DLPFC coordination and heart reactivity during aversive sensory challenge in women with recurrent pregnancy loss and anxiety

Altered Interhemispheric DLPFC Coordination and Cardiac Hyperreactivity During Multisensory Aversive Challenge in Recurrent Pregnancy Loss With Comorbid Anxiety: a Multicenter Simultaneous fNIRS-ECG Study (NEURO-CARD-fNIRS)

This study will test whether patterns of prefrontal brain activity and heart responses during unpleasant sensory stimulation differ in women with recurrent pregnancy loss who have anxiety compared with those who do not.

Quick facts

• Study type: Observational
• Enrollment: 70 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Shenyang Medical College (Academic / other)
• Locations: 3 sites (Shenyang, Liaoning and 2 other locations)
• Trial ID: NCT07045818 on ClinicalTrials.gov

What this trial studies

This observational study uses simultaneous functional near-infrared spectroscopy (fNIRS) and electrocardiography (ECG) to record dorsolateral prefrontal cortex (DLPFC) activity and cardiac responses during a standardized multisensory aversive emotional challenge. Right-handed women aged 18–45 with two or more consecutive pregnancy losses who are not currently pregnant will be enrolled and grouped by presence or absence of a DSM-5 anxiety disorder using structured psychiatric evaluation and Hamilton scale cutoffs. Cortical interhemispheric coordination and autonomic sympathetic markers (heart rate and heart rate variability) will be compared between groups within a Brain–Heart–Emotion framework. The goal is to identify neurobiological signatures of emotion–autonomic dysregulation that could guide future precision-targeted interventions.

Who should consider this trial

Good fit: Ideal participants are right-handed women aged 18–45 with a history of two or more consecutive pregnancy losses who are not currently pregnant and who have completed a DSM-5–based psychiatric evaluation to determine presence or absence of an anxiety disorder (anxiety group: HAM-A ≥14 and HAM-D ≤17; non-anxiety group: HAM-A <14).

Not a fit: People who are currently pregnant, male, outside the 18–45 age range, left-handed, without a history of recurrent pregnancy loss, or with uncontrolled major depression or other severe psychiatric or medical conditions are unlikely to benefit from this study's findings.

Why it matters

Potential benefit: If successful, the study could identify brain–heart biomarkers that help guide more targeted treatments for anxiety and autonomic risk in women with recurrent pregnancy loss.

How similar studies have performed: Prior neuroimaging and autonomic research has linked DLPFC asymmetry to anxiety and sympathetic overactivation, but applying simultaneous fNIRS and ECG specifically to recurrent pregnancy loss with comorbid anxiety is largely novel and exploratory.

Eligibility criteria

Inclusion Criteria:

* Female, age 18 to 45 years, right-handed;
* Diagnosis of recurrent pregnancy loss, defined as two or more consecutive spontaneous miscarriages before 28 weeks of gestation;
* Not currently pregnant, or diagnosed with missed abortion at the time of assessment;
* Completed a structured psychiatric evaluation conducted by licensed psychiatrists at each center, with diagnostic confirmation according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
* For participants assigned to the RPL with anxiety group: meets DSM-5 diagnostic criteria for an anxiety disorder, has a Hamilton Anxiety Rating Scale score of at least 14, and has a 17-item Hamilton Depression Rating Scale score of 17 or lower;
* For participants assigned to the RPL without anxiety group: does not meet DSM-5 diagnostic criteria for an anxiety disorder, has a Hamilton Anxiety Rating Scale score below 14, and has a 17-item Hamilton Depression Rating Scale score of 17 or lower.

Exclusion Criteria:

* Use of psychotropic medication within the past month, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, benzodiazepines, antipsychotics, or mood stabilizers;
* Unstable or uncontrolled blood pressure, defined as systolic blood pressure greater than 180 mmHg or less than 90 mmHg at screening;
* Major comorbid organic conditions that could affect autonomic or neural measurements, including hyperthyroidism, atrial fibrillation, clinically significant valvular heart disease, prior stroke, epilepsy, traumatic brain injury, or chronic pulmonary disease;
* Significant sensory or communication barriers that could impair task performance or stimulus perception, including hearing impairment, language difficulty, or sensory neuropathy;
* High suicide risk or severe psychiatric comorbidity, including psychotic disorders, bipolar disorder, or substance use disorders;
* Marked intolerance to auditory, visual, or cold stimuli based on medical history or pre-test report;
* Any other condition judged by the study physician to interfere with safe participation in the multisensory aversive stimulation protocol.

Where this trial is running

Shenyang, Liaoning and 2 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)
• 157 Hospital of Liaoning Health Industry Group — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Principal investigator: Lin Tao, MM — Shenyang Medical College
• Study coordinator: Yun-En Liu, MD

Conditions Recurrent Pregnancy Loss Without Current Pregnancy; Anxiety Disorder; recurrent pregnancy loss; anxiety; emotion-autonomic dysregulation; dorsolateral prefrontal cortex; functional near-infrared spectroscopy