Dynamic Changes of Functional Pain Connectome in Women with Primary Dysmenorrhea.
ABSTRACT: 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.
Project description:Primary dysmenorrhea (PDM) is a common complaint in women throughout the menstrual years. Acupuncture has been shown to be effective in dysmenorrhea; however, there are large interindividual differences in patients' responses to acupuncture treatment. Fifty-four patients with PDM were recruited and randomized into real or sham acupuncture treatment groups (over the course of three menstrual cycles). Pain-related functional connectivity (FC) matrices were constructed at baseline and post-treatment period. The different neural mechanisms altered by real and sham acupuncture were detected with multivariate analysis of variance. Multivariate pattern analysis (MVPA) based on a machine learning approach was used to explore whether the different FC patterns predicted the acupuncture treatment response in the PDM patients. The results showed that real but not sham acupuncture significantly relieved pain severity in PDM patients. Real and sham acupuncture displayed differences in FC alterations between the descending pain modulatory system (DPMS) and sensorimotor network (SMN), the salience network (SN) and SMN, and the SN and default mode network (DMN). Furthermore, MVPA found that these FC patterns at baseline could predict the acupuncture treatment response in PDM patients. The present study verified differentially altered brain mechanisms underlying real and sham acupuncture in PDM patients and supported the use of neuroimaging biomarkers for individual-based precise acupuncture treatment in patients with PDM.
Project description:Although several studies have found that chronic pain is characterized by increased cross-network connectivity between salience network, sensorimotor network, and default mode network (DMN), a large sample-size investigation allowing for a more reliable evaluation of somatotopic specificity and subgroup analyses with linkage to clinical pain intensity has been lacking. We enrolled healthy adults and a large cohort of patients (N = 181) suffering from chronic low back pain (cLBP). To specifically link brain connectivity with clinical pain intensity, patients were scanned at baseline and after performing physical maneuvers that exacerbated pain. Compared with healthy adults, patients with cLBP demonstrated increased connectivity between the functionally localized back representation in the primary somatosensory cortex (S1back) and both salience network and DMN. Pain exacerbation maneuvers increased S1back connectivity to salience network regions, but decreased connectivity to DMN, with greater pain intensity increase associated with greater shifts in these connectivity patterns. Furthermore, only in patients with cLBP reporting high pain catastrophizing, DMN connectivity was increased to a cardinal node of the salience network, anterior insula cortex, which was correlated with increased postmaneuver pain in this cLBP subgroup. Hence, increased information transfer between salience processing regions, particularly anterior insula, and DMN may be strongly influenced by pain catastrophizing. Increased information transfer between the salience network and S1 likely plays an important role in shifting nociceptive afference away from self-referential processing, reallocating attentional focus, and affective coding of nociceptive afference from specific body areas. These results demonstrate S1 somatotopic specificity for cross-network connectivity in encoding clinical back pain and moderating influence of catastrophizing for DMN/insula connectivity.
Project description:The serotonin-1A (5-HT1A) receptor is strongly implicated in major depression and other affective disorders due to its negative regulation of serotonin neurone firing rates. Behavioural and clinical studies have repeatedly reported that the -1019G allele carries a high susceptibility for affective disorders. However, the underlying pathophysiology remains unknown. Here, we employed a genetic neuroimaging strategy in 99 healthy human subjects to explore the effect of serotonin-1A receptor polymorphism on brain resting-state functional connectivity (FC). We used functional magnetic resonance imaging, along with a seed-based approach, to identify three main brain networks: the default mode network (DMN), the salience network (SN) and the central executive network. We observed a significant decrease in the FC of the DMN within the dorsolateral and ventromedial prefrontal cortices in G-carriers. Furthermore, compared with the C-homozygote group, we observed decreased FC of the SN within the ventromedial prefrontal cortex and subgenual anterior cingulate cortex in the G-carrier group. Our results indicate that 5-HT1A receptor genetic polymorphism modulates the activity of resting-state FC within brain networks including the DMN and SN. These genotype-related alterations in brain networks and FC may provide novel insights into the neural mechanism underlying the predisposition for affective disorders in G allele carriers.
