Cerebral Gray Matter Research Articles

Interhypothalamic adhesions: prevalence, structure, and location-based classification map in pediatric patients undergoing MRI.

Interhypothalamic adhesions (IHAs) have been reported only in the pediatric population, with unknown prevalence and histological composition. We aim to demonstrate their prevalence, assess their persistence through longitudinal imaging, classify IHAs by anatomical distribution, explore their structure, and report associated pathologies. A retrospective review was conducted on consecutive pediatric brain MRI studies obtained between January 2012, and December 2013. The presence of an IHA was only confirmed when observed on at least two planes. For each IHA, cross-sectional area was calculated, and signal intensities were measured at the center on sagittal T2WIs. Signal intensities were also measured in both cerebral white matter and gray matter for normalization and comparison. Patient demographics and clinical information were collected from electronic charts. Out of 1550 patients (0-17.9 years), 33 (19 males, 14 females) had an IHA, resulting in a 2.13% prevalence. Follow-up images were available for 19 IHA-positive patients, and IHAs were again seen in 92% of the follow-up scans (71/77). Normalized IHA signal highly correlated with normalized gray matter signal (r = 0.83, P < 0.001), but not with normalized white matter signal (r = -0.16, p = 0.494). Common co-occurring pathologies included hydrocephalus (n = 9), prematurity (n = 8), and corpus callosum abnormalities (n = 7). All type 3 IHAs (3/3) were accompanied by pituitary pathologies. IHAs have a prevalence of 2.13% in our cohort, and the majority persist in longitudinal studies. They showed gray matter signal intensity and Type 3 IHAs exclusively accompanied pituitary abnormalities.

Diffusion kurtosis imaging, MAP-MRI and NODDI can selectively track gray matter myelin density in the primate cerebral cortex

Abstract Diffusion magnetic resonance imaging (dMRI) has been widely used to model the trajectory of myelinated fiber bundles in the white matter. Increasingly, it is also used to evaluate the microstructure of the cerebral cortex gray matter. For example, in diffusion tensor imaging (DTI) of the cortex, fractional anisotropy (FA) correlates strongly with the anisotropy of cellular anatomy, while radial diffusivity (RD) tracks the anisotropy of myelinated fibers. However, no DTI parameter shows specificity to gray matter myelin density. Here we show that three higher order diffusion parameters - the mean diffusion kurtosis (MK), the Neurite Density Index (NDI) from NODDI, and the Non-Gaussian (NG) parameter from MAP-MRI— each track the laminar and regional myelin density of the primate cerebral cortex in fine detail. We carried out ultra-high resolution, multi-shelled dMRI in ex-vivo marmoset monkey brains. We compared the spatial mapping of the MK, NDI, and ND diffusion parameters to the cortical myelin distribution of these brains, with the latter obtained in two ways: First, using histological sections finely co-registered to the MRI, and second using magnetization transfer ratio MRI scans (MTR), an established non-diffusion method for imaging myelin density. We found that, in contrast to DTI parameters, each of these higher order diffusion measures captured the spatial variation of myelin density in the cortex. The demonstration that diffusion parameters exhibit both sensitivity and specificity for gray matter myelin density will allow dMRI to more effectively track human disease, in which myelinated and non-myelinated tissue compartments are affected differentially.

Optimal timing of ultra-early diffusion-weighted MRI in out-of-hospital cardiac arrest patients based on a retrospective multicenter cohort study

Diffusion-weighted magnetic resonance imaging (DW-MRI) performed before target temperature management, within 6 h of return of spontaneous circulation (ROSC), is defined as ultra-early DW-MRI. In previous studies, high-signal intensity (HSI) on ultra-early DW-MRI can predict poor neurological outcomes (Cerebral Performance Category 3–5 at 6-months post-ROSC). We aimed to assess the optimal-timing for ultra-early DW-MRI to avoid false-negative outcomes post out-of-hospital cardiac arrest, considering cardiopulmonary resuscitation (CPR) factors. The primary outcomes were HSI in the cerebral cortex or deep gray matter on ultra-early DW-MRI. The impact of CPR factors and ROSC to DW-MRI scan-interval on HSI-presence was assessed. Of 206 included patients, 108 exhibited HSI-presence, exclusively associated with poor neurological outcomes. In multivariate regression analysis, ROSC to DW-MRI scan-interval (adjusted odds ratio [aOR], 1.509; 95% confidence interval (CI): 1.113–2.046; P = 0.008), low-flow time (aOR, 1.176; 95%CI: 1.121–1.233; P < 0.001), and non-shockable rhythm (aOR, 9.974; 95%CI: 3.363–29.578; P < 0.001) were independently associated with HSI-presence. ROSC to DW-MRI scan-interval cutoff of ≥ 2.2 h was particularly significant in low-flow time ≤ 21 min or shockable rhythm group. In conclusion, short low-flow time and shockable rhythm require a longer ROSC to DW-MRI scan-interval. Prolonged low-flow time and non-shockable rhythm reduce the need to consider scan-interval.

