Longitudinal Differences in Human Hippocampal Connectivity During Episodic Memory Processing

Abstract

<jats:title>Abstract</jats:title> <jats:p>The question of longitudinal hippocampal functional specialization is critical to human episodic memory because an accurate understanding of this phenomenon would impact theories of mnemonic function and entail practical consequences for the clinical management of patients undergoing temporal lobe surgery. The implementation of the robotically assisted stereo electroencephalography technique for seizure mapping has provided our group with the opportunity to obtain recordings simultaneously from the anterior and posterior human hippocampus, allowing us to create an unparalleled data set of human subjects with simultaneous anterior and posterior hippocampal recordings along with several cortical regions. Using these data, we address several key questions governing functional hippocampal connectivity in human memory. First, we ask whether functional networks during episodic memory encoding and retrieval are significantly different for the anterior versus posterior hippocampus (PH). We also examine how connections differ across the 2–5 Hz versus 4–9 Hz theta frequency ranges, directly addressing the relative contribution of each of these separate bands in hippocampal–cortical interactions. While we report some overlapping connections, we observe evidence of distinct anterior versus posterior hippocampal networks during memory encoding related to frontal and parietal connectivity as well as hemispheric differences in aggregate connectivity. We frame these findings in light of the proposed AT/PM memory systems. We also observe distinct encoding versus retrieval connectivity patterns between anterior and posterior hippocampal networks, we find that overall connectivity is greater for the PH in the right hemisphere, and further that these networks significantly differ in terms of frontal and parietal connectivity. We place these findings in the context of existing theoretical treatments of human memory systems, especially the proposed AT/PM system. During memory retrieval, we observe significant differences between slow-theta (2–5 Hz) and fast-theta (4–9 Hz) connectivity between the cortex and hippocampus. Finally, we test how these distinct theta frequency oscillations propagate within the hippocampus, using phase slope index to estimate the direction slow-theta and fast-theta oscillations travel during encoding and retrieval. We uncover evidence that 2–5 Hz oscillations travel in the posterior-to-anterior direction, while 5–9 Hz oscillations travel from anterior-to-posterior. Taken together, our findings describe mnemonically relevant functional connectivity differences along the longitudinal axis of the human hippocampus that will inform interpretation of models of hippocampal function that seek to integrate rodent and human data.</jats:p>

Cross‐regional phase amplitude coupling supports the encoding of episodic memories

“…However, phase locking of single unit activity in the 5-9 Hz range reportedly may differ according to rated confidence in a recognition memory paradigm (Rutishauser et al, 2015), and oscillatory differences in this band (such as phase reset and cross frequency coupling) may support working memory (Axmacher et al, 2010;Chaieb et al, 2015;Mormann et al, 2005). A slow/fast theta distinction is further supported by recent findings incorporating spatial memory data, which specifically delineate separate functional properties for oscillations in the slow versus fast theta frequency range (Goyal et al, 2020), as well as hippocampal connectivity data supporting the existence of distinct fast versus slow theta oscillation networks (Choi et al, 2020). However, not all previous studies have used a demarcation exactly at 5 Hz; Goyal, for example, uses 4.5 Hz as a cutoff and extends the fast theta range to 11 Hz, while others do not segregate data into bands.…”

“…A recently articulated model of memory processing, the posterior medial/anterior temporal model (PMAT), posits that the PRC and ERC participate in different cortical networks, and if one extends this model to AH/PH distinctions, our findings of functionally significant PH/ERC coupling would seem surprising as the ERC is clearly identified within the AT but not PM network (Ranganath & Ritchey, 2012; Ritchey, Libby, & Ranganath, 2015). However, it is also possible that the entire hippocampus, both AH and PH, participate in both networks given its central role in mnemonic processing (Choi et al, 2020) Furthermore, this model relies mostly on noninvasive data collected during item retrieval and therefore may not apply as strictly to data collected during memory encoding, as we present here.…”

Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans

“…Experimental lesions in the dorsal hippocampus in mice affect spatial memory (Moser et al, 1993), while lesions in the ventral hippocampus result in emotional deficits (Henke, 1990;Kjelstrup et al, 2002). Such connectivity differences have also been observed in humans, although the functional significance of these has yet to be clar-ified (Bonner and Price, 2013;Bubb et al, 2017;Choi et al, 2020;Zeidman and Maguire, 2016).…”

Preliminary Comparison of Subcortical Structures in Elderly Subclinical Depression: Structural Analysis with 3T MRI

“…The level of verbal recall in the SD group was lower than that of the control group, followed by a negative correlation with interhemispheric hippocampal connectivity. The structural and functional characteristics of the hippocampus are particularly related to memory performance [ 76 , 77 ], with hippocampal asymmetry predicting accurate treatment response to memory dysfunction of depression [ 78 ]. Hippocampus, unlike other subcortical structures, establishes interhemispheric connection through the fornix [ 79 ].…”