NCT07423923

Representation of Spatiotemporal Information in Human Episodic Memory and Navigation

• Status: Enrolling By Invitation
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: University of Arizona · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

Neural diseases such as stroke can have distinct effects on the ability to navigate and orient compared to remembering daily events like when one last took medicine. This proposal seeks test rival hypotheses regarding the neural mechanisms underlying commonalities and differences in navigation and event-related memory, particularly as they relate to pre-existing knowledge. Such mechanistic insight could help inspire therapies that could be used to bolster intact brain function in a compensatory manner following strokes or other neural insults.

Detailed description

Contemporary models of spatial navigation and episodic memory (memory for events) postulate that their underlying computations emerge primarily from shared neural mechanisms within the medial temporal lobes. As part of the last two rounds of funding for this competitive renewal, the investigators began delineation of important cognitive and neural differences between navigation and episodic memory. The emerging new framework argues for navigation as a sensory-driven cognitive motor skill involving extracting spatial regularities and episodic memory as primarily internally driven and involving ordinal placeholders. The investigators hypothesize that navigation and episodic memory therefore involve partially distinct brain regions and macroscale networks, although where and how these differences emerge in the brain remains an area of active exploration. Here, the investigators test novel aspects of this theoretical framework: how pre-existing knowledge differentially affects the acquisition of new episodic memories compared to navigation-related representations over both longer (days and weeks; Aim 1) and shorter (hours; Aim 2) intervals. Throughout, the investigators propose meaningful alternative models, including the idea that connectivity to the hippocampus and neocortex, and cortical macroscale networks outside of the hippocampus, play critical and unique roles in episodic memory compared to navigation. In Aim 1, using high-resolution fMRI, the investigators propose to employ three different experiments to compare how schema (pre-existing spatial knowledge) and scripts (pre-existing temporal knowledge) differentially interact with new learning in the context of episodic memory and navigation. Together, the outcomes from these experiments will provide mechanistic insight into how humans organize episodic memories and navigation-relevant knowledge over longer intervals that could be meaningful for cognitive rehabilitation. In Aim 2, the investigators focus on how episodic memory interacts with navigation and pre-existing knowledge over shorter-term intervals (hours) by studying mental simulation before and after navigation. Mental simulation involves actively remembering or planning experiences and has direct links with cognitive processes central to episodic memory, particularly in our three different proposed experiments. Here, the PI's team will employ time-resolved intracranial EEG in conjunction with Dr. Brad Lega at University of Texas Southwestern to better identify the mnemonic content of both navigation and mental simulation, including a causal manipulation involving the muscarinic acetylcholine antagonist scopolamine and single cell recordings. Together, the experiments in Aim 2 will provide novel insight into the mechanistic basis of episodic memory and navigation-related representations. Such mechanistic could be helpful in developing neurostimulation or pharmacological protocols (e.g., involving acetylcholine) that could be used to bolster either impaired memory or navigation function following stroke, seizure damage, or other brain injuries affecting hippocampal function.

Conditions

• Scopolamine or Placebo
• Schema to Organize Memory or no Schema

Interventions

Type	Name	Description
DRUG	Scopolamine	effects of scopolamine on brain oscillations, navigation, and memory

Timeline

• Start date: 2025-05-01
• Primary completion: 2030-04-30
• Completion: 2030-04-30
• First posted: 2026-02-20
• Last updated: 2026-02-20

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study