BackgroundExcessive iron deposition is associated with migraine occurrence, disease severity, and related dysfunction. The migraine attack is a coordinated, whole-nervous-system event, while previous research has predominantly focused on discrete brain regions. This study aims to explore the associations between network-level iron deposition and both disease occurrence and clinical manifestations in migraine using the functional connectome.MethodsSeventy-three migraine patients, including 32 episodic migraine (EM) and 41 chronic migraine (CM), and 37 age- and sex-matched healthy controls (HCs) were recruited. All participants underwent magnetic resonance imaging (MRI) to acquire quantitative susceptibility mapping (QSM) data. First, individual iron deposition maps were defined by comparing iron levels in each patient versus HCs. Next, the network coupling with each patient's site of iron deposition was calculated using seed-based functional connectivity (FC) in a large (n = 1000) normative connectome, termed the iron deposition network map (IDNM). We then performed inter-group analysis to identify disease- and symptom-associated brain regions and measured the FC strength between these regions and the patients' iron deposition maps. Finally, we investigated the relationships between IDNM-derived metrics and various clinical manifestations, including headache characteristics, migraine-related symptoms, disability measures, and comorbidities.ResultsIDNM group comparisons revealed significant differences in the superior temporal gyrus (STG), insula, and cerebellum in both migraine vs. HCs and CM vs. HCs comparisons, whereas no statistically significant differences were found for EM compared to either CM or HCs. FC strength between the peak site of the regions and individual iron deposition maps showed good discriminative performance in receiver operating characteristic (ROC) analysis (AUC > 0.70), effectively distinguishing migraine patients from HCs. Moreover, we identified clinical manifestation-related networks based on the IDNMs: the cerebellum for monthly headache days (MHDs; r = 0.349, p = 0.003); the orbitofrontal cortex (OFC) and nucleus accumbens (NAC) for poor sleep quality (r = 0.604, p < 0.001); and the globus pallidus (GP) for vomiting (p < 0.001).ConclusionNetwork-level iron deposition may distinguish migraine patients from HCs and is associated with clinical manifestations including MHDs, poor sleep quality, and vomiting symptoms, suggesting that iron deposition may play a role in migraine through the functional connectome.

Migraine aura manifests as various neurological symptoms, which may occur before, during, or persist throughout the headache phase. We report a case of a 30-year-old female patient whose initial symptoms included persistent bilateral photopsia and ophthalmoplegia, accompanied by headache, with a medical history spanning over four years. The duration of her auras was up to one month. After admission, through detailed inquiry into her medical history and extensive etiological screening, the patient was diagnosed with chronic migraine (CM). Following preventive treatment for CM, her symptoms significantly improved. This case serves to encourage neurologists to expand their diagnostic thinking in clinical practice. When encountering sudden and unexplained persistent neurological symptoms, the possibility of migraine with persistent aura should be considered.

