Trancranial Pulse Stimulation on Anterior Insula Cortex and Dorsal Anterior Cingulate Cortex

NCT06635161 | Recruiting DMC

• 1 other identifier: HSEARS20240319006
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Transcranial pulse stimulation (TPS) is a newly developed non-invasive brain stimulation (NIBS) technique from Austria \& Germany with highly promising applicability in neuropsychiatric disorders. Clinical trials have shown a beneficial effect of TPS in patients with Alzheimer\'s disease and depression. Although TPS has the capability to noninvasively target deeper brain regions such as the dorsal anterior cingulate cortex (dACC) and anterior insula cortex (AIC), no TPS study has been conducted to investigate the feasibility and effectiveness of dACC or AIC stimulation. Here, a randomized, single-blind, sham-controlled clinical pilot trial is proposed to probe the effects of TPS over bilateral dACC and AIC on modulating cognitive, behavioral and emotional functions and functional connectivity of brain circuits.

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (4)

• The Chinese version of reading the mind in the eyes test

  The Chinese version of reading the mind in the eyes test (RMET) will be used to assess the AIC function of empathy. In this test, participants will be presented with a series of 28 photographs of the eye region of the face, followed by four mental state terms. Participants will be asked to choose which of four words best describes what the person in the photograph is thinking, feeling, and expressing. The order of trial presentation within each run will be randomized. Participants will be told to complete the task as quickly as possible although they are not timed.

  Baseline, midpoint (2 weeks after the first TPS session), endpoint (4 weeks after the first TPS session)

• The Balloon Analog Risk Task

  The Balloon Analog Risk Task will be used to assess the AIC function of risky decision-making. Participants have to inflate a virtual balloon that can either grow larger or explode. Each time participants pump up the balloon, they accumulate money, but each pump also carries the risk of the balloon exploding, which results in the participant losing all of their money from that balloon. In the task, participants will be required to complete 30 trials (balloons) with a maximum of 12 pumps. The probability of explosion will be increased with each pump from 2% for the first pump to 90% for the last pump.

  Baseline, midpoint (2 weeks after the first TPS session), endpoint (4 weeks after the first TPS session)

• The Go/No-go task

  The Go/No-go task (GNGT) will be used to assess the AIC and ACC function of response inhibition. The red circles and blue circles will serve as Go and No-go signals, respectively. Each trial will begin with the central fixation cross for a duration of 1000 ms, followed by a Go or No-go stimulus for 400 ms. A total of 100 trials will be randomly presented in two blocks, including high (50%) and low (20%) No-go trials. The participants will be instructed to respond as quickly as possible to the Go signal by pressing the space key on the keyboard with the right index finger and to withhold the response when a No-go signal appears. Before the test task, there will be a practice session with 20 trials. At the end of each trial in the test task, participants will receive feedback for 1000 ms indicating their answer is correct or not.

  Baseline, midpoint (2 weeks after the first TPS session), endpoint (4 weeks after the first TPS session)

• The counting Stroop task

  The counting Stroop task conflict will be used to assess the dACC function of the error monitoring. Participants will be required to report, via key-press, the number of identical words they see on a monitor, regardless of the word\'s meaning, as quickly and accurately as possible. The alphabets (A, S, K, L) on the keyboard correspond to the number of words (A to 1, S to 2, K to 3, L to 4). In incongruent blocks, the stimuli consisted of Chinese number words such as "一", "二", "三" and "四", while the number of words and meaning will be always inconsistent. During the neutral blocks, Chinese words such as "了", "人", "手", "口" which are irrelevant to the number will be displayed. Both sets of stimuli are common Chinese words with matched visual complexity. Each stimulus will change every 1.5 seconds. The inter-trial interval will be 500 ms. The task consisted of four 48-second blocks of 24 neutral trials alternating with four 48-second blocks of 24 incongruent trials.

