Changes in the hippocampal volume in chronic migraine, episodic migraine, and medication overuse headache patients.

Background and purpose:

Hippocampi are the structures located in the medial depths of both temporal lobes, mainly responsible for memory, navigation and regulation of emotions, and activated during the processing of pain and the modification of nociceptive stimuli. Chronic pain is thought to have stress-like detrimental modulatory effects on the hippocampal neurogenesis, and adults with chronic pain have been showed to have lower hippocampal volumes. The present study aims to show the relationship between headaches and hippocampal volume by comparing the right, left and total hippocampal volumes of patients with Episodic Migraine (EM), Chronic Migraine (CM) and Medication Overuse Headache (MOH) to those of the healthy control group using the Magnetic Resonance Imaging (MRI) technique, also by looking into the correlation between the number of painful days and attacks and the current hippocampal volumes.

A total of 30 patients (10 EM, 10 CM, 10 MOH) from 18 to 45 years of age diagnosed with migraine and also followed up by the neurology outpatient clinic from February to May 2022 and 30 healthy volunteers of similar ages and sexes to the patient group were included in the study. In addition to the routine cranial MRI protocols of all the participants, further cranial images were taken with the addition of the T1W 3D FSPGR sequence adjusted to the hippocampal body in the coronal plane and covering the whole brain. Hippocampal volumes were measured manually.

There were 27 females and 3 males in the patient group versus 28 females and 2 males in the control group, and no statistically significant differences in age and sex were found between the groups. The control group had higher average right, left and total hippocampal volumes than the whole patient group, but only the total hippocampal volume was significantly different between the groups. There was a negative correlation between the number of painful days and the measured right hippocampal and total hippocampal volumes; however, the measured values were not statistically significant. 

It was concluded that the changes in the hippocampal volume in migraine might be associated with the pain characteristics of the disorder. 

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study.

BACKGROUND: Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC). METHODS: RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. RESULTS: Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients. CONCLUSIONS: The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.

[Headache emergencies are easily overlooked]. / Kopfschmerzen als Notfall sind leicht übersehen.

This article presents secondary headache syndromes caused by life-threatening disease as well as symptomatic headaches requiring immediate treatment to prevent irreversible deficits. Clinical signs and symptoms indicating a secondary headache syndrome are summarized in the so-called SNOOP list (SNOOP: systemic symptoms, neurological symptoms, acute onset, older patients and previous history). The main topic of this publication is the diagnostic procedure, with a discussion of the pitfalls of computed tomography and magnetic resonance imaging investigations and the specificities of other methods such as lumbar puncture and duplex sonography.

Persistent post-traumatic headache: a migrainous loop or not? The clinical evidence.

BACKGROUND: Headache is a common complication of traumatic brain injury. The International Headache Society defines post-traumatic headache as a secondary headache attributed to trauma or injury to the head that develops within seven days following trauma. Acute post-traumatic headache resolves after 3 months, but persistent post-traumatic headache usually lasts much longer and accounts for 4% of all secondary headache disorders. MAIN BODY: The clinical features of post-traumatic headache after traumatic brain injury resemble various types of primary headaches and the most frequent are migraine-like or tension-type-like phenotypes. The neuroimaging studies that have compared persistent post-traumatic headache and migraine found different structural and functional brain changes, although migraine and post-traumatic headache may be clinically similar. Therapy of various clinical phenotypes of post-traumatic headache almost entirely mirrors the therapy of the corresponding primary headache and are currently based on expert opinion rather than scientific evidence. Pharmacologic therapies include both abortive and prophylactic agents with prophylaxis targeting comorbidities, especially impaired sleep and post-traumatic disorder. There are also effective options for non-pharmacologic therapy of post-traumatic headache, including cognitive-behavioral approaches, onabotulinum toxin injections, life-style considerations, etc. CONCLUSION: Notwithstanding some phenotypic similarities, persistent post-traumatic headache after traumatic brain injury, is considered a separate phenomenon from migraine but available data is inconclusive. High-quality studies are further required to investigate the pathophysiological mechanisms of this secondary headache, in order to identify new targets for treatment and to prevent disability.

Increased cerebral responses to salient transitions between alternating stimuli in chronic migraine with medication overuse headache and during migraine attacks.

