High-throughput ultrasound neuromodulation in awake and freely behaving rats

Transcranial ultrasound neuromodulation is a promising potential therapeutic tool for the noninvasive treatment of neuropsychiatric disorders. However, the expansive parameter space and difficulties in controlling for peripheral auditory effects make it challenging to identify ultrasound sequences a...

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Main Authors: Tommaso Di Ianni, Kyle P. Morrison, Brenda Yu, Keith R. Murphy, Luis de Lecea, Raag D. Airan
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Brain Stimulation
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X23019575
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author Tommaso Di Ianni
Kyle P. Morrison
Brenda Yu
Keith R. Murphy
Luis de Lecea
Raag D. Airan
author_facet Tommaso Di Ianni
Kyle P. Morrison
Brenda Yu
Keith R. Murphy
Luis de Lecea
Raag D. Airan
author_sort Tommaso Di Ianni
collection DOAJ
description Transcranial ultrasound neuromodulation is a promising potential therapeutic tool for the noninvasive treatment of neuropsychiatric disorders. However, the expansive parameter space and difficulties in controlling for peripheral auditory effects make it challenging to identify ultrasound sequences and brain targets that may provide therapeutic efficacy. Careful preclinical investigations in clinically relevant behavioral models are critically needed to identify suitable brain targets and acoustic parameters. However, there is a lack of ultrasound devices allowing for multi-target experimental investigations in awake and unrestrained rodents. We developed a miniaturized 64-element ultrasound array that enables neurointerventional investigations with within-trial active control targets in freely behaving rats. We first characterized the acoustic field with measurements in free water and with transcranial propagation. We then confirmed in vivo that the array can target multiple brain regions via electronic steering, and verified that wearing the device does not cause significant impairments to animal motility. Finally, we demonstrated the performance of our system in a high-throughput neuromodulation experiment, where we found that ultrasound stimulation of the rat central medial thalamus, but not an active control target, promotes arousal and increases locomotor activity.
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spelling doaj.art-6f9bb79b11734e90a54f64fedb568f682023-12-21T07:30:09ZengElsevierBrain Stimulation1935-861X2023-11-0116617431752High-throughput ultrasound neuromodulation in awake and freely behaving ratsTommaso Di Ianni0Kyle P. Morrison1Brenda Yu2Keith R. Murphy3Luis de Lecea4Raag D. Airan5Department of Radiology, Stanford University, Stanford, 94305, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, 94158, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, 94158, CA, USA; Corresponding author. Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, 94158, CA, USA.Sonic Concepts, Inc., Bothell, 98011, WA, USADepartment of Radiology, Stanford University, Stanford, 94305, CA, USADepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 94305, CA, USADepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 94305, CA, USADepartment of Radiology, Stanford University, Stanford, 94305, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 94305, CA, USA; Department of Materials Science and Engineering, Stanford University, Stanford, 94305, CA, USA; Corresponding author. Department of Radiology, Stanford University, Stanford, 94305, CA, USA.Transcranial ultrasound neuromodulation is a promising potential therapeutic tool for the noninvasive treatment of neuropsychiatric disorders. However, the expansive parameter space and difficulties in controlling for peripheral auditory effects make it challenging to identify ultrasound sequences and brain targets that may provide therapeutic efficacy. Careful preclinical investigations in clinically relevant behavioral models are critically needed to identify suitable brain targets and acoustic parameters. However, there is a lack of ultrasound devices allowing for multi-target experimental investigations in awake and unrestrained rodents. We developed a miniaturized 64-element ultrasound array that enables neurointerventional investigations with within-trial active control targets in freely behaving rats. We first characterized the acoustic field with measurements in free water and with transcranial propagation. We then confirmed in vivo that the array can target multiple brain regions via electronic steering, and verified that wearing the device does not cause significant impairments to animal motility. Finally, we demonstrated the performance of our system in a high-throughput neuromodulation experiment, where we found that ultrasound stimulation of the rat central medial thalamus, but not an active control target, promotes arousal and increases locomotor activity.http://www.sciencedirect.com/science/article/pii/S1935861X23019575Transcranial ultrasoundNeuromodulationFreely behaving ratsWearable arrayCentral medial thalamusCMT
spellingShingle Tommaso Di Ianni
Kyle P. Morrison
Brenda Yu
Keith R. Murphy
Luis de Lecea
Raag D. Airan
High-throughput ultrasound neuromodulation in awake and freely behaving rats
Brain Stimulation
Transcranial ultrasound
Neuromodulation
Freely behaving rats
Wearable array
Central medial thalamus
CMT
title High-throughput ultrasound neuromodulation in awake and freely behaving rats
title_full High-throughput ultrasound neuromodulation in awake and freely behaving rats
title_fullStr High-throughput ultrasound neuromodulation in awake and freely behaving rats
title_full_unstemmed High-throughput ultrasound neuromodulation in awake and freely behaving rats
title_short High-throughput ultrasound neuromodulation in awake and freely behaving rats
title_sort high throughput ultrasound neuromodulation in awake and freely behaving rats
topic Transcranial ultrasound
Neuromodulation
Freely behaving rats
Wearable array
Central medial thalamus
CMT
url http://www.sciencedirect.com/science/article/pii/S1935861X23019575
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