Our primary objective is to elucidate the neural and cognitive effects of short-term TUS to two thalamic subdivisions in humans. To this end, we target two thalamic subregions that are spatially adjacent yet feature divergent connectivity profiles…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
fundamental neuroscience in healthy adults
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Intrinsic dynamics and task sensitivity of the cortical network partners of the
stimulation targets (MD - prefrontal cortex, PUL - parietal cortex), estimated
from electroencephalography (EEG) recordings, assess TUS effects. Changes in
behavioural sensitivity to (1) perceptual and (2) task uncertainty
manipulations following TUS application assess effects on decision
computations. These are based on computational modelling of accuracy and
response time measures.
Secondary outcome
We will explore TUS-related changes in physiological arousal based on measured
of heart rate and pupil size. Anatomical MRI measurements will be acquired to
perform personalized simulations of ultrasonic wave propagation; functional MR
images will be used to test the dissociable involvement of the targeted
thalamocortical networks in the decision task.
Background summary
The thalamus makes multifaceted contributions to neuro-cognitive function. By
regulating cortical information processing, thalamocortical circuits define how
external information guides behavior and critically support fundamental
building blocks of cognition, including perception and executive function.
However, the thalamus* deep location and differentiated composition challenges
human research and limits causal interventions. The emerging technology of
low-intensity Transcranial Ultrasonic Stimulation (TUS) promises to overcome
such challenge. TUS enables reversible, non-invasive modulation of focal deep
brain tissue, including the human thalamus with millimeter precision. However,
no study to date has investigated the potential to interact with functionally
heterogeneous subregions of the thalamus -a prerequisite for targeted
engagement with this key structure. In this project, we aim to leverage TUS*s
unprecedented precision to clarify the contribution of anatomically adjacent,
yet distinctly projecting thalamic circuits to uncertainty resolution in human
decision-making.
Study objective
Our primary objective is to elucidate the neural and cognitive effects of
short-term TUS to two thalamic subdivisions in humans. To this end, we target
two thalamic subregions that are spatially adjacent yet feature divergent
connectivity profiles to distal cortical targets. We investigate the short-term
effects of TUS to either the mediodorsal (MD) or pulvinar (PUL) thalamus while
participants perform a perceptual decision-making task. Our primary outcomes
are target-specific changes in (1) the engagement of cortical targets, and (2)
decision computations relying on these circuits. As a secondary outcome, we
probe TUS effects on physiological parameters.
Study design
Three-visit, single-blind, randomized, crossover trial. During the first
session, structural and functional magnetic resonance imaging (MRI) scans will
be obtained. The second and third sessions are ultrasonic intervention
sessions. In these sessions, ultrasonic stimulation will be applied following
and preceding acquisition of electroencephalography (EEG) during a perceptual
decision-making task. We will use a factorial design with stimulation
(MD-thalamus-TUS, PUL-thalamus-TUS) as a within-subject factor.
Intervention
Transcranial Ultrasonic Stimulation (TUS) aimed at bilateral mediodorsal
thalamus, and bilateral pulvinar thalamus (in separate sessions). Experimental
manipulations of (1) perceptual uncertainty and (2) task uncertainty serve to
engage the two target networks.
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, EEG, and TUS. Participants will receive a standard financial compensation
where applicable (¤15/hour; ¤120 in total for all three 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. The EEG electrode application can cause a mild, transient skin
irritation. Participants are informed about both possibilities in advance. 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). Like
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), orjewellery/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
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86115.091.24 |