Differences In Gray Matter Structure Research Articles

Thalamic volume differentiates multiple sclerosis from neuromyelitis optica spectrum disorder: MRI-based retrospective study.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct demyelinating diseases of the central nervous system, each characterized by unique patterns of motor, sensory, and visual dysfunction. While MS typically affects the brain and spinal cord, NMOSD predominantly targets the optic nerves and spinal cord. This study aims to elucidate the morphometric differences between MS and NMOSD by focusing on gray matter volume changes in specific brain regions. We also examined if temporal changes in follow-up MRI differentiate the two disorders. We analyzed anatomical T1-weighted MRI scans from 24 patients with NMOSD and 25 patients with MS using the CAT12 toolbox. Our analysis revealed significant differences in gray matter structure between the two patient groups. Notably, the thalamus was found to be consistently smaller in patients with MS compared to those with NMOSD. This finding aligns with previous research highlighting thalamic atrophy as a hallmark of MS and further underscores the thalamus's role in the disease's pathology. These results provide valuable insights into the distinct neuroanatomical features of MS and NMOSD, contributing to a better understanding of the mechanisms underlying these diseases. The study also emphasizes the importance of advanced imaging techniques in differentiating between MS and NMOSD, which may have implications for diagnosis and treatment strategies.

The relationship between brain structure and function during novel grammar learning across development

Abstract In this study, we explored the relationship between developmental differences in gray matter structure and grammar learning ability in 159 Dutch-speaking individuals (8 to 25 yr). The data were collected as part of a recent large-scale functional MRI study (Menks WM, Ekerdt C, Lemhöfer K, Kidd E, Fernández G, McQueen JM, Janzen G. Developmental changes in brain activation during novel grammar learning in 8–25-year-olds. Dev Cogn Neurosci. 2024;66:101347. https://doi.org/10.1016/j.dcn.2024.101347) in which participants implicitly learned Icelandic morphosyntactic rules and performed a grammaticality judgment task in the scanner. Behaviorally, Menks et al. (2024) showed that grammaticality judgment task performance increased steadily from 8 to 15.4 yr, after which age had no further effect. We show in the current study that this age-related grammaticality judgment task performance was negatively related to cortical gray matter volume and cortical thickness in many clusters throughout the brain. Hippocampal volume was positively related to age-related grammaticality judgment task performance and L2 (English) vocabulary knowledge. Furthermore, we found that grammaticality judgment task performance, L2 grammar proficiency, and L2 vocabulary knowledge were positively related to gray matter maturation within parietal regions, overlapping with the functional MRI clusters that were reported previously in Menks et al. (2024) and which showed increased brain activation in relation to grammar learning. We propose that this overlap in functional and structural results indicates that brain maturation in parietal regions plays an important role in second language learning.

Neuroanatomical alterations in young boys and adolescents with Klinefelter syndrome

Klinefelter syndrome (KS, 47,XXY) is a common sex chromosome aneuploidy in males that is characterized by pubertal developmental delays and a wide range of alterations in cognitive, social and emotional functioning. The neural bases of these behavioral symptoms, however, are unclear. A total of 130 boys and adolescents, including 67 males with KS (11.5 ± 2.8 years) and 63 typically developing (TD; control) males (10.6 ± 2.8 years) underwent MRI scanning and pubertal assessment. Group differences in regional gray matter volume was examined using voxel-based morphometry while controlling for age at scan and total gray matter volume. Thresholded statistical significance maps indicated widespread reductions in frontal and temporal and cerebellar gray matter in males with KS relative to TD males, as well as increases in parietal and occipital gray matter. Secondary analyses explored potential associations between GMV in these regions and pubertal development. Lower testicular volume was a significant predictor of reduced GMV in frontal, temporal and cerebellar subregions, even after accounting for group status (KS, TD). Taken together, these findings add support for a neuroanatomical phenotype of KS and provide initial evidence for a role of pubertal development in KS-associated differences in gray matter structure. Future studies that examine the influence of testosterone supplementation on GMV in males with KS are warranted.

