Menstrual pain is the most prevalent gynecological complaint, and is usually without organic cause (termed primary dysmenorrhea, PDM). The high comorbidity in the later life of PDM with many functional pain disorders (associated with central dysfunction of pain inhibition, eg, fibromyalgia) suggests possible maladaptive functionality of pain modulatory systems already occurred in young PDM women, making them vulnerable to functional pain disorders. Periaqueductal gray (PAG) matter functions as a critical hub in the neuraxis of pain modulatory systems; therefore, we investigated the functional connectivity of PAG in PDM. Forty-six PDM subjects and 49 controls received resting-state functional magnetic resonance imaging during menstruation and periovulatory phases. The PAG of PDM subjects exhibited adaptive/reactive hyperconnectivity with the sensorimotor cortex during painful menstruation, whereas it exhibited maladaptive hypoconnectivity with the dorsolateral prefrontal cortex and default mode network (involving the ventromedial prefrontal cortex, posterior cingulate cortex, or posterior parietal cortex) during menstruation or periovulatory phase. We propose that the maladaptive descending pain modulatory systems in PDM may underpin the central susceptibility to subsequent development of various functional disorders later in life. This hypothesis is corroborated by the growing body of evidence that hypoconnectivity between PAG and default mode network is a coterminal to many functional pain disorders.

Primary dysmenorrhea (PDM) is the most prevalent gynecological problem. Many key brain systems are engaged in pain processing. In light of dynamic communication within and between systems (or networks) in shaping pain experience and behavior, the intra-regional functional connectivity (FC) in the hub regions of the systems may be altered and the functional interactions in terms of inter-regional FCs among the networks may be reorganized to cope with the repeated stress of menstrual pain in PDM. Forty-six otherwise healthy PDM subjects and 49 age-matched, healthy female control subjects were enrolled. Intra- and inter-regional FC were assessed using regional homogeneity (ReHo) and ReHo-seeded FC analyses, respectively. PDM women exhibited a trait-related ReHo reduction in the ventromedial prefrontal cortex, part of the default mode network (DMN), during the periovulatory phase. The trait-related hypoconnectivity of DMN-salience network and hyperconnectivity of DMN-executive control network across the menstrual cycle featured a dynamic transition from affective processing of pain salience to cognitive modulation. The altered DMN-sensorimotor network may be an ongoing representation of cumulative menstrual pain. The findings indicate that women with long-term PDM may develop adaptive neuroplasticity and functional reorganization with a network shift from affective processing of salience to the cognitive modulation of pain.

Primary dysmenorrhea (PDM), menstrual pain without an organic cause, is a prevailing problem in women of reproductive age. We previously reported alterations of structure and functional connectivity (FC) in the periaqueductal gray (PAG) of PDM subjects. Given that the brain derived neurotrophic factor (BDNF) acts as a pain modulator within the PAG and the BDNF Val66Met polymorphism contributes towards susceptibility to PDM, the present study of imaging genetics set out to investigate the influence of, firstly, the BDNF Val66Met single nucleotide polymorphism and, secondly, the genotype-pain interplays on the descending pain modulatory systems in the context of PAG-seeded FC patterning. Fifty-six subjects with PDM and 60 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; in parallel, blood samples were taken for genotyping. Our findings indicate that the BDNF Val66Met polymorphism is associated with the diverse functional expressions of the descending pain modulatory systems. Furthermore, PAG FC patterns in pain-free controls are altered in women with PDM in a genotype-specific manner. Such resilient brain dynamics may underpin the individual differences and shed light on the vulnerability for chronic pain disorders of PDM subjects.

The mu-opioid receptor (OPRM1) A118G polymorphism underpins different pain sensitivity and opioid-analgesic outcome with unclear effect on the descending pain modulatory system (DPMS). Primary dysmenorrhea (PDM), the most prevalent gynecological problem with clear painful and pain free conditions, serves as a good clinical model of spontaneous pain. The objective of this imaging genetics study was therefore to explore if differences in functional connectivity (FC) of the DPMS between the OPRM1 A118G polymorphisms could provide a possible explanation for the differences in pain experience. Sixty-one subjects with PDM and 65 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; blood samples were taken for genotyping. We studied 3 aspects of pain experience, namely, mnemonic pain (recalled overall menstrual pain), present pain (spontaneous menstrual pain), and experimental pain (thermal pain) intensities. We report that G allele carriers, in comparison to AA homozygotes, exhibited functional hypo-connectivity between the anterior cingulate cortex (ACC) and periaqueductal gray (PAG). Furthermore, G allele carriers lost the correlation with spontaneous pain experience and exhibited dysfunctional DPMS by means of PAG-seeded FC dynamics. This OPRM1 A118G-DPMS interaction is one plausible neurological mechanism underlying the individual differences in pain experience.

Theta oscillation (4–7 Hz) is well documented for its association with neural processes of memory. Pronounced increase of theta activity is commonly observed in patients with chronic neurogenic pain. However, its association with encoding of pain experience in patients with chronic pain is still unclear. The goal of the present study is to investigate the theta encoding of sensory and emotional information of long-term menstrual pain in women with primary dysmenorrhea (PDM). Forty-six young women with PDM and 46 age-matched control subjects underwent resting-state magnetoencephalography study during menstrual and periovulatory phases. Our results revealed increased theta activity in brain regions of pain processing in women with PDM, including the right parahippocampal gyrus, right posterior insula, and left anterior/middle cingulate gyrus during the menstrual phase and the left anterior insula and the left middle/inferior temporal gyrus during the periovulatory phase. The correlations between theta activity and the psychological measures pertaining to pain experience (depression, state anxiety, and pain rating index) implicate the role of theta oscillations in emotional and sensory processing of pain. The present study provides evidence for the role of theta oscillations in encoding the immediate and sustained effects of pain experience in young women with PDM.

Individuals with mild cognitive impairment (MCI) are at high risk of developing Alzheimer’s disease (AD). Repetitive photic stimulation (PS) is commonly used in routine electroencephalogram (EEG) examinations for rapid assessment of perceptual functioning. This study aimed to evaluate neural oscillatory responses and nonlinear brain dynamics under the effects of PS in patients with mild AD, moderate AD, severe AD, and MCI, as well as healthy elderly controls (HC). EEG power ratios during PS were estimated as an index of oscillatory responses. Multiscale sample entropy (MSE) was estimated as an index of brain dynamics before, during, and after PS. During PS, EEG harmonic responses were lower and MSE values were higher in the AD subgroups than in HC and MCI groups. PS-induced changes in EEG complexity were less pronounced in the AD subgroups than in HC and MCI groups. Brain dynamics revealed a “transitional change” between MCI and Mild AD. Our findings suggest a deficiency in brain adaptability in AD patients, which hinders their ability to adapt to repetitive perceptual stimulation. This study highlights the importance of combining spectral and nonlinear dynamical analysis when seeking to unravel perceptual functioning and brain adaptability in the various stages of neurodegenerative diseases.