Imbalanced temporal states of cortical blood-oxygen-level-dependent signal variability during rest in episodic migraine.

BACKGROUND: Migraine has been associated with functional brain changes including altered connectivity and activity both during and between headache attacks. Recent studies established that the variability of the blood-oxygen-level-dependent (BOLD) signal is an important attribute of brain activity, which has so far been understudied in migraine. In this study, we investigate how time-varying measures of BOLD variability change interictally in episodic migraine patients. METHODS: Two independent resting state functional MRI datasets acquired on 3T (discovery cohort) and 1.5T MRI scanners (replication cohort) including 99 episodic migraine patients (n3T = 42, n1.5T=57) and 78 healthy controls (n3T = 46, n1.5T=32) were analyzed in this cross-sectional study. A framework using time-varying measures of BOLD variability was applied to derive BOLD variability states. Descriptors of BOLD variability states such as dwell time and fractional occupancy were calculated, then compared between migraine patients and healthy controls using Mann-Whitney U-tests. Spearman's rank correlation was calculated to test associations with clinical parameters. RESULTS: Resting-state activity was characterized by states of high and low BOLD signal variability. Migraine patients in the discovery cohort spent more time in the low variability state (mean dwell time: p = 0.014, median dwell time: p = 0.022, maximum dwell time: p = 0.013, fractional occupancy: p = 0.013) and less time in the high variability state (mean dwell time: p = 0.021, median dwell time: p = 0.021, maximum dwell time: p = 0.025, fractional occupancy: p = 0.013). Higher uptime of the low variability state was associated with greater disability as measured by MIDAS scores (maximum dwell time: R = 0.45, p = 0.007; fractional occupancy: R = 0.36, p = 0.035). Similar results were observed in the replication cohort. CONCLUSION: Episodic migraine patients spend more time in a state of low BOLD variability during rest in headache-free periods, which is associated with greater disability. BOLD variability states show potential as a replicable functional imaging marker in episodic migraine.

Examining the Prevalence of Left Atrial Appendage Thrombus in a Cohort of Acute Stroke Patients with an Extended Computed Tomography Angiographic Protocol.

INTRODUCTION: Current guidelines recommend transthoracic echocardiography (TTE) for routine screening of cardiac emboli; however, the visualization of the left atrial appendage (LAA) where the thrombi are commonly found is poor. Transesophageal echocardiography (TEE) would provide better detectability of LAA thrombus, but it is a time-consuming and semi-invasive method. Extending non-gated carotid computed tomography angiography (CTA) examination to the LAA could reliably detect thrombi and could also aid treatment and secondary prevention of stroke. METHODS: We extended the CTA scan range of acute stroke patients 4 cm below the carina to include the left atrium and appendage. During the review, we evaluated LAA thrombi based on contrast relations. We then used gradient boosting to identify the most important predictors of LAA thrombi from a variety of different clinical parameters. RESULTS: We examined 240 acute stroke patients' extended CTA scans. We detected LAA thrombi in eleven cases (4.58%), eight of them had atrial fibrillation. 23.75% of all patients (57 cases) had recently discovered or previously known atrial fibrillation. Windsack morphology was the most commonly associated morphology with filling defects on CTA. According to the gradient-boosting analysis, LAA morphology showed the most predictive value for thrombi. CONCLUSION: Our extended CTA scans reliably detected LAA thrombi even in cases where TTE did not and showed that 2 patients' LAA thrombus would have been untreated based on electrocardiogram monitoring and TTE. We also showed that the benefits of CTA outweigh the disadvantages arising from the slight amount of excess radiation.

D-dimer levels to exclude pulmonary embolism and reduce the need for CT angiography in COVID-19 in an outpatient population.