BACKGROUND Migraine is increasingly recognized as a network disorder involving distributed structural and functional brain alterations. However, regional changes in the relationship between resting-state activity and white-matter organization remain unclear. We used the structural decoupling index (SDI), a graph signal processing measure of structure–function alignment, to characterize regional coupling alterations in migraine. METHODS After quality control, 108 participants (41 with episodic migraine [EM], 31 with chronic migraine [CM], and 36 healthy controls [HCs]) underwent resting-state functional, diffusion, and T1-weighted MRI. Regional SDI was computed for 246 Brainnetome regions using individual RD-weighted structural graphs. Group differences were tested by age- and sex-adjusted ANCOVA with Benjamini–Hochberg FDR correction. Partial Spearman correlations examined associations between clinical measures and SDI in regions differing between EM and CM, adjusting for age, sex, and migraine subtype. Exploratory classification used class-weighted linear SVMs with repeated nested fivefold cross-validation. PLS regression related the unthresholded migraine–HC SDI t-map to Allen Human Brain Atlas gene-expression data, followed by enrichment analysis of genes with positive and negative PLS1 weights. RESULTS Compared with HCs, patients with migraine had lower SDI in the left superior frontal gyrus and higher SDI in the right inferior temporal gyrus. Three-group analyses additionally identified differences in the left lateral occipital cortex, where CM showed lower SDI than EM; lower values were associated with more monthly migraine days. Regional SDI features showed preliminary discrimination, strongest for CM versus HCs (AUC = 0.866). Positive PLS1-weighted genes were enriched in chromatin regulation, transcriptional control, and RNA metabolism, whereas negative-weighted genes were enriched in mitochondrial energy metabolism, oxidative phosphorylation, ribosome-associated quality control, and calcium signaling. CONCLUSIONS This first application of SDI to migraine revealed bidirectional hierarchical structure–function disruptions across prefrontal, temporal, and occipital regions. Lower lateral occipital SDI was associated with more monthly migraine days, while regional SDI features showed preliminary within-sample discrimination, strongest for CM versus HCs (AUC = 0.866). Transcriptomic enrichment implicated chromatin regulation and mitochondrial energy metabolism. SDI may provide a useful framework for characterizing hierarchical brain network dysfunction in migraine.

Cluster headache (CH) is a highly disabling primary headache disorder with a complex underlying mechanism. However, there are currently no effective targeted therapeutic drugs available. Existing medications often have limited efficacy and numerous side effects, which frequently fail to meet clinical needs. This study aims to identify potential new therapeutic targets for CH through proteome-wide mendelian randomization (PWMR). We used PWMR to estimate the causal effects of plasma proteins on CH. This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association study (GWAS) results of CH phenotypes. In addition, we conducted various sensitivity analyses, enrichment analyses, phenome-wide MR assessments, protein–protein interaction network construction, and mediation MR analyses to further validate the drug potential of the identified protein targets. We identified 11 protein targets for CH (p < 2.41 × 10–5), with high-priority candidates exhibiting minimal side effects. Phenome-wide MR revealed novel targets—PXDNL, CCN4, PKD1, LGALS9, and MRC1—that show no significant disease-related adverse effects and interact with established preventive CH drug targets. Notably, PXDNL interacts with both acute and preventive CH drug targets. Furthermore, the causal effect of plasma proteins on CH is partially mediated by cortical surface area, with mediation proportions ranging from 3.2

OBJECTIVE:As a neurovascular disorder, migraine currently lacks well-established macroscopic biomarkers detectable by magnetic resonance angiography (MRA). While the basilar artery (BA) has been implicated in migraine pathophysiology, this relationship remains poorly characterized. This study investigates whether BA morphological parameters could serve as diagnostic biomarkers for migraine and predictive markers for disease progression. METHODS:This study included 41 healthy controls (HCs), 41 episodic migraine (EM) patients, and 95 chronic migraine (CM) patients who completed both MRI examinations and standardized questionnaires. Using established diagnostic criteria for vertebrobasilar dolichoectasia (VBD), we quantified the diameter, length, and height of the BA bifurcation. Furthermore, we measured the superior cerebellar artery (SUCA) outlet angle and basilar artery lateral displacement (BALD). These BA-derived metrics were subsequently incorporated into multivariable logistic regression models to assess their predictive value for migraine chronification. RESULTS:No significant differences were found in BA diameter, BA length, BADE, or VBD when comparing either EM or CM groups with HCs. However, both BALD and SUCA outlet angles showed significant intergroup differences. There was a statistically significant difference in BADE between EM and CM. In the logistic regression, migraine was significantly associated with both BALD and SUCA outlet angles. In the multinomial logistic regression analysis, EM was significantly associated with SUCA outlet angle, while CM was significantly associated with both BALD and SUCA outlet angle. CONCLUSIONS:Our data suggest that the reduced SUCA outlet angle may represent a risk factor for migraine and could potentially serve as an imaging biomarker. Additionally, BALD may constitute an independent risk factor for CM and could function as an MRA biomarker for migraine chronicity. Potential indicators related to the basilar artery may influence migraine attacks by affecting hemodynamic changes in migraine pathophysiology.

