Closed-Loop Neurofeedback Targeting the Left Dorsolateral Prefrontal Cortex for Cardiac Autonomic Modulation in Coronary Artery Disease With Anxiety

NCT07244484 | Recruiting DMC

• 1 other identifier: HEART-SET-2
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test whether closed-loop fNIRS-BCI neurofeedback(NF) targeting the left dorsolateral prefrontal cortex(DLPFC) can reduce cardiac autonomic arousal, indexed by baseline-corrected heart rate(HR) under cold-induced pain stress, in adults with stable coronary heart disease(CHD) and comorbid anxiety. The main questions it aims to answer are: Does real left DLPFC neurofeedback, compared with sham neurofeedback, lead to a greater reduction in baseline-corrected HR during the cold-induced pain stimulation window? Does real neurofeedback produce stronger volitional upregulation of left DLPFC activation and higher inter-hemispheric synchronisation between left and right DLPFC than sham neurofeedback? Are changes in baseline-corrected HR statistically associated with, and partly mediated by, changes in left DLPFC activation or DLPFC inter-hemispheric synchronisation? What adverse events(AEs) occur during adaptive training and the formal experimental session, and do AE rates differ between the two groups? Researchers will compare a real neurofeedback group with a sham neurofeedback group to determine whether targeting the left DLPFC via closed-loop fNIRS-BCI yields superior modulation of cardiac autonomic responses and prefrontal activation patterns in CHD patients with anxiety. Participants will: undergo cardiac and psychiatric screening to confirm stable CHD, DSM-5 anxiety disorder, and other eligibility criteria; attend three adaptive training sessions(days 1-3) with fNIRS-BCI neurofeedback targeting the left DLPFC, combined with slow-wave auditory stimulation and mild cold-water exposure, while ECG is recorded; on day 4, complete one formal experimental session consisting of 15 blocks of cold-induced pain stimulation and slow-wave auditory stimulation, with simultaneous fNIRS and ECG recording, receiving either real or sham left DLPFC neurofeedback according to randomisation, and continuous monitoring for adverse events.

Conditions

Coronary Heart Disease (CHD); Anxiety Disorders

Keywords

Coronary heart disease; Anxiety; Neurofeedback; the dorsolateral prefrontal cortex

Outcome Measures

Primary Outcomes (1)

• The between-group difference (real vs sham neurofeedback) in baseline-corrected heart rate (HR) during the task stimulation window.

  day 4 (formal experimental session)

Secondary Outcomes (3)

• Between-group difference in the volitional upregulation of left DLPFC activation in response to cold-induced pain stimulation.

  day 4 (formal experimental session).

• Between-group difference in inter-hemispheric synchronisation of DLPFC signals.

  day 4 (formal experimental session).

• Incidence of any adverse event (AE) during the experiment.

  From randomisation to completion of the experimental session.

Other Outcomes (2)

• Mediation effect: indirect association between group assignment and baseline-corrected HR via changes in left DLPFC activation.

  day 4 (formal experimental session).

• Mediation effect: indirect association between group assignment and baseline-corrected HR via changes in inter-hemispheric WTC values of the DLPFC.

  day 4 (formal experimental session).

Study Arms (2)

Real Neurofeedback Group

EXPERIMENTAL

Participants in this arm receive real closed-loop fNIRS-BCI neurofeedback targeting the left dorsolateral prefrontal cortex(DLPFC). After baseline cardiac and psychiatric assessment, they complete three adaptive training sessions(days1-3) to practice volitional upregulation of left DLPFC activation with visual feedback, slow-wave(1Hz) auditory stimulation, and mild cold-water exposure. On day4, they undergo one formal experimental session comprising 15 blocks(20s rest+40s stimulation) with simultaneous fNIRS and ECG recording. During stimulation, participants receive a 1Hz amplitude-modulated auditory tone and cold-induced pain stress(0-2°C bottle contact). In the real neurofeedback arm, the on-screen "energy bar" is tightly and directionally coupled to the real-time fNIRS-derived statistic from left DLPFC(HbO), using a stringent threshold(t≈+3.3), so that greater true activation produces a clear, interpretable change in visual feedback to support effective closed-loop self-regulation

Device: Real-time fNIRS-based neurofeedback

Sham Neurofeedback Group

SHAM COMPARATOR

Participants in this arm receive sham closed-loop fNIRS-BCI neurofeedback with the same procedures as the real neurofeedback group, but with feedback minimally coupled to true left DLPFC activity. After baseline cardiac and psychiatric assessment, they complete three adaptive training sessions (days 1-3) and one formal experimental session on day 4. Each session uses 15 blocks (20 s rest + 40 s stimulation) with simultaneous fNIRS and ECG recording, 1 Hz slow-wave auditory stimulation, and cold-induced pain stress (0-2°C bottle contact). The user interface, task instructions, and visual "energy bar" display are identical to the real arm. However, in the sham arm the feedback threshold is set near baseline (t≈+0.1), so that bar fluctuations are largely insensitive to actual left DLPFC HbO changes. This preserves the appearance of neurofeedback while preventing participants from achieving genuine volitional control over cortical activity.

