Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents

Background: Diffusion tensor imaging (DTI) has revealed microstructural aspects of adolescent brain development, the cognitive correlates of which remain relatively uncharacterized. Methods: DTI was used to assess white matter microstructure in 18 typically developing adolescents (ages 16–18). Fractional anisotropy (FA) and mean diffusion (MD) were evaluated within the splenium and body of the corpus callosum in relation to cognitive performance. Results: Visuospatial construction abilities were associated with white matter integrity in both the splenium and body of the corpus callosum, while only splenium integrity was associated with language and psychomotor function. Conclusion: Results suggest that, for typically developing adolescents, white matter coherence positively relates to visuospatial, psychomotor, and language skills. These findings may have implications for the cognitive functioning of clinical populations in which typical white matter development is altered.     

Altered White-Matter Microstructure in Conduct Disorder Is Specifically Associated with Elevated Callous-Unemotional Traits

Adolescents with conduct disorder (CD) and elevated callous-unemotional (CU) traits have been reported to present with a more severe and persistent pattern of antisocial behaviour than those with low levels of CU traits. However, relatively few studies have investigated whether there are differences in brain structure between these subgroups.We acquired diffusion tensor imaging data and used tract-based spatial statistics (TBSS) to compare adolescents with CD and high levels of CU traits (CD/CU+; n?=?18, CD and low levels of CU traits (CD/CU-; n?=?17) and healthy controls (HC; n?=?32) on measures of fractional anisotropy (FA), axial (AD), radial (RD) and mean (MD) diffusivity. Compared to CD/CU- adolescents, those with CD/CU+ presented increased FA and reduced RD and MD (lower diffusivity) in several tracts including: body and splenium of the corpus callosum, right inferior longitudinal fasciculus, ILF; right inferior fronto-occipital fasciculus, IFOF; left superior longitudinal fasciculus, SLF; left cerebral peduncle, bilateral internal capsule, left superior and posterior corona radiata, bilateral thalamic radiation and left external capsule. In addition, relative to CD/CU- individuals, adolescents with CD/CU+ showed lower diffusivity (indexed by reduced RD and MD) in left uncinate fasciculus and bilateral fornix. Finally, relative to healthy controls, CD/CU+ individuals showed lower diffusivity (reduced RD) in the genu and body of the corpus callosum and left anterior corona radiata. These results suggest that CD/CU+ individuals present with white-matter microstructural abnormalities compared to both CD/CU- individuals and age-matched healthy controls. This finding is consistent with emerging evidence suggesting that CD/CU+ represents a distinct subtype of CD, and illustrates the importance of accounting for heterogeneity within CD populations.     

Cognitive impairment and whole brain diffusion in patients with neuromyelitis optica after acute relapse

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive tests to assess cognitive function. Head diffusion tensor imaging (DTI) of all patients with NMO were collected with a 3-T MR system. Correlations of cognitive test scores and whole brain FA and MD were examined by voxel-based analysis. Region-of-interest analysis was applied to the significantly correlated regions which the most frequently appeared. We found that NMO patients without visible brain lesions had significantly impaired learning and memory, decreased information processing speed, and damaged attention compared with normal control subjects. These impaired cognitive domains were significantly correlated with FA and MD in local regions of corpus callosum, anterior cingulate and medial frontal cortex. In corpus callosum of NMO patients, mean FA was significantly lower and mean MD higher than normal control subjects. Our findings suggest that cognitive impairments in learning and memory, information processing speed and attention occur in NMO patients without visible brain lesions during acute relapse. The impairments in immediate and short-term memory in NMO patients may be due to information encoding deficits in the process of information acquisition. The corpus callosum of such patients may have local microscopic damages that play a role in cognitive impairments during acute relapse.     

Microstructural organization of corpus callosum projections to prefrontal cortex predicts bimanual motor learning

The corpus callosum (CC) is the largest white matter tract in the brain. It enables interhemispheric communication, particularly with respect to bimanual coordination. Here, we use diffusion tensor imaging (DTI) in healthy humans to determine the extent to which structural organization of subregions within the CC would predict how well subjects learn a novel bimanual task. A single DTI scan was taken prior to training. Participants then practiced a bimanual visuomotor task over the course of 2 wk, consisting of multiple coordination patterns. Findings revealed that the predictive power of fractional anisotropy (FA) was a function of CC subregion and practice. That is, FA of the anterior CC, which projects to the prefrontal cortex, predicted bimanual learning rather than the middle CC regions, which connect primary motor cortex. This correlation was specific in that FA correlated significantly with performance of the most difficult frequency ratios tested and not the innately preferred, isochronous frequency ratio. Moreover, the effect was only evident after training and not at initiation of practice. This is the first DTI study in healthy adults which demonstrates that white matter organization of the interhemispheric connections between the prefrontal structures is strongly correlated with motor learning capability.     