Multimodal classification of extremely preterm and term adolescents using the fusiform gyrus: A machine learning approach

ObjectiveExtremely preterm birth has been associated with atypical visual and neural processing of faces, as well as differences in gray matter structure in visual processing areas relative to full-term peers. In particular, the right fusiform gyrus, a core visual area involved in face processing, has been shown to have structural and functional differences between preterm and full-term individuals from childhood through early adulthood. The current study used multiple neuroimaging modalities to build a machine learning model based on the right fusiform gyrus to classify extremely preterm birth status. MethodExtremely preterm adolescents (n = 20) and full-term peers (n = 24) underwent structural and functional magnetic resonance imaging. Group differences in gray matter density, measured via voxel-based morphometry (VBM), and blood-oxygen level-dependent (BOLD) response to face stimuli were explored within the right fusiform. Using group difference clusters as seed regions, analyses investigating outgoing white matter streamlines, regional homogeneity, and functional connectivity during a face processing task and at rest were conducted. A data driven approach was utilized to determine the most discriminative combination of these features within a linear support vector machine classifier. ResultsGroup differences in two partially overlapping clusters emerged: one from the VBM analysis showing less density in the extremely preterm cohort and one from BOLD response to faces showing greater activation in the extremely preterm relative to full-term youth. A classifier fit to the data from the cluster identified in the BOLD analysis achieved an accuracy score of 88.64% when BOLD, gray matter density, regional homogeneity, and functional connectivity during the task and at rest were included. A classifier fit to the data from the cluster identified in the VBM analysis achieved an accuracy score of 95.45% when only BOLD, gray matter density, and regional homogeneity were included. ConclusionConsistent with previous findings, we observed neural differences in extremely preterm youth in an area that plays an important role in face processing. Multimodal analyses revealed differences in structure, function, and connectivity that, when taken together, accurately distinguish extremely preterm from full-term born youth. Our findings suggest a compensatory role of the fusiform where less dense gray matter is countered by increased local BOLD signal. Importantly, sub-threshold differences in many modalities within the same region were informative when distinguishing between extremely preterm and full-term youth.

Gray Matter Correlates of Creativity in Musical Improvisation.

Creativity has been defined as requiring both novelty and effectiveness, but little is known about how this standard definition applies in music. Here, we present results from a pilot study in which we combine behavioral testing in musical improvisation and structural neuroimaging to relate brain structure to performance in a creative musical improvisation task. Thirty-eight subjects completed a novel improvisation continuation task and underwent T1 MRI. Recorded performances were rated by expert jazz instructors for creativity. Voxel-based morphometric analyses on T1 data showed that creativity ratings were negatively associated with gray matter volume in the right inferior temporal gyrus and bilateral hippocampus. The duration of improvisation training, which was significantly correlated with creativity ratings, was negatively associated with gray matter volume in the rolandic operculum. Together, results show that musical improvisation ability and training are associated with gray matter volume in regions that are previously linked to learning and memory formation, perceptual categorization, and sensory integration. The present study takes a first step towards understanding the neuroanatomical basis of musical creativity by relating creative musical improvisation to individual differences in gray matter structure.

Revisiting Abnormalities in Brain Network Architecture Underlying Autism Using Topology-Inspired Statistical Inference.

A large body of evidence relates autism with abnormal structural and functional brain connectivity. Structural covariance magnetic resonance imaging (scMRI) is a technique that maps brain regions with covarying gray matter densities across subjects. It provides a way to probe the anatomical structure underlying intrinsic connectivity networks (ICNs) through analysis of gray matter signal covariance. In this article, we apply topological data analysis in conjunction with scMRI to explore network-specific differences in the gray matter structure in subjects with autism versus age-, gender-, and IQ-matched controls. Specifically, we investigate topological differences in gray matter structure captured by structural correlation graphs derived from three ICNs strongly implicated in autism, namely the salience network, default mode network, and executive control network. By combining topological data analysis with statistical inference, our results provide evidence of statistically significant network-specific structural abnormalities in autism.