Serum antinuclear antibodies (ANAs) facilitate the diagnosis and evaluation of patients with many systemic autoimmune conditions. However, there are no systematic reports concerning differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Therefore, we assessed the differences in serum ANAs in GBS and CIDP patients and control subjects in a Chinese cohort. A retrospective enrollment of 417 patients was conducted for this study, consisting of 158 clinically confirmed GBS patients, 115 CIDP patients, and 144 non-GBS and CIDP inpatients as a control group. The measurement of serum ANAs, including autoantibodies against the Ro52 protein (anti-Ro52 antibody), anti-Sjogren's-syndrome-related antigen A antibodies (anti-SSA), anti-mitochondrial antibody M2 (AMA-M2), etc., was performed on all enrolled patients. Additionally, erythrocyte sedimentation rate (ESR), anti-streptolysin O (ASO), and C-reactive protein (CRP) values were also assessed. The results revealed significantly higher positive rates of Anti-Ro52 antibody, AMA-M2, and Anti-SSA antibody in the GBS group compared to the CIDP and control groups (adjusted p < 0.001). In the GBS group, Anti-Ro52 and AMA-M2 antibody positivity was moderate to severe, while anti-SSA antibody positivity was mild. In the GBS group, the most common finding for a serum ANAs burden score was 3 (58, 36.71%), which was higher than the CIDP group where a score of 1 was the most common finding (14, 12.17%). Anti-Ro52 antibodies, anti-SSA antibodies, and AMA-M2 were closely associated with GBS. Differential positivity of serum ANAs in GBS and CIDP patients was proposed to provide a reference for clinical diagnosis and treatment methods.

Abnormal iron deposition may be a biomarker for a disrupted central antinociceptive neuronal network, and the relationship between iron deposition and the pathophysiological mechanisms of chronic migraine (CM) with medication overuse (MOH) remains unclear. We investigated iron deposition in the deep gray matter (DGM) of the brain in CM patients with and without MOH using quantitative susceptibility mapping (QSM). Forty-eight healthy controls (HCs) and 69 CM patients (36 with MOH; 33 without MOH) were recruited. QSM data were acquired using a 3.0 T Magnetic resonance imaging (MRI). Regions of interest (ROI) in the DGM, including the bilateral caudate, putamen, globus pallidus (GP), hippocampus, nucleus accumbens, and amygdala, were segmented from the T1-weighted images (T1WI) of the whole brain of each individual patient using FreeSurfer. QSM images were registered to T1WI. QSM values within each ROI were extracted and compared between CM and HCs, as well as between CM with MOH and CM without MOH. Correlations between QSM values and clinical assessment scale scores were calculated. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of QSM values in these DGM for detecting CM and CM with MOH. Compared to HCs, CM patients exhibited increased iron deposition in the caudate (p = 0.013) and putamen (p < 0.001). In the CM without MOH group, headache duration correlated positively with iron deposition in the caudate (r = 0.502, p = 0.010) and putamen (r = 0.514, p = 0.009). CM with MOH patients showed greater iron deposition in the caudate (p < 0.001), putamen (p < 0.001), and GP (p = 0.049) than those without MOH, with medication use frequency correlating positively with iron deposition in the caudate (r = 0.427, p = 0.023) and putamen (r = 0.445, p = 0.018). ROC curve analysis indicated that the caudate (AUC = 0.736) and putamen (AUC = 0.729) exhibited high sensitivity and specificity in diagnosing CM with MOH. CM patients with MOH had excessive iron deposition in basal ganglia regions, including the caudate, putamen, and GP, which may be related to the medication overuse behavior. Iron deposition in the caudate and putamen may be a potential biomarker for CM with MOH. These findings provide insight into the common pathophysiological mechanisms underlying MOH and potential addiction.

