Stable Network Motifs with Divergent Engagement Across Memory Outcomes

Abstract

Visual recognition memory depends on coordinated interactions across distributed medial temporal, prefrontal, and limbic networks, yet the sub-second large-scale network dynamics distinguishing successful from unsuccessful recognition remain poorly understood. Here we used intracranial EEG recordings from seven patients (4 female, 3 male) with medically refractory epilepsy performing a new–old visual recognition memory task to characterize time-resolved directed functional connectivity and dynamic network organization. Directed effective connectivity was estimated using bivariate Granger causality in a sliding-window framework, and dynamic community structure was identified using the Louvain modularity algorithm. Successful recognition (Hits) was associated with a qualitatively distinct network configuration: low modularity (Q = 0.05 vs. 0.09–0.15 in other conditions), a cross-hemispheric community structure integrating left medial temporal lobe (MTL) with right prefrontal cortex, and sustained network integration throughout the post-stimulus period. Right-hemisphere nodes within this cross-hemispheric community showed stronger within-community directed connectivity than left-hemisphere nodes (mean asymmetry index = 0.33, p < 0.001), consistent with right prefrontal dominance in driving network integration during successful retrieval. In contrast, Correct Rejections were characterized by early transient network segregation (onset 32 ms) dominated by right-hemisphere activity. Hub regions were non-overlapping across conditions—left-lateralized during Hits, right-lateralized during Correct Rejections. These findings imply that successful visual recognition is distinguished not by stronger connectivity per se, but by a reorganization of large-scale network topology that transiently integrates left MTL with right prefrontal cortex into a unified functional community. Significance Statement How does the brain recognize something it has seen before? This study used direct intracranial brain recordings in epilepsy patients to examine how networks of brain regions communicate during successful and unsuccessful recognition memory. We found that successful recognition is not simply a matter of greater connectivity strength. It requires a qualitatively different pattern of large-scale network organization in which left-hemisphere memory regions and right-hemisphere evaluation regions form a unified, cross-hemispheric network. Unsuccessful rejection of novel images, by contrast, was characterized by early, segregated right-hemisphere activity. These findings therefore present a potential, specific, circuit-level mechanism supporting recognition memory, with implications for understanding memory dysfunction in neurological disorders such as epilepsy and Alzheimer’s disease.