Headache in juvenile myoclonic epilepsy

The objective of this study was to assess the prevalence of and risk factors for primary headaches in juvenile myoclonic epilepsy (JME). Headache was classified in 75 patients with JME using a questionnaire, and its prevalence was correlated with the literature on the general population and clinical data. Headache was present in 47 patients. Thirty-one had migraine [20 migraine without aura (MO), 11 migraine with aura (MA)]. Fourteen patients with migraine had tension-type headache (TTH) in addition. Sixteen had only TTH. Comparison with the general population revealed a significantly higher prevalence of migraine (RR 4.4), MO (3.6), MA (7.3) and TTH (3.4) in JME. Risk factors for migraine and MO were female gender and for MA family history of migraine in first-degree relatives. Migraine and MA were associated with fairly controlled generalized tonic clonic seizures, MO with absences. Together with its strong genetic background, JME appears to be an attractive homogenous subtype of epilepsy for genetic research on migraine.     

Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.     

Regional grey matter changes in patients with migraine: a voxel-based morphometry study

We used voxel-based morphometry (VBM) to compare grey matter volume (GMV) between 20 migraine patients (five with aura and 15 without aura) with normal conventional magnetic resonance imaging findings and 33 healthy controls matched for age and sex. A separate analysis was also performed to delineate a possible correlation between the GMV changes and the headache duration or lifetime headache frequency. When compared with controls, migraine patients had significant GMV reductions in the bilateral insula, motor/premotor, prefrontal, cingulate cortex, right posterior parietal cortex, and orbitofrontal cortex ( P  < 0.001, uncorrected for multiple comparisons at a voxel level; corrected P  < 0.05 after small volume corrections). All regions of the GMV changes were negatively correlated with headache duration and lifetime headache frequency ( P  < 0.05, Pearson's correlation test). We found evidence for structural grey matter changes in patients with migraine. Our findings of progressive GMV reductions in relation to increasing headache duration and increasing headache frequency suggest that repeated migraine attacks over time result in selective damage to several brain regions involved in central pain processing.     

Pain sensitisers exhibit grey matter changes after repetitive pain exposure: A longitudinal voxel-based morphometry study

Previous research in health and disease has shown that exposure to pain changes the density of cortical grey matter (GM). Such structural changes of the brain might, however, depend crucially on how this pain experience is evaluated and processed in the brain. In the present study we aimed to detect pain-rating patterns and underlying GM changes after the application of repetitive painful stimulation using voxel-based morphometry (VBM). Healthy volunteers were investigated (n = 27), receiving 8 noxious and 8 innocuous thermal stimuli on the right forearm for 11 consecutive working days. Data were compared with a control group without any intervention (n = 18). Behavioural data demonstrated that a subgroup of volunteers (n = 14) sensitised, whereas the others (n = 13) habituated over the stimulation days. The VBM analysis revealed no increase but a significant reduction of GM density, eg, in the anterior cingulate cortex, the insular cortex and the frontal cortex, exclusively in the group of sensitisers. By contrast, pain habituaters did not show any density changes in the GM.     

Regional gray and white matter volume associated with Stroop interference: evidence from voxel-based morphometry

During Stroop tasks, subjects experience cognitive interference when they resolve interferences such as identifying the ink color of a printed word while ignoring the word's identity. Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating the functions of the frontal lobes and other associated structures. Despite these uses and the vast amount of attention given to Stroop paradigms, the regional gray matter volume/regional white matter volume (rGMV/rWMV) correlates of Stroop interference have not yet been identified at the whole brain level in normal adults. We examined this issue using voxel-based morphometry in right-handed healthy young adults. We found significant negative relationships between the Stroop interference rate and rGMV in the anterior cingulate cortex (ACC), right inferior frontal gyrus, and cerebellum. Furthermore, we found relationships between the Stroop interference rate and rWMV in bilateral anatomical clusters that extended around extensive WM regions in the dorsal part of the frontal lobe. These findings are the first to reveal rGMV/rWMV that underlie the performance of the Stroop task, a widely used psychological paradigm at the whole brain level. Of note, our findings support the notion that ACC contributes to Stroop performance and show the involvement of regions that have been implicated in response inhibition and attention.     

Grey matter volume alterations in CADASIL: a voxel-based morphometry study

CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized.     

Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks

The purpose of this study is to determine regions of cerebral cortex activated during the onset and propagation of dense array electroencephalographic (dEEG) epileptiform discharges in patients with juvenile myoclonic epilepsy (JME), through the use of 256 channel, dense array scalp EEG recordings. Ten patients (16–58 years old) with the clinical diagnosis of JME comprised the study group. In all cases the MRI and neurological exams were normal, while standard EEG recordings documented typical “generalized” 4–6 Hz epileptiform patterns. Outpatient dEEG recordings captured epileptiform discharges in each patient. Localization of onset and spread of discharges in relation to a standard MRI model was accomplished by applying dipole fits and a distributed linear inverse method of cortically constrained source analysis. All patients showed epileptiform discharges that localized to sources that included orbitofrontal/medial frontopolar cortex, while basal–medial temporal lobe sources were observed in 5/10 subjects. In many ways similar to discharges of typical absence, epileptiform patterns in JME are usually irregular and frequently include temporal lobe structures as the dominant contributors to the discharges. We find that epileptiform discharges in patients with JME are not “generalized” in the sense of bilaterally synchronous diffuse onset. Rather, discharges have both localized onsets and a restricted cortical network during propagation that includes regions of frontal and temporal cortex.     

基于体素的形态学测量原发性三叉神经痛患者脑灰质体积

目的 应用基于体素形态学测量(VBM)技术观察原发性三叉神经痛(ITN)患者脑内灰质体积(GMV)变化。方法 将43例ITN患者(ITN组)分为左侧ITN组(LITN组,21例)及右侧ITN组(RITN组,22例)。另选25名健康志愿者作为对照组。对3组均行MR检查,采集VBM数据,测量GMV,并进行统计学分析。结果 LITN组与对照组比较,双侧小脑半球、右侧丘脑GMV增加,左后扣带回、左楔前叶GMV减少(P均<0.001)。RITN组与对照组比较,双侧小脑半球、左海马旁回、左岛叶、右楔叶、中脑导水管周围灰质GMV增加,左颞中回、左中央后回、右颞下回GMV减少(P均<0.001)。RITN组与LITN组比较,左侧小脑半球、双侧岛叶、右中央后回、左扣带回GMV增加,右颞下回、右侧丘脑GMV减少(P均<0.001)。结论 ITN患者脑内GMV发生改变,VBM技术有助于客观反映ITN患者脑内GMV变化。     

帕金森病轻度认知功能障碍:基于体素的全脑灰质形态学研究

目的采用基于体素的形态学测量方法,分析帕金森病(PD)伴轻度认知功能损害(MCI)患者全脑灰质结构的变化。方法利用3.0T MR仪对22例伴MCI的PD患者(PD伴MCI组)、21例认知功能正常的PD患者(单纯PD组)及20名健康对照(NC组)进行T1W扫描。采用SPM8为基础的VBM8工具箱进行数据处理。结果与NC组比较,PD伴MCI组脑灰质萎缩见于双侧额叶、左侧颞叶、双侧枕叶、双侧小脑、左侧后扣带回及左侧海马区域;单纯PD组脑灰质萎缩集中出现于左侧额叶、颞叶。与单纯PD组相比,PD伴MCI组左侧颞中回和海马旁回出现灰质萎缩。结论伴有MCI的PD患者的脑灰质结构改变范围比不伴MCI者更广,提示PD患者认知功能改变存在脑形态结构水平的异常。     

基于体素变化的阿尔茨海默病临床前期灰质形态学特点

目的 利用磁共振T1WI分组分析阿尔茨海默病(AD)的早期灰质密度的改变。方法 采用开放式系列图像研究数据库中的146例样本组成样本数据集。经跟踪,其中13例在随访过程中由AD临床前期转化为极轻度痴呆,组成"转化"(CS)组;69例始终未出现痴呆症状,组成"未痴呆"(NS)组;另以64例AD患者样本组成"痴呆"(DS)组作为对照研究。应用基于体素的形态测量学(VBM)技术观察灰质密度特征,并采用双样本t检验进行统计学分析。结果 相较于NS 组,CS组在双侧颞上回、右侧颞极、外侧枕叶、顶叶及顶下小叶、额叶皮质和前扣带回以及双侧尾状核、角回及边缘叶出现灰质密度降低(P<0.05)。结论 在临床前期,AD患者大脑灰质即发生变化,使用VBM方法可早于其临床症状出现前数年检出这些变化;中央前回、额下回、顶叶、顶下小叶和角形脑回病变可能是预测AD的关键。     

