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Author Notes:

Bilal Haider, Email: bilal.haider@bme.gatech.edu

A.N., A.C.Y. and B.W. assembled original hardware components and developed software; A.N. and S.W. optimized hardware and software; A.N. wrote analysis code and analyzed all experiments; A.N. and D.S. optimized signal processing; A.N., J.D.R. and T.L.A. carried out ISI imaging; J.D.R. and T.L.A. performed silicon probe experiments; A.N. and B.H. wrote the manuscript with feedback from all authors.

We thank Anderson Speed for technical support, members of the Haider lab and Jordan Hamm for feedback, and Ruben Uribe and Chris Howard (Physimetrics, Inc.) for assistance in machine development. This work was supported by the Whitehall Foundation, the Alfred P. Sloan Foundation, National Institutes of Health Neurological Disorders and Stroke (NS107968), National Institutes of Health BRAIN Initiative (NS109978), and a grant from the Simons Foundation (SFARI 600343).

The authors declare no competing interests.



  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MICE
  • V1

Optimizing intact skull intrinsic signal imaging for subsequent targeted electrophysiology across mouse visual cortex


Journal Title:



Volume 12, Number 1


, Pages 2063-2063

Type of Work:

Article | Final Publisher PDF


Understanding brain function requires repeatable measurements of neural activity across multiple scales and multiple brain areas. In mice, large scale cortical neural activity evokes hemodynamic changes readily observable with intrinsic signal imaging (ISI). Pairing ISI with visual stimulation allows identification of primary visual cortex (V1) and higher visual areas (HVAs), typically through cranial windows that thin or remove the skull. These procedures can diminish long-term mechanical and physiological stability required for delicate electrophysiological measurements made weeks to months after imaging (e.g., in subjects undergoing behavioral training). Here, we optimized and directly validated an intact skull ISI system in mice. We first assessed how imaging quality and duration affect reliability of retinotopic maps in V1 and HVAs. We then verified ISI map retinotopy in V1 and HVAs with targeted, multi-site electrophysiology several weeks after imaging. Reliable ISI maps of V1 and multiple HVAs emerged with ~ 60 trials of imaging (65 ± 6 min), and these showed strong correlation to local field potential (LFP) retinotopy in superficial cortical layers (r2 = 0.74–0.82). This system is thus well-suited for targeted, multi-area electrophysiology weeks to months after imaging. We provide detailed instructions and code for other researchers to implement this system.

Copyright information:

© The Author(s) 2022

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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