Modulating Amygdala and dACC activity during reward volatility in affective decision-making

Traditionally, only neuroimaging studies have been used to map the neural
mechanisms of approach/avoidance behaviour. The limitations of these types of
studies is that the correlations they find between neural activity and
behaviour is purely correlational. We want to go one step further by
stimulating network nodes found to be related to approach/avoidance behaviour
by said studies using non-invasive brain stimulation. To be specific, we want
to stimulate the Amygdala and dACC using Transcranial Ultrasonic Stimulation
(TUS) to map what effects stimulating these areas has on both behavioural
changes and cortical oxygen usage by having the participants complete an
'approach/avoidance' task in the functional Magnetic Resonance Imaging (fMRI)
scanner. With this, we hope to provide causal neuromodulation evidence for the
roles of the Amygdala and dACC in approach/avoidance behaviour.

Our main goal is to clarify the behavioural and neurophysiological effects of
short-term TUS on deep brain circuits in humans. We will compare the effects of
Amygdala-TUS, dACC-TUS and sham-TUS to one-another using a behavioural task and
fMRI. Our secondary objective is to map learning behaviour and tracking of the
volatility of stimuli-outcome relations using computational modelling.

The study will be a four-visit, single-blind, randomised, crossover trial.
During the first session, structural MRI scans will be obtained and the
participants will practice the behavioural task in the scanner. The second,
third, and fourth sessions are ultrasound intervention sessions. We will use a
factorial design with stimulation (Amygdala-TUS, dACC-TUS, sham-TUS) as a
within-subject factor.

Participants will receive sham and verum TUS targeted at the amygdala/dACC.

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; ¤135 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
relatively 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), the
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 are considered minimal, and we do not expect any (serious)
adverse events during the project.