Cross-modality image translation of 3 Tesla Magnetic Resonance Imaging to 7 Tesla using Generative Adversarial Networks.

The rapid advancements in magnetic resonance imaging (MRI) technology have precipitated a new paradigm wherein cross-modality data translation across diverse imaging platforms, field strengths, and different sites is increasingly challenging. This issue is particularly accentuated when transitioning from 3 Tesla (3T) to 7 Tesla (7T) MRI systems. This study proposes a novel solution to these challenges using generative adversarial networks (GANs)-specifically, the CycleGAN architecture- to create synthetic 7T images from 3T data. Employing a dataset of 1112 and 490 unpaired 3T and 7T MR images, respectively, we trained a 2-dimensional (2D) CycleGAN model, evaluating its performance on a paired dataset of 22 participants scanned at 3T and 7T. Independent testing on 22 distinct participants affirmed the model's proficiency in accurately predicting various tissue types, encompassing cerebral spinal fluid, gray matter, and white matter. Our approach provides a reliable and efficient methodology for synthesizing 7T images, achieving a median Dice of 6.82%,7,63%, and 4.85% for Cerebral Spinal Fluid (CSF), Gray Matter (GM), and White Matter (WM), respectively, in the testing dataset, thereby significantly aiding in harmonizing heterogeneous datasets. Furthermore, it delineates the potential of GANs in amplifying the contrast-to-noise ratio (CNR) from 3T, potentially enhancing the diagnostic capability of the images. While acknowledging the risk of model overfitting, our research underscores a promising progression towards harnessing the benefits of 7T MR systems in research investigations while preserving compatibility with existent 3T MR data. This work was previously presented at the ISMRM 2021 conference (Diniz, Helmet, Santini, Aizenstein, & Ibrahim, 2021).

A novel missense variant in the RELN gene in sheep with lissencephaly and cerebellar hypoplasia.

Lissencephaly and cerebellar hypoplasia (LCH) represents a spectrum of congenital developmental malformations of the cerebral cortex and cerebellum, mostly occurring as inherited conditions caused by variants in an increasingly recognized number of genes. LCH has been identified in three Dorset-cross lambs with congenital neurological signs in Australia. Lambs were unable to walk and had reduced vision, and one lamb developed a hypermetric gait and intention tremors. Grossly, the lambs had diffuse pachygyria with reduction in white matter, mild bilateral ventriculomegaly of the lateral ventricles, and a markedly hypoplastic cerebellum. Histologically, there was disorganization of neurons within the cerebral cortex and hippocampus. The cerebellar vermis had disorganized, thin, and hypocellular gray matter with frequent ectopic Purkinje cells, while identifiable folia were largely absent within the hemispheres. Luxol fast blue stain and glial fibrillary acidic protein, neuronal nuclear protein, synaptophysin, and neuron-specific enolase immunohistochemistry confirmed the thickened, disorganized cerebral cortical gray matter and reduced white matter. Within the cerebellum, immunohistochemistry demonstrated marked dysplasia. Whole-genome sequencing analysis and prediction of variant effects identified a missense variant of interest in the candidate gene reelin (RELN; NC_040255.1:g.50288685C>T; NM_001306121.1:c.7088G>A; NP_001293050.1:p.(R2363H)) with a deleterious Sorting Intolerant from Tolerant (SIFT) score. Sanger sequencing identified that the variant segregated with LCH disease in the 3 affected individuals, their sire, and 6 unaffected flock members. The NP_001293050.1: p.(R2363H) substitution is predicted to decrease the stability of the protein (ΔΔG = -1.55 kcal/mol). Pathological and genetic findings are consistent with previously described phenotypes of RELN variants in Churra sheep, dogs, and humans.

Early regional cerebral grey matter damage predicts long-term cognitive impairment phenotypes in multiple sclerosis: a 20-year study.