INTRODUCTION: In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on the foot activated the "salience matrix". Knowing that central sensory processing is abnormal in migraine, we searched in the present study for possible abnormalities of these salient transitional responses in different forms of migraine and at different time points of the migraine cycle. METHODS: Participants of both sexes, mostly females, took part in a conditioned pain modulation experiment: Migraineurs between (n = 14) and during attacks (n = 5), chronic migraine patients with medication overuse headache (n = 7) and healthy volunteers (n = 24). To evoke the salience response, continuous noxious cold or innocuous warm stimulations were alternatively applied on the right foot. Cerebral blood oxygenation level dependent responses were recorded with fMRI. RESULTS: Switching between the two stimulations caused a significant transition response in the "salience matrix" in all subject groups (effect of the condition). Moreover, some group effects appeared on subsequent post-hoc analyses. Augmented transitional blood oxygenation level dependent responses in the motor cortex and superior temporal sulcus were found in two patient groups compared to healthy controls: chronic migraine with medication overuse headache patients and migraineurs recorded during an attack. In chronic migraine with medication overuse headache patients, salience-related responses were moreover greater in the premotor cortex, supplementary motor area, lingual gyrus and dorso-medial prefrontal cortex and other "salience matrix" areas, such as the anterior cingulate and primary somatosensory cortices. CONCLUSION: This study shows salience-related hyperactivation of affective and motor control areas in chronic migraine with medication overuse headache patients and, to a lesser extent, in episodic migraine patients during an attack. The greater extension of exaggerated blood oxygenation level dependent responses to unspecific salient stimuli in chronic migraine with medication overuse headache than during a migraine attack could be relevant for headache chronification.

Lower hippocampal subfields volume in relation to anxiety in medication-overuse headache.

Background Hippocampus (HIP) was an important limbic structure, and concurrent emotion disorders may occur in medication-overuse headache patients. The aim of this study is to investigate altered HIP and HIP subfields volume in relation with the anxiety in medication-overuse headache patients using a state-of-the-art hippocampal segment method. Results The current study presented that a significant lower HIP and HIP subfields volume were identified in medication-overuse headache compared with that in normal controls except right HIP tail, bilateral parasubiculums, and HIP fissure. The left HIP and right subiculum presented negative correlation with headache variables, and the right subiculum, Cornu Ammonis 4, granule cell layer of dentate gyrus, bilateral Cornu Ammonis 1, molecular layer, and whole HIP presented negative correlation with Hamilton Anxiety Scale score, which were further confirmed by the linear regression analysis with the exclusion of psychological variables and headache variables, respectively. Conclusions The lower HIP and HIP subfields volume were identified in medication-overuse headache patients, and negatively related with anxiety condition. The potential mechanism for the comorbidity medication-overuse headache and anxiety might be interpreted as the reciprocal causation relationship and co-occurrence relationship.

Modulation of salience network intranetwork resting state functional connectivity in women with chronic migraine.

Objective To investigate the intranetwork resting state fMRI connectivity within the Salience Network of chronic migraine with and without medication overuse headache. Methods We compared 351 pairs of intranetwork connectivity in chronic migraine (n = 13) and chronic migraine with medication overuse headache (n = 16) compared to matched controls, and between each chronic migraine subgroup. Results Compared to controls, 17 pairs of intranetwork connections in chronic migraine and 27 pairs in chronic migraine with medication overuse headache were decreased. When comparing chronic migraine with medication overuse headache versus chronic migraine, connectivity between bilateral extended amygdala, and between paracingulate to right ventral tegmental area/substantia nigra were decreased in chronic migraine (chronic migraine < chronic migraine with medication overuse headache). Connectivity between left dorsolateral prefrontal cortex to bilateral ventral striatum/pallidum, to bilateral dorsal anterior cingulate cortex; left anterior prefrontal cortex to contralateral orbitofrontal insula; and left ventral striatum/pallidum to ipsilateral supplementary motor area (SMA)/preSMA were decreased in chronic migraine with medication overuse headache (chronic migraine with medication overuse headache < chronic migraine). Conclusion Both chronic migraine subgroups had shared intranetwork connectivity abnormality, however, each subgroup had unique pattern of disruption within the salience network. The results suggest that the aberrant assignment of salience to external and internal stimuli plays an important role in chronic migraine and chronic migraine with medication overuse headache interictally, mostly involving mesolimbic pathways (especially bilateral extended amygdala) in chronic migraine, and prefrontal-subcortical limbic pathways in chronic migraine with medication overuse headache.

