RecruitingNCT07045818

DLPFC and Sympathetic Reactivity in RPL With Anxiety

DLPFC Desynchronization and Sympathetic Cardiac Hyperarousal During Aversive Emotional Processing in Women With Recurrent Pregnancy Loss and Comorbid Anxiety: a Multimodal fNIRS-ECG Study (NEURO-CARD-fNIRS)

Sponsor

Shenyang Medical College

Enrollment

50 participants

Start Date

Jul 1, 2025

Study Type

OBSERVATIONAL

Conditions

Anxiety Disorder Recurrent Pregnancy Loss Without Current Pregnancy

Summary

We propose an exploratory clinical study (NEURO-CARD-2) that employs simultaneous functional near-infrared spectroscopy (fNIRS) and electrocardiography (ECG) to investigate interhemispheric dysfunction in the dorsolateral prefrontal cortex (DLPFC) and its relationship 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 the framework of the Brain-Heart-Emotion interaction model. The objective is to identify neurobiological signatures underlying emotion-autonomic dysregulation in this population, thereby informing future development of precision-targeted interventions.

Eligibility

Sex: FEMALEMin Age: 18 YearsMax Age: 45 Years

Inclusion Criteria4

Female, aged 18-45 years, right-handed;
Diagnosis of recurrent pregnancy loss-defined as ≥2 consecutive spontaneous miscarriages before 28 weeks' gestation;
Not currently pregnant, or diagnosed with missed abortion at the time of assessment;
Completed structured psychiatric evaluation by licensed psychiatrists at each center, with diagnostic confirmation per DSM-5.

Exclusion Criteria7

Use of psychotropic medications in the past month (e.g., SSRIs, SNRIs, TCAs, benzodiazepines, antipsychotics, mood stabilizers);
Unstable or uncontrolled hypertension (SBP \> 180 mmHg or \< 90 mmHg);
Major comorbid organic conditions (e.g., hyperthyroidism, atrial fibrillation, valvular heart disease, stroke, epilepsy, traumatic brain injury, chronic pulmonary disease);
Significant sensory or communication barriers (e.g., hearing impairment, language difficulty, sensory neuropathy) that could impair task performance or stimulus perception;
High suicide risk or severe psychiatric comorbidity (e.g., schizophrenia, bipolar disorder, psychotic disorders, substance use disorders);
Extreme intolerance to auditory, visual, or cold stimuli, based on medical history or pre-test report;
Any other condition judged by the research physician to interfere with participation in the multisensory emotional stimulation protocol.

Interventions

BEHAVIORALEmotional provocation task involving multisensory aversive stimuli

To elicit hemodynamic responses in the dorsolateral prefrontal cortex (DLPFC) and activate the sympathetic nervous system, we used a standardized multisensory aversive stimulation protocol comprising: (i) Visual stimuli: 72 high-arousal images from the GAPED database (moral violations, legal violations, fear-related) shown in 12 blocks (6 images/block, 5 s each) with 20 s baseline and 30 s stimulation; (ii) Auditory stimuli: each block paired with 30 s of calibrated 90 dB(A) high-frequency narrowband white noise (4 kHz center frequency), shown to increase heart rate; (iii) Cold-pain stimuli: during each block, participants placed both hands on 0 °C ice-filled bottles for pain-induced sympathetic activation. This tri-modal task reliably provokes DLPFC engagement and autonomic responses.