Despite grey matter atrophy in cortical and subcortical regions has been related to cognitive impairment in multiple sclerosis, only a few studies evaluated its predictive value for alterations in the long-term. We aimed to determine early predictors of cognitive status after 20 years of multiple sclerosis. In this longitudinal retrospective study, participants underwent a 1.5 T MRI scanning at diagnosis (T0) and after two years (T2), which included the evaluation of regional grey matter volume loss patterns. All individuals with multiple sclerosis underwent a comprehensive neuropsychological assessment at the end of the study and were classified considering their global and specific cognitive domains status (memory, attention/information processing speed, executive functioning). Clinical and MRI characteristics were assessed as predictors of long-term cognitive impairment. Analysis of covariance, t-test, unadjusted and adjusted (for age, sex, disease duration, volume of white matter lesions, volume of cortical lesions) logistic regression were conducted. One hundred seventy-five people with multiple sclerosis (118 females; mean ± SD age at the end of study = 47.7 ± 9.4 years) clinically followed for 20 years from onset (mean ± SD = 19.9 ± 5.1) were evaluated. At the end of the study, 81 (47%) were classified as cognitively impaired: 38 as mildly impaired (22%), and 43 as severely impaired (25%). In particular, 46 were impaired in memory (27%), 66 were impaired in attention/information processing speed (38%), and 71 were impaired in executive functioning (41%). Regression models identified precuneus (adjusted odds ratio = 3.37; P < 0.001), insula (adjusted odds ratio = 2.33; P = 0.036), parahippocampal gyrus (adjusted odds ratio = 2.07; P < 0.001) and cingulate (adjusted odds ratio = 1.81; P = 0.009) as the most associated regions with global cognitive impairment and domains-specific cognitive alterations after a mean of 20 years of multiple sclerosis, after adjusting for demographic and clinical variables as well as for focal white matter and grey matter damage. Early grey matter volume loss of specific cortical and deep grey matter regions predicts global and domain cognitive alterations after 20 years from multiple sclerosis diagnosis.

Dimethyl Fumarate Strongly Ameliorates Gray and White Matter Brain Injury and Modulates Glial Activation after Severe Hypoxia-Ischemia in Neonatal Rats.

Neonatal hypoxia-ischemia is a major cause of infant death and disability. The only clinically accepted treatment is therapeutic hypothermia; however, cooling is less effective in the most severely encephalopathic infants. Here, we wanted to test the neuroprotective effect of the antioxidant dimethyl fumarate after severe hypoxia-ischemia in neonatal rats. We used a modified Rice-Vannucci model to generate severe hypoxic-ischemic brain damage in day 7 postnatal rats, which were randomized into four experimental groups: Sham, Sham + DMF, non-treated HI, and HI + DMF. We analyzed brain tissue loss, global and regional (cortex and hippocampus) neuropathological scores, white matter injury, and microglial and astroglial reactivity. Compared to non-treated HI animals, HI + DMF pups showed a reduced brain area loss (p = 0.0031), an improved neuropathological score (p = 0.0016), reduced white matter injuries by preserving myelin tracts (p < 0.001), and diminished astroglial (p < 0.001) and microglial (p < 0.01) activation. After severe hypoxia-ischemia in neonatal rats, DMF induced a strong neuroprotective response, reducing cerebral infarction, gray and white matter damage, and astroglial and microglial activation. Although further molecular studies are needed and its translation to human babies would need to evaluate the molecule in piglets or lambs, DMF may be a potential treatment against neonatal encephalopathy.

Gray Matter Volumes Mediate the Relationship Between Disease Duration and Balance Control Performance in Chronic Ankle Instability.

The relationship between structural changes in the cerebral gray matter and diminished balance control performance in patients with chronic ankle instability (CAI) has remained unclear. This paper aimed to assess the difference in gray matter volume (GMV) between participants with CAI and healthy controls (HC) and to characterize the role of GMV in the relationship between disease duration and balance performance in CAI. 42 participants with CAI and 33 HC completed the structural brain MRI scans, one-legged standing test, and Y-balance test. Regional GMV was measured by applying voxel-based morphometry methods. The result showed that, compared with HC, participants with CAI exhibited lower GMV in multiple brain regions (familywise error [FWE] corrected p < 0.021). Within CAI only, but not in HC, lower GMV in the thalamus (β = -0.53, p = 0.003) and hippocampus (β = -0.57, p = 0.001) was associated with faster sway velocity of the center of pressure (CoP) in eyes closed condition (i.e., worse balance control performance). The GMV in the thalamus (percentage mediated [PM] = 32.02%; indirect effect β = 0.119, 95% CI = 0.003 to 0.282) and hippocampus (PM = 33.71%; indirect effect β = 0.122, 95% CI = 0.005 to 0.278) significantly mediated the association between the disease duration and balance performance. These findings suggest that the structural characteristics of the supraspinal elements is critical to the maintenance of balance control performance in individuals suffering from CAI, which deserve careful consideration in the management and rehabilitation programs in this population.

