterns of inward surface deformity were associated with amyloid-beta or transactive response DNA-binding protein of 43 kDA after including covariates. Our findings indicate that hippocampal shape deformity measures in surface zones approximating CA1 may represent a biomarker for postmortem AD pathology.

Elevated Markers of Inflammation Are Associated With Longitudinal Changes in Brain Function in Older Adults.

Background: Chronic inflammation has been linked to memory and other cognitive impairments, as well as Alzheimer's disease. Here, we investigate the association between inflammatory markers and changes in brain activity measured by regional cerebral blood flow (rCBF) to assess the relationship between inflammation and brain function in older individuals. Methods: Annual 15O water resting-state positron emission tomography (PET) scans collected over a 5-year period were assessed in 138 cognitively normal older participants (77 males; mean age at baseline = 71.3; mean scans per participant = 3.5) in the Baltimore Longitudinal Study of Aging. Voxel-wise linear mixed models were used to investigate associations between rCBF and C-reactive protein (CRP) and interleukin-6 (IL-6) at the time of scanning. We examined relationships between baseline CRP and IL-6 levels and baseline rCBF, and relationships between baseline and mean inflammatory levels over time and longitudinal rCBF changes. Results: Higher baseline CRP and IL-6 were each associated with lower baseline rCBF primarily in frontal and occipital regions, with only the lingual gyrus surviving atrophy correction. Higher baseline and mean CRP were also associated with greater rCBF declines over time in anterior cingulate and hippocampal regions, whereas higher baseline and mean IL-6 levels were associated with greater rCBF declines in orbitofrontal and hippocampal regions. Conclusions: Higher levels of inflammation are associated with longitudinal changes in brain function in regions important for cognition. These results, along with previous studies, suggest that chronic inflammation in older adults may contribute to age-associated declines in cognitive function.