Offline impact of transcranial focused ultrasound on cortical activation in primates

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 r...

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Veröffentlicht in:eLife Jg. 8
Hauptverfasser: Verhagen, Lennart, Gallea, Cécile, Folloni, Davide, Constans, Charlotte, Jensen, Daria EA, Ahnine, Harry, Roumazeilles, Léa, Santin, Mathieu, Ahmed, Bashir, Lehericy, Stéphane, Klein-Flügge, Miriam C, Krug, Kristine, Mars, Rogier B, Rushworth, Matthew FS, Pouget, Pierre, Aubry, Jean-François, Sallet, Jerome
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England eLife Sciences Publications Ltd 12.02.2019
eLife Sciences Publication
eLife Sciences Publications, Ltd
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ISSN:2050-084X, 2050-084X
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Abstract 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. Ultrasound is well known for making visible what is hidden, for example, when giving parents a glimpse of their child before birth. But researchers are now using these high-frequency sound waves – beyond the range of human hearing – for a wholly different purpose: to manipulate the activity of the brain. Conventional brain stimulation techniques use electric currents or magnetic fields to alter brain activity. These techniques, however, have limitations. They can only reach the surface of the brain and are not particularly precise. By contrast, beams of ultrasound can be focused at a millimetre scale, even deep within the brain. Ultrasound thus has the potential to provide new insights into how the brain works. Most studies of ultrasound stimulation have looked at what happens to the brain during the stimulation itself. But could ultrasound also induce longer-lasting changes in brain activity? Changes that persist after the stimulation has ended would be valuable for research. They would also make it more likely that we could use ultrasound to treat brain disorders by changing brain activity. Verhagen, Gallea et al. used a brain scanner to measure brain activity in macaque monkeys after ultrasound stimulation. The results showed that 40 seconds of repetitive ultrasound changed brain activity for up to two hours. Ultrasound caused the stimulated brain area to interact more selectively with the rest of the brain. Notably, only the stimulated area changed its activity in this way. This helps rule out the possibility that the changes reflect non-specific effects. If the monkeys had been able to hear the ultrasound, for example, it would have changed the activity of the parts of the brain related to hearing. Most important of all, the changes were reversible and did not harm the brain. The results of Verhagen, Gallea et al. show that repetitive ultrasound can induce long-lasting alterations in brain activity. It can target areas deep within the brain, including those that are out of reach with other techniques. If this procedure also shows longer-lasting effects in people, it could yield valuable insights into the links between brain and behaviour. It could also help us develop new treatments for neurological and psychiatric disorders.
AbstractList 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.
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.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.
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. Ultrasound is well known for making visible what is hidden, for example, when giving parents a glimpse of their child before birth. But researchers are now using these high-frequency sound waves – beyond the range of human hearing – for a wholly different purpose: to manipulate the activity of the brain. Conventional brain stimulation techniques use electric currents or magnetic fields to alter brain activity. These techniques, however, have limitations. They can only reach the surface of the brain and are not particularly precise. By contrast, beams of ultrasound can be focused at a millimetre scale, even deep within the brain. Ultrasound thus has the potential to provide new insights into how the brain works. Most studies of ultrasound stimulation have looked at what happens to the brain during the stimulation itself. But could ultrasound also induce longer-lasting changes in brain activity? Changes that persist after the stimulation has ended would be valuable for research. They would also make it more likely that we could use ultrasound to treat brain disorders by changing brain activity. Verhagen, Gallea et al. used a brain scanner to measure brain activity in macaque monkeys after ultrasound stimulation. The results showed that 40 seconds of repetitive ultrasound changed brain activity for up to two hours. Ultrasound caused the stimulated brain area to interact more selectively with the rest of the brain. Notably, only the stimulated area changed its activity in this way. This helps rule out the possibility that the changes reflect non-specific effects. If the monkeys had been able to hear the ultrasound, for example, it would have changed the activity of the parts of the brain related to hearing. Most important of all, the changes were reversible and did not harm the brain. The results of Verhagen, Gallea et al. show that repetitive ultrasound can induce long-lasting alterations in brain activity. It can target areas deep within the brain, including those that are out of reach with other techniques. If this procedure also shows longer-lasting effects in people, it could yield valuable insights into the links between brain and behaviour. It could also help us develop new treatments for neurological and psychiatric disorders.
