Diffusion tensor magnetic resonance imaging at 3.0 tesla shows subtle cerebral grey matter abnormalities in patients with migraine

BACKGROUND AND OBJECTIVE: Diffusion tensor (DT) magnetic resonance imaging (MRI) has the potential to disclose subtle abnormalities in the brain of migraine patients. This ability may be increased by the use of high field magnets. A DT MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the brain normal appearing white (NAWM) and grey matter in migraine patients with T2 visible abnormalities. METHODS: Dual echo, T1 weighted and DT MRI with diffusion gradients applied in 32 non-collinear directions were acquired from 16 patients with migraine and 15 sex and age matched controls. Lesion load on T2 weighted images was measured using a local thresholding segmentation technique, and brain atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and fractional anisotropy histograms of the NAWM and mean diffusivity histograms of the grey matter were also derived. RESULTS: Brain atrophy did not differ between controls and patients. Compared with healthy subjects, migraine patients had significantly reduced mean diffusivity histogram peak height of the grey matter (p=0.04). No diffusion changes were detected in patients' NAWM. In migraine patients, no correlation was found between T2 weighted lesion load and brain DT histogram derived metrics, whereas age was significantly correlated with grey matter mean diffusivity histogram peak height (p=0.05, r=-0.52). CONCLUSIONS: DT MRI at high field strength discloses subtle grey matter damage in migraine patients, which might be associated with cognitive changes in these patients.     

Disrupted resting‐state functional connectivity and its changing trend in migraine suffers

Chronic pain has been linked with learning and memory processes and functional changes in brain plasticity in its development and maintenance via neuroimaging studies. However, the principle of reorganization of the migraine brain network as the brain progresses into chronic pain remain poorly understood. Here, using resting‐state functional magnetic resonance imaging (rs‐fMRI) and graph theory approaches, we aimed to investigate the dynamic dysfunctional connectivity in 108 patients with migraine without aura (MWoA) and 30 gender‐matched healthy controls (HC). All patients were divided into 40 groups using a sliding boxcar grouping of subjects in disease duration order. As compared with HC, nonparametric permutation tests were applied for between‐group comparisons of functional connectivity strength in each patient group. We focused only on the between‐group differences of functional connections in MWoA, and the situation how these different connections were organized along with the changing trend. As the disease duration increased, the presence of chronic headache altered the functional connectivity from the local central nervous system (CNS) to a disruption in the whole‐brain networks. These dysfunctional connections integrated into a connected component in relatively longer migraine duration groups, suggesting an abnormal integrated network configuration with ongoing central changes for long‐term migraine. Within these between‐group differences of the connected component, there were contained a small number of brain regions that had disproportionately numerous connections. Moreover, these brain regions exhibited a tendency to link to each other were organized into a strongly interconnected community. These interconnected brain regions were mainly located in the sensory‐discriminative brain areas. Our results exhibited a working model of the central mechanisms of migraine where the brain functional connectivity was altered from the local central nervous system to a densely interconnected center, which may extend our understanding of the role of learning mechanisms which are likely involved in maintenance of chronic pain. Hum Brain Mapp 36:1892–1907, 2015. © 2015 Wiley Periodicals, Inc .     

Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients

Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8‐week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within‐subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow‐up placebo treatment. Our findings suggested that the trait‐like individual differences in pain‐related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250–5259, 2017. © 2017 Wiley Periodicals, Inc.     

Diffusion kurtosis imaging reveals abnormal gray matter and white matter development in some brain regions of children with attention-deficit/hyperactivity disorder