BACKGROUND:The pathophysiological mechanism of migraine remains elusive, thereby impeding the effective treatment of the disease. Current neuroimaging research focuses on changes in brain functional connectivity, functional networks, and macrostructural alterations, which reflect abnormal neuronal function during the disease process. The plasticity changes in neuronal structures and neurotransmitter system dysregulations potentially play a crucial role in migraine onset and chronicity of migraine. This study utilizes multimodal neuroimaging techniques to investigate the microstructural and neurotransmitter alterations in migraine and provides new insights into its pathological mechanisms and therapeutic method. METHODS:Microstructural alterations in both white matter (WM) and cortical gray matter (GM) were evaluated among 40 chronic migraine (CM) patients, 35 episodic migraine (EM) patients, and 45 healthy controls (HCs) using Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) models. Tract-based spatial statistics (TBSS) and Surface-based analysis (SBA) were performed to compare groupwise differences in white and gray matter microstructure, respectively. Furthermore, the cross-modal toolbox JuSpace was used to analyze the correlation between cortical gray matter neurite alterations and neurotransmitter. RESULTS:In the WM, compared to HC, a decrease in neurite density index (NDI) was identified in the migraine group, and both NDI and fractional anisotropy (FA) were decreased in the CM group. No significant alterations were observed in the EM group. An increase in radial diffusivity (RD) was found in the CM group compared to the EM group. In the cortical GM, compared to HC, the migraine group had fewer neurites in the right insula and temporal pole cortex, and the CM group showed a reduction in neurites in the right middle temporal and fusiform cortex. The cortical GM of neurite damage was negatively correlated with neurotransmitters in migraine and CM. There was no correlation between NODDI and DTI metrics of these brain regions and clinical data after the Bonferroni correction. CONCLUSION:Our findings indicated that neurite loss was detected in both WM and cortical GM of migraineurs. As the migraine progresses into chronicity, the axonal damage may become more pronounced. The neurite damage of cortical GM was negatively related to neurotransmitters.

BACKGROUND:New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. METHODS:The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. RESULTS:T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. CONCLUSIONS:Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

OBJECTIVE:To delineate the structural connectome alterations in patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs). BACKGROUND:The pathogenesis of migraine chronification remains elusive, with structural brain network changes potentially playing a key role. However, there is a paucity of research employing graph theory analysis to explore changes in the whole brain structural networks in patients with CM and EM. METHODS:The individual structural brain connectome of 60 patients with CM, 34 patients with EM, and 39 healthy control participants were constructed by using deterministic diffusion-tensor tractography. Graph metrics including global efficiency, characteristic path length, local efficiency, clustering coefficient, and small-world parameters were evaluated to describe the topologic organization of the white matter structural networks. Additionally, nodal clustering coefficient and efficiency were considered to assess the regional characteristics of the brain connectome. A graph-based statistic was used to assess brain network properties across the groups. RESULTS:Graph theory analysis revealed significant disruptions in the structural brain networks of CM patients, characterized by reduced global efficiency, local efficiency, and increased characteristic path length compared to HCs. Additionally, CM patients exhibited significantly lower local efficiency than EM patients. Notably, the CM group demonstrated marked reductions in local clustering coefficient and nodal local efficiency in the frontal and temporal regions compared with the healthy control group and EM group. Nodal local efficiency can effectively distinguish CM from EM and HCs. Moreover, the disrupted topologic efficiency was significantly associated with attack frequency and MIDAS score in patients with migraine after Bonferroni correction. CONCLUSION:Decreased structural connectivity in the frontal and temporal regions may serve as a neuroimaging marker for migraine chronification and disease progression, providing valuable insights into the pathophysiology of chronic migraine.

OBJECTIVES:The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed-based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting-state functional magnetic resonance imaging (MRI).METHODS:The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well-matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations.RESULTS:Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus-central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area-parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016).CONCLUSIONS:Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions.