OBJECTIVES: Emerging results indicate that, in COVID-19, thromboembolic complications contribute to the high mortality and morbidity. Previous research showed that the prevalence of pulmonary embolism (PE) is between 25-50% in COVID-19 patients, however, most of these reports are based on data from patients with severe pneumonia, treated in intensive care units. MATERIALS AND METHODS: We conducted a retrospective, single-center, observational study to estimate the prevalence of PE in COVID-19 patients who underwent CT angiography and to identify the most important predictors. Adult outpatients with COVID-19, who presented at our COVID Outpatient Clinic between 1st and 31st of March in 2021 and underwent CTA examination were included in this study. Multiple linear regression analysis was used to identify predictors of PE in COVID-19 patients. The predictors were: age, gender, disease duration, CT severity index and log-transformed quantitative D-dimer (logQDDIM) value. RESULTS: 843 COVID-19 patients were included into the study. 82.56% (693 patients) of the infected patients had a pulmonary CTA examination and D-dimer levels (mean age: 59.82 years ± 15.66). 7.61% (53 patients) of the patients had PE. 2.02% (14 patients) of the patients had main branch or lobar PE. The multiple regression analysis found that only logQDDIM was a significant predictor. A logQDDIM cut-off value of 0.0169 (1.0171 ug/ml serum D-dimer) predicted PE with 99% sensitivity (p<0.0001, degree-of-freedom = 570, AUC = 0.72). CONCLUSIONS: We demonstrated in a large cohort of COVID-19 patients that a cut-off value of QDDIM of 1ug/ml can exclude pulmonary embolism in an outpatient setting, implicating that QDDIM might potentially supersede CTA as a screening approach in COVID-19 outpatient clinics.

Modulating Visuomotor Sequence Learning by Repetitive Transcranial Magnetic Stimulation: What Do We Know So Far?

Predictive processes and numerous cognitive, motor, and social skills depend heavily on sequence learning. The visuomotor Serial Reaction Time Task (SRTT) can measure this fundamental cognitive process. To comprehend the neural underpinnings of the SRTT, non-invasive brain stimulation stands out as one of the most effective methodologies. Nevertheless, a systematic list of considerations for the design of such interventional studies is currently lacking. To address this gap, this review aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS) is a viable method of modulating visuomotor sequence learning and to identify the factors that mediate its efficacy. We systematically analyzed the eligible records (n = 17) that attempted to modulate the performance of the SRTT with rTMS. The purpose of the analysis was to determine how the following factors affected SRTT performance: (1) stimulated brain regions, (2) rTMS protocols, (3) stimulated hemisphere, (4) timing of the stimulation, (5) SRTT sequence properties, and (6) other methodological features. The primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) were found to be the most promising stimulation targets. Low-frequency protocols over M1 usually weaken performance, but the results are less consistent for the DLPFC. This review provides a comprehensive discussion about the behavioral effects of six factors that are crucial in designing future studies to modulate sequence learning with rTMS. Future studies may preferentially and synergistically combine functional neuroimaging with rTMS to adequately link the rTMS-induced network effects with behavioral findings, which are crucial to develop a unified cognitive model of visuomotor sequence learning.

Evaluation of transorbital sonography measures of optic nerve diameter in the context of global and regional brain volume in multiple sclerosis.

Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing-remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p < 0.019) and we found significant correlation between average OND and normalised whole brain (ß = 0.42, p < 0.005), grey matter (ß = 0.33, p < 0.035), white matter (ß = 0.38, p < 0.012) and ventricular cerebrospinal fluid volume (ß = - 0.36, p < 0.021) in the MS group. History of ON had no impact on the association between OND and volumetric data. In conclusion, OND is a promising surrogate marker in MS, that can be simply and reliably measured using TOS, and its derived measures correspond to brain volumetric measures. It should be further explored in larger and longitudinal studies.

Manipulating the Rapid Consolidation Periods in a Learning Task Affects General Skills More than Statistical Learning and Changes the Dynamics of Learning.