In this study, we explored the application of diffusion kurtosis imaging (DKI) technology in the brains of children with attention-deficit/hyperactivity disorder (ADHD). Seventy-two children with ADHD and 79 age- and sex-matched healthy controls were included in the study. All children were examined by means of 3D T1-weighted image, DKI, and conventional sequence scanning. The volume and DKI parameters of each brain region were obtained by software postprocessing (GE ADW 4.6 workstation) and compared between the two groups of children to determine the imaging characteristics of children with ADHD. The result showed the total brain volume was lower in children with ADHD than in healthy children (p < .05). The gray and white matter volumes in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, putamen, globus pallidus, and other brain regions were lower in children with ADHD than in healthy children (p < .05). The axial kurtosis (Ka), mean kurtosis (MK), fractional anisotropy (FA), and radial kurtosis(Kr) values in the frontal lobe, temporal lobe, and caudate nucleus of children with ADHD were lower than those of healthy children, while the mean diffusivity(MD) and fractional anisotropy of kurtosis (FAK) values were higher than those of healthy children (p < .05). Additionally, the Ka, MK, FA, and Kr values in the frontal lobe, caudate nucleus, and temporal lobe could be used to distinguish children with ADHD (AUC > .05, p < .05). In conclusion, DKI showed abnormal gray matter and white matter development in some brain regions of children with ADHD.     

Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions

While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre‐injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non‐emergent revascularization surgery, allowing the collection of pre and post‐operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post‐operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185–2194, 2016. © 2016 Wiley Periodicals, Inc.     

Multimodal analysis of functional and structural disconnection in Alzheimer's disease using multiple kernel SVM

Alzheimer's disease (AD) patients exhibit alterations in the functional connectivity between spatially segregated brain regions which may be related to both local gray matter (GM) atrophy as well as a decline in the fiber integrity of the underlying white matter tracts. Machine learning algorithms are able to automatically detect the patterns of the disease in image data, and therefore, constitute a suitable basis for automated image diagnostic systems. The question of which magnetic resonance imaging (MRI) modalities are most useful in a clinical context is as yet unresolved. We examined multimodal MRI data acquired from 28 subjects with clinically probable AD and 25 healthy controls. Specifically, we used fiber tract integrity as measured by diffusion tensor imaging (DTI), GM volume derived from structural MRI, and the graph‐theoretical measures ‘local clustering coefficient’ and ‘shortest path length’ derived from resting‐state functional MRI (rs‐fMRI) to evaluate the utility of the three imaging methods in automated multimodal image diagnostics, to assess their individual performance, and the level of concordance between them. We ran the support vector machine (SVM) algorithm and validated the results using leave‐one‐out cross‐validation. For the single imaging modalities, we obtained an area under the curve (AUC) of 80% for rs‐fMRI, 87% for DTI, and 86% for GM volume. When it came to the multimodal SVM, we obtained an AUC of 82% using all three modalities, and 89% using only DTI measures and GM volume. Combined multimodal imaging data did not significantly improve classification accuracy compared to the best single measures alone. Hum Brain Mapp 36:2118–2131, 2015. © 2015 Wiley Periodicals, Inc.     

Multimodal frontostriatal connectivity underlies individual differences in self-esteem

A heightened sense of self-esteem is associated with a reduced risk for several types of affective and psychiatric disorders, including depression, anxiety and eating disorders. However, little is known about how brain systems integrate self-referential processing and positive evaluation to give rise to these feelings. To address this, we combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to test how frontostriatal connectivity reflects long-term trait and short-term state aspects of self-esteem. Using DTI, we found individual variability in white matter structural integrity between the medial prefrontal cortex and the ventral striatum was related to trait measures of self-esteem, reflecting long-term stability of self-esteem maintenance. Using fMRI, we found that functional connectivity of these regions during positive self-evaluation was related to current feelings of self-esteem, reflecting short-term state self-esteem. These results provide convergent anatomical and functional evidence that self-esteem is related to the connectivity of frontostriatal circuits and suggest that feelings of self-worth may emerge from neural systems integrating information about the self with positive affect and reward. This information could potentially inform the etiology of diminished self-esteem underlying multiple psychiatric conditions and inform future studies of evaluative self-referential processing.     