Objectives: To investigate the glymphatic function in patients with new daily persistent headache (NDPH) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Background: NDPH, a rare and treatment-refractory primary headache disorder, is poorly understood. There is limited evidence to suggest that headaches are associated with glymphatic dysfunction. Thus far, no studies have evaluated glymphatic function in patients with NDPH. Methods: In this cross-sectional study conducted in the Headache Center of Beijing Tiantan Hospital, patients with NDPH and healthy controls were enrolled. All participants underwent brain magnetic resonance imaging examinations. Clinical characteristics and neuropsychological evaluation were examined in patients with NDPH. ALPS indexes for both hemispheres were measured to determine the glymphatic system function in patients with NDPH and healthy controls. Results: In total, 27 patients with NDPH (14 males, 13 females; age [mean +/- standard deviation (SD)]: 36.6 +/- 20.6) and 33 healthy controls (15 males, 18 females; age [mean +/- SD]: 36.0 +/- 10.8) were included in the analysis. No significant differences between groups were observed in the left ALPS index (1.583 +/- 0.182 vs. 1.586 +/- 0.175, mean difference = 0.003, 95% confidence interval [CI] of difference = -0.089 to 0.096, p = 0.942), or right ALPS index (1.578 +/- 0.230 vs. 1.559 +/- 0.206, mean difference = -0.027, 95% CI of difference = - 0.132 to 0.094, p = 0.738). Additionally, ALPS indexes were not correlated with clinical characteristics or neuropsychiatric scores. Conclusion: No glymphatic dysfunction was detected in patients with NDPH by means of the ALPS method. Additional studies with larger samples are needed to confirm these preliminary findings and improve the understanding of glymphatic function in NDPH.

Background The brain functional network topology in new daily persistent headache (NDPH) is not well understood. In this study, we aim to assess the cortical functional network topological characteristics of NDPH using non-invasive neural signal recordings. Methods Resting-state magnetoencephalography (MEG) was used to measure power fluctuations in neuronal oscillations from distributed cortical parcels in 35 patients with NDPH and 40 healthy controls (HCs). Their structural data were collected by 3T MRI. Functional connectivity (FC) of neural networks from 1 to 80 Hz frequency ranges was analyzed with topographic patterns and calculated network topological parameters with graph theory. Results In the delta (1–4 Hz) and beta (13–30 Hz) bands, the lateral occipital cortex and superior frontal gyrus FC were increased in NDPH groups compared to HCs. Graph theory analysis revealed that the NDPH had significantly increased global efficiency in the delta band and decreased nodal clustering coefficient (left medial orbitofrontal cortex) in the theta (4–8 Hz) band. The clinical characteristics had a significant correlation with network topological parameters. Age at onset of patients showed a positive correlation with global efficiency in the delta band. The degree of depression of patients showed a negative correlation with the nodal clustering coefficient (left medial orbitofrontal cortex) in the theta band. Conclusion The FC and topology of NDPH in brain networks may be altered, potentially leading to cortical hyperexcitability. Moreover, medial orbitofrontal cortex is involved in the pathophysiological mechanism of depression in patients with NDPH. Increased FC observed in the lateral occipital cortex and superior frontal gyrus during resting-state MEG could serve as one of the imaging characteristics associated with NDPH.

