Abnormal Offline Memory Consolidation During Learning in Schizophrenia

Bailey Driscoll, BS

Massachusetts General Hospital – Clinical Research Coordinator

Scientific Abstract

Background: Schizophrenia (SZ) is a neurodevelopmental disorder characterized by debilitating cognitive deficits that incur enormous economic and psychosocial costs. Hippocampal functional abnormalities and cell loss have been demonstrated in SZ. Since the hippocampus is critical to memory replay and consolidation during wake and sleep, impairments may be a source of memory deficits in SZ. Recently, hippocampal activity has been tied to offline performance improvements, or micro-offline gains, during inter-trial rest periods on a motor sequence learning task (MST) in healthy controls (HC) [Jacobacci 2020, Buch 2021]. We aimed to compare micro-offline gains in HC to those of patients with SZ. We hypothesized that, due to hippocampal impairments and resulting memory deficits, the SZ sample would display lower micro-offline gains than HC. 

Methods: Forty-six chronic medicated SZ participants and 73 HC trained on the MST, where they typed a sequence of numbers for twelve 30-second training blocks with interspersed 30-second rest blocks. 

Results: Despite a normal amount of learning during training (F(1,234)=.006, p=.94), learning was distributed differently by group. HC showed higher improvements during rest periods (micro-offline gains) than improvements across typing blocks (micro-online gains), while SZ patients showed the opposite pattern (F(1,234)=6.10, p=.01). 

Conclusions: Our results support the hypothesis that hippocampal dysfunction in SZ impairs memory consolidation during wake. Despite intact total learning, SZ patients are learning differently, which we attribute to hippocampal dysfunction. We plan to determine if impaired micro-offline gains correlate with reduced sleep-dependent memory consolidation, which would suggest hippocampal dysfunction as a common underlying mechanism.


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research Areas


Bailey Driscoll, BS, Martin Sjøgård, PhD, Dimitrios Mylonas, PhD, Megan Thompson, PhD, Bryan Baxter, PhD, Robert Stickgold, PhD, Dara Manoach, PhD

Principal Investigator

Dara Manoach, PhD