Concept: Corpus callosum
Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.
The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.
The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified.
BACKGROUND: Although diffusion tensor imaging has been a major research focus for Alzheimer’s disease in recent years, it remains unclear whether it has sufficient stability to have biomarker potential. To date, frequently inconsistent results have been reported, though lack of standardisation in acquisition and analysis make such discrepancies difficult to interpret. There is also, at present, little knowledge of how the biometric properties of diffusion tensor imaging might evolve in the course of Alzheimer’s disease. METHODS: The biomarker question was addressed in this study by adopting a standardised protocol both for the whole brain (tract-based spatial statistics), and for a region of interest: the midline corpus callosum. In order to study the evolution of tensor changes, cross-sectional data from very mild (N = 21) and mild (N = 22) Alzheimer’s disease patients were examined as well as a longitudinal cohort (N = 16) that had been rescanned at 12 months. FINDINGS AND SIGNIFICANCE: The results revealed that increased axial and mean diffusivity are the first abnormalities to occur and that the first region to develop such significant differences was mesial parietal/splenial white matter; these metrics, however, remained relatively static with advancing disease indicating they are suitable as ‘state-specific’ markers. In contrast, increased radial diffusivity, and therefore decreased fractional anisotropy-though less detectable early-became increasingly abnormal with disease progression, and, in the splenium of the corpus callosum, correlated significantly with dementia severity; these metrics therefore appear ‘stage-specific’ and would be ideal for monitoring disease progression. In addition, the cross-sectional and longitudinal analyses showed that the progressive abnormalities in radial diffusivity and fractional anisotropy always occurred in areas that had first shown an increase in axial and mean diffusivity. Given that the former two metrics correlate with dementia severity, but the latter two did not, it would appear that increased axial diffusivity represents an upstream event that precedes neuronal loss.
BACKGROUND: Diffusion tensor imaging (DTI) is increasingly used in various diseases as a clinical tool for assessing the integrity of the brain’s white matter. Reduced fractional anisotropy (FA) and an increased apparent diffusion coefficient (ADC) are nonspecific findings in most pathological processes affecting the brain’s parenchyma. At present, there is no gold standard for validating diffusion measures, which are dependent on the scanning protocols, methods of the softwares and observers. Therefore, the normal variation and repeatability effects on commonly-derived measures should be carefully examined. METHODS: Thirty healthy volunteers (mean age 37.8 years, SD 11.4) underwent DTI of the brain with 3T MRI. Region-of-interest (ROI) -based measurements were calculated at eleven anatomical locations in the pyramidal tracts, corpus callosum and frontobasal area. Two ROI-based methods, the circular method (CM) and the freehand method (FM), were compared. Both methods were also compared by performing measurements on a DTI phantom. The intra- and inter-observer variability (coefficient of variation, or CV%) and repeatability (intra-class correlation coefficient, or ICC) were assessed for FA and ADC values obtained using both ROI methods. RESULTS: The mean FA values for all of the regions were 0.663 with the CM and 0.621 with the FM. For both methods, the FA was highest in the splenium of the corpus callosum. The mean ADC value was 0.727 x10-3 mm2/s with the CM and 0.747 x10-3 mm2/s with the FM, and both methods found the ADC to be lowest in the corona radiata. The CV percentages of the derived measures were < 13% with the CM and < 10% with the FM. In most of the regions, the ICCs were excellent or moderate for both methods. With the CM, the highest ICC for FA was in the posterior limb of the internal capsule (0.90), and with the FM, it was in the corona radiata (0.86). For ADC, the highest ICC was found in the genu of the corpus callosum (0.93) with the CM and in the uncinate fasciculus (0.92) with FM. CONCLUSIONS: With both ROI-based methods variability was low and repeatability was moderate. The circular method gave higher repeatability, but variation was slightly lower using the freehand method. The circular method can be recommended for the posterior limb of the internal capsule and splenium of the corpus callosum, and the freehand method for the corona radiata.
- Cortex; a journal devoted to the study of the nervous system and behavior
- Published over 7 years ago
Patients with alien hand syndrome (AHS) experience making apparently deliberate and purposeful movements with their hand against their will. However, the mechanisms contributing to these involuntary actions remain poorly understood. Here, we describe two experimental investigations in a patient with corticobasal syndrome (CBS) with alien hand behaviour in her right hand. First, we show that responses with the alien hand are made significantly more quickly to images of objects which afford an action with that hand compared to objects which afford an action with the unaffected hand. This finding suggests that involuntary grasping behaviours in AHS might be due to exaggerated, automatic motor activation evoked by objects which afford actions with that limb. Second, using a backwards masked priming task, we found normal automatic inhibition of primed responses in the patient’s unaffected hand, but importantly there was no evidence of such suppression in the alien limb. Taken together, these findings suggest that grasping behaviours in AHS may result from exaggerated object affordance effects, which might potentially arise from disrupted inhibition of automatically evoked responses.
