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

Abstract

Visual exploration is related to activity in the hippocampus (HC) and/or extended medial temporal lobe system (MTL), is influenced by stored memories, and is altered in amnesic cases. An extensive set of polysynaptic connections exists both within and between the HC and oculomotor systems such that investigating how HC responses ultimately influence neural activity in the oculomotor system, and the timing by which such neural modulation could occur, is not trivial. We leveraged TheVirtualBrain, a software platform for large-scale network simulations, to model the functional dynamics that govern the interactions between the two systems in the macaque cortex. Evoked responses following the stimulation of the MTL and some, but not all, subfields of the HC resulted in observable responses in oculomotor regions, including the frontal eye fields, within the time of a gaze fixation. Modeled lesions to some MTL regions slowed the dissipation of HC signal to oculomotor regions, whereas HC lesions generally did not affect the rapid MTL activity propagation to oculomotor regions. These findings provide a framework for investigating how information represented by the HC/MTL may influence the oculomotor system during a fixation and predict how HC lesions may affect visual exploration.

Keywords: Eye movements; Functional Dynamics; Hippocampus; Memory; Oculomotor guidance.

Figure 1.

Dissipation of activity over time across the cortex following simulated stimulation of CA1. Average above-threshold simulated activation (arbitrary units) for each node for a 10-ms epoch following each time point is plotted on the macaque cortical surface. Activations were log scaled for the purposes of visualization. From left to right: ventral, dorsal, medial, and lateral views of the macaque cortical surface.

Figure 2.

(A) Simulated stimulation of the CA1 (red circle) resulted in observable responses (blue circles) in multiple hippocampus (HC)/medial temporal lobe (MTL) nodes, intermediary nodes, and in regions governing oculomotor control, including the frontal eye fields (FEFs). (B) Simulated stimulation of the CA3 (red circle) resulted in observable responses (blue circles) limited to HC/MTL nodes. Very few responses were observed in cortical areas and none were observed in oculomotor areas. Size and shade of the circles scale with elapsed time prior to an observed response. Gray lines denote direct structural connections between nodes. For visualization purposes, only regions that contribute to the shortest paths from HC/MTL to oculomotor nodes are shown. Connections between intermediary nodes (middle column) are not shown. Connections that are unidirectional and away from oculomotor areas (i.e., to HC/MTL) are indicated by dashed lines.

Figure 3.

Simulated response profiles (envelope of region time series) of oculomotor areas following stimulation of PrS (A), CA1 (B), S (C), and PaS (D). Activation is given in arbitrary units (a.u.). The onsets of the responses for each oculomotor area indicated by arrows. Area LIP did not exhibit a response that exceeded its baseline threshold following S and PaS stimulation.

Figure 4.

Changes in simulated activation times following HC lesions. Subicular stimulation following CA1 (A) and ERC (B) lesions. Only nodes of interest are presented on the brain surface plots. Activation time differences were computed by subtracting the prelesion activation times from the postlesion ones. Absence of response following a lesion indicated in gray. From left to right: ventral, dorsal, medial, and lateral views of the macaque cortical surface.