Abnormal Resting-State Spontanous Brain Activity In Patients With Migraine Without Aura

Migraine is a common, chronic disorder typically characterized by recurrentattacks of disabling headache. Given the heavy burden that migraine disability places onthe individual and society, it is imperative to develop a better understanding of migrainepathophysiology. Neuroimaging has helped to increase our knowledge about neuralmechanisms underlying migraine. Converging evidences of structural and functionalcerebral abnormalities in patients with migraine have been accumulated. All of thesefindings demonstrated that migraine is associated with altered central processing of painstimulus, and recurrent migraine attacks may result in selective damage of brain areasinvolved in pain processing. Despite such progress, migraine remains underdiagnosedand the available therapies underused. By focusing on the neural responses under taskconditions, resting-state analysis has been utilized to investigate the integration level ofneural systems when no explicit task is engaged. Until recently, few studies haveevaluated the abnormalities of the resting state in subjects with migraine.The details of researches and the main innovations were listed as follows:Firstly, although previous resting-state studies have reported abnormal functionalcerebral changes in patients with migraine without aura (MwoA), few have focused onthe alterations of regional spontaneous neuronal activity and the corresponding braincircuits’ changes collectively. In the present study, we first investigated alterations ofregional spontaneous neuronal activity during the resting-state in MwoA patients byapplying the amplitude of low-frequency fluctuation (ALFF) approach. Then weextracted the regions with significant ALFF differences between MwoA patients andhealthy controls (HC) as regions of interest (ROIs) for resting-state functionalconnectivity (FC) analysis, which was used to assess the corresponding brain circuits’changes in MwoA. We found that MwoA patients have altered resting-state spontaneousneuronal activity in pain-processing areas, including the left rostral anterior cingulatecortex (rACC), bilateral prefrontal cortex (PFC), and right thalamus (TH), as well asaltered FCs associated with these areas. ROI-based FC analysis also revealed increasedFCs associated with these areas. In addition, the ALFF values of the left rACC werecorrelated with duration of disease in MwoA. Our findings may lead to a betterunderstanding of intrinsic functional architecture of the baseline brain activity in MwoA,providing both regional and the corresponding brain circuits’ spontaneous neuronalactivity properties.Secondly, numerous neuroimaging studies have defined low-frequency, spatially consistent intrinsic connectivity networks (ICN) in resting-state functional magneticresonance imaging (fMRI) data which reflect functional interactions among distinctbrain areas, in the current study, we applied independent component analysis (ICA) toidentify the group differences of three important networks, i.e., the default modenetwork (DMN), bilateral central executive network (CEN) and salience network (SN)between the MwoA patients and HC. One of the key features of ICA is its ability toperform a spatial-temporal decomposition of the signal without any a priori anatomical(spatial) or neural (temporal) information. Compared with the HC, MwoA patientsshowed greater intra-network connectivity within the right middle frontal gyrus (rMFG)for the right CEN (rCEN) and left inferior frontal gyrus (lIFG) for the left CEN (lCEN),and decreased intra-network connectivity within the right supplementary motor area(rSMA) for the SN. Moreover, MwoA patients demonstrated greater intrinsic DMN andrCEN connectivity to brain regions outside of the classical boundaries of these networks,namely the right anterior insula (rAI). Greater connectivity between both the DMN andrCEN and the insula correlated with duration of migraine. Our findings may haveimplications for understanding brain mechanisms of MwoA, potentially pointingtowards “markers” for disease progression. More broadly, these findings haveimplications for how such complex interplay amongst multiple brain networks can beinfluenced by frequent ongoing migraine attacks.Thirdly, we applied multivariate Granger causality analysis (mGCA) to directlyassess the causal interactions of specific nodes within and among the intrinsic networks.One distinguishing feature of the human brain is the amount of cognitive controlavailable for selecting, switching, and attending to salient events in the environments.Recent researches have suggested that the human brain is intrinsically organized intodistinct functional networks that support these processes. We used mGCA to examinethe interaction between the DMN, CEN, and SN. Our findings emphaszied a key rolefor the rFIC in the hierarchical initiation of control signals, specifically with respect toactivation and deactivation in the CEN and DMN, and the dynamics of switchingbetween these two networks. Compared with the HC, the SN did have a weaker causalinfluence on the CEN in MwoA patients. This might be related to cognitive impairmentin migraine patients.Finally, we discussed potential acupuncture effectiveness for treatment of migraine.The pathogenesis of migraine is complex, and there are various clinical treatments ofthe disease. In terms of acute treatment, migraine can be managed effectively withwestern medicine. However, the western medicine oftern have side effects that limit their utility. The Traditional Chinese Medicine (TCM), especially acupuncture therapy,has proven to be effective in treatment of migraine; and it has been widely used in theclinical treatment of the disease. The fMRI technique, with its non-invasive and higherresolution characterstics, has been widely applied in the detection of the brainactivations evoked by acupunture stimuli. In the current study, we introduced adata-driven based multivariate approach namely support vector machine (SVM) toexplore the spatial neural response patterns evoked by acupuncture at two differentacupoints. The results showed that acupuncture at the acupoints can evoke distinctneural response patterns. Our findings may suggest potentially selective efficacy-relatedneural actions in response to acupuncture at different acupoints, which might provide atheoretical basis for clinical application of acupuncture in treatment of migraine.In summary, these resting-state functional abnormalities in MwoA patientsprovided additional evidence for abnormal brain function in MwoA patients. Thesefindings may be beneficial for understanding migraine, as well as providing potentialdiagnostic information and treatment strategies.