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

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.

This exploratory clinical trial is grounded in the emerging field of psycho-cardiology, which highlights the close interaction between mental health and cardiovascular outcomes in patients with coronary heart disease(CHD). Converging epidemiological data indicate that anxiety is common in CHD and is associated with higher rates of in-hospital complications, rehospitalisation, major adverse cardiovascular events, and mortality. Experimental and clinical studies further suggest that heightened sympathetic arousal and disturbed cardiac autonomic regulation may form a physiological link between anxiety and adverse cardiac prognosis in this population. At the neural level, the central autonomic network(CAN)-including the insula, cingulate cortex, prefrontal cortex, amygdala, hypothalamus, and brainstem nuclei-provides a structural and functional substrate for brain-heart coupling. Within this network, the dorsolateral prefrontal cortex(DLPFC) plays a key role in executive control, conflict monitoring, and cognitive reappraisal, and interacts with interoceptive and autonomic control circuits. Prior work supports functional lateralisation: the right DLPFC is more strongly associated with threat monitoring and sympathetic mobilisation, whereas the left DLPFC is more involved in top-down cognitive control and reappraisal. Under stress, robust recruitment of left DLPFC activity is thought to dampen excessive interoceptive drive and hyperarousal, potentially facilitating engagement of parasympathetic pathways and supporting emotional regulation. On this mechanistic background, the present trial focuses on patients with stable CHD and comorbid anxiety disorders, a group characterised by more pronounced autonomic imbalance and substantial pharmacological and comorbidity-related confounding. The central hypothesis is that closed-loop neurofeedback(NF) targeting the left DLPFC can, under experimentally induced stress, strengthen prefrontal control and thereby attenuate cardiac autonomic arousal, indexed by heart rate(HR), relative to a sham control condition. The study further postulates that inter-hemispheric synchronisation between left and right DLPFC will increase under real NF, reflecting a more coordinated prefrontal response pattern, and that changes in HR will be associated with, and partially mediated by, changes in left DLPFC activation and DLPFC inter-hemispheric coupling. Study design and population The study is designed as a prospective, randomised, sham-controlled, parallel-group exploratory clinical trial. Adults with stable CHD and comorbid anxiety disorders are screened using predefined cardiac and psychiatric criteria. Key features include confirmed CHD(stress testing, prior myocardial infarction, or angiographic stenosis), DSM-5 anxiety disorder, right-handedness, and resting HR within a prespecified range; individuals with major arrhythmias, unstable angina, advanced heart failure, severe valvular disease, high-risk blood pressure profile Покажи пълното описание...

Inclusion Criteria: * 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. Exclusion Criteria: * 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.