Hypoactivation of autonomtic nervous system-related orbitofrontal and motor cortex during acute stress in women with premenstrual syndrome

Premenstrual syndrome (PMS) is a menstrual-related disorder, which refers to a series of cyclical and relapsing physical, emotional, and cognitive symptoms that regularly recur during the late luteal phase of each menstrual cycle (Ryu and Kim, 2015; Wu et al., 2016). Studies have shown that PMS is closely related to impaired stress reaction (Hamaideh et al., 2014; Klatzkin et al., 2014; Tamaki Matsumoto, Ushiroyama, Kimura, Hayashi and Moritani, 2007; Sadler et al., 2010). Therefore, numerous studies have explored the mechanism of PMS from the perspective of stress reactivity. Among them, the autonomic nervous system (ANS), one of the stress physiological responses (Kreibig, 2010; Dragomir, Gentile, Nolan, & D’Antono., 2014; Bruce S. Mcewen, 2007), has received much attention. ANS comprises the sympathetic and parasympathetic systems, and it is closely related to emotion (Kreibig, 2010). When people’s ANS shows blunted activation or delayed recovery under pressure, their negative emotions increase (Conti et al., 2011; Gisela et al., 2003; Lupis et al., 2014; Bruce S. Mcewen, 2007; Shcheslavskaya et al., 2010; Sherman et al., 2009). Similarly, a low ANS activity has been observed in women with PMS, by either focusing on chronic stress (Baker et al., 2008) and acute stressors (Girdler et al., 1993; Klatzkin et al., 2014). Furthermore, the blunted response to stress predicts greater premenstrual symptoms and higher negative emotions (Klatzkin et al., 2014; Verkuil et al., 2009). However, it is not well understood how the neural functional dysregulation of ANS is involved in the etiology of PMS. Actually, the ANS response at rest is related to the activation of relevant brain areas; for example, fluorodeoxyglucose positron emission tomography (FDG–PET) has been used to study glucose metabolism in the brain under different heart rates, heart rate variability, and blood pressure changes. The sympathetic activity of ANS shows a positive correlation with the motor cortex area (Schlindwein et al., 2008). Moreover, a previous study showed that women with PMS involves the abnormal neural functional regulation of ANS-related regions during the resting state. Which were abnormal regional homogeneity and fractional amplitude of low-frequency fluctuation (fALFF), including the anterior cingulate cortex, prefrontal cortex (PFC), and precuneus (Liao et al., 2017). However, no neuroimaging studies have evaluated the neural functional regulation of ANS during acute stress in the late luteal phase of women with PMS. It is acknowledged that ANS is easily triggered in the face of stress stimuli, therefore, it is better to introduce acute stress to detect the response of ANS-related brain areas. Under acute stressors, the ANS response is also related to the activation of certain brain areas, such as motor cortex (MC), PFC and orbitofrontal cortex (OFC) (Dum, 2016; Fechir et al., 2010; Holsen et al., 2012). Dum (2016) showed a positive correlation between the adrenal medulla that affects sympathetic function and the activity of the motor and medial PFC based on rabies virus neural traceability. Furthermore, Holsen et al. (2012) found that the imbalanced ANS response is associated with dysfunction in neural regions, i.e., a dull parasympathetic response can result in the inactivation of the OFC among people with mood disorders. Presumably, in women with PMS, a blunted ANS response involved in acute stressful tasks may be accompanied by an inactivation reaction in the ANS-related regions. Moreover, indicated that PMS women with a lower ANS response also have a higher subjective negative emotional experience (Matsumoto et al., 2007). Neuroimaging studies showed that the ANS and emotional responses share a part of the neural mechanism. Specifically, the OFC, amygdala, and other areas not only control the body’s ANS response but also are inseparable from emotional reactions (Arnsten and Amy, 2015; Drevets, 2010; Protopopescu et al., 2008; Vitaly et al., 2008). Therefore, even if there is decreased activation in the ANS-related brain area of women with PMS during stressful tasks, it may have a close relationship with their subjective negative emotional