Memory consolidation processes have traditionally been investigated from the perspective of hours or days. However, recent developments in memory research have shown that memory consolidation processes could occur even within seconds, possibly because of the neural replay of just practiced memory traces during short breaks. Here, we investigate this rapid form of consolidation during statistical learning. We aim to answer (1) whether this rapid consolidation occurs in implicit statistical learning and general skill learning, and (2) whether the duration of rest periods affects these two learning types differently. Human participants performed a widely used statistical learning task-the alternating serial reaction time (ASRT) task-that enables us to measure implicit statistical and general skill learning separately. The ASRT task consisted of 25 learning blocks with a rest period between the blocks. In a between-subjects design, the length of the rest periods was fixed at 15 or 30 s, or the participants could control the length themselves. We found that the duration of rest periods does not affect the amount of statistical knowledge acquired but does change the dynamics of learning. Shorter rest periods led to better learning during the learning blocks, whereas longer rest periods promoted learning also in the between-block rest periods, possibly because of the higher amount of replay. Moreover, we found weaker general skill learning in the self-paced group than in the fixed rest period groups. These results suggest that distinct learning processes are differently affected by the duration of short rest periods.

Modulation of cortical resting state functional connectivity during a visuospatial attention task in Parkinson's disease.

Visual dysfunction is a recognized early symptom of Parkinson's disease (PD) that partly scales motor symptoms, yet its background is heterogeneous. With additional deficits in visuospatial attention, the two systems are hard to disentangle and it is not known whether impaired functional connectivity in the visual cortex is translative in nature or disrupted attentional modulation also contributes. In this study, we investigate functional connectivity modulation during a visuospatial attention task in patients with PD. In total, 15 PD and 16 age-matched healthy controls performed a visuospatial attention task while undergoing fMRI, in addition to a resting-state fMRI scan. Tensorial independent component analysis was used to investigate task-related network activity patterns. Independently, an atlas-based connectivity modulation analysis was performed using the task potency method. Spearman's rank correlation was calculated between task-related network expression, connectivity modulation, and clinical characteristics. Task-related networks including mostly visual, parietal, and prefrontal cortices were expressed to a significantly lesser degree in patients with PD (p < 0.027). Resting-state functional connectivity did not differ between the healthy and diseased cohorts. Connectivity between the precuneus and ventromedial prefrontal cortex was modulated to a higher degree in patients with PD (p < 0.004), while connections between the posterior parietal cortex and primary visual cortex, and also the superior frontal gyrus and opercular cortex were modulated to a lesser degree (p < 0.001 and p < 0.011). Task-related network expression and superior frontal gyrus-opercular cortex connectivity modulation were significantly associated with UPDRSIII motor scores and the Hoehn-Yahr stages (R = -0.72, p < 0.006 and R = -0.90, p < 0.001; R = -0.68, p < 0.01 and R = -0.71, p < 0.007). Task-related networks function differently in patients with PD in association with motor symptoms, whereas impaired modulation of visual and default-mode network connectivity was not correlated with motor function.

Reproducibility of Lesion Count in Various Subregions on MRI Scans in Multiple Sclerosis.

Purpose: Lesion number and burden can predict the long-term outcome of multiple sclerosis, while the localization of the lesions is also a good predictive marker of disease progression. These biomarkers are used in studies and in clinical practice, but the reproducibility of lesion count is not well-known. Methods: In total, five raters evaluated T2 hyperintense lesions in 140 patients with multiple sclerosis in six localizations: periventricular, juxtacortical, deep white matter, infratentorial, spinal cord, and optic nerve. Black holes on T1-weighted images and brain atrophy were subjectively measured on a binary scale. Reproducibility was measured using the intraclass correlation coefficient (ICC). ICCs were also calculated for the four most accurate raters to see how one outlier can influence the results. Results: Overall, moderate reproducibility (ICC 0.5-0.75) was shown, which did not improve considerably when the most divergent rater was excluded. The areas that produced the worst results were the optic nerve region (ICC: 0.118) and atrophy judgment (ICC: 0.364). Comparing high- and low-lesion burdens in each region revealed that the ICC is higher when the lesion count is in the mid-range. In the periventricular and deep white matter area, where lesions are common, higher ICC was found in patients who had a lower lesion count. On the other hand, juxtacortical lesions and black holes that are less common showed higher ICC when the subjects had more lesions. This difference was significant in the juxtacortical region when the most accurate raters compared patients with low (ICC: 0.406 CI: 0.273-0.546) and high (0.702 CI: 0.603-0.785) lesion loads. Conclusion: Lesion classification showed high variability by location and overall moderate reproducibility. The excellent range was not achieved, owing to the fact that some areas showed poor performance. Hence, putting effort toward the development of artificial intelligence for the evaluation of lesion burden should be considered.

