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      Altered amplitude of low-frequency fluctuation and regional cerebral blood flow in females with primary dysmenorrhea: a resting-state fMRI and arterial spin labeling study

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          Purpose: The current study aimed to explore the central mechanism of primary dysmenorrhea (PD) by investigating the alterations in resting state amplitude of low-frequency fluctuation (ALFF) and regional cerebral blood flow (CBF) between PD patients and healthy controls (HCs).

          Patients and methods: A total of 34 female subjects including 20 PD patients and 14 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling technique (ASL) MRI during menstrual phase. Subsequently, the differences in ALFF and CBF were compared in the two groups. The visual analog scores for pain (VAS-P) and for anxiety (VAS-A) were applied to assess cramping pain and related symptoms in PD patients. Finally, Pearson’s correlation analysis was performed to analyze relationships between the neuroimaging findings and clinical characteristics.

          Results: Compared to HCs, PD patients had decreased ALFF in the right cerebellum posterior lobe, right middle temporal gyrus, right parahippocampal gyrus, right hippocampus, right brainstem and left parietal lobe. In addition, elevated CBF values were observed in the right inferior frontal gyrus, right precentral gyrus, and right superior temporal gyrus. There was no significant correlation between ALFF, CBF values and clinical characteristics including onset age of dysmenorrhea, VAS-A, and VAS-P in PD patients.

          Conclusion: The preliminary alterations of ALFF and CBF values in PD patients were observed in different pain-related brain regions, which were involved in multiple dimensions of pain and pain modulation. The combination of rs-fMRI and ASL MRI might provide complementary information for a better understanding of the central mechanism in PD.

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          Most cited references 30

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          Functional imaging of brain responses to pain. A review and meta-analysis (2000).

          Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated.
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            The cerebellum and pain: passive integrator or active participator?

            The cerebellum is classically considered to be a brain region involved in motor processing, but it has also been implicated in non-motor, and even cognitive, functions. Though previous research suggests that the cerebellum responds to noxious stimuli, its specific role during pain is unclear. Pain is a multidimensional experience that encompasses sensory discriminative, affective motivational, and cognitive evaluative components. Cerebellar involvement during the processing of pain could thus potentially reflect a number of different functional processes. This review will summarize the animal and human research to date that indicates that (1) primary afferents conduct nociceptive (noxious) input to the cerebellum, (2) electrical and pharmacological stimulation of the cerebellum can modulate nociceptive processing, and (3) cerebellar activity occurs during the presence of acute and chronic pain. Possible functional roles for the cerebellum relating to pain will be considered, including perspectives relating to emotion, cognition, and motor control in response to pain. Copyright © 2010 Elsevier B.V. All rights reserved.
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              Reproducibility of R-fMRI metrics on the impact of different strategies for multiple comparison correction and sample sizes.

               Xiao Chen,  Bin Lu,  Chao-Gan Yan (corresponding) (2017)
              Concerns regarding reproducibility of resting-state functional magnetic resonance imaging (R-fMRI) findings have been raised. Little is known about how to operationally define R-fMRI reproducibility and to what extent it is affected by multiple comparison correction strategies and sample size. We comprehensively assessed two aspects of reproducibility, test-retest reliability and replicability, on widely used R-fMRI metrics in both between-subject contrasts of sex differences and within-subject comparisons of eyes-open and eyes-closed (EOEC) conditions. We noted permutation test with Threshold-Free Cluster Enhancement (TFCE), a strict multiple comparison correction strategy, reached the best balance between family-wise error rate (under 5%) and test-retest reliability/replicability (e.g., 0.68 for test-retest reliability and 0.25 for replicability of amplitude of low-frequency fluctuations (ALFF) for between-subject sex differences, 0.49 for replicability of ALFF for within-subject EOEC differences). Although R-fMRI indices attained moderate reliabilities, they replicated poorly in distinct datasets (replicability < 0.3 for between-subject sex differences, < 0.5 for within-subject EOEC differences). By randomly drawing different sample sizes from a single site, we found reliability, sensitivity and positive predictive value (PPV) rose as sample size increased. Small sample sizes (e.g., < 80 [40 per group]) not only minimized power (sensitivity < 2%), but also decreased the likelihood that significant results reflect "true" effects (PPV < 0.26) in sex differences. Our findings have implications for how to select multiple comparison correction strategies and highlight the importance of sufficiently large sample sizes in R-fMRI studies to enhance reproducibility. Hum Brain Mapp 39:300-318, 2018. © 2017 Wiley Periodicals, Inc.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                16 April 2019
                : 12
                : 1243-1250
                [1 ]Department of Radiology, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University , Beijing 100010, People’s Republic of China
                [2 ]School of Acupuncture-Moxibustion & Tuina, Beijing University of Chinese Medicine , Beijing, 100029, People’s Republic of China
                [3 ]Beijing International Center for Mathematical Research, Peking University , Beijing 100871, People’s Republic of China
                [4 ]Department of Acupuncture and Moxibustion, Yanshan Hospital , Beijing 102500, People’s Republic of China
                Author notes
                Correspondence: Jian-Wei HuoDepartment of Radiology, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University , 23 Meishuguanhou Street, Dongcheng District, Beijing100010, People’s Republic of ChinaTel +86 105 217 6785Email huojw1234@ 123456sina.com
                Yi-Ran HuangSchool of Acupuncture-Moxibustion & Tuina, Beijing University of Chinese Medicine , Beijing100029, People’s Republic of ChinaTel +86 105 217 6785Email caicai13@ 123456126.com

                These authors contributed equally to this work

                © 2019 Zhang et al.

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                Page count
                Figures: 2, Tables: 2, References: 38, Pages: 8
                Original Research


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