Our primary objective is to elucidate the neurophysiologic effects of short-term TUS on deep brain circuits in humans. We will map the effects of TUS targeting the amygdala vs. two subregions of the thalamus (mediodorsal & pulvinar nucleus) on…
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Brief title
Condition
- Other condition
Synonym
Health condition
fundamental neuroscience in healthy adults
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Intrinsic functional connectivity profiles and task sensitivity of the target
regions (amygdala, mediodorsal thalamus, pulvinar thalamus) are the primary
dependent measures that will be used to assess TUS target engagement.
Secondary outcome
We will test the activation of the mediodorsal thalamus and pulvinar thalamus
when a flexible processing task engages these regions.
Background summary
To understand mind and brain, and to intervene in their disorders, we need
techniques to safely interact with specific brain circuits. A critical step in
the development of non-invasive neuromodulation is the ability to verify target
engagement. Such verification remains particularly challenging for deeper brain
structures, despite their fundamental contributions to brain function and
cognition. Here, we propose to leverage the high spatial resolution and
whole-brain coverage of functional magnetic resonance imaging (fMRI). We will
image circuit-specific neuromodulation following Transcranial Ultrasonic
Stimulation (TUS) to three deep brain targets: (a) the amygdala, and two
regions of the thalamus: the (b) mediodorsal nucleus and (c) the pulvinar
nucleus. By probing the spatial, temporal, and state specificity of TUS effects
using neuroimaging, the current study aims to validate TUS as a rigorous tool
for non-invasive deep brain modulation. The study aims to bridge the gap
between correlational neuroimaging and causal neuromodulation, and to pave the
way for targeted interventions.
Study objective
Our primary objective is to elucidate the neurophysiologic effects of
short-term TUS on deep brain circuits in humans. We will map the effects of TUS
targeting the amygdala vs. two subregions of the thalamus (mediodorsal &
pulvinar nucleus) on spontaneous coupling profiles using resting-state fMRI.
Our secondary objectives are to (1) assess the duration of TUS effects and to
(2) examine the functional relevance of TUS target engagement during task
recruitment of the target region.
Study design
The study will be a four-visit, single-blind, randomized, crossover trial.
During the first session, structural and baseline fMRI scans will be obtained.
The second, third, and fourth sessions are ultrasound intervention sessions. We
will use a factorial design with stimulation (amygdala TUS, mediodorsal
thalamus-TUS, pulvinar thalamus-TUS) as a within-subject factor.
Intervention
Participants receive TUS targeting the amygdala/mediodorsal thalamus/pulvinar
thalamus.
Study burden and risks
Participants will receive no direct benefit from participating, though they
often report enjoying their participation and the opportunity to experience MRI
and TUS. Participants will receive a standard financial compensation where
applicable (¤15/hour; ¤165 in total for all four sessions). Before
participation, all subjects will be screened for contraindications with respect
to non-invasive brain stimulation and MRI. The estimated risk for participating
in MRI measurements and TUS-based interventions is minimal. The noise and the
relative confined space of the MRI scanner may cause discomfort to some
subjects. TUS for human neuromodulation has never resulted in serious adverse
events (Blackmore, Shrivastava, Sallet, Butler, & Cleveland, 2019; Pasquinelli,
Hanson, Siebner, Lee, & Thielscher, 2019; Sarica et al., 2022). Similar to
applications of well-established biomedical ultrasound (ter Haar, 2010), safety
of study participants is ensured by adherence to internationally recognized
practices and guidelines (e.g., from the U.S. Food and Drug Administration
(2017)). In all cases we will adhere to the recommendations of the
International expert group on Transcranial Ultrasonic Stimulation Safety and
Standards (ITRUSST, https://itrusst.com). Minor side effects of participating
in a TUS experiment may include light transient headache and fatigue (Legon et
al., 2020). To conclude, the risk and burden associated with participation is
considered minimal, and we do not expect any (serious) adverse events during
the project.
Thomas van Aquinostraat 4
Nijmegen 6525
NL
Thomas van Aquinostraat 4
Nijmegen 6525
NL
Listed location countries
Age
Inclusion criteria
- Between 18-40 years of age;
- The ability and agreement to provide informed consent in sound body and mind,
and the ability to fulfil the study*s requirements.
Exclusion criteria
• Under 18 years of age;
• Current pregnancy;
• Claustrophobia;
• A history or brain surgery or serious head trauma;
• A history of or any close relatives (parents, siblings, children) with
epilepsy, convulsion, or seizure;
• Predisposition for fainting spells (syncope);
• A cardiac pacemaker or intra-cardiac lines;
• An implanted neurostimulator;
• Implanted medication infusion device;
• Implanted metal devices or large ferromagnetic fragments in the head or upper
body (excluding dental wire), or jewellery/piercing that cannot be removed;
• Use of a medical plaster that cannot or may not be taken off (e.g., nicotine
plaster);
• Cochlear implants;
• Metal in the brain, skull, or elsewhere in your body (fragments, clips, etc.);
• Diagnosed neurological or psychiatric disorders;
• Use of psychoactive (prescription) medication (excluding anti-conception);
• Skin disease at intended stimulation sites;
• The consumption of more than four alcoholic units within 24 hours before
participation
• The consumption of recreational drugs within 48 hours before participation;
• Calcifications in the brain.
• All other criteria relevant to non-invasive brain stimulation as reported in
the Donders Standard Operating Procedures for Non-Invasive Brain Stimulation.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL83639.091.23 |