The effect of lesion location on visuospatial attentional bias in patients with multiple sclerosis.

OBJECTIVE: Lateralization of visuospatial attention in healthy people, known as pseudoneglect, results in leftward bias during the Landmark or line bisection tasks. Cognitive dysfunctions in patients with multiple sclerosis (MS) might affect the visuospatial attentional abilities as well. In this study, we aimed to examine the association between atrophy and lesion location and the extent of lateralization of visuospatial attentional bias in patients with MS. METHOD: Visuospatial attentional bias was measured in 35 relapsing-remitting MS patients using the Landmark task. To evaluate the relation between spatial attentional bias and gray matter atrophy, voxel-based morphometry was performed on T1-weighted magnetic resonance (MR) images. In order to examine the effect of lesion location on visuospatial attentional bias, lesion-symptom mapping was conducted on the manually segmented lesions. RESULTS: The variability of visuospatial attentional bias was higher in MS patients compared to healthy controls (p < .04). Lesion probability mapping showed that lesions located along the left superior longitudinal fascicle are associated with the extent of visuospatial bias (p < .05). No correlation was found between gray matter atrophy and the attentional bias of the patients. CONCLUSIONS: Our results indicate that lesions affecting the integrity of white matter pathways in the fronto-parietal attentional network might be accountable for the higher variability of spatial attentional bias in patients with MS. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Functional Connectivity Lateralisation Shift of Resting State Networks is Linked to Visuospatial Memory and White Matter Microstructure in Relapsing-Remitting Multiple Sclerosis.

Laterality patterns of resting state networks (RSN) change in various neuropsychiatric conditions. Multiple sclerosis (MS) causes neuro-cognitive symptoms involving dysfunctional large-scale brain networks. Yet, whether healthy laterality patterns of RSNs are maintained in MS and whether altered laterality patterns explain disease symptoms has not been explicitly investigated. We analysed functional MRI and diffusion tensor imaging data from 24 relapsing-remitting MS patients and 25 healthy participants. We performed group-level independent component analysis and used dual regression to estimate individual versions of well-established RSNs. Voxelwise laterality indices were calculated for each RSN. Group differences were assessed via a general linear model-based approach. The relationship between functional laterality and white matter microstructural asymmetry was assessed using Tract-Based Spatial Statistics. Spearman's correlation was calculated between laterality indices and Brief International Cognitive Assessment for Multiple Sclerosis scores. Functional laterality of the dorsal attention network showed a significant leftward shift in the MS group in the posterior intraparietal sulcus (p < 0.033). Default-mode network laterality showed a significant leftward shift in the MS group in the angular gyrus (p < 0.005). Diminished dorsal attention network laterality was associated with increased fractional anisotropy asymmetry in the superior longitudinal fasciculus (p < 0.02). In the default-mode network, leftward laterality of the angular gyrus was associated with higher BVMT-R scores (R = - 0.52, p < 0.023). Our results confirm previous descriptions of RSN dysfunction in relapsing-remitting MS and show that altered functional connectivity lateralisation patterns of RSNs might contibute to cognitive performance and structural remodellation even in patients with mild clinical symptoms.

Resting-state functional heterogeneity of the right insula contributes to pain sensitivity.

