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  • Cross-frequency Coupling in the Human Hippocampus During Item Retrieval in Episodic Memory

    Final Number:

    Bradley Lega MD; John Burke; Joshua J. Jacobs MD; Ashwini Dayal Sharan MD; Gordon H. Baltuch MD, PhD; Michael J. Kahana PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Episodic memory, memory for specific items or events within a temporal context, is an important form of memory that is implicated in the memory dysfunction associated aging and with disease. Cross-frequency coupling (CFC) has been observed in the rodent hippocampus during learning of episodic memory items. In CFC, the phase of a slower oscillation modulates the amplitude of high frequency (i.e. gamma band) oscillations. Increases in CFC are associated with item retention and retrieval. Further, extensive theoretical modeling supports the role of phase coding in memory retrieval. Different theta phase preference of CFC may signal whether a memory item is being actively encoded or is being retrieved, thereby sorting the contextual information necessary for appropriate episodic associations.

    Methods: We analyzed 278 electrodes located in the hippocampi of 46 epilepsy patients. The patients performed the Free Recall task, a standard test of episodic memory. We recorded iEEG signal during both item encoding and retrieval, using a phase-bin ANOVA and circular regression to identify electrodes exhibiting CFC and the preferred phase of coupling.

    Results: CFC occurs during both encoding and item retrieval. The magnitude of CFC is greater during successful encoding compared to unsuccessful encoding (p<0.001, ttest), but is not significantly different between encoding and retrieval. The distribution of phase values for CFC during encoding and retrieval was not significantly different (p = 0.52, Fisher circular means test). In both instances, a biphasic distribution of phase values (180 and ~75 degrees) was identified.

    Conclusions: CFC supports both item encoding and retrieval during episodic memory. In our analysis, we found no evidence of differential phase coding to distinguish encoding and retrieval for individual items. Differential phase coding may not be observable with macro-scale electrode recordings, or it may not be a feature of human memory.

    Patient Care: Exploring the electrophysiological underpinnings of human memory will help elucidate brain changes during normal aging and disease processes lead to dysfunction in episodic memory. Characterization of these patterns may ultimately serve as the basis for a memory prosthetic device that attempts to recapitulate normal physiological patterns to assist item encoding and retrieval.

    Learning Objectives: By the conclusion of this session, participants should be able to 1)Understand what cross-frequency coupling is and how it is measured, 2) Understand the importance of CFC to episodic memory and 3) Understand what distinguishes episodic memory from other forms of memory formation


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