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Reusable Multielectrode Array Technique for Electroencephalography in Awake Freely Moving Mice.

ABSTRACT: Translational comparison of rodent models of neurological and neuropsychiatric diseases to human electroencephalography (EEG) biomarkers in these conditions will require multisite rodent EEG on the skull surface, rather than local area electrocorticography (ECoG) or multisite local field potential (LFP) recording. We have developed a technique for planar multielectrode array (MEA) implantation on the mouse skull surface, which enables multisite EEG in awake and freely moving mice and reusability of the MEA probes. With this method, we reliably obtain 30-channel low-noise EEG from awake mice. Baseline and stimulus-evoked EEG recordings can be readily obtained and analyzed. For example, we have demonstrated EEG responses to auditory stimuli. Broadband noise elicits reliable 30-channel auditory event-related potentials (ERPs), and chirp stimuli induce phase-locked EEG responses just as in human sound presentation paradigms. This method is unique in achieving chronic implantation of novel MEA technology onto the mouse skull surface for chronic multisite EEG recordings. Furthermore, we demonstrate a reliable method for reusing MEA probes for multiple serial implantations without loss of EEG quality. This skull surface MEA methodology can be used to obtain simultaneous multisite EEG recordings and to test EEG biomarkers in diverse mouse models of human neurological and neuropsychiatric diseases. Reusability of the MEA probes makes it more cost-effective to deploy this system for various studies.

SUBMITTER: Jonak CR

PROVIDER: S-EPMC6213968 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.

Project description:This work presents and evaluates a 12-electrode intracranial electroencephalography system developed at the National Institute of Mental Health (Klecany, Czech Republic) in terms of an electrical source imaging (ESI) technique in rats. The electrode system was originally designed for translational research purposes. This study demonstrates that it is also possible to use this well-established system for ESI, and estimates its precision, accuracy, and limitations. Furthermore, this paper sets a methodological basis for future implants. Source localization quality is evaluated using three approaches based on surrogate data, physical phantom measurements, and in vivo experiments. The forward model for source localization is obtained from the FieldTrip-SimBio pipeline using the finite-element method. Rat brain tissue extracted from a magnetic resonance imaging template is approximated by a single-compartment homogeneous tetrahedral head model. Four inverse solvers were tested: standardized low-resolution brain electromagnetic tomography, exact low-resolution brain electromagnetic tomography (eLORETA), linear constrained minimum variance (LCMV), and dynamic imaging of coherent sources. Based on surrogate data, this paper evaluates the accuracy and precision of all solvers within the brain volume using error distance and reliability maps. The mean error distance over the whole brain was found to be the lowest in the eLORETA solution through signal to noise ratios (SNRs) (0.2 mm for 25 dB SNR). The LCMV outperformed eLORETA under higher SNR conditions, and exhibiting higher spatial precision. Both of these inverse solvers provided accurate results in a phantom experiment (1.6 mm mean error distance across shallow and 2.6 mm across subcortical testing dipoles). Utilizing the developed technique in freely moving rats, an auditory steady-state response experiment provided results in line with previously reported findings. The obtained results support the idea of utilizing a 12-electrode system for ESI and using it as a solid basis for the development of future ESI dedicated implants.

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Reusable Multielectrode Array Technique for Electroencephalography in Awake Freely Moving Mice.

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