Background Preliminary evidence suggests that several headache disorders may be associated with glymphatic dysfunction. However, no studies have been conducted to examine the glymphatic activity in migraine chronification. Purposes To investigate the glymphatic activity of migraine chronification in patients with episodic migraine (EM) and chronic migraine (CM) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Methods In this cross-sectional study, patients with EM, CM, and healthy controls (HCs) were included. All participants underwent a standard brain magnetic resonance imaging (MRI) examination. Bilateral DTI-ALPS indexes were calculated for all participants and compared among EM, CM, and HC groups. Correlations between the DTI-ALPS index and clinical characteristics were analyzed. Results A total of 32 patients with EM, 24 patients with CM, and 41 age- and sex-matched HCs were included in the analysis. Significant differences were found in the right DTI-ALPS index among the three groups ( p = 0.011), with CM showing significantly higher values than EM ( p = 0.033) and HCs ( p = 0.015). The right DTI-ALPS index of CM group was significantly higher than the left DTI-ALPS index ( p = 0.005). And the headache intensity was correlated to DTI-ALPS index both in the left hemisphere ( r = 0.371, p = 0.011) and in the right hemisphere ( r = 0.307, p = 0.038), but there were no correlations after Bonferroni correction. Conclusions Glymphatic system activity is shown to be increased instead of impaired during migraine chronification. The mechanism behind this observation suggests that increased glymphatic activity is more likely to be a concomitant phenomenon of altered vascular reactivity associated with migraine pathophysiology rather than a risk factor of migraine chronification.

BACKGROUND:Amygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). METHODS:Twenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. RESULTS:Compared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P < 0.05). There were no significant differences of CBF and aCBV values in the bilateral amygdala between the HC and EM groups, the EM and CM groups, as well as the CM without and with MOH groups (all P > 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI). CONCLUSION:Hyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.

Background New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. The pathogenesis of NDPH remains unclear, and there are few white matter imaging studies related to NDPH. The purpose of this study was to investigate the micro-structural abnormalities of white matter in NDPH and provided insights into the pathogenesis of this disease based on tract-based spatial statistics (TBSS). Methods Twenty-one patients with NDPH and 25 healthy controls (HCs) were included in this study. T1 structural and diffusion magnetic resonance imaging (MRI) were acquired from all participants. Differences in the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between patients with NDPH and HCs were investigated using TBSS analysis. Results Significantly decreased FA, increased MD and RD were found in patients with NDPH compared to HCs. White matter regions overlaid with decreased FA, increased MD and RD were found in 16 white matter tracts from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas and Johns Hopkins University White-Matter Tractography Atlas. Specifically, these white matter regions included the right anterior thalamic radiation (ATR), body of the corpus callosum (BCC), bilateral cingulum, left hippocampal cingulum (CGH), left corticospinal tract (CST), forceps major, fornix, left inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), left posterior limb of the internal capsule (PLIC), right retrolenticular part of the internal capsule (RPIC), splenium of the corpus callosum (SCC), right superior longitudinal fasciculus (SLF) and left uncinate fasciculus (UF). After Bonferroni correction, there were no correlations between the FA, MD, AD and RD values and the clinical characteristics of patients with NDPH ( p > 0.05/96). Conclusion The results of our research indicated that patients with NDPH might have widespread abnormalities in the white matter of the brain.

Abstract Background New daily persistent headache (NPDH) is a rare primary headache that is highly disabling. The pathophysiology of NDPH is still unclear, and we aimed to reveal the underlying mechanism of NDPH through functional magnetic resonance imaging (fMRI) analysis. Methods In this cross-sectional study, thirty patients with NDPH and 30 healthy controls (HCs) were recruited. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the GE 3.0 T system. We performed ReHo, ALFF (conventional band: 0.01–0.08 Hz, slow-5: 0.01–0.027 Hz, slow-4: 0.027–0.073 Hz) and seed-based to the whole brain functional connectivity (FC) analysis in the NDPH and HC groups. The sex difference analysis of ReHo, ALFF, and FC values was conducted in the NDPH group. We also conducted Pearson’s correlation analysis between ReHo, ALFF, FC values and clinical characteristics (pain intensity, disease duration, HIT-6, GAD-7, PHQ-9, and PSQI scores). Results Both increased ReHo (PFWE-corr = 0.012) and ALFF values (0.01–0.08 Hz, PFWE-corr = 0.009; 0.027–0.073 Hz, PFWE-corr =0.044) of the left middle occipital gyrus (MOG_L) were found in the NDPH group compared to the HC group. There was no significant difference in FC maps between the two groups. Compared to the HC group, no difference was found in ReHo (p = 0.284), ALFF (p = 0.246), and FC (p = 0.118) z scores of the MOG_L in the NDPH group. There was also no sex difference in ReHo (p = 0.288), ALFF (p = 0.859), or FC z score (p = 0.118) of the MOG_L in patients with NDPH. There was no correlation between ReHo, ALFF, FC z scores and clinical characteristics after Bonferroni correction (p < 0.05/18). Conclusions Patients with NDPH may have abnormal activation of the visual system. Abnormal visual activation may occur mainly in higher frequency band of the classical band. No sex differences in brain activity were found in patients with NDPH.

