Rapid fluctuations in functional connectivity of cortical networks encode spontaneous behavior
Open accessAbstract
Experimental work across species has demonstrated that spontaneously generated behaviors are robustly coupled to variations in neural activity within the cerebral cortex. Functional magnetic resonance imaging data suggest that temporal correlations in cortical networks vary across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these data generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior observed in awake animals. Here, we used wide-field mesoscopic calcium imaging to monitor cortical dynamics in awake mice and developed an approach to quantify rapidly time-varying functional connectivity. We show that spontaneous behaviors are represented by fast changes in both the magnitude and correlational structure of cortical network activity. Combining mesoscopic imaging with simultaneous cellular-resolution two-photon microscopy demonstrated that correlations among neighboring neurons and between local and large-scale networks also encode behavior. Finally, the dynamic functional connectivity of mesoscale signals revealed subnetworks not predicted by traditional anatomical atlas-based parcellation of the cortex. These results provide new insights into how behavioral information is represented across the neocortex and demonstrate an analytical framework for investigating time-varying functional connectivity in neural networks.
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Glx and GABA levels, particularly in anterior cingulate and prefrontal cortex, correlate with resting connectivity and default-mode interactions.
“Glx and GABA levels, particularly in anterior cingulate and prefrontal cortex, correlate with resting connectivity and default-mode interactions, while trimodal PET–MR–EEG indicates that inhibitory processes strongly constrain canonical networks, refining interpretation of E to I balance in vivo.”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [402]
The Results sections on cortical connectivity examine calcium-imaging correlations and behavior in mice, while the Discussion mentions resting-state connectivity only as background. Searches for Glx, GABA, anterior cingulate and prefrontal metabolite levels, and default-mode interactions found no passage linking those measures to connectivity in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredTrimodal PET-MR-EEG indicates that inhibitory processes strongly constrain canonical networks, refining interpretation of E to I balance in vivo.
“Glx and GABA levels, particularly in anterior cingulate and prefrontal cortex, correlate with resting connectivity and default-mode interactions, while trimodal PET–MR–EEG indicates that inhibitory processes strongly constrain canonical networks, refining interpretation of E to I balance in vivo.”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [402]
The Introduction and Discussion describe calcium imaging in mice and rapid changes in cortical connectivity, not trimodal PET–MR–EEG. Searches for PET–MR–EEG, inhibitory processes, and E/I balance found no passage in our copy addressing the attributed finding. Page numbers were not available in the indexed passages. (LLM, conf=0.76)
Experimental — accuracy not yet measuredUnimodal MRS shows inconsistent prognostic utility, reinforcing the need for multimodal designs and larger samples.
“Importantly, unimodal MRS shows inconsistent prognostic utility, reinforcing the need for multimodal designs and larger samples [401,402].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [402]
The Results section, “Dynamic connectivity across spatial scales encodes behavior” (page unavailable), examines calcium imaging and prediction of spontaneous behavior in mice, not MRS prognosis. Searches for MRS, prognostic utility, multimodal designs, and larger samples found no passage addressing the attributed claim. (LLM, conf=0.75)
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Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery
Tanaka, M. (2026) · Biomedicines · doi:10.3390/biomedicines14061265
- Authors
- Benisty, H., Barson, D., Moberly, A. H., Lohani, S., Tang, L., Coifman, R. R., Crair, M. C., Mishne, G., Cardin, J. A., & Higley, M. J.
- Affiliations
- Yale University (US)
- University of California San Diego (US)
- Corresponding author
- Higley, Michael J.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2023-11-30
- Volume
- 27
- Issue
- 1
- Pages
- 148-158
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC11316935
- OpenAlex
- W4389173155
- Cited by
- 65
- References
- 71
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 11 · 2023: 5 · 2022: 6
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH099045, MH121841, MH113852)
- U.S. Department of Health & Human Services | NIH | National Eye Institute (EY033975, EY022951, EY029581, EY031133, EY026878)
- U.S. Department of Health && Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (EB026936)
- National Science Foundation (CCF-2217058)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- functional connectivity, spontaneous behavior, cortical networks, two-photon microscopy, neural correlations, awake mice, neocortex, cortical parcellation, behavioral representation, time-varying connectedness
- MeSH terms
- Animals, Brain Mapping, Magnetic Resonance Imaging, Neural Pathways, Neurons, Wakefulness, Neocortex, Mice
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