Resting State Functional Connectivity After Sphenopalatine Ganglion Blocks in Chronic Migraine With Medication Overuse Headache: A Pilot Longitudinal fMRI Study.

OBJECTIVE: In this pilot study, the purpose is to investigate if a series of sphenopalatine ganglion (SPG) blockade treatments modulate the functional connectivity within the salience and central executive network (CEN) in chronic migraine with medication overuse headaches (CMw/MOH ). BACKGROUND: Using intranasal local anesthesia to block the SPG for the treatment of various headache disorders has been employed in clinical practice since the early 1900s. However, the exact mechanism of how SPG modulate resting state intrinsic functional brain networks connectivity remains to be elucidated. This pilot study seeks to understand the resting state connectivity changes in salience and CENs, with emphasis on the mesocorticolimbic systems, before and after a series of SPG block treatments. METHODS: Using fMRI, resting state connectivity was derived from predefined networks of nodes (regions of interests) for the salience (27 nodes, 351 connections) and CENs (17 nodes, 136 connections). After treatments, a paired samples t-test (with 10,000 permutations to correct for multiple comparison) was used to evaluate changes in the intranetwork resting state functional connectivity within the salience and executive networks, as well as the overall network connectivity strength. RESULTS: When comparing connectivity strength at baseline to that at the end of treatment in our cohort of 10 CMw/MOH participants, there were several connections within the salience (n = 9) and executive (n = 8) networks that were significantly improved. Within the salience network, improved connectivity was observed between the prefrontal cortex and various regions of the insula, basal ganglia, motor, and frontal cortex. Additionally, changes in connectivity were observed between regions of the temporal cortex with the basal ganglia and supramarginal gyrus. Within the CEN, improved connectivity was observed between the prefrontal cortex and regions of the anterior thalamus, caudate, and frontal cortex. After treatment, the overall CEN connectivity was significantly improved (Baseline 0.00 ± 0.08; 6 weeks 0.03 ± 0.09, P = .01); however, the overall salience network connectivity was not significantly improved (Baseline -0.01 ± 0.10; 6 weeks 0.01 ± 0.12, P = .26). Additionally, after treatment, there was a significant reduction in the number of moderate/severe headache days per month (Baseline 21.1 ± 6.6; 6 weeks 11.2 ± 6.5, P < .001), HIT-6 (Baseline 66.1 ± 2.6; 6 weeks 60.2 ± 3.6, P < .001), and PHQ-9 (Baseline 12.4 ± 5.7; 6 weeks 6.1 ± 3.6, P = .008) scores. CONCLUSION: In this longitudinal fMRI study, we observed improved functional connectivity within both networks, primarily involving connectivity between regions of the prefrontal cortex and limbic (cortical-limbic) structures, and between different cortical (cortical-cortical) regions after a series of repetitive SPG blockades. The overall CEN strength was also improved. Our results suggest that recurrent parasympathetic inhibition via SPG is associated with improved functional connectivity in brain regions critical to pain processing in CMw/MOH .

Secondary Headaches in Children and Adolescents: What Not to Miss.

INTRODUCTION: Headaches are a common occurrence in childhood and adolescence. Most children presenting with a chief complaint of headache have a self-limited infectious disorder or primary headache syndrome that should not require extensive workup. PURPOSE OF REVIEW: Differentiating these conditions from other more serious causes of headache in children can sometimes be difficult. This article aims to provide information regarding "red flags" that should indicate a need for concern for disorders that require more urgent evaluation. RECENT FINDINGS: Long-held beliefs about specific "red flags" that have been analyzed in recent years as to their validity and new criteria for the diagnosis of idiopathic intracranial hypertension have been elaborated based on study. These publications are reviewed in this article. Knowledge of past and current literature on secondary headache in children, combined with thorough history taking and examination, should help determine when there is concern for a serious secondary cause for headache in children and adolescents and direct workup.

Neuroimaging Findings in Patients with Medication Overuse Headache.

