Manganese-enhanced magnetic resonance imaging detects activation of limbic structures in response to auditory stimuli of different frequencies

Purpose: As we are exposed to stress on a daily basis, it is important to detect and treat stress during the subclinical period. However, methods to quantify and confirm stress are currently unavailable, and the detection of subclinical stressors is difficult. This study aimed to determine whether manganese-enhanced magnetic resonance imaging (MEMRI) could be used to assess stress in rat brains. Methods: We exposed male Wistar/ST rats bred in a specific pathogen-free environment to ultrasound stimuli (22 kHz and 55 kHz) for 10 days and then assessed brain activities using MEMRI, the light/dark box test, and ΔFosB immunohistochemical staining. Results: In the MEMRI assessments, exposure at 22 kHz activated the periaqueductal gray, while exposure at 55 kHz specifically enhanced activity in the nucleus accumbens core and the orbitofrontal cortex. The exploratory behavior of the 55-kHz group increased sharply, while that of the 22-kHz group showed a lower exploratory value. ΔFosB expression increased in the orbitofrontal cortex, nucleus accumbens, periaqueductal gray, and amygdaloid nucleus in the 22-kHz group. Conclusion: Ultrasound stimuli at 22 kHz suppressed weight gain in rats and excessive ΔFosB induction in the nucleus accumbens caused excessive sensitization of the neural circuit, thereby contributing to pathological behavior. We thus demonstrated that MEMRI can be useful to objectively assess the pathophysiology of stress-related disorders.