Previous studies have described the structure and function of the insular cortex in terms of spatially continuous gradients. Here we assess how spatial features of insular resting state functional organization correspond to individual pain sensitivity. From a previous multicenter study, we included 107 healthy participants, who underwent resting state functional MRI scans, T1-weighted scans and quantitative sensory testing on the left forearm. Thermal and mechanical pain thresholds were determined. Connectopic mapping, a technique using non-linear representations of functional organization was employed to describe functional connectivity gradients in both insulae. Partial coefficients of determination were calculated between trend surface model parameters summarizing spatial features of gradients, modal and modality-independent pain sensitivity. The dominant connectopy captured the previously reported posteroanterior shift in connectivity profiles. Spatial features of dominant connectopies in the right insula explained significant amounts of variance in thermal (R2 = 0.076; p < 0.001 and R2 = 0.031; p < 0.029) and composite pain sensitivity (R2 = 0.072; p < 0.002). The left insular gradient was not significantly associated with pain thresholds. Our results highlight the functional relevance of gradient-like insular organization in pain processing. Considering individual variations in insular connectopy might contribute to understanding neural mechanisms behind pain and improve objective brain-based characterization of individual pain sensitivity.

Diffusion kurtosis imaging detects the time-dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease.

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments.

Prolonged Infection of Canine Distemper Virus in a Mixed-Breed Dog.

Canine distemper virus (CDV) is a major viral pathogen in domestic dogs, belonging to the Paramyxoviridae family, in the Morbillivirus genus. It is present worldwide, and a wide range of domestic animals and wild carnivores are at risk. In the absence of vaccination, dogs have a low chance of survival; however, if and when a dog survives, it can take an average of a few weeks to a few months to fully wipe out the virus. In the present study, we traced the course of infection of a 1-year-old mixed-breed male dog. The animal had an unusually long course of persistent CDV infection with a vector-borne heartworm (Dirofilaria immitis) co-infection. The dog excreted the CDV for 17 months with PCR positivity in urine samples collected from February 2019 through June 2020. The sequencing and phylogenetic analysis of the hemagglutinin gene revealed the CDV to be the member of the endemic Arctic-like genetic lineage. To the best of our knowledge, this report represents the longest documented canine infection of CDV. Notably, we highlight the necessity regarding CDV infectivity studies to better comprehend the transmission attributes of the virus.

Two Classes of T1 Hypointense Lesions in Multiple Sclerosis With Different Clinical Relevance.

Background: Hypointense lesions on T1-weighted images have important clinical relevance in multiple sclerosis patients. Traditionally, spin-echo (SE) sequences are used to assess these lesions (termed black holes), but Fast Spoiled Gradient-Echo (FSPGR) sequences provide an excellent alternative. Objective: To determine whether the contrast difference between T1 hypointense lesions and the surrounding normal white matter is similar on the two sequences, whether different lesion types could be identified, and whether the clinical relevance of these lesions types are different. Methods: Seventy-nine multiple sclerosis patients' lesions were manually segmented, then registered to T1 sequences. Median intensity values of lesions were identified on all sequences, then K-means clustering was applied to assess whether distinct clusters of lesions can be defined based on intensity values on SE, FSPGR, and FLAIR sequences. The standardized intensity of the lesions in each cluster was compared to the intensity of the normal appearing white matter in order to see if lesions stand out from the white matter on a given sequence. Results: 100% of lesions on FSPGR images and 69% on SE sequence in cluster #1 exceeded a standardized lesion distance of Z = 2.3 (p < 0.05). In cluster #2, 78.7% of lesions on FSPGR and only 17.7% of lesions on SE sequence were above this cutoff value, meaning that these lesions were not easily seen on SE images. Lesion count in the second cluster (lesions less identifiable on SE) significantly correlated with the Expanded Disability Status Scale (EDSS) (R: 0.30, p ≤ 0.006) and with disease duration (R: 0.33, p ≤ 0.002). Conclusion: We showed that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. This emphasizes the joint role of FSPGR and SE sequences in the monitoring of MS patients and provides insight into the role of black holes in MS.