Medication overuse headache (MOH) is a secondary headache syndrome defined as the deterioration of the headache associated with the overuse of analgesics. The prevalence of MOH is 1-2% in the general population and even up to 50% in special clinics. Overuse of abortive medications is highly associated with chronic daily headaches and also a known risk factor for headache evolution. Possible mechanisms include neural plasticity changes such as sensitization and defective endogenous pain inhibition. Psychological studies have suggested dependence, even addiction, in patients with MOH. Neuroimaging studies have provided valuable information concerning MOH pathophysiology. Magnetic resonance imaging analyzed by voxel-based morphometry showed gray matter volume changes in brain areas participating the pain modulations. Changes of brain function at similar areas have been revealed by positron emission tomography and functional magnetic resonance imaging studies. Many of these changes were correlated with either headache and/or analgesics parameters such as frequency and duration. These changes are typically reversible after successful treatment. Though the cause or consequence debate remains unsettled, we are more in favor of these findings as maladaptive changes to the frequent headaches or medication overuse. Of these brain areas involved in MOH, orbitofrontal cortex is of interest in several ways. In an early positron emission tomography study, the hypometabolism persists after successful treatment which implied a causal role. The following morphological studies showed the orbitofrontal cortex volume could predict treatment responses. Functional magnetic resonance imaging studies, task positive and also resting-state ones, also reported changes within the mesocorticolimbic dopamine system, also known as reward system. Important brain areas of this system include ventral tegmental area, striatum, and orbitofrontal cortex. The system plays an important role in decision-making, dependence, and addiction, as implicated in psychological studies of MOH. Further studies on neuromodulation of this system may be considered in the treatment of MOH.

[Altered Brainstem Volume in Medication-overuse Headache: A Pilot Magnetic Resonance Imaging Evaluation].

Objective To investigate the altered brainstem volume in patients with medication-overuse headache(MOH). Methods The high-resolution structural images were obtained from 36 MOH patients and 32 normal controls(NC).The brainstem was segmented into midbrain,pons,and medulla,whose volume were measured respectively.Results There was a significantly smaller midbrain volume in MOH patients [(5.80±0.53) ml] than that in NC [(6.14±0.67)ml](t=2.36,P=0.02).The volumes of pons,medulla,and whole brainstem showed no significant difference in MOH patients [(13.13±1.42)ml,(4.55±0.51)ml,and(23.48±2.23)ml,respectively] compared with those in NC [(13.67±1.61) ml,(4.66±0.44) ml,and(24.47±2.56) ml,respectively](tpons=1.47,Ppons=0.15;tmedulla=0.93,Pmedulla=0.35;and tbrainstem=1.71,Pbrainstem=0.09,respectively).Conclusion A smaller midbrain volume may be one of the specific features of pain pathway in MOH,and the automated brainstem subfield segmentation and volumetry may be useful tools for evaluating brainstem alternation in MOH patients.

Brain structural investigation and hippocampal tractography in medication overuse headache: a native space analysis.

BACKGROUND: Spatial normalization of brain images, a prerequisite for voxel based morphometry analysis, may account for the large variability of the volumetric data in medication overuse headache (MOH); possibly because this disease concerns patients differing on both sex and age, and hence with different brain size and shape. METHODS: The present study aimed at providing a subject-based analysis of macrostructure using a native space volumes segmentation (Freesurfer), and microstructure using a region of interest (ROI: i.e. hippocampus) tractography approach in MOH patients. RESULTS: The results show that MOH patients had decreased volumes of left hemisphere temporal gyri (temporal superior, fusiform) and occipital middle gyrus, together with an increased volume of the left inferior (temporal) lateral ventricle. The left temporal volume was negatively correlated with depression score and medication dependence parameters. Seed-based tractography of the hippocampus revealed a decreased number of reconstructed fibers passing through the left hippocampus. CONCLUSION: To our knowledge, these alterations have not been described with methods involving brain normalization, and they indicate that left hemisphere temporal areas, including the hippocampus, may play a role in MOH pathophysiology. Trial registration number NCT00833209. Registered 29 January 2009.

Pain modulation is affected differently in medication-overuse headache and chronic myofascial pain - A multimodal MRI study.

Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.

Cortical Alterations in Medication-Overuse Headache.

OBJECTIVE: Using surface-based morphometry we aimed to provide a detailed examination of cortical alterations in medication-overuse headache (MOH), by disentangling between altered cortical thickness and gyrification (folding). BACKGROUND: In MOH, pain modulation is probably dysfunctional at the cortical and subcortical level, resulting in a disequilibrium between pain inhibition and facilitation. Both increased and decreased cortical volumes have been reported in individuals with MOH. There is however no detailed examination to date that distinguishes between altered cortical thickness and gyrification. Such distinction would help to identify the nature and timing of neurodevelopmental mechanisms at play in affected individuals. METHODS: We investigated cortical thickness and gyrification in 29 patients with MOH according to International Headache Society criteria and 29 age- and gender-matched controls, using high-resolution structural MRIs of the brain analyzed with FreeSurfer. This is a secondary analysis of data from a previously published voxel-based morphometry study. RESULTS: In patients with MOH compared to controls, reduced cortical thickness was observed in the left prefrontal cortex. We also observed higher local gyrification in one cluster extending from the fusiform cortex to adjacent medial temporal regions, and in another cluster in the right occipital pole. Higher gyrification in the right occipital pole predicted poor response after detoxification. CONCLUSIONS: Corroborating previous volumetric results, our study adds information on the putative neurobiological mechanisms involved in MOH, suggesting neurodevelopmental changes in MOH.

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

BACKGROUND: Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). METHODS: This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. RESULTS AND CONCLUSIONS: MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH.

Texture features of periaqueductal gray in the patients with medication-overuse headache.

BACKGROUND: Periaqueductal gray (PAG) is the descending pain modulatory center, and PAG dysfunction had been recognized in migraine. Here we propose to investigate altered PAG texture features (quantitative approach for extracting texture descriptors for images) in the patients with medication-overuse headache (MOH) based on high resolution brain structural image to understand the MOH pathogenesis. METHODS: The brain structural images were obtained from 32 normal controls (NC) and 44 MOH patients on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template, and the individual PAG segment was performed by applying the deformation field to the PAG template after structural image segment. Grey-level co-occurrence matrix (GLCM) was performed to measure the texture parameters including angular second moment (ASM), Contrast, Correlation, inverse difference moment (IDM) and Entropy. RESULTS: Contrast was increased in MOH patients (9.28 ± 3.11) compared with that in NC (7.94 ± 0.65) (P < 0.05), and other texture features showed no significant difference between MOH and NC (P > 0.05). The area under the ROC curve was 0.697 for Contrast in the distinction of MOH from NC, and the cut-off value of Contrast was 8.11 with sensitivity 70.5% and specificity 62.5%. The contrast was negatively with the sleep scores (r = -0.434, P = 0.003). CONCLUSION: Texture Contrast could be used to identify the altered MR imaging characteristics in MOH in understanding the MOH pathogenesis, and it could also be considered as imaging biomarker in for MOH diagnosis.

Volume gain of periaqueductal gray in medication-overuse headache.

BACKGROUND: Periaqueductal gray (PAG) is a substantial descending pain modulatory center, and previous voxel-based morphometry study confirmed the clusters with increased volume in PAG region in medication-overuse headache (MOH). The aim of this study is to investigate altered PAG volume in MOH using an automated PAG segment method to measure the true PAG volume. METHODS: High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 22 patients with MOH and 22 normal controls (NC). PAG template was created based on ICBM 152 gray template, and the individual PAG was generated by applying the deformation field from structural image segment to the PAG template, and individual PAG volume was calculated. RESULTS: There was a significant increased volume of PAG in MOH (0.366 ± 0.005 ml) than that in NC (0.341 ± 0.005 ml)(P < 0.05). There was no significant correlation between the PAG volume and the clinical variables in MOH patients (P > 0.05). The area of receiver operating characteristic (ROC) curve was 0.845, and the cut-off of PAG volume was 0.341 ml with sensitivity 95.5% and specificity 63.6%. CONCLUSION: The present study demonstrated that the PAG volume gain was confirmed in MOH patients, and the automated individual PAG volume measure may be considered as a simple and effective imaging biomarker in MOH diagnosis.

Volumetric abnormalities of thalamic subnuclei in medication-overuse headache.