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. Ultrasound is well known for making visible what is hidden, for example, when giving parents a glimpse of their child before birth. But researchers are now using these high-frequency sound waves – beyond the range of human hearing – for a wholly different purpose: to manipulate the activity of the brain. Conventional brain stimulation techniques use electric currents or magnetic fields to alter brain activity. These techniques, however, have limitations. They can only reach the surface of the brain and are not particularly precise. By contrast, beams of ultrasound can be focused at a millimetre scale, even deep within the brain. Ultrasound thus has the potential to provide new insights into how the brain works. Most studies of ultrasound stimulation have looked at what happens to the brain during the stimulation itself. But could ultrasound also induce longer-lasting changes in brain activity? Changes that persist after the stimulation has ended would be valuable for research. They would also make it more likely that we could use ultrasound to treat brain disorders by changing brain activity. Verhagen, Gallea et al. used a brain scanner to measure brain activity in macaque monkeys after ultrasound stimulation. The results showed that 40 seconds of repetitive ultrasound changed brain activity for up to two hours. Ultrasound caused the stimulated brain area to interact more selectively with the rest of the brain. Notably, only the stimulated area changed its activity in this way. This helps rule out the possibility that the changes reflect non-specific effects. If the monkeys had been able to hear the ultrasound, for example, it would have changed the activity of the parts of the brain related to hearing. Most important of all, the changes were reversible and did not harm the brain. The results of Verhagen, Gallea et al. show that repetitive ultrasound can induce long-lasting alterations in brain activity. It can target areas deep within the brain, including those that are out of reach with other techniques. If this procedure also shows longer-lasting effects in people, it could yield valuable insights into the links between brain and behaviour. It could also help us develop new treatments for neurological and psychiatric disorders.
Author Gallea, Cécile
Krug, Kristine
Constans, Charlotte
Roumazeilles, Léa
Lehericy, Stéphane
Aubry, Jean-François
Klein-Flügge, Miriam C
Pouget, Pierre
Santin, Mathieu
Verhagen, Lennart
Rushworth, Matthew FS
Ahnine, Harry
Folloni, Davide
Jensen, Daria EA
Mars, Rogier B
Ahmed, Bashir
Sallet, Jerome
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  orcidid: 0000-0003-3207-7929
  surname: Verhagen
  fullname: Verhagen, Lennart
  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  givenname: Cécile
  surname: Gallea
  fullname: Gallea, Cécile
  organization: Institute du Cerveau et de la Moelle épinière (ICM), Centre for NeuroImaging Research (CENIR), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France
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  givenname: Davide
  orcidid: 0000-0003-1653-5969
  surname: Folloni
  fullname: Folloni, Davide
  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  givenname: Charlotte
  orcidid: 0000-0001-6378-9158
  surname: Constans
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  organization: Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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  givenname: Daria EA
  surname: Jensen
  fullname: Jensen, Daria EA
  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  fullname: Ahnine, Harry
  organization: Institute du Cerveau et de la Moelle épinière (ICM), Centre for NeuroImaging Research (CENIR), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France
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  givenname: Léa
  surname: Roumazeilles
  fullname: Roumazeilles, Léa
  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  givenname: Mathieu
  surname: Santin
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  givenname: Bashir
  surname: Ahmed
  fullname: Ahmed, Bashir
  organization: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
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  surname: Lehericy
  fullname: Lehericy, Stéphane
  organization: Institute du Cerveau et de la Moelle épinière (ICM), Centre for NeuroImaging Research (CENIR), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France
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  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  givenname: Kristine
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  surname: Krug
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  givenname: Rogier B
  surname: Mars
  fullname: Mars, Rogier B
  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands
– sequence: 14
  givenname: Matthew FS
  surname: Rushworth
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  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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  givenname: Jean-François
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  givenname: Jerome
  orcidid: 0000-0002-7878-0209
  surname: Sallet
  fullname: Sallet, Jerome
  organization: Wellcome Centre for Integrative Neuroimaging (WIN), Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30747105$$D View this record in MEDLINE/PubMed
https://hal.science/hal-04073656$$DView record in HAL
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Keywords brain stimulation
rhesus macaque
connectivity
neuroscience
frontal lobe
transcranial ultrasound stimulation
resting-state fMRI
neuroimaging
Language English
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These authors contributed equally to this work.
These authors also contributed equally to this work.
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Snippet To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising...
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SubjectTerms Animals
Auditory pathways
Brain research
brain stimulation
Cerebral Cortex - physiology
Cerebral Cortex - radiation effects
Cognitive science
connectivity
Cortex (frontal)
frontal lobe
Macaca
Magnetic Resonance Imaging
Medical imaging
Medical research
Neuroimaging
Neuromodulation
Neuroscience
NMR
Nuclear magnetic resonance
Protocol
resting-state fMRI
Supplementary motor area
transcranial ultrasound stimulation
Ultrasonic imaging
Ultrasonography - methods
Ultrasound
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Title Offline impact of transcranial focused ultrasound on cortical activation in primates
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