Project description:To investigate changes of vision-related resting-state activity in pituitary adenoma (PA) patients with visual damage through comparison to healthy controls (HCs).25 PA patients with visual damage and 25 age- and sex-matched corrected-to-normal-vision HCs underwent a complete neuro-ophthalmologic evaluation, including automated perimetry, fundus examinations, and a magnetic resonance imaging (MRI) protocol, including structural and resting-state fMRI (RS-fMRI) sequences. The regional homogeneity (ReHo) of the vision-related cortex and the functional connectivity (FC) of 6 seeds within the visual cortex (the primary visual cortex (V1), the secondary visual cortex (V2), and the middle temporal visual cortex (MT+)) were evaluated. Two-sample t-tests were conducted to identify the differences between the two groups.Compared with the HCs, the PA group exhibited reduced ReHo in the bilateral V1, V2, V3, fusiform, MT+, BA37, thalamus, postcentral gyrus and left precentral gyrus and increased ReHo in the precuneus, prefrontal cortex, posterior cingulate cortex (PCC), anterior cingulate cortex (ACC), insula, supramarginal gyrus (SMG), and putamen. Compared with the HCs, V1, V2, and MT+ in the PAs exhibited decreased FC with the V1, V2, MT+, fusiform, BA37, and increased FC primarily in the bilateral temporal lobe (especially BA20,21,22), prefrontal cortex, PCC, insular, angular gyrus, ACC, pre-SMA, SMG, hippocampal formation, caudate and putamen. It is worth mentioning that compared with HCs, V1 in PAs exhibited decreased or similar FC with the thalamus, whereas V2 and MT+ exhibited increased FCs with the thalamus, especially pulvinar.In our study, we identified significant neural reorganization in the vision-related cortex of PA patients with visual damage compared with HCs. Most subareas within the visual cortex exhibited remarkable neural dysfunction. Some subareas, including the MT+ and V2, exhibited enhanced FC with the thalamic pulvinar, which indicates an important role in the compensatory mechanism following visual impairment. In addition, neural dysfunction within the visual cortex was associated with neural activity alternation in the higher-order cognitive cortex, especially subareas in default mode network (DMN) and salience network (SN).
Project description:Acupuncture and imagery interventions for pain management have a long history. The present study comparatively investigated whether acupuncture and video-guided acupuncture imagery treatment (VGAIT, watching a video of acupuncture on the participant's own body while imagining it being applied) could modulate brain regional connectivity to produce analgesic effects. The study also examined whether pre-intervention brain functional and structural features could be used to predict the magnitude of analgesic effects. Twenty-four healthy participants were recruited and received four different interventions (real acupuncture, sham acupuncture, VGAIT, and VGAIT control) in random order using a cross-over design. Pain thresholds and magnetic resonance imaging (MRI) data were collected before and after each intervention. We first compared the modulatory effects of real acupuncture and VGAIT on intra- and inter-regional intrinsic brain connectivity and found that real acupuncture decreased regional homogeneity (ReHo) and functional connectivity (FC) in sensorimotor areas, whereas VGAIT increased ReHo in basal ganglia (BG) (i.e., putamen) and FC between the BG subcortical network and default mode network. The altered ReHo and FC were associated with changes in pain threshold after real acupuncture and VGAIT, respectively. A multimodality fusion approach with pre-intervention ReHo and gray matter volume (GMV) as features was used to explore the brain profiles underlying individual variability of pain threshold changes by real acupuncture and VGAIT. Variability in acupuncture responses was associated with ReHo and GMV in BG, whereas VGAIT responses were associated with ReHo and GMV in the anterior insula. These results suggest that, through different pathways, both real acupuncture and VGAIT can modulate brain systems to produce analgesic effects.