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior–posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application.     

What Does Diffusion Tensor Imaging Reveal About the Brain and Cognition in Fetal Alcohol Spectrum Disorders?

Over the past 5 years, Diffusion Tensor Imaging (DTI) has begun to provide new evidence about the effects of prenatal alcohol exposure on white matter development. DTI, which examines microstructural tissue integrity, is sensitive to more subtle white matter abnormalities than traditional volumetric MRI methods. Thus far, the available DTI data suggest that white matter microstructural abnormalities fall on a continuum of severity in Fetal Alcohol Spectrum Disorder (FASD). Abnormalities are prominent in the corpus callosum, but also evident in major anterior-posterior fiber bundles, corticospinal tracts, and cerebellum. These subtle abnormalities are correlated with neurocognitive deficits, especially in processing speed, non-verbal ability, and executive functioning. Future studies using larger samples, increasingly sophisticated DTI methods, and additional functional MRI connectivity measures will better characterize the full range of abnormalities in FASD. Ultimately, these measures may serve as indices of change in future longitudinal studies and in studies of interventions for FASD.     

Mapping the development of white matter tracts with diffusion tensor imaging

In this study, the development of white matter was studied using an optimized diffusion tensor imaging (DTI) protocol in 20 normal subjects (10–40 years old). The normal development of white matter tracts was addressed by comparing the diffusion anisotropy results between two sub‐groups: eight adults (26–38 years old) and eight adolescents (13–15 years old). The difference in myelination extent between these two groups as indexed by the fractional anisotropy was identified by conducting a student t‐test of the measured diffusion anisotropy maps. Significant differences (p < 0.01) were detected in the gyrus frontalis medialis (GFM), gyrus temporalis medialis (GTM) and gyrus cinguli (GC), in addition to the developmental changes in corpus callosum. A brief overview of previous published DTI studies in developmental science and current progress in DTI techniques is also given at the end of this paper. It may be useful for readers interested in using DTI to study developmental problems but who are not familiar with the various technical aspects.     

Occult white matter damage contributes to intellectual disability in tuberous sclerosis complex

Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of the mean diffusivity (MD) and fractional anisotropy (FA) were performed in the NAWM. Correlations between diffusion indices and the full-scale intelligence quotient (FSIQ) and normalized lesion volume were also investigated. Compared with controls, both histogram and ROI analyses showed significant (P < .05) increased MD and decreased FA in the NAWM of TSC patients. In TSC patients, some of the histogram- and ROI-derived diffusion indices of the NAWM were correlated with FSIQ (P < .01), but none of them were correlated with the normalized lesion volume. These findings indicate that TSC patients have occult damage in the NAWM, which might be an important neural basis for intellectual disability in these patients.     

A Comparison of Structural Brain Imaging Findings in Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder

ASD and ADHD are regarded as distinct disorders in the current DSM-5. However, recent research and the RDoC initiative are recognizing considerable overlap in the clinical presentation of ASD, ADHD, and other neurodevelopmental disorders. In spite of numerous neuroimaging findings in ASD and ADHD, the extent to which either of the above views are supported remains equivocal. Here we compare structural MRI and DTI literature in ASD and ADHD. Our main findings reveal both distinct and shared neural features. Distinct expressions were in total brain volume (ASD: increased volume, ADHD: decreased volume), amygdala (ASD: overgrowth, ADHD: normal), and internal capsule (ASD: unclear, ADHD: reduced FA in DTI). Considerable overlap was noted in the corpus callosum and cerebellum (lower volume in structural MRI and decreased FA in DTI), and superior longitudinal fasciculus (reduced FA in DTI). In addition, we identify brain regions which have not been studied in depth and require more research. We discuss relationships between brain features and symptomatology. We conclude by addressing limitations of current neuroimaging research and offer approaches that account for clinical heterogeneity to better distinguish brain-behavior relationships.     

