scholarly journals Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification

2020 ◽  
Author(s):  
Sangjin Yoo ◽  
David R. Mittelstein ◽  
Robert Hurt ◽  
Jerome Lacroix ◽  
Mikhail G. Shapiro
Keyword(s):  
Ion Channels ◽  
Large Scale ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Cellular Mechanisms ◽  
Temperature Changes ◽  
Non Invasive ◽  
Neuroscience Research ◽  
Ultrasonic Stimulation ◽  
Further Development

ABSTRACTUltrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, the biomolecular and cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for the use of this technology in research and potential clinical applications. Here, we show that focused ultrasound excites neurons through a primarily mechanical mechanism mediated by specific calcium-selective mechanosensitive ion channels. The activation of these channels results in a gradual build-up of calcium, which is amplified by calcium- and voltage-gated channels, generating a burst firing response. Cavitation, temperature changes, large-scale deformation, and synaptic transmission are not required for this excitation to occur. Pharmacological and genetic inhibition of specific ion channels leads to reduced responses to ultrasound, while over-expressing these channels results in stronger ultrasonic stimulation. These findings provide a critical missing explanation for the effect of ultrasound on neurons and facilitate the further development of ultrasonic neuromodulation and sonogenetics as unique tools for neuroscience research.

scholarly journals The role of anatomical connection strength for interareal communication in macaque cortex

2020 ◽  
Author(s):  
Julien Vezoli ◽  
Martin Vinck ◽  
Conrado A. Bosman ◽  
Andre M. Bastos ◽  
Christopher M Lewis ◽  
...  
Keyword(s):  
Large Scale ◽  
Functional Organization ◽  
Brain Regions ◽  
Connection Strength ◽  
Non Invasive ◽  
Large Scale Networks ◽  
Invasive Techniques ◽  
The Relationship ◽  
Anatomical Connection

What is the relationship between anatomical connection strength and rhythmic synchronization? Simultaneous recordings of 15 cortical areas in two macaque monkeys show that interareal networks are functionally organized in spatially distinct modules with specific synchronization frequencies, i.e. frequency-specific functional connectomes. We relate the functional interactions between 91 area pairs to their anatomical connection strength defined in a separate cohort of twenty six subjects. This reveals that anatomical connection strength predicts rhythmic synchronization and vice-versa, in a manner that is specific for frequency bands and for the feedforward versus feedback direction, even if interareal distances are taken into account. These results further our understanding of structure-function relationships in large-scale networks covering different modality-specific brain regions and provide strong constraints on mechanistic models of brain function. Because this approach can be adapted to non-invasive techniques, it promises to open new perspectives on the functional organization of the human brain.

scholarly journals A Noninvasive Approach to Optogenetics Using Focused Ultrasound Blood Brain Barrier Disruption for the Delivery of Radioluminescent Particles

2020 ◽  
Author(s):  
Megan Rich ◽  
Eric Zhang ◽  
Ashley Dickey ◽  
Haley Jones ◽  
Kelli Cannon ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Brain Barrier ◽  
Receptor Subtype ◽  
Spatiotemporal Resolution ◽  
Light Emitting ◽  
Non Invasive ◽  
Blood Brain ◽  
Essential Components

AbstractOptogenetics, the genetic incorporation of light-sensitive proteins such as Channelrhodopsin-2 (ChR2) into target mammalian neurons, has enabled activation, silencing, and receptor subtype specific neuromodulation with high spatiotemporal resolution. However, the essential components of the ontogenetic system require invasive procedures with very few non-invasive alternatives preventing its use as a translational tool. The implantation of light emitting fibers deep within brain structures is both technically demanding and causes tissue scarring in target brain regions. To overcome these limitations, while maintaining the highly-tuned components of optogenetics we have developed a novel noninvasive alternative. Our approach replaces fibers with light-emitting radioluminescent particles (RLPs) that can be activated non-invasively with X-ray exposure. Here, we report successful noninvasive delivery of RLPs to target brain regions using MRI-guided focused ultrasound (FUS) blood brain barrier opening. In addition, FUS BBBO can be used to deliver viral vectors for light sensitive channel expression. Combined, these components can provide a completely non-invasive optogenetic system.

scholarly journals Brainstem modulation of large-scale intrinsic cortical activity correlations

2019 ◽  
Author(s):  
Ruud L. van den Brink ◽  
Thomas Pfeffer ◽  
Tobias Donner
Keyword(s):  
Psychiatric Disorders ◽  
Large Scale ◽  
Brain Activity ◽  
Cortical Activity ◽  
Brain Regions ◽  
Intrinsic Activity ◽  
Non Invasive ◽  
Correlated Activity ◽  
Intrinsic Fluctuations ◽  
Specific Receptors

Brain activity fluctuates continuously, even in the absence of changes in sensory input or motor output. These intrinsic activity fluctuations are correlated across brain regions and are spatially organized in macroscale networks. Variations in the strength, topography, and topology of correlated activity occur over time, and unfold upon a backbone of long-range anatomical connections. Subcortical neuromodulatory systems send widespread ascending projections to the cortex, and are thus ideally situated to shape the temporal and spatial structure of intrinsic correlations. These systems are also the targets of the pharmacological treatment of major neurological and psychiatric disorders, such as Parkinson’s disease, depression, and schizophrenia. Here, we review recent work that has investigated how neuromodulatory systems shape correlations of intrinsic fluctuations of large-scale cortical activity. We discuss studies in the human, monkey, and rodent brain, with a focus on non-invasive recordings of human brain activity. We provide a structured but selective overview of this work and distill a number of emerging principles. Future efforts to chart the effect of specific neuromodulators and, in particular, specific receptors, on intrinsic correlations may help identify shared or antagonistic principles between different neuromodulatory systems. Such principles can inform models of healthy brain function and may provide an important reference for understanding altered cortical dynamics that are evident in neurological and psychiatric disorders, potentially paving the way for mechanistically-inspired biomarkers and individualized treatments of these disorders.