  Baseline, midpoint (2 weeks after the first TPS session), endpoint (4 weeks after the first TPS session)

Secondary Outcomes (1)

• Magnetic resonance imaging measurement

  baseline (one week before the 1st TPS session), endpoint (4 weeks after the first TPS session)

Study Arms (3)

TPS on AIC

EXPERIMENTAL

1\. Healthy adults aged 18-65 years old will receive ten sessions of real TPS (1000 pulses per session) on the bilateral anterior insula cortex (AIC) within 2 weeks (5 sessions per week). 2. Before and after TPS, participants will perform four psychological tasks (the reading the mind in the eyes test, the balloon analog risk task, the Go/No-go task, the counting stroop task). 3. The stimulation target on the bilateral AIC will be determined by transforming MNI coordinates (left AIC: x=-41, y=6, z=3; right AIC: x=44, y=9, z=2) into the individual T1-weighted space. 4. To optimize the penetration depth of TPS pulses, a standard stand-off device (Neurology) will be used when stimulating AIC.

Device: Transcranial pulse stimulation (with Neurology stand-off device)

TPS on dACC

EXPERIMENTAL

1\. Healthy adults aged 18-65 years old will receive ten sessions of real TPS (1000 pulses per session) on the bilateral dorsal anterior cingulate cortex (dACC) within 2 weeks (5 sessions per week). 2. Before and after TPS, participants will perform four psychological tasks (the reading the mind in the eyes test, the balloon analog risk task, the Go/No-go task, the counting stroop task). 3. The stimulation target on the bilateral dACC will be determined by transforming MNI coordinates (left dACC: x=-4, y=26, z=45; right dACC: x=7, y=30, z=40) into the individual T1-weighted space. 4. To optimize the penetration depth of TPS pulses, no stand-off device will be used when stimulating dACC.

Device: Trancranial pulse stimulation (without a stand-off device)

sham TPS on vertex

SHAM COMPARATOR

1\. Healthy adults aged 18-65 years old will receive ten sessions of sham TPS (1000 pulses per session) on the vertex within 2 weeks (5 sessions per week). 2. Before and after TPS, participants will perform four psychological tasks (the reading the mind in the eyes test, the balloon analog risk task, the Go/No-go task, the counting stroop task). 3. The stimulation target on the vertex will be determined by transforming MNI coordinates (x=0, y=-30, z=60) into the individual T1-weighted space. 4. A sham stand-off device will be used when stimulating the vertex.

Device: Transcranial pulse stimulation (with a sham stand-off device)

Interventions

Trancranial pulse stimulation (without a stand-off device) DEVICE

A single session of TPS will be performed, applying 1000 pulses in the session (single ultrashort (3 μs) ultrasound pulses, 0.2 mJ mm-2, 4 Hz pulse frequency). No stand-off device will be used to target dorsal anteior cingulate cortex.

TPS on dACC

Transcranial pulse stimulation (with Neurology stand-off device) DEVICE

A single session of TPS will be performed, applying 1000 pulses in the session (single ultrashort (3 μs) ultrasound pulses, 0.2 mJ mm-2, 4 Hz pulse frequency). A Neurology stand-off device will be used to target the anterior insula cortex.

TPS on AIC

Transcranial pulse stimulation (with a sham stand-off device) DEVICE

A single session of TPS will be performed, applying 1000 pulses in the session (single ultrashort (3 μs) ultrasound pulses, 0.2 mJ mm-2, 4 Hz pulse frequency). A sham stand-off device will be used to target vertex.

sham TPS on vertex

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65
• Biological and mental health, based on a clinical interview
• Able to understand and follow instructions by the study team

You may not qualify if:

• Major internal diseases, neurological disorders, or mental disorders
• Having a metal implant in the brain
• Pregnancy or breastfeeding
• Previous TPS experience
• Color blindness

Sponsors & Collaborators

• The Hong Kong Polytechnic University: lead

Study Sites (1)

The Hong Kong Polytechnic University

Hong Kong, Hung Hom, Kowloon, Hong Kong

RECRUITING

Study Officials

• Georg S Kranz, PhD

  The Hong Kong Polytechnic University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georg Kranz, PhD

CONTACT

+85227664838; georg.kranz@polyu.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 2, 2024
• First Posted: October 10, 2024
• Study Start: August 5, 2024
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)