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.

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Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH 3 mutations, is characterized by recurrent ischemic strokes and progressive cognitive decline. It remains unclear whether cerebral microbleeds ( CMB s) can serve as a surrogate marker for disease progression in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. We aimed to investigate the CMB burdens in NOTCH 3 mutation carriers at different disease stages and test their associations with cognitive performance. Methods and Results Forty‐nine individuals carrying NOTCH 3 cysteine‐altering mutations received brain magnetic resonance imaging with T1‐weighted and susceptibility‐weighted images. Whole brain images were segmented into 14 regions using Statistical Parametric Mapping and FreeSurfer software, and semiautomatic methods were used to locate and quantify the number and volume of CMB s. In our study participants, the median of CMB counts was 13, with a wide individual variation (range, 0–286). CMB s were most frequently present in thalamus, followed by temporal lobe. In the whole brain, the CMB counts and CMB volume ratios (ie, CMB volume divided by the volume of corresponding brain region) gradually increased as the disease advanced. CMB counts in the thalamus and temporal and frontal lobes increased more rapidly than other brain regions as disease progressed. There were significant associations between Mini‐Mental State Examination scores and CMB counts in the frontal lobe, temporal lobe, and pons. Conclusions CMB s may have an influential role in the clinical manifestations of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CMB burdens and their distribution in different brain regions may be capable to serve as a disease marker for monitoring the disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.