Impairments of gray matter in MRI-negative epileptic patients with different seizure types

Objective: To investigate the damage of gray matter structure in MRI-negative epilepsy patients with different symptoms by voxel-based morphometry (VBM). Methods: From June, 2009 to October, 2016, ninety MRI-negative epilepsy patients and thirty-five healthy volunteers underwent the 3T magnetic resonance imaging scan in Nanjing General Hospital. The patients were divided into three groups, including idiopathic generalized tonic-clonic seizure (I-GTCS), secondarily generalized tonic-clonic seizure (S-GTCS), and partial seizure (PS) according to different symptoms. The three-dimensional high-resolution T1 structural MRI data was obtained for the voxel-based morphometry. Data of gray matter structure from four groups were compared using one-way analysis of variance (ANOVA). An independent-sample t test was performed in order to compare gray matter volume of the three patient groups with controls respectively. According the results of ANOVA, impaired brain regions were selected as regions of interest in order to carry out correlation analysis between gray matter volume and disease duration. Results: ANOVA showed significant differences in gray matter structure of bilateral thalamus and frontal lobe between four groups (alphasim correction, P<0.01). Independent-sample t test showed that the volume of bilateral thalamus and frontal lobe decreased in all three patients groups (alphasim correction, P<0.01) .The volume of bilateral thalamus showed significantly negatively correlation with disease duration in I-GTCS patients (r=-0.466, P<0.01). Conclusions: Generalized seizures and partial seizures all can cause damage to the gray matter structure, especially in thalamus and frontal lobe. The impairments of thalamus and frontal lobe in patients with different seizure types are different with the progression of disease, which suggests that influences of different epilepsy seizures on the thalamo-cortical network are different.

Differences in gray matter structure correlated to nationalism and patriotism.

Nationalism and patriotism both entail positive evaluations of one’s nation. However, the former inherently involves derogation of other nations, whereas the latter is independent of comparisons with other nations. We used voxel-based morphometry and psychological measures and determined nationalism and patriotism’s association with gray matter density (rGMD) and their cognitive nature in healthy individuals (433 men and 344 women; age, 20.7 ± 1.9 years) using whole-brain multiple regression analyses and post hoc analyses. We found higher nationalism associated with greater rGMD in (a) areas of the posterior cingulate cortex and greater rGMD in (b) the orbitofrontal cortex, and smaller rGMD in (c) the right amygdala area. Furthermore, we found higher patriotism associated with smaller rGMD in the (d) rostrolateral prefrontal cortex. Post hoc analyses revealed the mean rGMD of the cluster (a) associated with compassion, that of (b) associated with feeling of superiority, that of (c) associated with suicide ideation, and that of (d) associated with quality of life. These results indicate that individual nationalism may be mediated by neurocognitive mechanisms in social-related areas and limbic neural mechanisms, whereas patriotism may be mediated by neurocognitive mechanisms in areas related to well-being.

Structural Gray Matter Differences During Childhood Development in Autism Spectrum Disorder: A Multimetric Approach

BackgroundAutism spectrum disorder is a complex neurodevelopmental disorder characterized by impaired social interaction and communication, repetitive behaviors, and restricted interests. Gray matter differences linked to autism spectrum disorder have been studied using a variety of structural imaging methods, but yielded little consensus; the extent to which disparate results reflect differences in methodology or heterogeneity within autism spectrum disorder is not yet clear. Moreover, very few studies have examined gray matter changes as a function of age in autism spectrum disorder. MethodA detailed investigation of gray matter structural development was performed via voxel-based morphometry, cortical thickness, and cortical surface area analyses in 38 autism spectrum disorder versus 46 typically developing children. ResultsRelative to typically developing children, the autism spectrum disorder group showed gray matter increases most prominently in the frontal and temporal lobes (including regions such as medial frontal gyrus, Broca's area and posterior temporal cortex), as well as certain parietal and occipital subcortical regions. Gray matter decreases were found only near the temporoparietal junction. Subcortical gray matter increases were found in the putamen and caudate nucleus, while decreases were found in cerebellum. There were age-dependent GM differences in distributed regions including prefrontal cortex, primary sensorimotor cortex, and temporoparietal junction. ConclusionThe results underline the distributed nature of gray matter structural differences in autism spectrum disorder and provide a more comprehensive characterization of autism spectrum disorder–related cortical and subcortical gray matter structural differences during childhood and adolescent development.

Is there a bit of autism in all of us? Autism spectrum traits are related to cortical thickness differences in both autism and typical development

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction, as well as repetitive behaviors and interests. However, these traits are highly variable across individuals with ASD and are also present in the typically developing population. Brain structural correlates of ASD are also heterogeneous. Recent findings have indicated that ASD traits as measured by the autism quotient (AQ) are reflected in white matter structural differences in a continuous way across both typically-developed and ASD individuals. Here, we tested for the first time, how ASD traits are related to gray matter structural differences (and particularly cortical thickness) in both ASD and typically developing adults. The present results show that ASD traits are primarily correlated with reductions in cortical thickness in a continuous fashion across ASD and typically developing adults in social brain areas and the default mode network including the orbitofrontal cortex, postcentral gyrus, and lingual gyrus. These findings provide new evidence that ASD traits are primarily reflected in neural structure that exists along a continuum extending into the typically developing population.

