Evidence map›Paper›PMID 42182441›Full record

ArticlebioRxiv : the preprint server for biology2026

Opposing effects of slow and fast theta synchrony on working memory in the human hippocampal-orbitofrontal network.

Samantha M Gray, Adam J O Dede, Zachariah R Cross, Ignacio Saez, Fady Girgis, Edward F Chang, Kurtis I Auguste, Ammar Shaikhouni, Robert T Knight, Elizabeth L Johnson

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Samantha M GrayNorthwestern University, Department of Medical Social Sciences.ORCID 0009-0003-2277-3338
Adam J O DedeNorthwestern University, Department of Medical Social Sciences.
Zachariah R CrossNorthwestern University, Department of Medical Social Sciences.
Ignacio SaezIcahn School of Medicine at Mount Sinai, Departments of Neuroscience, Neurosurgery, and Neurology.ORCID 0000-0003-0651-2069
Fady GirgisUniversity of California, Davis, Department of Neurology and Center for Mind and Brain.
Edward F ChangUniversity of California, San Francisco, Department of Neurological Surgery, and UCSF Benioff Children's Hospital, Department of Pediatric Surgery.ORCID 0000-0003-2480-4700
Kurtis I AugusteUniversity of California, San Francisco, Department of Neurological Surgery, and UCSF Benioff Children's Hospital, Department of Pediatric Surgery.
Ammar ShaikhouniOhio State University, Department of Neurological Surgery, and Nationwide Children's Hospital.
Robert T KnightUniversity of California, Berkeley, Helen Wills Neuroscience Institute and Departments of Neuroscience and Psychology.
Elizabeth L JohnsonNorthwestern University, Department of Medical Social Sciences.

Funding

Attention, Orientation and the Human Prefrontal CortexR01NS021135 · NINDS · UNIVERSITY OF CALIFORNIA DAVIS · PI Robert Thomas Knight · 1985 to 2026
$6.5M
Measuring Electrical Activity from the Human Brain to Predict Memory Formation and Behavior Across the LifespanR00NS115918 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI JOHNSON, ELIZABETH · 2022 to 2024
$843k
NINDS NIH HHS R00 NS115918NINDS NIH HHS R01 NS021135
6 · The paper itself

Abstract

Working memory (WM) enables us to maintain and manipulate information over time, but how the brain organizes sequential information locally and across networks remains unclear. Recent work suggests that slow and fast theta oscillations serve different roles in memory, yet their distinct contributions to sequential WM are unknown. Based on evidence that the hippocampus (HC) and orbitofrontal cortex (OFC) support sequential WM and that slower theta cycles provide optimal temporal windows for organizing items in WM, we predicted that these regions would coordinate via slow theta dynamics. We analyzed intracranial EEG from the HC, OFC, and amygdala (AMY) in 21 neurosurgical patients (7 female, 13-54 years of age; M ± SD, 30 ± 11.2 years) performing a delayed match-to-sample WM task. We assessed phase locking between regions, phase-amplitude coupling within regions, and neuronal phase coding for slow (~1-4.5 Hz) and fast (~4.5-8 Hz) theta oscillations. We found significant slow and fast theta synchrony between all regions, but identical anatomical pathways produced opposing behavioral effects depending on oscillatory frequency, particularly during higher cognitive demand. Slow theta synchrony was associated with faster response times (RTs), while fast theta synchrony between HC and OFC hindered both accuracy and RTs. Unexpectedly, AMY modulated RT through demand-dependent slow theta synchrony, where AMY-OFC synchrony predicted faster RTs during maintenance and HC-AMY synchrony predicted faster RTs during higher cognitive demand. Sustained coupling between slow theta oscillations and high-frequency broadband activity within each region suggests that local organization coincides with beneficial network behavioral effects. These results establish a frequency-opponent mechanism in which theta oscillation frequencies determine whether HC-OFC circuits facilitate or impair sequential WM.

Identifiers

PMID42182441
PMCPMC13192648

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.