Right DLPFC fNIRS neurofeedback for anxiety in women with recurrent pregnancy loss

Right Dorsolateral Prefrontal Cortex-Targeted fNIRS-BCI Closed-loop Neurofeedback for Anxiety Relief and Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss: a Randomized, Sham-controlled Clinical Trial

This trial will see if right dorsolateral prefrontal cortex-targeted fNIRS closed-loop neurofeedback with slow-wave sound cues can reduce anxiety and improve heart-rate regulation in women with recurrent pregnancy loss aged 18–45.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 62 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Shenyang Medical College (Academic / other)
• Locations: 2 sites (Shenyang, Liaoning and 1 other locations)
• Trial ID: NCT07325370 on ClinicalTrials.gov

What this trial studies

This is a randomized, sham-controlled, parallel-group trial comparing real versus sham right DLPFC-targeted fNIRS-BCI closed-loop neurofeedback delivered with slow-wave acoustic cueing in women with recurrent pregnancy loss and comorbid anxiety. Participants will be randomized 1:1 to real or sham feedback with identical visit structure, and fNIRS will be recorded across all training sessions while ECG is recorded during the first formal session. Primary clinical outcomes focus on anxiety severity and treatment response (≥50% reduction in HAMA) measured at end of treatment and at 3-month follow-up, with safety monitoring of adverse events. Mechanistic analyses will examine right DLPFC activation and short-term brain–heart coupling via fNIRS and ECG data.

Who should consider this trial

Good fit: Women aged 18–45 who are right-handed, have recurrent pregnancy loss (≥2 consecutive losses before 28 weeks), are not currently pregnant (or are in a missed miscarriage state), meet DSM-5 criteria for an anxiety disorder with CGI-S ≥4, and have HAMA ≥16 with HAMD-17 <17.

Not a fit: Patients with unstable blood pressure, significant organic or neurological comorbidities, high suicide risk, major uncontrolled medical illnesses, or currently pregnant are unlikely to be eligible or to benefit from this intervention.

Why it matters

Potential benefit: If successful, the intervention could meaningfully reduce anxiety symptoms and improve cardiac autonomic regulation in affected women, potentially lowering stress-related reproductive risk factors.

How similar studies have performed: Neurofeedback and brain–computer interface approaches have shown preliminary promise for anxiety and autonomic regulation in small or early-phase studies, but right DLPFC-targeted fNIRS-BCI closed-loop approaches remain novel with limited randomized evidence.

Eligibility criteria

Inclusion Criteria:

* (i) Women aged 18-45 years, right-handed;
* (ii) Diagnosis of recurrent pregnancy loss (RPL), defined as ≥2 consecutive spontaneous pregnancy losses occurring before 28 weeks of gestation;
* (iii) Not currently pregnant, or currently in a missed miscarriage state;
* (iv) Meet DSM-5 diagnostic criteria for an anxiety disorder, with at least moderate severity, defined as Clinical Global Impression-Severity (CGI-S) ≥4;
* (v) Hamilton Anxiety Rating Scale (HAMA) ≥16, with 17-item Hamilton Depression Rating Scale (HAMD-17) \<17, to ensure anxiety is the predominant affective disturbance.

Exclusion Criteria:

* (i) Markedly unstable blood pressure (systolic BP \>180 mmHg or \<90 mmHg);
* (ii) Clinically important comorbid organic diseases, including but not limited to hyperthyroidism, history of atrial fibrillation, sinus bradycardia, major neurological disorders, cerebrovascular disease, or severe pulmonary disease;
* (iii) Significant suicide risk, judged by psychiatric assessment to be unsuitable for study participation;
* (iv) Other severe psychiatric disorders, including substance use disorder, schizophrenia, delusional disorder, unspecified psychotic disorder, bipolar disorder, or delirium;
* (v) Use of any oral antidepressant, anxiolytic, or antipsychotic medication within the past 4 weeks, or fluoxetine within the past 6 weeks, or any long-acting injectable antipsychotic within the past 3 months.

Where this trial is running

Shenyang, Liaoning and 1 other locations

• The Second Affiliated Hospital of Shenyang Medical College — Shenyang, Liaoning, China (Recruiting)
• Central Hospital Affiliated to Shenyang Medical College — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Principal investigator: Lin Tao, MM — Shenyang Medical College
• Study coordinator: Fei Meng, MD

Conditions Recurrent Pregnancy Loss; Anxiety; Recurrent pregnancy loss; Anxiety disorders; Right dorsolateral prefrontal cortex; Functional near-infrared spectroscopy; Brain-computer interface; Closed-loop neurofeedback