早期盲人大脑灰质不对称的基于体素脑形态学初步研究

目的初步探讨视觉剥夺对人脑灰质结构不对称的影响。方法早期失明的成年盲人组（14例，右利手）与正常对照组（16例，右利手，年龄、性别匹配）在1．5T磁共振成像系统下获取全脑高分辨率的脑结构像（T1W）。通过基于体素的脑形态学（VBM）方法比较两组间脑灰质不对称的异同。结果与正常对照相比，早期盲人的一些脑区呈灰质左侧化增高，包括额叶（BA 10／8）、体感区（BA 3）及颞极（BA 43），以及枕叶视皮层（中枕回，BA 18／19）灰质右侧化增高。结论早期盲人大脑多个系统发生了结构重组，可以表现为灰质不对称的变化。     

Visceral sensitivity correlates with decreased regional gray matter volume in healthy volunteers: A voxel-based morphometry study

Regional changes in brain structure have been reported in patients with altered visceral sensitivity and chronic abdominal pain, such as in irritable bowel syndrome. It remains unknown whether structural brain changes are associated with visceral sensitivity. Therefore, we present the first study in healthy individuals to address whether interindividual variations in gray matter volume (GMV) in pain-relevant regions correlate with visceral sensitivity. In 92 healthy young adults (52 female), we assessed rectal sensory and pain thresholds and performed voxel-based morphometry (VBM) to compute linear regression models with visceral sensory and pain thresholds, respectively, as independent variable and GMV in a priori-defined regions of interest (ROIs) as dependent variable. All results were familywise error (FWE) corrected at a level of P_FWE < .05 and covaried for age. The mean (±SEM) rectal thresholds were 14.78 ± 0.46 mm Hg for first sensation and 33.97 ± 1.13 mm Hg for pain, without evidence of sex differences. Lower rectal sensory threshold (ie, increased sensitivity) correlated significantly with reduced GMV in the thalamus, insula, posterior cingulate cortex, ventrolateral and orbitofrontal prefrontal cortices, amygdala, and basal ganglia (all P_FWE < .05). Lower rectal pain threshold was associated with reduced GMV in the right thalamus (P_FWE = .051). These are the first data supporting that increased visceral sensitivity correlates with decreased gray matter volume in pain-relevant brain regions. These findings support that alterations in brain morphology not only occur in clinical pain conditions but also occur according to normal interindividual variations in visceral sensitivity.     

Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder

Previous neuromorphometric investigations of major depressive disorder (MDD) have reported abnormalities in gray matter in several regions, although the results have been inconsistent across studies. Some discrepancies in the results across studies may reflect design limitations such as small sample sizes, whereas others may reflect biological variability that potentially manifests as differences in clinical course. For example, it remains unclear whether the abnormalities found in persistently depressed MDD subjects extend to or persist in patients who experience prolonged remission. The aim of the present study was to investigate gray matter (GM) differences in unmedicated, currently-depressed participants (dMDD) and unmedicated, currently-remitted (rMDD) participants with MDD compared to healthy controls (HC). The GM density and volume were compared across groups using voxel-based morphometry, a quantitative neuroanatomical technique, and high-resolution MRI images from 107 HC, 58 dMDD and 27 rMDD subjects. Relative to the HC group the dMDD group had reduced GM in the dorsal anterolateral (DALPFC), the dorsomedial (DMPFC) and the ventrolateral prefrontal cortex (VLPFC). Relative to the rMDD group the dMDD group showed reduced GM in the DALPFC, the VLPFC, the anterior cingulate cortex (ACC), the precuneus and the inferior parietal lobule. No regions were identified in which the rMDD group showed significantly lower GM compared to the HC group after p-values were corrected for the number of comparisons performed. In unmedicated patients in the depressed phase of MDD, we found evidence of morphometric abnormalities in DALPFC and in medial prefrontal cortical regions belonging to the visceromotor network. These findings, along with the absence of GM abnormalities in the remitted sample imply a possible link between greater GM tissue and better clinical outcome. Consistent with other neuroimaging and post-mortem neuropathological studies of MDD, we also found evidence of decreased white matter in patients with dMDD and rMDD.     

