A Descriptive Observation of Brain Region Involvement During Unclear Stress Responses Across Heterogeneous Populations
DOI:
https://doi.org/10.61919/0c78fb13Keywords:
Anterior Cingulate Cortex; Amygdala; Cortisol; Functional Magnetic Resonance Imaging; Perceived Stress; Prefrontal Cortex; Stress Response.Abstract
Background: Stress experienced without a clearly identifiable precipitating event may involve altered engagement of neural circuits responsible for emotional salience, cognitive regulation, and physiological stress processing. Objective: To characterize regional brain activation during an ambiguous stress condition and examine its associations with perceived stress and salivary cortisol in adults. Methods: This cross-sectional task-based functional magnetic resonance imaging study included 60 adults aged 18–50 years from the Islamabad–Rawalpindi region. Perceived stress was assessed using the PSS-10, anxiety and depressive symptoms using HADS, and physiological assessment included resting heart rate and morning salivary cortisol. Participants underwent 3-Tesla functional magnetic resonance imaging during an ambiguous stress-induction task incorporating social-evaluative uncertainty and cognitive interference. Regional BOLD responses were evaluated in the amygdala, anterior cingulate cortex (ACC), prefrontal cortex, hippocampus, and insula. Pearson correlations and independent-samples t-tests were applied. Results: Mean ACC activation was 0.91 ± 0.25%, followed by amygdala activation at 0.84 ± 0.22%. PSS-10 scores correlated positively with amygdala activation (r=0.46, p=0.001) and ACC activation (r=0.41, p=0.002) and inversely with prefrontal activation (r=−0.31, p=0.017). Cortisol correlated positively with ACC activation (r=0.39, p=0.003). Females demonstrated higher amygdala activation than males (0.92 ± 0.20% vs 0.78 ± 0.21%; p=0.014). Conclusion: Perceived stress under uncertain conditions was associated with differential engagement of limbic, cingulate, and prefrontal regions, with convergent associations across subjective, biochemical, and neural measures. These findings represent cross-sectional neural correlates and should not be interpreted as causal or predictive biomarkers
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Copyright (c) 2026 Asfand Yar Wali Khan, Muhammad Zia Iqbal, Farhan Ali, Sumera Kanwal, Iraj Siddiqui, Khan Deen, Sundas Farhat (Author)
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