Abnormal resting state FMRI activity predicts processing speed deficits in first-episode psychosis.

Little is known regarding the neuropsychological significance of resting state functional magnetic resonance imaging (rs-fMRI) activity early in the course of psychosis. Moreover, no studies have used different approaches for analysis of rs-fMRI activity and examined gray matter thickness in the same cohort. In this study, 41 patients experiencing a first-episode of psychosis (including N=17 who were antipsychotic drug-naive at the time of scanning) and 41 individually age- and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and neuropsychological assessments. We computed correlation matrices for 266 regions-of-interest across the brain to assess global connectivity. In addition, independent component analysis (ICA) was used to assess group differences in the expression of rs-fMRI activity within 20 predefined publicly available templates. Patients demonstrated lower overall rs-fMRI global connectivity compared with healthy volunteers without associated group differences in gray matter thickness assessed within the same regions-of-interest used in this analysis. Similarly, ICA revealed worse rs-fMRI expression scores across all 20 networks in patients compared with healthy volunteers, with posthoc analyses revealing significant (p<0.05; corrected) abnormalities within the caudate nucleus and planum temporale. Worse processing speed correlated significantly with overall lower global connectivity using the region-of-interest approach and lower expression scores within the planum temporale using ICA. Our findings implicate dysfunction in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic treatment using different analytic approaches (in the absence of concomitant gray matter structural differences) that predict processing speed.

Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative

A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor, high-homocysteine levels in the blood, is known to increase risk for Alzheimer's disease and vascular disorders. Here, we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, and surface area) computed from brain magnetic resonance imaging in 803 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative data set. Individuals with higher plasma levels of homocysteine had lower gray matter thickness in bilateral frontal, parietal, occipital, and right temporal regions and lower gray matter volumes in left frontal, parietal, temporal, and occipital regions, after controlling for diagnosis, age, and sex and after correcting for multiple comparisons. No significant within-group associations were found in cognitively healthy people, patients with mild cognitive impairment, or patients with Alzheimer's disease. These regional differences in gray matter structure may be useful biomarkers to assess the effectiveness of interventions, such as vitamin B supplements, that aim to prevent homocysteine-related brain atrophy by normalizing homocysteine levels.

Structural gray matter abnormalities in migraine relate to headache lateralization, but not aura.

The hallmark of migraine aura (MA) is transient cortical dysfunction but it is not known if MA is associated with structural cortical or subcortical changes. To determine the relation between MA and structural gray matter abnormalities, we studied a unique sample of 20 patients with frequent side-locked MA, i.e. visual aura consistently occurring in the same hemifield. We applied a highly sensitive within-patient design to assess anatomical differences with both voxel-based morphometry and surface-based morphometry on a whole-hemisphere level and for specific anatomical regions of interest. Within-subject comparisons were made with regard to aura symptoms (N = 20 vs 20) and with regard to headache (N = 13 vs 13). We found no differences in gray matter structure with regard to aura symptoms in MA patients. Comparing the typical migraine headache side of the patients to the contralateral side revealed a difference in cortical thickness in the inferior frontal gyrus (mean difference 0.12 mm, p = 0.036). MA per se is associated with abnormal function but not with lateralized abnormalities of gray matter structure. Alteration of the inferior frontal cortex suggests structural reorganization of pain inhibitory circuits in response to the repeated intense nociceptive input due to the headache attacks.