BACKGROUND: The thalamus exerts a pivotal role in pain processing and cortical excitability control and a previous voxel-based morphometry study confirmed increased volume in bilateral thalamus in medication-overuse headache (MOH). The aim of this study is to investigate altered thalamic subnuclei volume in MOH compared with normal controls, and to evaluate the relationship of each thalamic subnuclei volume with the clinical variables. METHODS: High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 27 patients with MOH and 27 normal controls (NC). Thalamic subnuclei templates were created based on Talairach template with MNI space transformation, and the individual thalamic subnuclei templates were generated by applying the deformation field from structural image segment to the thalamic subnuclei templates, and then individual thalamci subnuclei volume were calculated. RESULTS: The whole thalamus and each thalamic subnuclei presented increased volume compared with NC (P < 0.05). The correlation analysis demonstrated that the whole thalamus volume and each thalamic subnuclei volume showed a negative relationship with HAMD scores(P < 0.05), and no any correlation with HAMA, VAS score and disease duration (P > 0.05). CONCLUSION: Increased gray matter volume in the whole thalamus and all the thalamus subnuclei may reflect central sensitization and higher-order of pain alteration in MOH. These structural changes in the thalamus may also be influenced by mood disturbances related to the MOH.

Alteration of gray matter texture features over the whole brain in medication-overuse headache using a 3-dimentional texture analysis.

BACKGROUND: Imaging studies have provided valuable information in understanding the headache neuromechanism for medication-overuse headache (MOH), and the aim of this study is to investigate altered texture features of MR structural images over the whole brain in MOH using a 3-dimentional texture analysis. METHODS: Brain three-dimensional T1-weighted structural images were obtained from 44 MOH patients and 32 normal controls (NC). The imaging processing included two steps: gray matter (gray images) segment and a 3-dimensional texture features mapping. Voxel-based gray-level co-occurrence matrix (VGLCM) was performed to measure the texture parameters mapping including Contrast, Correlation, Energy, Entropy and inverse difference moment (IDM). RESULTS: The texture parameters of increased Contrast and Entropy, decreased Energy and IDM were identified in cerebellar vermis of MOH patients compared to NCs. Increased Contrast and decreased Energy were found in left cerebellum. Increased Correlation located in left dorsolateral periaqueductal gray (L-dlPAG), right parahippocampal gyrus (R-PHG), and left middle frontal gyrus (L-MFG) and decreased Correlation located in right superior parietal lobule(R-SPL). Disease duration was positively correlated with Contrast of vermis and negatively correlated with Correlation of R-SPL.HAMD score was negatively correlated with Correlation of R-PHG. MoCA score was positively correlated with Correlation of R-SPL. CONCLUSION: The altered textures in gray matter related to pain discrimination and modulation, affective and cognitive processing were helpful in understanding the pathogenesis of MOH. Texture analysis using VGLCM is a sensitive and efficient method to detect subtle gray matter changes in MOH.

Altered functional connectivity architecture of the brain in medication overuse headache using resting state fMRI.

BACKGROUND: Functional connectivity density (FCD) could identify the abnormal intrinsic and spontaneous activity over the whole brain, and a seed-based resting-state functional connectivity (RSFC) could further reveal the altered functional network with the identified brain regions. This may be an effective assessment strategy for headache research. This study is to investigate the RSFC architecture changes of the brain in the patients with medication overuse headache (MOH) using FCD and RSFC methods. METHODS: 3D structure images and resting-state functional MRI data were obtained from 37 MOH patients, 18 episodic migraine (EM) patients and 32 normal controls (NCs). FCD was calculated to detect the brain regions with abnormal functional activity over the whole brain, and the seed-based RSFC was performed to explore the functional network changes in MOH and EM. RESULTS: The decreased FCD located in right parahippocampal gyrus, and the increased FCD located in left inferior parietal gyrus and right supramarginal gyrus in MOH compared with NC, and in right caudate and left insula in MOH compared with EM. RSFC revealed that decreased functional connectivity of the brain regions with decreased FCD anchored in the right dorsal-lateral prefrontal cortex, right frontopolar cortex in MOH, and in left temporopolar cortex and bilateral visual cortices in EM compared with NC, and in frontal-temporal-parietal pattern in MOH compared with EM. CONCLUSIONS: These results provided evidence that MOH and EM suffered from altered intrinsic functional connectivity architecture, and the current study presented a new perspective for understanding the neuromechanism of MOH and EM pathogenesis.