The primary objective is to assess the causal role of the human amygdala in fear learning, by indexing the impact of TUS targeting the amygdala on physiological markers of fear. The secondary objectives are to (1) discern the neuromodulatory effects…
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Electrodermal activity (EDA) is used to index differential skin-conductance
responses (SCRs) to the conditioned stimuli (CS+ vs. CS-). EDA is measured
using Ag/AgCl electrodes placed on the palmar side of the distal phalanges of
the ring and little finger of the left hand.
The main study parameter falls under the blanket approval for standard research
(CMO2014/288, version 3; titled: *Imaging Human Cognition*).
Secondary outcome
- Heart rate (HR) is used to index differential heart rate responses (HRRs) to
the conditioned stimuli (CS+ vs. CS-). HR is measured using electrocardiography
(ECG), using lead electrodes attached to the skin surface.
- Pupil diameter (PD) is used to index differential pupil dilation responses
(PDRs) to the conditioned stimuli (CS+ vs. CS-). PD is recorded by video-based
eye-tracking.
The secondary study parameters fall under the blanket approval for standard
research (CMO2014/288, version 3; titled: *Imaging Human Cognition*).
Background summary
How do humans learn about threats? This question lies at the core of our
understanding of anxiety disorders and is critical to develop novel treatment
options, grounded in neurocognition. Pavlovian fear conditioning is a
well-established paradigm to model fear learning in the laboratory. This simple
and robust approach is extensively used in animal work to elucidate the brain
circuits and mechanisms. The most consistent finding across rodent and
non-human primate studies is that fear learning depends on the amygdala. Our
understanding of these systems in humans is primarily based on correlational
evidence from neuroimaging studies. The observational and correlational nature
of these studies limits their potential for clinical translation. Indeed,
non-invasive neuromodulation approaches in humans are critical for a causal
understanding of fear learning processes and to develop targeted treatment
options.
Transcranial Ultrasonic Stimulation (TUS) is a non-invasive neuromodulation
technique that can achieve focal modulation of deep brain structures such as
the amygdala. Here, we will combine TUS with well-validated fear conditioning
procedures, exploiting the unique opportunity for a causal test of
amygdala-dependent fear learning processes in healthy humans. TUS has
previously been used in non-human primates to successfully modulate amygdala
activation. In human studies, TUS induces changes in cognitive processes by
neuromodulation of deep brain structures. Hence, we expect TUS to modulate the
amygdala contribution to fear learning.
Study objective
The primary objective is to assess the causal role of the human amygdala in
fear learning, by indexing the impact of TUS targeting the amygdala on
physiological markers of fear.
The secondary objectives are to (1) discern the neuromodulatory effects of
amygdala-TUS on standard physiological indices of fear learning, (2) determine
the role of the amygdala in unconditioned fear expression and (3) predict
interindividual variability in intervention response.
Study design
Two-visit, single-blind, randomized, sham-controlled, parallel trial. During
the first session, structural and functional MRI scans will be obtained. The
second session is the intervention session. We will use a mixed factorial
design with CS (CS+, CS-) and Stimulation (verum TUS, sham TUS) as
within-subject factors and Site (amygdala, medial temporal lobe) as
between-subjects factor. The CS+ is paired with a mild electrical shock (US) on
half of the trials using a 50% reinforcement rate.
Intervention
Verum TUS targeted at the amygdala.
Study burden and risks
Participants will receive no direct benefit from participating, though they
often report enjoying their participation and the opportunity to experience
this technique. Participants will receive a standard financial compensation
where applicable (¤10/hour). Before participation, all subjects will be
screened for contraindications with respect to non-invasive brain stimulation
and magnetic resonance imaging (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, and the requirement to remain
seated during the TUS experiment, may cause discomfort to some subjects. TUS
for human neuromodulation has never resulted in serious adverse events
(Blackmore et al., 2019; Pasquinelli et al., 2019). 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 Food and Drug Administration). Minor side
effects of TUS 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.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
- Healthy participants between 18-40 years of age;
- The ability and agreement to provide informed consent, and the ability to
fulfil the study's requirements.
Exclusion criteria
• Under 18 years of age
• Current or planned 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 or any recreational drugs within 48 hours before participation
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
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL77274.091.21 |