EEG and functional ultrasound imaging in mobile rats

Abstract

We developed an integrated experimental framework which extends the brain exploration capabilities of functional ultrasound imaging to awake/mobile animals. In addition to hemodynamic data, this method further allows parallel access to EEG recordings of neuronal activity. This approach is illustrated with two proofs of concept: first, a behavioral study, concerning theta rhythm activation in a maze running task and, second, a disease-related study concerning spontaneous epileptic seizures.In vivo brain activity recordings provide a unique contribution to neuroscience to unravel the underlying mechanisms of complex behaviors and pathologies. Ideally we would like to capture instantly both neuronal activity and metabolic events, which form two major facets of global brain equilibrium, in the most natural conditions, that is when the subject is awake and freely moving. There is an increasing awareness today that major issues of neurophysiology need to be addressed with such global approaches. Notably, the basic mechanisms involved in functional network dynamics and pathologies including epilepsy can be deciphered only if the electrographic and metabolic components are sensed concomitantly [Logothetis 2008, Sada 2015. More generally, the multiple feedbacks between electrographic and metabolic signals represent the rule, rather than the exception. They have been tackled separately only by lack of appropriate methods for accessing the global picture, prompting the development of multimodal strategies.In practice there is a compromise between the size of imaging field, time resolution, sensitivity, separability of processing and metabolism, and physical constraint on the animal.Corresponding author: IC, ivan.cohen@upmc.fr. Author contributions LAS designed the surgical procedure and prosthetic skull, and performed and analyzed epilepsy experiments; AB designed intrahippocampal recording procedure and performed and analyzed navigation experiments; ET and TD developed the "burst mode" ultrasound recording sequence; MP and JLG developed the "continuous mode" ultrasound recording sequence; JLG and MT designed and supervised the ultrasound scanner and probe; IC designed and supervised the experiments, designed the probe holder, programmed acquisition and analysis software; IC, LAS, AB wrote the paper.

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