Project description:Purpose:The present study combined fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) to explore brain functional abnormalities in acute tinnitus patients (AT) with hearing loss. Methods:We recruited twenty-eight AT patients and 31 healthy controls (HCs) and ran resting-state functional magnetic resonance imaging (fMRI) scans. fALFF, ReHo, and FC were conducted and compared between AT patients and HCs. After that, we calculated correlation analyses among abnormal fALFF, ReHo, FC, and clinical data in AT patients. Results:Compared with HCs, AT showed increased fALFF values in the right inferior temporal gyrus (ITG). In contrast, significantly decreased ReHo values were observed in the cerebellar vermis, the right calcarine cortex, the right precuneus, the right supramarginal gyrus (SMG), and the right middle frontal gyrus (MFG). Based on the differences in the fALFF and ReHo maps, the latter of which we defined as region-of-interest (ROI) for FC analysis, the right ITG exhibited increased connectivity with the right precentral gyrus. In addition, the right MFG demonstrated decreased connectivity with both the bilateral anterior cingulate cortex (ACC) and the left precentral gyrus. Conclusion:By combining ReHo, fALFF, and FC analyses, our work indicated that AT with hearing loss had abnormal intraregional neural activity and disrupted connectivity in several brain regions which mainly involving the non-auditory area, and these regions are major components of default mode network (DMN), attention network, visual network, and executive control network. These findings will help us enhance the understanding of the neuroimaging mechanism in tinnitus populations. Moreover, these abnormalities remind us that we should focus on the early stages of this hearing disease.
Project description:Resting-state functional connectivity (FC) has proven a powerful approach to understand the neural underpinnings of chronic pain, reporting altered connectivity in 3 main networks: the default mode network (DMN), central executive network, and the salience network (SN). The interrelation and possible mechanisms of these changes are less well understood in chronic pain. Based on emerging evidence of its role to drive switches between network states, the right anterior insula (rAI, an SN hub) may play a dominant role in network connectivity changes underpinning chronic pain. To test this hypothesis, we used seed-based resting-state FC analysis including dynamic and effective connectivity metrics in 25 people with chronic osteoarthritis (OA) pain and 19 matched healthy volunteers. Compared with controls, participants with painful knee OA presented with increased anticorrelation between the rAI (SN) and DMN regions. Also, the left dorsal prefrontal cortex (central executive network hub) showed more negative FC with the right temporal gyrus. Granger causality analysis revealed increased negative influence of the rAI on the posterior cingulate (DMN) in patients with OA in line with the observed enhanced anticorrelation. Moreover, dynamic FC was lower in the DMN of patients and thus more similar to temporal dynamics of the SN. Together, these findings evidence a widespread network disruption in patients with persistent OA pain and point toward a driving role of the rAI.
Project description: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.
Project description:While pain behaviors are increased in Alzheimer's disease (AD) patients compared to healthy seniors (HS) across multiple disease stages, autonomic responses are reduced with advancing AD. To better understand the neural mechanisms underlying these phenomena, we undertook a controlled cross-sectional study examining behavioral (Pain Assessment in Advanced Dementia, PAINAD scores) and autonomic (heart rate, HR) pain responses in 24 HS and 20 AD subjects using acute pressure stimuli. Resting-state fMRI was utilized to investigate how group connectivity differences were related to altered pain responses. Pain behaviors (slope of PAINAD score change and mean PAINAD score) were increased in patients vs.<h4>Controls</h4>Autonomic measures (HR change intercept and mean HR change) were reduced in severe vs. mildly affected AD patients. Group functional connectivity differences associated with greater pain behavior reactivity in patients included: connectivity within a temporal limbic network (TLN) and between the TLN and ventromedial prefrontal cortex (vmPFC); between default mode network (DMN) subcomponents; between the DMN and ventral salience network (vSN). Reduced HR responses within the AD group were associated with connectivity changes within the DMN and vSN-specifically the precuneus and vmPFC. Discriminant classification indicated HR-related connectivity within the vSN to the vmPFC best distinguished AD severity. Thus, altered behavioral and autonomic pain responses in AD reflects dysfunction of networks and structures subserving affective, self-reflective, salience and autonomic regulation.
Project description:Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting-state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19-37?years) underwent a randomized, three-way, cross-over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long-distance (seed-based and dual-regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13?±?0.28, p = 4.0 × 10-3 ), auditory network (d: 0.67?±?0.26, p = .04) and default mode network (DMN, d: 0.63?±?0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77?±?0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia-related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = -.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug.