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

NCT07238920 | Recruiting DMC

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

Brief Summary

The goal of this clinical trial is to test whether real-time fNIRS-BCI neurofeedback targeting the right dorsolateral prefrontal cortex (right DLPFC), using active volitional control during a slow-wave auditory acoustic paradigm, can suppress cardiac sympathetic activity and improve autonomic regulation in right-handed patients with stable coronary heart disease (CHD) and comorbid DSM-5 anxiety. The main questions it aims to answer are: Does real neurofeedback, compared with sham, reduce baseline-corrected heart rate during the auditory stimulation window? Does real neurofeedback, compared with sham, increase HRV spectral power around 0.0167 Hz (1/60 Hz) and produce stronger suppression of right DLPFC activation? Does suppression of right DLPFC activation mediate the effect of group assignment on heart rate? If there is a comparison group: Researchers will compare the real neurofeedback group with the sham (non-contingent) feedback group, which uses identical audio and interface, to determine whether coupling feedback to right DLPFC activity yields autonomic benefits. Participants will: Complete eligibility screening in cardiology and psychiatry and provide informed consent; baseline demographics, medical history, vital signs, and medications are recorded (HAMA/HAMD used for eligibility only). Undergo a 3-day adaptation phase to practice active volitional self-regulation while viewing a real-time energy bar mapped to right DLPFC statistics; adaptation data are not analyzed for outcomes. Attend two formal sessions (Days 4-5), each with 15 blocks of 60 s (20 s rest + 40 s stimulus). The auditory stimulus is a 1 Hz amplitude-modulated pure tone at approximately 60 dB; 10-second white-noise bursts are randomly embedded within the 40-second window. During the stimulation period, participants receive real or sham feedback on right DLPFC activation and act to push the energy bar below an unlabeled threshold line using active volitional strategies. Undergo synchronous fNIRS (HbO) and 3-lead ECG (1,000 Hz) recording throughout; online processing and rendering performance metrics are logged; adverse events are monitored and managed per protocol.

Conditions

Coronary Heart Disease (CHD); Anxiety Disorders

Keywords

Coronary heart disease; Anxiety; Neurofeedback; Heart rate variability

Outcome Measures

Primary Outcomes (1)

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

  The formal experimental phase (day 4 and 5).

Secondary Outcomes (2)

• Between-group difference in task-related activation of the right dorsolateral prefrontal cortex (right DLPFC).

  The formal experimental phase (day 4 and 5).

• Between-group difference in HRV spectral power at 0.0167 Hz during the task stimulation window, based on wavelet time-frequency analysis.

  The formal experimental phase (day 4 and 5).

Other Outcomes (2)

• Mediation analysis: to assess the indirect effect of group assignment on baseline-corrected HR via changes in right DLPFC activation.

  The formal experimental phase (day 4 and 5).

• Incidence of any adverse events during training or stimulation (e.g., mild dizziness or drowsiness, transient bradycardia or blood pressure-related discomfort, headache, or nausea).

  From the adaptation phase until completion of the formal experimental sessions (Days 1-5).

Study Arms (2)

Real Neurofeedback Group

EXPERIMENTAL

Participants receive real-time visual feedback based on activation of the right dorsolateral prefrontal cortex (right DLPFC), computed with a stringent statistical threshold (T = -3.3). This threshold enables high-sensitivity coupling between neural activity and the energy bar displayed on screen. The interface omits numerical values, and participants are blinded to both group allocation and threshold settings, ensuring a causally interpretable closed-loop training.

Device: Real-time fNIRS-ECG neurofeedback

Sham Neurofeedback Group

SHAM COMPARATOR

Participants receive feedback using a lenient threshold (T = -1), greatly reducing the effective coupling between right DLPFC activation and the visual feedback. The screen interface is identical to the real group, and no numerical values are shown. Participants are blinded to their group and threshold settings, limiting the possibility of meaningful self-regulation.

Device: Real-time fNIRS-ECG neurofeedback

Interventions

Real-time fNIRS-ECG neurofeedback DEVICE

This intervention uses real-time neurofeedback based on right dorsolateral prefrontal cortex (right DLPFC) activity measured by functional near-infrared spectroscopy (fNIRS), with simultaneous ECG recording. During a slow-wave auditory paradigm (1 Hz amplitude-modulated tone with embedded white noise), participants attempt to downregulate right DLPFC activation via active volitional strategies, guided by a visual energy bar. Before formal intervention, a 3-day adaptation phase familiarises participants with the interface and task, under guidance. The formal training occurs on Days 4-5 (15 blocks/day), using identical auditory input and recording protocol. Participants are randomised to real or sham feedback groups, differing only in the statistical threshold used to generate feedback (T = -3.3 vs T = -1.0). Participants and assessors are blinded to allocation.

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)

The 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

• Yun-En Liu, MD

  Shenyang Medical College

  STUDY CHAIR

• Lin Tao, MM

  Shenyang Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yun-En Liu, MD

CONTACT

86-24-62215130; lye9901@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Real Neurofeedback Group Participants receive real-time visual feedback based on activation of the right dorsolateral prefrontal cortex (right DLPFC), computed with a stringent statistical threshold (T = -3.3). This threshold enables high-sensitivity coupling between neural activity and the energy bar displayed on screen. The interface omits numerical values, and participants are blinded to both group allocation and threshold settings, ensuring a causally interpretable closed-loop training. Sham Neurofeedback Group Participants receive feedback using a lenient threshold (T = -1), greatly reducing the effective coupling between right DLPFC activation and the visual feedback. The screen interface is identical to the real group, and no numerical values are shown. Participants are blinded to their group and threshold settings, limiting the possibility of meaningful self-regulation. Both groups undergo identical auditory stimulation paradigms, noise overlay protocols, and testing procedures
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.

Model Details: This study adopts a parallel-group, randomised, sham-controlled design to investigate whether real-time fNIRS-based neurofeedback targeting the right dorsolateral prefrontal cortex (right DLPFC) can modulate cardiac autonomic function in patients with stable coronary heart disease (CHD) and comorbid anxiety. Participants are randomly assigned (1:1) to either the real neurofeedback group or the sham feedback group. Both groups receive visual feedback derived from their own right DLPFC activation data during an identical auditory stimulation paradigm (1 Hz amplitude-modulated pure tone at \~60 dB with randomly embedded 10-second white noise segments), while fNIRS and ECG are recorded simultaneously.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 20, 2025
• Study Start: November 19, 2025
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): August 21, 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 formal publication

Locations

CN (1)