Altered Interhemispheric DLPFC Coordination and Cardiac Hyperreactivity During Multisensory Aversive Challenge in Recurrent Pregnancy Loss With Comorbid Anxiety

This exploratory clinical study, NEURO-CARD-2, will use simultaneous functional near-infrared spectroscopy (fNIRS) and electrocardiography (ECG) to investigate interhemispheric dysfunction in the dorsolateral prefrontal cortex (DLPFC) and its association with autonomic sympathetic activation in women with recurrent pregnancy loss (RPL) and comorbid anxiety. Using a standardized multisensory aversive emotional stimulation paradigm, the study will assess cortical and cardiac responses within a Brain-Heart-Emotion interaction framework. The objective will be to identify neurobiological signatures of emotion-autonomic dysregulation in this population and to inform the future development of precision-targeted interventions.

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 generalized 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 generalized 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.