Modelling the influence of the hippocampal memory system on the oculomotor system

Abstract

Visual exploration is influenced by what we remember. Amnesic cases, who have damage to the hippocampus (HC) and/or extended medial temporal lobe (MTL), show alterations in their gaze patterns relative to neurologically intact adults on tasks of memory. Recent work has revealed an extensive set of polysynaptic connections between the hippocampus and oculomotor system. However, little is known about how activation within the HC may impact the oculomotor system. In the present work, we conducted simulations of the functional interactions between the two systems by leveraging a computational modeling platform (The Virtual Brain; thevirtualbrain.org) with structural connectivity as defined through the CoCoMac database and tractography data from macaques. We examined how activity dissipated throughout the pre-identified polysynaptic pathways when subregions of the HC, and regions of the broader MTL, were stimulated. Stimulation of CA1, pre-and para-subiculum, and entorhinal, perirhinal, and parahippocampal cortices each resulted in observable responses in regions of the oculomotor system, including the frontal eye fields. Stimulation of the subiculum and CA3 did not culminate in responses in the frontal eye fields, and in such instances, activity was also not observed in parietal areas, posterior cingulate, and V4, suggesting that these regions may be important for transmitting information from the HC to regions within the oculomotor system. These findings provide novel evidence that activity originating within the HC and/or MTL may travel through specific nodes and pathways to influence the oculomotor system.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/303511 doi: bioRxiv preprint first posted online Apr. 18, 2018; Significance StatementNo major account of oculomotor (eye movement) guidance considers the influence of the hippocampus and broader medial temporal lobe system, yet it is clear that information is exchanged between the two systems. Prior experience influences current viewing, and cases of amnesia due to compromised hippocampal/medial temporal lobe function show specific alterations in viewing behaviour. Using computational modeling, we show that stimulation of subregions of the hippocampus and regions of the medial temporal lobe results in observable responses in brain regions that are involved in the control of eye movements. These findings suggest that information from memory may be readily provided to the oculomotor system, and calls for a reconsideration of the neural circuitry involved in oculomotor guidance.

The intersection between the oculomotor and hippocampal memory systems: empirical developments and clinical implications

“…[138][139][140] Additional models mimicked lesions to the network and subsequently examined the propagation of activity. 134 Lesions to hippocampal subfields did not generally influence activity propagation from the MTL cortices, which showed quite rapid signal resolution within oculomotor regions (<100 ms). Lesions in each of the PRC, ERC, and PHC resulted in slower signal from the hippocampus throughout the network and, ultimately, to oculomotor regions.…”

“…Additional models mimicked lesions to the network and subsequently examined the propagation of activity . Lesions to hippocampal subfields did not generally influence activity propagation from the MTL cortices, which showed quite rapid signal resolution within oculomotor regions (<100 ms).…”

“…Dysfunction in the hippocampus and the broader MTL leads to changes in the manner by which visual exploration unfolds . When such findings are considered alongside computational modeling research that details how neural activity may traverse the myriad of structural connections between the memory and oculomotor systems within the time of a gaze fixation, it becomes apparent that eye movements reveal the use of stored information on a moment‐to‐moment basis. The research we have reviewed here collectively aligns with theoretical accounts that suggest hippocampally mediated representations are used in service of multiple cognitive functions beyond memory, including allocating overt attention, biasing ongoing perceptual processing, and directing further actions .…”

“…133 Although hypotheses could be generated from the knowledge of structural connectivity regarding whether activity would be relatively faster or slower via one route over another, the temporal detail (e.g., within the time of a gaze fixation) of such information required direct or modeled examination of neural responses. Using a connectome-based model to simulate network dynamics, Ryan et al 134 examined the dissipation of activity from the memory system to oculomotor areas. Subregions of the hippocampus and regions of the MTL were each stimulated separately, and the resultant neural activity was observed as it traversed through the rest of the modeled brain.…”

Eye movements support behavioral pattern completion

“…For example, a recent study from Bone et al (2018) found that participants reinstated encoding-related EMs during stimulusfree visualization, and this reinstatement was positively correlated with whole-brain neural reactivation (i.e., similarity between image-specific patterns of brain activity evoked during perception and imagery), which in turn was correlated with objective (change detection performance) and subjective (vividness ratings) measures of memory. Gaze reinstatement that differentiates hits from misses for configurally similar scene images has also been correlated with activity in the hippocampus (Ryals, Wang, Polnaszek, & Voss, 2015), supporting the existence of a functional link between EMs and hippocampally-mediated relational memory processes (also see, Bicanski & Burgess, 2019;Kragel et al, 2019;Liu, Shen, Olsen, & Ryan, 2017;Nau, Julian, & Doeller, 2018;Ryan et al, 2018;Shen, Bezgin, Selvam, McIntosh, & Ryan, 2016;Voss, Bridge, Cohen, & Walker, 2017; for review, see Hannula, Ryan, & Warren, 2017). Thus, given that EMs and memory retrieval, and the neural networks underlying them, are intimately related, the present study used EM monitoring to assess the online reactivation of previously encoded stimuli during mnemonic discrimination of lure images via gaze reinstatement.…”