Mesoscopic Imaging: Shining a Wide Light on Large-Scale Neural Dynamics
Open accessAbstract
Optical imaging has revolutionized our ability to monitor brain activity, spanning spatial scales from synapses to cells to circuits. Here, we summarize the rapid development and application of mesoscopic imaging, a widefield fluorescence-based approach that balances high spatiotemporal resolution with extraordinarily large fields of view. By leveraging the continued expansion of fluorescent reporters for neuronal activity and novel strategies for indicator expression, mesoscopic analysis enables measurement and correlation of network dynamics with behavioral state and task performance. Moreover, the combination of widefield imaging with cellular resolution methods such as two-photon microscopy and electrophysiology is bridging boundaries between cellular and network analyses. Overall, mesoscopic imaging provides a powerful option in the optical toolbox for investigation of brain function.
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Time-resolved metrics such as dwell time in coactivation states forecast early response and capture consolidation dynamics.
“At the network scale, resting-state fMRI yields robust predictors of treatment outcome, including strengthened frontoparietal integration and reliable default-mode suppression; time-resolved metrics such as dwell time in coactivation states forecast early response and capture consolidation dynamics.”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [404]
The References section mentions transient neuronal coactivations in a study of resting-state connectivity, and the Acquisition and analysis of mesoscopic data section discusses spatiotemporal activity patterns. Neither reports dwell time in coactivation states as a predictor of early treatment response or a measure of consolidation dynamics (searched: dwell time, treatment response, consolidation). No page numbers were provided for these passages. (LLM, conf=0.76)
Experimental — accuracy not yet measuredResting EEG topology differentiates responders.
“Resting EEG topology differentiates responders, while spectral slope and rostral anterior cingulate theta index cortical excitability and plasticity readiness, offering rapid, repeatable assays that complement imaging-derived connectivity maps.”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [404]
The 'Recent biological insights from mesoscopic analysis' section discusses resting-state networks identified through mesoscopic calcium imaging, not resting EEG topology or differences between treatment responders. Searches for the claim, EEG, and treatment response found no passage addressing whether resting EEG topology differentiates responders; the indexed passages provide no page numbers. (LLM, conf=0.76)
Experimental — accuracy not yet measuredResting-state fMRI yields robust predictors of treatment outcome, including strengthened frontoparietal integration and reliable default-mode suppression.
“At the network scale, resting-state fMRI yields robust predictors of treatment outcome, including strengthened frontoparietal integration and reliable default-mode suppression; time-resolved metrics such as dwell time in coactivation states forecast early response and capture consolidation dynamics.”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [404]
The Future advances section discusses simultaneous mesoscopic imaging and fMRI as a way to investigate the origins of BOLD signals, not to predict treatment outcomes. Searches for treatment response, frontoparietal integration, and default-mode suppression found no passage addressing those claims in our copy; page numbers were unavailable. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSpectral slope and rostral anterior cingulate theta index cortical excitability and plasticity readiness.
“Resting EEG topology differentiates responders, while spectral slope and rostral anterior cingulate theta index cortical excitability and plasticity readiness, offering rapid, repeatable assays that complement imaging-derived connectivity maps.”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [404]
The 'Recent biological insights from mesoscopic analysis' section discusses cortical activity and resting-state networks measured with mesoscopic imaging, not EEG markers of excitability or plasticity readiness. Searches for spectral slope, rostral anterior cingulate theta, and EEG predictors found no passage in our copy addressing the attributed claim; page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredActigraphy supplies the behavioral layer, quantifying circadian alignment and sleep regularity that gate synaptic renormalization and stabilize network states across days.
“Actigraphy supplies the behavioral layer, quantifying circadian alignment and sleep regularity that gate synaptic renormalization and stabilize network states across days [403,404].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [404]
The Acquisition and analysis of mesoscopic data section describes monitoring mouse locomotion, whisking, and pupil diameter, not actigraphy. The Recent biological insights section discusses patterns of cortical activity, but the searched passages do not address circadian alignment, sleep regularity, synaptic renormalization, or stabilization of network states across days. (LLM, conf=0.75)
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References 121 · Cited by 135
Research works printed but not linked: 4
- Lake EMR, Ge X, Shen X, Herman P, Hyder F, Cardin JA, Higley MJ, Scheinost D, Papademetris X, Crair MC, (2018). Spanning spatiotemporal scales with simultaneous mesoscopic Ca2+ imaging and functional MRI. BioRXiv.
- Musall S, Kaufman MT, Gluf S, and Churchland AK (2018). Movement-related activity dominates cortex during sensory-guided decision making. BioRXiv.
- Stern M, Shea-Brown E, and Witten D (2020). Inferring the Spiking Rate of a Population of Neurons from Wide-Field Calcium Imaging. BioRxiv 2020.02.01.930040.
- Zatka-Haas P, Steinmetz NA, Carandini M, and Harris KD (2019). Distinct contributions of mouse cortical areas to visual discrimination. BioRxiv 501627.
- Authors
- Cardin, J. A., Crair, M. C., & Higley, M. J.
- Affiliations
- Yale University (US)
- Corresponding author
- Higley, Michael J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 108
- Issue
- 1
- Pages
- 33-43
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC7577373
- OpenAlex
- W3093146038
- Cited by
- 135
- References
- 121
- Citations by year
- 2026: 24 · 2025: 22 · 2024: 26 · 2023: 30 · 2022: 23 · 2021: 10
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke
- National Institute of Mental Health
- Simons Foundation
- National Eye Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mesoscopic imaging, neural network dynamics, behavioral state, task performance, two-photon microscopy, electrophysiology, brain function
- MeSH terms
- Intravital Microscopy, Animals, Brain, Calcium, Humans, Neurons, Microscopy, Fluorescence, Multiphoton, Optical Imaging
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