Tracking tDCS induced grey matter changes in episodic migraine: a randomized controlled trial

BackgroundOccipital transcranial direct current stimulation (tDCS) is an effective and safe treatment for migraine attack prevention. Structural brain alterations have been found in migraineurs in regions related to pain modulation and perception, including occipital areas. However, whether these structural alterations can be dynamically modulated through tDCS treatment is understudied.ObjectiveTo track longitudinally grey matter volume changes in occipital areas in episodic migraineurs during and up to five months after occipital tDCS treatment in a single-blind, and sham-controlled study.Methods24 episodic migraineurs were randomized to either receive verum or sham occipital tDCS treatment for 28 days. To investigate dynamic grey matter volume changes patients underwent structural MRI at baseline (prior to treatment), 1.5 months and 5.5 months (after completion of treatment). 31 healthy controls were scanned with the same MRI protocol. Morphometry measures assessed rate of changes over time and between groups by means of tensor-based morphometry.ResultsBefore treatment, migraineurs reported 5.6 monthly migraine days on average. A cross-sectional analysis revealed grey matter volume increases in the left lingual gyrus in migraineurs compared to controls. Four weeks of tDCS application led to a reduction of 1.9 migraine days/month and was paralleled by grey matter volume decreases in the left lingual gyrus in the treatment group; its extent overlapping with that seen at baseline.ConclusionThis study shows that migraineurs have increased grey matter volume in the lingual gyrus, which can be modified by tDCS. Tracking structural plasticity in migraineurs provides a potential neuroimaging biomarker for treatment monitoring.Trial registrationClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03237754","term_id":"NCT03237754"}}NCT03237754. Registered 03 August 2017 – retrospectively registered, https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03237754","term_id":"NCT03237754"}}NCT03237754.     

Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans

Neural regions modulating prepulse inhibition (PPI) of the startle response, an operational measure of sensorimotor gating, are well established from animal studies using surgical and pharmacological procedures. The limbic and cortico-pallido-striato-thalamic circuitry is thought to be responsible for modulation of PPI in the rat. The involvement of this circuitry in human PPI is suggested by observations of deficient PPI in a number of neuropsychiatric disorders characterized by abnormalities at some level in this circuitry and recent functional neuroimaging studies in humans. The current study sought to investigate structural neural correlates of PPI in a sample of twenty-four right-handed, healthy subjects (10 men, 14 women). Subjects underwent magnetic resonance imaging (MRI) at 1.5 T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimized volumetric voxel-based morphometry (VBM) implemented in SPM99 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120 ms) to regional grey matter volumes, covarying for sex. Significant positive correlations were obtained between PPI and grey matter volume in the hippocampus extending to parahippocampal gyrus, basal ganglia including parts of putamen, globus pallidus, and nucleus accumbens, superior temporal gyrus, thalamus, and inferior frontal gyrus. These findings identify the relationship between PPI and grey matter availability on a highly spatially localized scale in brain regions shown to be activated in recent functional neuroimaging studies in association with PPI in healthy humans and demonstrate the validity of structural neuroimaging methods in delineating the neural mechanisms underlying human PPI.     

基于体素形态学观察帕金森病患者全脑灰质:2年纵向MR研究

目的 探讨无痴呆症状的帕金森病(PD)患者全脑灰质结构随时间变化的特征。方法 采用T1W三维磁化准备快速梯度回波序列对20例无痴呆症状的PD患者(PD组)进行间隔2年的随访。纳入25名年龄和性别匹配的健康体检者作为对照组,采用SPM8进行基于体素的形态学分析技术的数据处理。结果 与对照组比较,PD组灰质萎缩区域包括双侧颞中回及小脑后叶;纵向比较发现,PD患者灰质萎缩区域集中在左侧额中回和扣带回、左侧顶下小叶及右侧小脑前叶和小脑蚓。结论 PD患者大脑灰质改变集中在颞叶和小脑,但随病情发展,左侧额顶叶和右侧小脑更为明显;这些特征性形态学变化可能是PD患者出现运动功能障碍的结构基础。     

Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study

The striatum, a subcortical structure, is the principal target of the neurodegenerative process in Huntington's disease (HD). The measurement of striatal atrophy using the bicaudate ratio on CT scanner images has therefore been used for years to assess disease progression, but this measure only takes into account unidimensional changes in the head of the caudate nucleus. Recently, voxel-based morphometry (VBM), which permits automated statistical comparisons of whole-brain MRI images, has been proposed to quantify striatal atrophy. However, VBM was not originally designed to study subcortical structures, and severe deep brain deformations that occur in HD may hamper the automatic processing of VBM. Here, we validate the use of the optimised protocol of VBM to quantify subcortical atrophy in HD by comparing results obtained with this method to those provided by manual segmentation of subcortical structures. We studied 20 patients with early HD and 12 controls matched for age, sex and handedness using an improved T1-weighted sequence that eased grey matter segmentation. Both manual and automated methods evidenced the dorso-ventral gradient of striatal atrophy, a loss of grey matter in the globus pallidus and the thalamus, and similar correlations between clinical scores and subcortical atrophy. Furthermore, we were able to detect with VBM grey matter loss in the substantia nigra, the hypothalamus, the amygdala, the insular cortex and the premotor and sensorimotor cortices. Finally, VBM provided results consistent with previous post mortem results and proved to be a sensitive biomarker capable of correctly managing subcortical distortions throughout HD patients' brains.     

Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy

BackgroundThe reasons for surgical failure in 30% of patients with unilateral mesial temporal lobe epilepsy (MTLE) are still unclear. We investigated if different outcomes could be associated to different patterns of subtle gray matter atrophy (GMA) and white matter atrophy (WMA), and searched for postoperative magnetic resonance imaging (MRI) changes.MethodsWe studied 69 controls and 67 operated patients with refractory unilateral MTLE. Patients were grouped as seizure-free (SF) group (34 patients Engel's IA), worthwhile improvement group (23 patients, Engel's IB–IIA) and failure group (10 patients Engel's IIB–IV). We created a voxel-based morphometry/MATLAB code to mask the surgical lacuna, and performed t-test and paired t-test to evaluate preoperative and postoperative MRI scans.ResultsFailure group showed a widespread pattern of preoperative GMA. On SF and improvement groups we identified a more restricted pattern of GMA. The three groups presented a widespread, bilateral pattern of WMA. In contrast, postoperative analyses showed bilateral hemispheric recovery (a relative increase of WM concentration) on SF and improvement groups, but few changes on failure group. We also identified areas with relative postoperative increase of GM on both SF and improvement groups, more widespread on SF group.ConclusionAreas of subtle GMA may be related to poorer surgical outcome. In addition, we demonstrated a postoperative relative increase of WM and GM concentration associated with seizure control. These changes may represent neuroplasticity related to improvement of brain function after seizure control. Further studies with a multimodal approach may help to predict surgical outcome and improve selection of patients for surgical treatment of MTLE.     

中国人群帕金森病患者灰质萎缩:采用中国人脑图谱Chinese2020的基于体素的形态学研究

目的 采用基于体素的形态学测量（VBM）方法探讨中国人脑图谱Chinese2020检测中国人群帕金森病（PD）患者灰质体积改变的价值。方法 收集15例PD患者（PD组）和15名性别和年龄匹配的健康志愿者为对照组。分别采用基于中国人群的脑图谱Chinese2020和基于高加索人群的脑图谱MNI152进行空间标准化,比较配准到这2种标准空间所引起的脑结构形变差异,并采用VBM方法比较2种图谱检出PD患者灰质体积萎缩的脑区以及萎缩脑区灰质占比的差异。结果 采用MNI152脑图谱发现PD患者灰质萎缩脑区包括双侧颞叶并扩展至同侧脑岛/海马/海马旁回、左侧枕上回/楔叶/楔前叶及右侧壳核;采用Chinese2020图谱后,除上述脑区外,右侧额中回亦可见灰质体积萎缩。PD组和对照组受试者脑结构配准到Chinese2020空间发生形变小于配准到MNI152空间,且基于Chinese2020检测灰质萎缩脑区灰质占比高于采用MNI152图谱（t=2.502,P=0.037）。结论 基于中国人群的神经影像学研究应该采用中国人脑图谱进行空间标准化,其脑结构形变更小、所识别出的脑区灰质占比更高,从而提高检测的准确性。