A High‐resolution study of hippocampal and medial temporal lobe correlates of spatial context and prospective overlapping route memory

Abstract

When navigating our world we often first plan or retrieve an ideal route to our goal, avoiding alternative paths that lead to other destinations. The medial temporal lobe (MTL) has been implicated in processing contextual information, sequence memory, and uniquely retrieving routes that overlap or “cross paths.” However, the identity of subregions of the hippocampus and neighboring cortex that support these functions in humans remains unclear. The present study used high-resolution functional magnetic resonance imaging (hr-fMRI) in humans to test whether the CA3/DG hippocampal subfield and para-hippocampal cortex are important for processing spatial context and route retrieval, and whether the CA1 subfield facilitates prospective planning of mazes that must be distinguished from alternative overlapping routes. During hr-fMRI scanning, participants navigated virtual mazes that were well-learned from prior training while also learning new mazes. Some routes learned during scanning shared hallways with those learned during pre-scan training, requiring participants to select between alternative paths. Critically, each maze began with a distinct spatial contextual Cue period. Our analysis targeted activity from the Cue period, during which participants identified the current navigational episode, facilitating retrieval of upcoming route components and distinguishing mazes that overlap. Results demonstrated that multiple MTL regions were predominantly active for the contextual Cue period of the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal cortex being consistently recruited across trials for Cue periods of both novel and familiar mazes. During early trials of the task, both CA3/DG and CA1 were more active for overlapping than non-overlapping Cue periods. Trial-by-trial Cue period responses in CA1 tracked subsequent overlapping maze performance across runs. Together, our findings provide novel insight into the contributions of MTL subfields to processing spatial context and route retrieval, and support a prominent role for CA1 in distinguishing overlapping episodes during navigational “look-ahead” periods.

Viewpoints: how the hippocampus contributes to memory, navigation and cognition

“…Activity patterns in the hippocampal network will be relatively similar across different objects that are co-localized in space or time, but hippocampal neurons will sharply distinguish between encounters with the same object in different contexts. To put it another way, the data in rats 69,73,74 and in human functional MRI (fMRI) studies 5,72,75 overwhelmingly show that spatial and temporal information are the most significant dimensions by which representations are organized in the hippocampus. Dimensions other than space and time can be encoded by the hippocampus 68,76 if those dimensions are behaviorally relevant.…”

Structural and functional neuroplasticity in human learning of spatial routes

“…The specificity of the changes in learning-related functional connectivity was remarkable. Connectivity increased between the posterior dorsal region of the human dentate gyrus (a region known to be involved in spatial learning) (Moser and Moser, 1998;Brown et al, 2014), and the right intra-parietal sulcus, right anterior and posterior temporal areas (cortical regions activated strongly in navigation and spatial memory tasks). These findings are consistent with both the anatomical connectivity among these regions (Schmahmann and Pandya, 2006), and with the functional activation of these particular cortical areas in navigation and spatial memory tasks (Gomez et al, 2014).…”

Noninvasive Functional and Anatomical Imaging of the Human Medial Temporal Lobe

“…For memory researchers, this increased spatial resolution is particularly beneficial as it allows fine-grained investigation of functional distinctions within the human MTL (e.g., Kirwan et al 2007;Bakker et al 2008;Ekstrom et al 2009;reviewed in Carr et al 2010;Chadwick et al 2011;Bonnici et al 2012Bonnici et al , 2013Libby et al 2012;LaRocque et al 2013;Brown et al 2014a). The MTL has long been understood to be critical for episodic memory, based on decades of research that was spurred by the landmark case of Henry Molaison (HM), whose ability to remember new experiences from his daily life was dramatically impaired following bilateral resection of the hippocampus, and portions of the neighboring MTL cortical structures ( perirhinal, parahippocampal, and entorhinal cortex) (Scoville and Milner 1957;Corkin 2013;Squire and Dede 2015).…”

“…Brown et al (Staresina et al 2013) are an important step toward understanding how spatial and nonspatial memory signals combine within the hippocampus to support the expression (in addition to the encoding and construction) of such integrated knowledge. Moreover, recent high-resolution fMRI data show that, when scene information is presented as a cue for memory of a specific navigational episode, trial-by-trial responses in the parahippocampal cortex and the hippocampal CA1 subfield during cue processing correlate with prospective retrieval of the desired navigational event (Brown et al 2014a). CA1 represents a final stage of processing in the hippocampal circuit, and theories of hippocampal function propose that the convergence in CA1 of representations from the CA3 subfield and the MTL cortex facilitates sequential retrieval, and gates hippocampal output to memories that are congruent with current context (Hasselmo and Wyble 1997;Hasselmo and Eichenbaum 2005;Kesner 2007).…”