Abstract
Hippocampal hypo- as well as hyper-activation have been reported during memory encoding in older individuals. Prefrontal cortex (PFC) provides top-down state signals to the hippocampus that bias its computation during memory encoding and retrieval, and disturbed top-down signals could contribute to hippocampal hyper-activation. Here, we used >500 cross-sectional and longitudinal observations from a face-name encoding-retrieval fMRI task to examine hippocampal hypo- and hyper-activation in aging. Age-related anterior hippocampal hypo-activation was observed during memory encoding. Next, older individuals who longitudinally dropped-out were compared with those who remained in the study. Older dropouts had lower memory performance and higher dementia risk, and hyper-activated right anterior and posterior hippocampus during memory encoding. During encoding, the dropouts also activated right prefrontal regions that instead were active during retrieval in younger and older remainers. Moreover, the dropouts showed altered frontal-hippocampal functional connectivity, notably elevated right PFC to anterior hippocampus (aHC) connectivity during encoding. In the context of a general pattern of age-related anterior hippocampal hypo-activation during encoding, these findings support a top-down contribution to paradoxically high anterior hippocampal activity in older dropouts who were at elevated risk of pathology.
Highlights
The prefrontal cortex (PFC) is fundamental for cognitive control (Miller and Cohen, 2001)
Anterior and posterior hippocampus were recruited during both encoding and retrieval, a plot of responses confirmed previous findings (Kim, 2015) of greater encoding- than retrieval activity in the anterior hippocampus (aHC) along with greater retrieval- than encoding-related activity in the posterior hippocampus (Figure 1B)
In line with our prediction and prior studies, here we focused on the right ventrolateral PFC (VLPFC) (x, y, z = 34, 22, −2) that was more strongly activated at retrieval than at encoding (Figure 1C) at both the baseline (t(322) = 18.90) and follow-up (t(185) = 16.98) sessions
Summary
The prefrontal cortex (PFC) is fundamental for cognitive control (Miller and Cohen, 2001). The exact nature of fronto-hippocampal functional interactions is not known, but one possibility is that the PFC provides a state signal to the hippocampus that biases its computations to either pattern separation or completion processes, depending on goals and task instructions (e.g., whether episodic memories are to be encoded or retrieved). The two processes rely on differential but partially overlapping configurations of hippocampal circuitry; in pattern separation the entorhinal cortex conveys sensory signals to the dentate gyrus that performs an orthogonalization allowing a code with minimal overlap with. A sensory signal from the entorhinal cortex instead bypasses the dentate gyrus and is directly propagated to the CA3 subregion as a perceptual cue engaging an auto-associative network to recover a previously stored representation (Yassa and Stark, 2011). The same hippocampal subfield might be engaged in pattern separation during encoding and pattern completion during retrieval (Hunsaker and Kesner, 2013; Deuker et al, 2014), suggesting that external state signals may be required for flexible and voluntary shifts between modes of computations
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