Device: Real-time fNIRS-based neurofeedback

Interventions

Real-time fNIRS-based neurofeedback DEVICE

Real-time fNIRS-based neurofeedback is a non-invasive brain-computer interface procedure that uses functional near-infrared spectroscopy to monitor cortical haemodynamic activity online and return it as visual feedback. In this trial, an optode montage is placed over the bilateral prefrontal cortex, with the left dorsolateral prefrontal cortex (DLPFC) defined as the target region. Oxygenated haemoglobin (HbO) signals from the left DLPFC are preprocessed in real time and entered into a sliding-window general linear model to generate a task-related test statistic. A sign-inverted version of this statistic is mapped to an on-screen "energy bar", such that stronger left DLPFC activation corresponds to a lower bar. Participants are instructed to use self-regulation strategies to push the bar below a preset threshold while exposed to cold-induced pain and 1 Hz slow-wave auditory stimulation, thereby forming a closed loop between prefrontal activation and feedback.

Real Neurofeedback Group; Sham Neurofeedback Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years, any sex.
• Right-handed, with resting heart rate between 60 and 100 beats per minute.
• Confirmed diagnosis of CHD, defined as at least one of the following:
• (i) positive stress test; (ii) documented myocardial infarction (MI) with electrocardiographic changes and concurrent elevation of creatine kinase MB isoenzyme or troponin; (iii) angiographically confirmed coronary atherosclerosis with ≥50% stenosis in at least one coronary artery.
• Diagnosis of an anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
• Hamilton Anxiety Rating Scale (HAMA) score ≥16 and 17-item Hamilton Depression Rating Scale (HAMD-17) score ≤17.

You may not qualify if:

• Acute unstable angina.
• Severe congestive heart failure (New York Heart Association \[NYHA\] class IV).
• Valvular heart disease.
• History of atrial fibrillation.
• Unstable blood pressure, defined as systolic blood pressure \>180 mmHg or \<90 mmHg.
• Pregnancy.
• History of unstable medical conditions, including cerebrovascular disease, dementia, hyperthyroidism, pulmonary disease, or malignancy. These are assessed through medical history, electronic health records, physical examination, and ECG findings.
• High risk of suicide or homicide.
• Presence of other psychiatric disorders, including psychotic disorders, bipolar disorder, or active substance use disorders.
• Use of psychotropic medication within 1 month prior to enrolment, to avoid potential interference with haemodynamic measurements.

Sponsors & Collaborators

• Shenyang Medical College: lead
• The Second Hospital of Shenyang Medical College: collaborator

Study Sites (1)

Second Affiliated Hospital of Shenyang Medical College

Shenyang, Liaoning, 110001, China

RECRUITING

MeSH Terms

Conditions

Coronary Disease; Anxiety Disorders

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Mental Disorders

Study Officials

• Lin Tao, MM

  Shenyang Medical College

  PRINCIPAL INVESTIGATOR

• Yun-En Liu, MD

  Shenyang Medical College

  STUDY CHAIR

Central Study Contacts

Lin Tao, MM

CONTACT

86-18802401698; 1939908868@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and all clinical assessors (cardiology and psychiatry staff conducting eligibility assessment and rating scales) are masked to group allocation. Outcome assessors and statisticians performing the primary and secondary analyses are also blinded and receive only coded group labels. The neurofeedback operator is aware of allocation solely to configure the real vs sham feedback thresholds and has no role in clinical evaluation, endpoint assessment, or data analysis. The user interface and experimental procedures are identical across groups, minimising the risk of unblinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.

Model Details: The study uses a parallel-group, randomised, sham-controlled interventional model. Adults with stable CHD and comorbid anxiety are allocated 1:1 to real or sham fNIRS-BCI neurofeedback targeting the left DLPFC. All participants complete three adaptive training sessions (days 1-3), followed by a single formal experimental session (day 4) consisting of 15 blocks combining cold-induced pain stress and slow-wave auditory stimulation, with simultaneous fNIRS and ECG recording. Only the strength of coupling between cortical activity and visual feedback differs between groups; all other procedures are identical.

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: November 23, 2025
• Primary Completion (Estimated): May 23, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: April 22, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Available at the time of publication

Locations

CN (1)