Abstract Objective To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

The pathogenesis of new daily persistent headache (NDPH) is not fully understood. We aim to map aberrant functional connectivity (FC) in patients with NDPH using resting-state functional magnetic resonance imaging (MRI).Brain structural and functional MRI data were acquired from 29 patients with NDPH and 37 well-matched healthy controls (HCs) in this cross-sectional study. Region of interest (ROI) based analysis was used to compare FC between patients and HCs, with 116 brain regions in the automated anatomical labeling (AAL) atlas were defined as seeds. The correlations between aberrant FC and patients' clinical characteristics, and neuropsychological evaluation were also investigated.Compared with HCs, patients with NDPH showed increased FC in the left inferior occipital gyrus, right thalamus and decreased FC in right lingual gyrus, left superior occipital gyrus, right middle occipital gyrus, left inferior occipital gyrus, right inferior occipital gyrus, right fusiform gyrus, left postcentral gyrus, right postcentral gyrus, right thalamus and right superior temporal gyrus. There were no correlation between FC of these brain regions and clinical characteristics, neuropsychological evaluation after Bonferroni correction (p > 0.05/266).Patients with NDPH showed aberrant FC in multiple brain regions involved in perception and regulation of emotion and pain.ClinicalTrials.gov Identifier: NCT05334927.

New daily persistent headache (NDPH) is a rare but debilitating primary headache disorder that poses a significant burden on individuals and society. Despite its clinical importance, the underlying pathophysiological mechanisms of NDPH remain unclear. In this study, we aimed to investigate the brain structural changes and neural activity patterns in patients with NDPH using multimodal brain imaging analysis of structural magnetic resonance imaging (sMRI) combined with magnetoencephalography (MEG). Twenty-eight patients with NDPH and 37 healthy controls (HCs) were recruited for this study, and their structural and resting-state data were collected by 3.0 Tesla MRI and MEG. We analyzed the brain morphology using voxel-based morphometry and source-based morphometry. In each brain region, MEG sensor signals from 1 to 200 Hz were analyzed using an adapted version of Welch's method. MEG source localization was conducted using the dynamic statistical parametric mapping, and the difference of source distribution between patients with NDPH and HCs was examined. Our results revealed significant differences in the regional grey matter volume, cortical thickness, and cortical surface area between the two groups. Specifically, compared with HCs, patients with NDPH showed a significant decrease in cortical thickness of the left rostral cortex in the middle frontal gyrus, decreased cortical surface area of the left fusiform gyrus, decreased grey matter volume of the left superior frontal gyrus and the left middle frontal gyrus, and increased grey matter volume of the left calcarine. Furthermore, the power of the whole brain, bilateral frontal lobes, and right temporal lobe in the NDPH group were higher than that in HCs in the ripple frequency band (80-200 Hz). Functional and structural analysis suggested that there were structural changes and abnormal high frequency cortical activity in both frontal and temporal lobes in patients with NDPH. Our findings indicated that patients with NDPH have abnormalities in brain morphology, such as cortical area, cortical thickness, and grey matter volume, accompanied by abnormal cortical neural activity. Brain structural changes in the frontotemporal cortex and abnormalities in cortical ripple activity may be involved in the pathogenesis of NDPH.