The Combination of Presurgical Cortical Gray Matter Volumetry and Cerebral Perfusion Improves the Efficacy of Predicting Postoperative Cognitive Impairment of Elderly Patients.

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.

Alterations in Gray Matter Structural Networks in Amnestic Mild Cognitive Impairment: A Source-Based Morphometry Study.

Amnestic mild cognitive impairment (aMCI), considered as the prodromal stage of Alzheimer's disease, is characterized by isolated memory impairment and cerebral gray matter volume (GMV) alterations. Previous structural MRI studies in aMCI have been mainly based on univariate statistics using voxel-based morphometry. We investigated structural network differences between aMCI patients and cognitively normal older adults by using source-based morphometry, a multivariate approach that considers the relationship between voxels of various parts of the brain. Ninety-one aMCI patients and 80 cognitively normal controls underwent structural MRI and neuropsychological assessment. Spatially independent components (ICs) that covaried between participants were estimated and a multivariate analysis of covariance was performed with ICs as dependent variables, diagnosis as independent variable, and age, sex, education level, and site as covariates. aMCI patients exhibited reduced GMV in the precentral, temporo-cerebellar, frontal, and temporal network, and increased GMV in the left superior parietal network compared to controls (pFWER < 0.05, Holm-Bonferroni correction). Moreover, we found that diagnosis, more specifically aMCI, moderated the positive relationship between occipital network and Mini-Mental State Examination scores (pFWER < 0.05, Holm-Bonferroni correction). Our results showed GMV alterations in temporo-fronto-parieto-cerebellar networks in aMCI, extending previous results obtained with univariate approaches.

Magnetic resonance imaging pattern recognition of metabolic and neurodegenerative encephalopathies in dogs and cats.

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

Ageing-related tau astrogliopathy severely affecting the substantia nigra.

Astrocytic tau pathology is a major feature of tauopathies and ageing-related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement. We aimed to identify cases with prominent astrocytic tau pathology in the SN. We use the term nigral tau-astrogliopathy (NITAG) to describe cases showing an unusually high density of ARTAG with less neuronal tau pathology in the SN. We collected clinical information and studied the distribution of tau pathology, morphological features and immunostaining profiles in three cases. Three cases, all males with parkinsonism, were identified with the following clinicopathological diagnoses: (i) atypical parkinsonism with tau pathology reminiscent to that in postencephalitic parkinsonism (69-year-old); (ii) multiple system atrophy (73-year-old); (iii) traumatic encephalopathy syndrome/chronic traumatic encephalopathy (84-year-old). Double-labelling immunofluorescence confirmed co-localization of GFAP and phosphorylated tau in affected astrocytes. Staining profiles of NITAG revealed immunopositivity for various phosphorylated tau antibodies. Some astrocytic tau lesions were also seen in other brainstem regions and cerebral grey matter. We propose NITAG is a rare neuropathological feature, and not a distinct disease entity, in the frame of multiple system ARTAG, represented by abundant tau-positive astrocytes in various brain regions but having the highest density in the SN. The concept of NITAG allows the stratification of cases with various background pathologies to understand its relevance and contribution to neuronal dysfunction.

Mild neonatal hypoxia disrupts adult hippocampal learning and memory and is associated with CK2-mediated dysregulation of synaptic calcium-activated potassium channel KCNN2.

Although nearly half of preterm survivors display persistent neurobehavioral dysfunction including memory impairment without overt gray matter injury, the underlying mechanisms of neuronal or glial dysfunction, and their relationship to commonly observed cerebral white matter injury are unclear. We developed a mouse model to test the hypothesis that mild hypoxia during preterm equivalence is sufficient to persistently disrupt hippocampal neuronal maturation related to adult cellular mechanisms of learning and memory. Methods: Neonatal (P2) mice were exposed to mild hypoxia (8%O 2 ) for 30 min and evaluated for acute injury responses or survived until adulthood for assessment of learning and memory and hippocampal neurodevelopment. Neonatal mild hypoxia resulted in clinically relevant oxygen desaturation and tachycardia without bradycardia and was not accompanied by cerebral gray or white matter injury. Neonatal hypoxia exposure was sufficient to cause hippocampal learning and memory deficits and abnormal maturation of CA1 neurons that persisted into adulthood. This was accompanied by reduced hippocampal CA3-CA1 synaptic strength and LTP and reduced synaptic activity of calcium-sensitive SK2 channels, key regulators of spike timing dependent neuroplasticity, including LTP. Structural illumination microscopy revealed reduced synaptic density, but intact SK2 localization at the synapse. Persistent loss of SK2 activity was mediated by altered casein kinase 2 (CK2) signaling. Clinically relevant mild hypoxic exposure in the neonatal mouse is sufficient to produce morphometric and functional disturbances in hippocampal neuronal maturation independently of white matter injury. Additionally, we describe a novel persistent mechanism of potassium channel dysregulation after neonatal hypoxia. Collectively our findings suggest an unexplored explanation for the broad spectrum of neurobehavioral, cognitive and learning disabilities that paradoxically persist into adulthood without overt gray matter injury after preterm birth.