Altered brain network function during attention-modulated visual processing in multiple sclerosis.

BACKGROUND: Multiple sclerosis may damage cognitive performance in several domains, including attention. Although attention network deficits were described during rest, studies that investigate their function during task performance are scarce. OBJECTIVE: To investigate connectivity within and between task-related networks in multiple sclerosis during a visual attention task as a function of cognitive performance. METHODS: A total of 23 relapsing-remitting multiple sclerosis (RRMS) patients and 29 healthy controls underwent task-functional magnetic resonance imaging (fMRI) scans using a visual attention paradigm on a 3T scanner. Scans were analysed using tensor-independent component analysis (TICA). Functional connectivity was calculated within and between components. We assessed cognitive function with the Brief International Cognitive Assessment for MS (BICAMS) battery. RESULTS: TICA extracted components related to visual processing, attention, executive function and the default-mode network. Subject scores of visual/attention-related and executive components were greater in healthy controls (p < 0.032, p < 0.023). Connectivity between visual/attention-related and default-mode components was higher in patients (p < 0.043), correlating with Brief Visuospatial Memory Test-Revised (BVMT-R) scores (R = -0.48, p < 0.036). Patients showed reduced connectivity between the right intraparietal sulcus (rIPS) and frontal eye field (rFEF), and bilateral frontal eye fields (p < 0.012, p < 0.003). Reduced rIPS-rFEF connectivity came with lower Symbol Digit Modalities Test (SDMT)/BVMT-R scores in patients (R = 0.53, p < 0.02, R = 0.46, p < 0.049). CONCLUSION: Attention-related networks show altered connectivity during task performance in RRMS patients, scaling with cognitive disability.

Brain MRI Diffusion Encoding Direction Number Affects Tract-Based Spatial Statistics Results in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is a promising approach to detect the underlying brain pathology. These alterations can be seen in several diseases such as multiple sclerosis. Tract-based spatial statistics (TBSS) is an easy to use and robust way for analyzing diffusion data. The effect of acquisition parameters of DTI on TBSS has not been evaluated, especially the number of diffusion encoding directions (NDED), which is directly proportional with scan time. METHODS: We analyzed a large set of DTI data of healthy controls (N = 126) and multiple sclerosis patients (N = 78). The highest NDED (60 directions) was reduced and a tensor calculation was done separately for every subset. We calculated the mean and standard deviation of DTI parameters under the white matter mask. Moreover, the FMRIB Software Library TBSS pipeline was used on DTI images with 15, 30, 45, and 60 directions to compare differences between groups. Mean DTI parameters were compared between groups as a function of NDED. RESULTS: The mean value of FA and AD decreased with increasing number of directions. This was more pronounced in areas with smaller FA values. RD and MD were constant. The skeleton size reduced with elevating NDED along with the number of significant voxels. The TBSS analysis showed significant differences between groups throughout the majority of the skeleton and the group difference was associated with NDED. CONCLUSION: Our results suggested that results of TBSS depended on the NDED, which should be considered when comparing DTI data with varying protocols.

Temporal instability of salience network activity in migraine with aura.

This study aims to investigate whether intranetwork dynamic functional connectivity and causal interactions of the salience network is altered in the interictal term of migraine. Thirty-two healthy controls, 37 migraineurs without aura, and 20 migraineurs with aura were recruited. Participants underwent a T1-weighted scan and resting-state fMRI protocol inside a 1.5T MR scanner. We obtained average spatial maps of resting-state networks using group independent component analysis, which yielded subject-specific time series through a dual regression approach. Salience network regions of interest (bilateral insulae and prefrontal cortices, dorsal anterior cingulate cortex) were obtained from the group average map through cluster-based thresholding. To describe intranetwork connectivity, average and dynamic conditional correlation was calculated. Causal interactions between the default-mode, dorsal attention, and salience network were characterised by spectral Granger's causality. Time-averaged correlation was lower between the right insula and prefrontal cortex in migraine without aura vs with aura and healthy controls (P < 0.038, P < 0.037). Variance of dynamic conditional correlation was higher in migraine with aura vs healthy controls and migraine with aura vs without aura between the right insula and dorsal anterior cingulate cortex (P < 0.011, P < 0.026), and in migraine with aura vs healthy controls between the dorsal anterior cingulate and left prefrontal cortex (P < 0.021). Causality was weaker in the <0.05 Hz frequency range between the salience and dorsal attention networks in migraine with aura (P < 0.032). Overall, migraineurs with aura exhibit more fluctuating connections in the salience network, which also affect network interactions, and could be connected to altered cortical excitability and increased sensory gain.

