Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition

Shai Sabbah*, Michael S. Worden, Dimitrios D. Laniado, David M. Berson, Jerome N. Sanes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Studies with experimental animals have revealed a mood-regulating neural pathway linking intrinsically photosensitive retinal ganglion cells (ipRGCs) and the prefrontal cortex (PFC), involved in the pathophysiology of mood disorders. Since humans also have light-intensity-encoding ipRGCs, we asked whether a similar pathway exists in humans. Here, functional MRI was used to identify PFC regions and other areas exhibiting light-intensity-dependent signals. We report 26 human brain regions having activation that either monotonically decreases or monotonically increases with light intensity. Luxotonic-related activation occurred across the cerebral cortex, in diverse subcortical structures, and in the cerebellum, encompassing regions with functions related to visual image formation, motor control, cognition, and emotion. Light suppressed PFC activation, which monotonically decreased with increasing light intensity. The sustained time course of light-evoked PFC responses and their susceptibility to prior light exposure resembled those of ipRGCs. These findings offer a functional link between light exposure and PFC-mediated cognitive and affective phenomena.

Original languageAmerican English
Article numbere2118192119
Pages (from-to)1-10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number28
StatePublished - Jul 2022

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank Rebecca Waugh, a former research assistant at the Brown University MRI Research Facility, for her work on data collection and initial analyses, and Eli Shmueli for valuable comments on the manuscript. This project was supported by grants from the National Institute of Psychobiology of Israel and the Banting Postdoctoral Fellowship of Canada (S.S.); NIH Grant R01 EY12793 and an Alcon Research Institute award (to D.M.B.); and NIH Grants P20GM103645 and S10OD025181 and the Division of Biology and Medicine, Brown University (to J.N.S.).

Publisher Copyright:
Copyright © 2022 the Author(s).


  • fMRI
  • frontal lobe
  • humans
  • light-sensitive brain regions


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