A study of the correlation between gray matter atrophy in multiple sclerosis and impairment of cognitive function domains

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

Perinatal influences on academic achievement and the developing brain: a scoping systematic review.

In this PRISMA-compliant systematic review, we identify and synthesize the findings of research in which neuroimaging and assessments of achievement have been used to examine the relationships among aspects of developmental programming, neurodevelopment, and achievement in reading and mathematics. Forty-seven studies met inclusion criteria. The majority examined the impact of prematurity (n = 32) and prenatal alcohol exposure (n = 13). Several prematurity studies reported a positive correlation between white-matter integrity of callosal fibers and executive functioning and/or achievement, and white matter properties were consistently associated with cognitive and academic performance in preterm and full-term children. Volumetric studies reported positive associations between academic and cognitive abilities and white and gray matter volume in regions such as the insula, putamen, and prefrontal lobes. Functional MRI studies demonstrated increased right-hemispheric language processing among preterm children. Altered activation of the frontoparietal network related to numerical abilities was also reported. Prenatal alcohol exposure studies reported alterations in white matter microstructure linked to deficits in cognitive functioning and academic achievement, including mathematics, reading, and vocabulary skills. Volumetric studies reported reductions in cerebral, cerebellar, and subcortical gray matter volumes associated with decreased scores on measures of executive functioning, attention, working memory, and academic performance. Functional MRI studies demonstrated broad, diffuse activation, reduced activation in canonical regions, and increased activation in non-canonical regions during numeric tasks. A preponderance of studies linked prematurity and prenatal alcohol exposure to altered neurodevelopmental processes and suboptimal academic achievement. Limitations and recommendations for future research are discussed. Identifier: DOI 10.17605/OSF.IO/ZAN67.

Cerebral Gray Matter May Not Explain Sleep Slow-Wave Characteristics after Severe Brain Injury.

Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that gray matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between gray matter volume (GMV) and slow-wave characteristics in 27 patients with moderate-to-severe traumatic brain injury (TBI, 32.0 ± 12.2 years old, eight women) and compared that with 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3 Tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6 Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and gray matter in regions implicated in the generation and/or propagation of slow waves. Compared with controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, but only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.

Cerebellar gray matter and white matter damage among older adults with prediabetes

AimsTo investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. MethodsThe current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. ResultsParticipants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. ConclusionsCerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.

Repeated caffeine intake suppresses cerebral grey matter responses to chronic sleep restriction in an A1 adenosine receptor-dependent manner: a double-blind randomized controlled study with PET-MRI

Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

Multimodal brain age prediction using machine learning: combining structural MRI and 5-HT2AR PET-derived features

To better assess the pathology of neurodegenerative disorders and the efficacy of neuroprotective interventions, it is necessary to develop biomarkers that can accurately capture age-related biological changes in the human brain. Brain serotonin 2A receptors (5-HT2AR) show a particularly profound age-related decline and are also reduced in neurodegenerative disorders, such as Alzheimer’s disease. This study investigates whether the decline in 5-HT2AR binding, measured in vivo using positron emission tomography (PET), can be used as a biomarker for brain aging. Specifically, we aim to (1) predict brain age using 5-HT2AR binding outcomes, (2) compare 5-HT2AR-based predictions of brain age to predictions based on gray matter (GM) volume, as determined with structural magnetic resonance imaging (MRI), and (3) investigate whether combining 5-HT2AR and GM volume data improves prediction. We used PET and MR images from 209 healthy individuals aged between 18 and 85 years (mean = 38, std = 18) and estimated 5-HT2AR binding and GM volume for 14 cortical and subcortical regions. Different machine learning algorithms were applied to predict chronological age based on 5-HT2AR binding, GM volume, and the combined measures. The mean absolute error (MAE) and a cross-validation approach were used for evaluation and model comparison. We find that both the cerebral 5-HT2AR binding (mean MAE = 6.63 years, std = 0.74 years) and GM volume (mean MAE = 6.95 years, std = 0.83 years) predict chronological age accurately. Combining the two measures improves the prediction further (mean MAE = 5.54 years, std = 0.68). In conclusion, 5-HT2AR binding measured using PET might be useful for improving the quantification of a biomarker for brain aging.