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Dementia is related to the cellular accumulation of β-amyloid plaques, tau aggregates, or α-synuclein aggregates, or to neurotransmitter deficiencies in the dopaminergic and cholinergic pathways. Cellular and neurochemical changes are both involved in dementia pathology. However, the role of dopaminergic and cholinergic networks in metabolic connectivity at different stages of dementia remains unclear. The altered network organisation of the human brain characteristic of many neuropsychiatric and neurodegenerative disorders can be detected using persistent homology network (PHN) analysis and algebraic topology. We used 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging data to construct dopaminergic and cholinergic metabolism networks, and used PHN analysis to track the evolution of these networks in patients with different stages of dementia. The sums of the network distances revealed significant differences between the network connectivity evident in the Alzheimer’s disease and mild cognitive impairment cohorts. A larger distance between brain regions can indicate poorer efficiency in the integration of information. PHN analysis revealed the structural properties of and changes in the dopaminergic and cholinergic metabolism networks in patients with different stages of dementia at a range of thresholds. This method was thus able to identify dysregulation of dopaminergic and cholinergic networks in the pathology of dementia.

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen’s d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.

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.

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.

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.

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.