Early Musical Training Is Linked to Gray Matter Structure in the Ventral Premotor Cortex and Auditory–Motor Rhythm Synchronization Performance

Evidence in animals and humans indicates that there are sensitive periods during development, times when experience or stimulation has a greater influence on behavior and brain structure. Sensitive periods are the result of an interaction between maturational processes and experience-dependent plasticity mechanisms. Previous work from our laboratory has shown that adult musicians who begin training before the age of 7 show enhancements in behavior and white matter structure compared with those who begin later. Plastic changes in white matter and gray matter are hypothesized to co-occur; therefore, the current study investigated possible differences in gray matter structure between early-trained (ET; <7) and late-trained (LT; >7) musicians, matched for years of experience. Gray matter structure was assessed using voxel-wise analysis techniques (optimized voxel-based morphometry, traditional voxel-based morphometry, and deformation-based morphometry) and surface-based measures (cortical thickness, surface area and mean curvature). Deformation-based morphometry analyses identified group differences between ET and LT musicians in right ventral premotor cortex (vPMC), which correlated with performance on an auditory motor synchronization task and with age of onset of musical training. In addition, cortical surface area in vPMC was greater for ET musicians. These results are consistent with evidence that premotor cortex shows greatest maturational change between the ages of 6-9 years and that this region is important for integrating auditory and motor information. We propose that the auditory and motor interactions required by musical practice drive plasticity in vPMC and that this plasticity is greatest when maturation is near its peak.

ScMRI Reveals Large-Scale Brain Network Abnormalities in Autism

Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a ‘posteriorization’ of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI.

Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes

By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC). We assessed white matter integrity and gray matter volume using diffusion tensor tractography-based analysis of fractional anisotropy and voxel-based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic-clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE-GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic-clonic seizures and fractional anisotropy were investigated for both groups. Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE-GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic-clonic seizures for either JME or IGE-GTC. Although false discovery rate-corrected voxel-based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster-corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE-GTC. The findings support the idea that the clinical syndromes of JME and IGE-GTC have unique anatomic substrates. The fact that the primary clinical difference between JME and IGE-GTC is the occurrence of myoclonus in the former raises the possibility that disruption of white matter integrity may be the underlying mechanism responsible for myoclonus in JME. The cross-sectional study design and relatively small number of subjects limits the conclusions that can be drawn here; however, the absence of a correlation between fractional anisotropy and lifetime seizures is suggestive that the white matter abnormalities observed in JME may not be secondary to seizures.

Stress reduction correlates with structural changes in the amygdala

Stress has significant adverse effects on health and is a risk factor for many illnesses. Neurobiological studies have implicated the amygdala as a brain structure crucial in stress responses. Whereas hyperactive amygdala function is often observed during stress conditions, cross-sectional reports of differences in gray matter structure have been less consistent. We conducted a longitudinal MRI study to investigate the relationship between changes in perceived stress with changes in amygdala gray matter density following a stress-reduction intervention. Stressed but otherwise healthy individuals (N = 26) participated in an 8-week mindfulness-based stress reduction intervention. Perceived stress was rated on the perceived stress scale (PSS) and anatomical MR images were acquired pre- and post-intervention. PSS change was used as the predictive regressor for changes in gray matter density within the bilateral amygdalae. Following the intervention, participants reported significantly reduced perceived stress. Reductions in perceived stress correlated positively with decreases in right basolateral amygdala gray matter density. Whereas prior studies found gray matter modifications resulting from acquisition of abstract information, motor and language skills, this study demonstrates that neuroplastic changes are associated with improvements in a psychological state variable.

Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: A preliminary voxel-based morphometry study

Neuroimaging studies have identified alterations in frontostriatal circuitry in obsessive-compulsive disorder (OCD). Voxel-based morphometry (VBM) allows for the assessment of differences in gray matter density across the whole brain. VBM has not previously been used to examine regional gray matter density in pediatric OCD patients and the siblings of pediatric OCD patients. Volumetric magnetic resonance imaging (MRI) studies were conducted in 10 psychotropic naïve pediatric patients with OCD, 10 unaffected siblings of pediatric patients with OCD, and 10 healthy controls. VBM analysis was conducted using SPM2. Statistical comparisons were performed with the general linear model, implementing small volume random field corrections for a priori regions of interest (anterior cingulate cortex or ACC, striatum and thalamus). VBM analysis revealed significantly lower gray matter density in OCD patients compared to healthy in the left ACC and bilateral medial superior frontal gyrus (SFG). Furthermore, a small volume correction was used to identify a significantly greater gray matter density in the right putamen in OCD patients as compared to unaffected siblings of OCD patients. These findings in patients, siblings, and healthy controls, although preliminary, suggest the presence of gray matter structural differences between affected subjects and healthy controls as well as between affected subjects and individuals at risk for OCD.