Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex

Paul F. Hill, Sarah E. Seger, Hye Bin Yoo, Danielle R. King, David X. Wang, Bradley C. Lega, Michael D. Rugg

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Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood oxygenation level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modeling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70–150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30–70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.

Original languageEnglish
Pages (from-to)6343-6352
Number of pages10
JournalThe Journal of Neuroscience
Issue number29
Early online date15 Jun 2021
Publication statusPublished - 21 Jul 2021


  • Electrophysiology
  • Episodic memory
  • FMRI
  • Gamma
  • Hippocampus
  • Neocortex

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