Are Migraine With and Without Aura Really Different Entities?

Background: Migraine research is booming with the rapidly developing neuroimaging tools. Structural and functional alterations of the migrainous brain were detected with MRI. The outcome of a research study largely depends on the working hypothesis, on the chosen measurement approach and also on the subject selection. Against all evidence from the literature that migraine subtypes are different, most of the studies handle migraine with and without aura as one disease. Methods: Publications from PubMed database were searched for terms of "migraine with aura," "migraine without aura," "interictal," "MRI," "diffusion weighted MRI," "functional MRI," "compared to," "atrophy" alone and in combination. Conclusion: Only a few imaging studies compared the two subforms of the disease, migraine with aura, and without aura, directly. Functional imaging investigations largely agree that there is an increased activity/activation of the brain in migraine with aura as compared to migraine without aura. We propose that this might be the signature of cortical hyperexcitability. However, structural investigations are not equivocal. We propose that variable contribution of parallel, competing mechanisms of maladaptive plasticity and neurodegeneration might be the reason behind the variable results.

Distinctive Patterns of Seizure-Related White Matter Alterations in Right and Left Temporal Lobe Epilepsy.

Background: We hypothesized that right and left temporal lobe epilepsy (RTLE and LTLE, respectively) have distinctive spatial patterns of white matter (WM) changes that can be differentiated and interpreted with the use of multiple diffusion parameters. We compared the global microstructure of fiber bundles with regard to WM alterations in both RTLE and LTLE, addressing some of the methodological issues of previous studies. Methods: Diffusion tensor imaging data from 17 patients with RTLE (age: 40.7 ± 10.4), 15 patients with LTLE (age: 37.3 ± 10.4), and 15 controls (age: 34.8 ± 11.2) were used in the study. WM integrity was quantified by fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity (LD), and radial diffusivity (RD). The diffusion parameters were compared between the groups in tracts representing the core of the fiber bundles. The volumes of hippocampi and amygdala were subsequently compared across the groups, while the data were adjusted for the effect of hippocampal sclerosis. Results: Significantly reduced FA and increased MD, LD, and RD were found bilaterally over widespread brain regions in RTLE. An increase in MD and RD values was observed in widespread WM fiber bundles ipsilaterally in LTLE, largely overlapping with regions where FA was lower, while no increase in LD was observed. We also found a difference between the LTLE and RTLE groups for the right hippocampal volume (with and without adjustment for HS), whereas no significant volume differences were found between patients and controls. Conclusions: It appears that patients with RTLE exhibit a more widespread pattern of WM alterations that extend far beyond the temporal lobe in both ipsilateral and contralateral hemisphere; furthermore, these changes seem to reflect more severe damage related to chronic degeneration. Conversely, more restrained changes in the LTLE may imply a pattern of less severe axonal damage, more restricted to ipsilateral hemisphere. Comprehensive finding of more prominent hippocampal atrophy in the RTLE raises an interesting issue of seizure-induced implications on gray matter and WM microstructure that may not necessarily mean a straightforward causal relationship. Further correlations of diffusion-derived metrics with neuropsychological and functional imaging measures may provide complementary information on underlying WM abnormalities with regard to functional hemispheric specialization.