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.
Age >18 years, any sex.
Right-handed, with resting heart rate between 60 and 100 beats per minute.
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.
Acute unstable angina.
Severe congestive heart failure (New York Heart Association [NYHA] class IV).
Valvular heart disease.
History of atrial fibrillation.
Parallel
Real-time fNIRS-based neurofeedback
DeviceReal-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.
The between-group difference (real vs sham neurofeedback) in baseline-corrected heart rate (HR) during the task stimulation window.
Between-group difference in the volitional upregulation of left DLPFC activation in response to cold-induced pain stimulation.
Between-group difference in inter-hemispheric synchronisation of DLPFC signals.
Inter-hemispheric synchronisation is quantified using wavelet transform coherence (WTC) to characterise time-frequency coupling between homologous left and right DLPFC channels. For each participant, WTC values are averaged within the target frequency band (0.01-0.08 Hz) and over the relevant time window, then transformed to Fisher z values for group-level statistical analysis.
Incidence of any adverse event (AE) during the experiment.
The occurrence of any AE is recorded as a binary variable (yes/no, n \[%\]). AEs include: * premature termination of a training session due to discomfort or safety concerns; * symptomatic bradycardia or hypotension-related discomfort (e.g., dizziness, nausea, cold sweating); * marked manifestations of sympathetic arousal (e.g., tension, pronounced HR increase, worsening of subjective anxiety); * discomfort related to cold-pain stress (e.g., local skin pain, numbness, erythema); * discomfort related to acoustic stimulation (e.g., headache, tinnitus, startle responses). Safety endpoints will be analysed in the intention-to-treat population, defined as all participants randomised to a treatment group, irrespective of whether they ultimately receive the allocated intervention. Analyses of the primary, secondary, and exploratory endpoints will be restricted to participants who, on the formal experimental day, successfully complete all 15 consecutive stimulation blocks. Data from sessions int
Mediation effect: indirect association between group assignment and baseline-corrected HR via changes in left DLPFC activation.
Mediation effect: indirect association between group assignment and baseline-corrected HR via changes in inter-hemispheric WTC values of the DLPFC.
Click on the lead sponsor to view all of their trials.
Shenyang Medical College
Lead sponsor
The Second Hospital of Shenyang Medical College
Collaborator