Diffusion Kurtosis Imaging (DKI) is a diffusion-weighted technique which overcomes limitations of the commonly used diffusion tensor imaging approach. This technique models non-Gaussian behaviour of water diffusion by the diffusion kurtosis tensor (KT), which can be used to provide indices of tissue heterogeneity and a better characterisation of the spatial architecture of tissue microstructure. In this study, the geometry of the KT is elucidated using synthetic data generated from multi-compartmental models, where diffusion heterogeneity between intra and extra-cellular media are taken into account, as well as the sensitivity of the results to each model parameter and to synthetic noise. Furthermore, based on the assumption that maxima of the KT are distributed perpendicularly to the direction of well aligned fibres, a novel algorithm for estimating fibre direction directly from the KT is proposed and compared to the fibre directions extracted from DKI based orientation distribution function (ODF) estimates previously proposed in the literature. Synthetic data results showed that, for fibres crossing at high intersection angles, direction estimates extracted directly from the KT have smaller errors than the DKI based ODF estimation approaches (DKI-ODF). Nevertheless, the proposed method showed smaller angular resolution and lower stability to changes of the simulation parameters. On real data, tractography performed on these KT fibre estimates suggests a higher sensitivity than the DKI based ODF in resolving lateral corpus callosum fibres reaching the pre-central cortex when diffusion acquisition is performed with five b-values. Using faster acquisition schemes, KT based tractography did not show improved performance over the DKI-ODF procedures. Nevertheless, it is shown that direct KT fibres estimates are more adequate for computing a generalized version of radial kurtosis maps.
The use of cannabis with higher ��9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users. Method The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment.
Smaller splenium in children with nonverbal learning disability compared to controls, high-functioning autism and ADHD
- Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence
- Published over 6 years ago
The current study investigated morphological differences in the corpus callosum in children ages 8 to 18 years old with nonverbal learning disability (NLD; n = 19), high-functioning autism (HFA; n = 23), predominantly inattentive ADHD (ADHD:PI; n = 23), and combined type ADHD (ADHD:C; n = 25), as well as those demonstrating typical development (n = 57). Midsagittal area of the corpus callosum and five midsagittal anterior-to-posterior corpus callosum segments were examined using magnetic resonance imaging. Controlling for midsagittal brain area and age, no group differences were found for total corpus callosum area. This finding indicates that higher functioning children on the autistic spectrum do not have smaller corpus callosi as has been found in previous research with heterogeneous samples. Following segmentation of the corpus callosum, the NLD group was observed to have significantly smaller splenia compared to all other groups. Smaller splenia in the NLD group was associated with lower WASI PIQ scores but not WASI VIQ scores. Children with HFA were observed to have larger midbody areas than children with NLD and neurotypically developing children. Children with HFA and NLD demonstrated behavioral symptoms of inattention and hyperactivity similar to the ADHD groups indicating that corpus callosum differences seen in the NLD and HFA groups are not related to these behaviors.
OBJECTIVES: To assess in a large population of patients with clinically isolated syndrome (CIS) the relevance of brain lesion location and frequency in predicting 1-year conversion to multiple sclerosis (MS). METHODS: In this multicenter, retrospective study, clinical and MRI data at onset and clinical follow-up at 1 year were collected for 1,165 patients with CIS. On T2-weighted MRI, we generated lesion probability maps of white matter (WM) lesion location and frequency. Voxelwise analyses were performed with a nonparametric permutation-based approach (p < 0.05, cluster-corrected). RESULTS: In CIS patients with hemispheric, multifocal, and brainstem/cerebellar onset, lesion probability map clusters were seen in clinically eloquent brain regions. Significant lesion clusters were not found in CIS patients with optic nerve and spinal cord onset. At 1 year, clinically definite MS developed in 26% of patients. The converting group, despite a greater baseline lesion load compared with the nonconverting group (7 ± 8.1 cm(3) vs 4.6 ± 6.7 cm(3), p < 0.001), showed less widespread lesion distribution (18% vs 25% of brain voxels occupied by lesions). High lesion frequency was found in the converting group in projection, association, and commissural WM tracts, with larger clusters being in the corpus callosum, corona radiata, and cingulum. CONCLUSIONS: Higher frequency of lesion occurrence in clinically eloquent WM tracts can characterize CIS subjects with different types of onset. The involvement of specific WM tracts, in particular those traversed by fibers involved in motor function and near the corpus callosum, seems to be associated with a higher risk of clinical conversion to MS in the short term.