scholarly journals Offline impact of transcranial focused ultrasound on cortical activation in primates

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Lennart Verhagen ◽  
Cécile Gallea ◽  
Davide Folloni ◽  
Charlotte Constans ◽  
Daria EA Jensen ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Brain Regions ◽  
Cortical Activation ◽  
Transcranial Ultrasound ◽  
Full Potential ◽  
Non Invasive ◽  
Specific Effects ◽  
Ultrasound Stimulation ◽  
Induced Signal ◽  
Stimulation Technique

To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting ‘offline’ changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS caused stimulated areas to interact more selectively with the rest of the brain. In a within-subject design, we observe regionally specific TUS effects for two medial frontal brain regions – supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.

scholarly journals Offline impact of transcranial focused ultrasound on cortical activation in primates

2018 ◽  
Author(s):  
Lennart Verhagen ◽  
Cécile Gallea ◽  
Davide Folloni ◽  
Charlotte Constans ◽  
Daria EA Jensen ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Brain Regions ◽  
Cortical Activation ◽  
Transcranial Ultrasound ◽  
Full Potential ◽  
Non Invasive ◽  
Specific Effects ◽  
Brain Circuits ◽  
Induced Signal ◽  
Stimulation Technique

AbstractTo understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound (TUS) is a promising non-invasive brain stimulation technique. To date, investigations have focused on short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting ‘offline’ changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 seconds of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS’ impact can be demonstrated by showing such patterns change for stimulated areas. We report regionally specific TUS effects for two medial frontal brain regions – supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.

scholarly journals Real Time and Delayed Effects of Subcortical Low Intensity Focused Ultrasound

2020 ◽  
Author(s):  
Joshua A. Cain ◽  
Shakthi Visagan ◽  
Micah A. Johnson ◽  
Julia Crone ◽  
Robin Blades ◽  
...  
Keyword(s):  
Large Scale ◽  
Focused Ultrasound ◽  
Blood Oxygenation ◽  
Brain Nuclei ◽  
Delayed Effects ◽  
Non Invasive ◽  
Low Intensity ◽  
Oxygenation Level ◽  
Basal Ganglia Structures ◽  
Deep Brain

ABSTRACTDeep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.

scholarly journals The universal language network: A cross-linguistic investigation spanning 45 languages and 11 language families.

2021 ◽  
Author(s):  
Dima Ayyash ◽  
Saima Malik-Moraleda ◽  
Jeanne Gallee ◽  
Josef Affourtit ◽  
Malte Hoffman ◽  
...  
Keyword(s):  
Language Processing ◽  
Cognitive Neuroscience ◽  
Large Scale ◽  
Functional Integration ◽  
Brain Regions ◽  
European Languages ◽  
Universal Language ◽  
Neuroscience Research ◽  
Temporal Language ◽  
Language Network

To understand the architecture of human language, it is critical to examine diverse languages; yet most cognitive neuroscience research has focused on a handful of primarily Indo-European languages. Here, we report a large-scale investigation of the fronto-temporal language network across 45 languages and establish the cross-linguistic generality of its key functional properties, including general topography, left-lateralization, strong functional integration among its brain regions, and functional selectivity for language processing. 

scholarly journals Non-Invasive Brain Stimulation in Dementia: A Complex Network Story

2018 ◽  
Vol 18 (5-6) ◽  
pp. 281-301 ◽  
Author(s):  
Lorenzo Pini ◽  
Rosa Manenti ◽  
Maria Cotelli ◽  
Francesca B. Pizzini ◽  
Giovanni B. Frisoni ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Complex Network ◽  
Brain Stimulation ◽  
Neurodegenerative Disorders ◽  
Large Scale ◽  
Clinical Manifestations ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Non Invasive ◽  
Large Scale Networks

Non-invasive brain stimulation (NIBS) is emerging as a promising rehabilitation tool for a number of neurodegenerative diseases. However, the therapeutic mechanisms of NIBS are not completely understood. In this review, we will summarize NIBS results in the context of brain imaging studies of functional connectivity and metabolites to gain insight into the possible mechanisms underlying recovery. We will briefly discuss how the clinical manifestations of common neurodegenerative disorders may be related with aberrant connectivity within large-scale neural networks. We will then focus on recent studies combining resting-state functional magnetic resonance imaging with NIBS to delineate how stimulation of different brain regions induce complex network modifications, both at the local and distal level. Moreover, we will review studies combining magnetic resonance spectroscopy and NIBS to investigate how microscale changes are related to modifications of large-scale networks. Finally, we will re-examine previous NIBS studies in dementia in light of this network perspective. A better understanding of NIBS impact on the functionality of large-scale brain networks may be useful to design beneficial treatments for neurodegenerative disorders.

scholarly journals Real time and delayed effects of subcortical low intensity focused ultrasound

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua A. Cain ◽  
Shakthi Visagan ◽  
Micah A. Johnson ◽  
Julia Crone ◽  
Robin Blades ◽  
...  
Keyword(s):  
Large Scale ◽  
Focused Ultrasound ◽  
Blood Oxygenation ◽  
Brain Nuclei ◽  
Delayed Effects ◽  
Non Invasive ◽  
Low Intensity ◽  
Oxygenation Level ◽  
Basal Ganglia Structures ◽  
Deep Brain

AbstractDeep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.

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