Age‐associated patterns in gray matter volume,cerebral perfusion and BOLD oscillations in children and adolescents

Healthy brain development involves changes in brain structure and function that are believed to support cognitive maturation. However, understanding how structural changes such as grey matter thinning relate to functional changes is challenging. To gain insight into structure‐function relationships in development, the present study took a data driven approach to define age‐related patterns of variation in gray matter volume (GMV), cerebral blood flow (CBF) and blood‐oxygen level dependent (BOLD) signal variation (fractional amplitude of low‐frequency fluctuations; fALFF) in 59 healthy children aged 7–18 years, and examined relationships between modalities. Principal components analysis (PCA) was applied to each modality in parallel, and participant scores for the top components were assessed for age associations. We found that decompositions of CBF, GMV and fALFF all included components for which scores were significantly associated with age. The dominant patterns in GMV and CBF showed significant (GMV) or trend level (CBF) associations with age and a strong spatial overlap, driven by increased signal intensity in default mode network (DMN) regions. GMV, CBF and fALFF additionally showed components accounting for 3–5% of variability with significant age associations. However, these patterns were relatively spatially independent, with small‐to‐moderate overlap between modalities. Independence of age effects was further demonstrated by correlating individual subject maps between modalities: CBF was significantly less correlated with GMV and fALFF in older children relative to younger. These spatially independent effects of age suggest that the parallel decline observed in global GMV and CBF may not reflect spatially synchronized processes. Hum Brain Mapp 38:2398–2407, 2017. © 2017 Wiley Periodicals, Inc.     

Charting shared developmental trajectories of cortical thickness and structural connectivity in childhood and adolescence

The cortex is organised into broadly hierarchical functional systems with distinct neuroanatomical characteristics reflected by macroscopic measures of cortical morphology. Diffusion‐weighted magnetic resonance imaging allows the delineation of areal connectivity, changes to which reflect the ongoing maturation of white matter tracts. These developmental processes are intrinsically linked with timing coincident with the development of cognitive function. In this study, we use a data‐driven multivariate approach, nonnegative matrix factorisation, to define cortical regions that co‐vary together across a large paediatric cohort (n = 456) and are associated with specific subnetworks of cortical connectivity. We find that age between 3 and 21 years is associated with accelerated cortical thinning in frontoparietal regions, whereas relative thinning of primary motor and sensory regions is slower. Together, the subject‐specific weights of the derived set of cortical components can be combined to predict chronological age. Structural connectivity networks reveal a relative increase in strength in connection within, as opposed to between hemispheres that vary in line with cortical changes. We confirm our findings in an independent sample.     

Relationship between white matter connectivity loss and cortical thinning in cerebral amyloid angiopathy

Patients with cerebral amyloid angiopathy (CAA) show loss of white matter connectivity and cortical thinning on MRI, primarily in posterior brain regions. Here we examined whether a potential causal relationship exists between these markers of subcortical and cortical brain injury by examining whether changes in cortical thickness progress in tandem with changes in their underlying connections. Thirty‐one patients with probable CAA with brain MRI at two time points were included (follow‐up time: 1.3 ± 0.4 years). Brain networks were reconstructed using diffusion MRI‐based fiber tractography. Of each network node, we calculated the change in fractional anisotropy‐weighted connectivity strength over time and the change in cortical thickness. The association between change in connectivity strength and cortical thickness was assessed with (hierarchical) linear regression models. Our results showed that decline in posterior network connectivity over time was strongly related to thinning of the occipital cortex (β = 0.65 (0.35–0.94), P < 0.001), but not to thinning of the other posterior or frontal cortices. However, at the level of individual network nodes, we found no association between connectivity strength and cortical thinning of the corresponding node (β = 0.009 ± 0.04, P = 0.80). Associations were independent of age, sex, and other brain MRI markers of CAA. To conclude, CAA patients with greater progressive loss of posterior white matter connectivity also have greater progression of occipital cortical thinning, but our results do not support a direct causal relationship between them. The association can be better explained by a shared underlying mechanism, which may form a potential target for future treatments. Hum Brain Mapp 38:3723–3731, 2017. © 2017 Wiley Periodicals, Inc.     

Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder

OBJECTIVE: Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD) have investigated the entire cerebral cortex. Cortical gray matter (GM) volume deficits have been reported in some studies of adults with BPD; this study assessed the presence of such deficits in children with BPD. METHODS: Thirty-two youths with DSM-IV BPD (mean age 11.2 +/- 2.8 years) and 15 healthy controls (HC) (11.2 +/- 3.0 years) had structured and clinical interviews, neurological examinations, neurocognitive testing, and MRI scanning on a 1.5 T GE Scanner. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere, and these units were combined into frontal (FL), temporal (TL), parietal (PL), and occipital (OL) lobe volumes. Volumetric differences were examined using univariate linear regression models with alpha = 0.05. RESULTS: Relative to controls, the BPD youth had significantly smaller bilateral PL, and left TL. Analysis of PL and TL gyri showed significantly smaller volume in bilateral postcentral gyrus, and in left superior temporal and fusiform gyri, while the parahippocampal gyri were bilaterally increased in the BPD group. Although the FL overall did not differ between groups, an exploratory analysis showed that the right middle frontal gyrus was also significantly smaller in the BPD group. CONCLUSIONS: Children with BPD showed deficits in PL and TL cortical GM. Further analyses of the PL and TL found differences in areas involved in attentional control, facial recognition, and verbal and declarative memory. These cortical deficits may reflect early age of illness onset.     

Family history of alcohol dependence and gray matter abnormalities in non-alcoholic adults

Abstract

Objectives. Alcohol-use disorders in adolescents are associated with gray matter (GM) abnormalities suggesting neurotoxicity by alcohol. However, recently similar GM abnormalities were found in non-drinking children with a family history (FH) of alcohol dependence (AD). The question thus rises whether these abnormalities represent a transient delay in brain maturation or a persistent risk factor for developing neuropsychiatric disorders, rather than a (neurotoxic) consequence of AD. This study investigated whether a FH of AD in non-drinking adults is associated with abnormal GM-volumes similar to those observed in drinking and non-drinking adolescents with a FH of AD. Methods. GM-images were analyzed using Voxel-Based Morphometry in non-alcoholics with (FH+; N = 36) and without (FH–; N = 107) familial AD. Additionally we controlled for possible confounders: diagnosis of depression/anxiety, childhood trauma and familial depression/anxiety. Results. Smaller GM-volumes were shown in the right parahippocampal gyrus in FH+ compared with FH–. Results were unaffected by confounders. Conclusions. We demonstrated an effect of familial AD in non-alcoholic adults on GM volume in the parahippocampal gyrus, similar to drinking and non-drinking FH+ adolescents. These findings suggest that GM abnormalities in the parahippocampal gyrus represent a persistent biological susceptibility for AD or related psychopathology and not neurotoxicity of alcohol or delayed brain maturation.     

A multiparametric analysis of white matter maturation during late childhood and adolescence

White matter development has been well described using diffusion tensor imaging (DTI), but the microstructural processes driving development remain unclear due to methodological limitations. Here, using neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT), and multicomponent driven equilibrium single‐pulse observation of T1/T2 (mcDESPOT), we describe white matter development at the microstructural level in a longitudinal cohort of healthy 6–15 year olds. We evaluated age and gender‐related trends in fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), orientation dispersion index (ODI), quantitative ihMT (qihMT), myelin volume fraction (VF_m), and g‐ratio. We found age‐related increases of VF_m in most regions, showing ongoing myelination in vivo during late childhood and adolescence for the first time. No relationship was observed between qihMT and age, suggesting myelin volume increases are driven by increased water content. Age‐related increases were observed for NDI, suggesting axonal packing is also occurring during this time. g‐ratio decreased with age in the uncinate fasciculus, implying changes in communication efficiency are ongoing in this region. FA increased and MD decreased with age in most regions. Gender effects were present in the left cingulum for FA, and an age‐by‐gender interaction was found for MD in the left uncinate fasciculus. These findings suggest that FA and MD remain useful markers of gender‐related processes, and gender differences are likely driven by factors other than myelin. We conclude that white matter development during late childhood and adolescence is driven by a combination of axonal packing and myelin volume increases.     

Volume changes and brain‐behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure

Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1–15.9 years) each received two structural magnetic resonance scans, ～2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC‐IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group‐by‐age interactions and group‐score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group‐score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain‐behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE. Hum Brain Mapp 36:2318–2329, 2015. © 2015 Wiley Periodicals, Inc.