Fetal alcohol syndrome and the developing socio-emotional brain

Fetal alcohol syndrome (FAS) is currently recognized as the most common known cause of mental retardation, affecting from 1 to 7 per 1000 live-born infants. Individuals with FAS suffer from changes in brain structure, cognitive impairments, and behavior problems. Researchers investigating neuropsychological functioning have identified deficits in learning, memory, executive functioning, hyperactivity, impulsivity, and poor communication and social skills in individuals with FAS and fetal alcohol effects (FAE). Investigators using autopsy and brain imaging methods have identified microcephaly and structural abnormalities in various regions of the brain (including the basal ganglia, corpus callosum, cerebellum, and hippocampus) that may account for the neuropsychological deficits. Results of studies using newer brain imaging and analytic techniques have indicated specific alterations (i.e., displacements in the corpus callosum, increased gray matter density in the perisylvian regions, altered gray matter asymmetry, and disproportionate reductions in the frontal lobes) in the brains of individuals prenatally exposed to alcohol, and their relations with brain function. Future research, including using animal models, could help inform our knowledge of brain-behavior relations in the context of prenatal alcohol exposure, and assist with early identification and intervention.     

DEVELOPMENTAL SEX DIFFERENCES IN THE RELATION OF NEUROANATOMICAL CONNECTIVITY TO INTELLIGENCE

Recent neuroimaging research has shown sex-related differences in the relationship between brain structure and cognitive function. Anatomical studies have shown a greater reliance for cognitive function on white matter structure in adult females, and a greater reliance on gray matter structure in adult males. Functional neuroimaging studies have also shown a greater correlation between brain connectivity and cognitive function in females. However, this relationship is not present in young childhood (5 years old) but appears during the developmental period. Here sex differences in structure–function relationships and their developmental trajectory are investigated using diffusion tensor imaging (DTI) on a large cohort of over 100 normal children ages 5–18. Significant sex–X–IQ interactions on fractional anisotropy (FA), a marker for white matter organization, were seen in the left frontal lobe, in fronto-parietal areas bilaterally, and in the arcuate fasciculus bilaterally, with girls showing positive correlations of FA with IQ, and boys showing a negative correlation. Significant sex–X–IQ–X–age interactions on FA were also seen in the left frontal lobe and in fronto-parietal areas bilaterally, showing a developmental effect. These results strongly corroborate previous findings regarding sex differences in structure–function relationships regarding intelligence. Results also indicate that a naïve interpretation of “more is better” with respect to FA may not be accurate, especially in adult males.     

长期高策略性技能训练对运动员大脑白质结构的影响：一项DTI研究

目前关于运动员经验优势的脑机制还存在争议, 尤其对于涉及较多认知过程参与的高策略性技能项目运动员, 其大脑白质结构可塑性变化还需进一步探究。研究横向对比了乒乓球运动员和非运动员大脑白质纤维束的弥散张量成像数据。结果发现, 相比于非运动员, 乒乓球运动员在连接背侧和腹侧通路脑区的双侧皮质脊髓束、左侧上纵束、左侧下纵束和双侧额枕下束的各向异性值(FA)更大, 进一步分析发现, 部分腹侧通路白质纤维束FA增加的原因是径向扩散系数(RD)下降。研究结果支持了动作双通路模型。提示经过长期高策略性技能训练, 乒乓球运动员在背侧和腹侧通路上的白质纤维束结构完整性增强。     

White matter development during adolescence as shown by diffusion MRI

Previous volumetric developmental MRI studies of the brain have shown white matter development continuing through adolescence and into adulthood. This review presents current findings regarding white matter development and organization from diffusion MRI studies. The general trend during adolescence (age 12–18 years) is towards increasing fractional anisotropy (FA) with age and decreasing mean diffusivity (MD) with age, findings primarily due to decreasing radial diffusivity with age. However, results of studies vary as to the regional specificity of such age-related changes, likely due in part to methodological issues. Another general trend is for FA to positively correlate and MD to negatively correlate with cognitive function. This trend is however region-specific, task-specific, and population-specific; some studies have in fact found negative correlations of FA and positive correlations of MD in specific regions with specific measures of cognitive performance. There are also published reports of sexual dimorphism in white matter development, indicating differing developmental trajectories between males and females as well as differing relationships developmentally between white matter architecture and cognitive function. There is a need for more research to further elucidate the development of white matter and its relation to cognitive function during this critical developmental period.     

Neurocognitive correlates of white matter quality in adolescent substance users

Background

Progressive myelination during adolescence implicates an increased vulnerability to neurotoxic substances and enduring neurocognitive consequences. This study examined the cognitive manifestations of altered white matter microstructure in chronic marijuana and alcohol-using (MJ + ALC) adolescents.

Methods

Thirty-six MJ + ALC adolescents (ages 16–19) and 36 demographically similar controls were evaluated with diffusion tensor imaging (Bava et al., 2009) and neurocognitive tests. Regions of group difference in fractional anisotropy (FA) and mean diffusivity (MD) were analyzed in relation to cognitive performance.

Results

In users, lower FA in temporal areas related to poorer performance on attention, working memory, and speeded processing tasks. Among regions where users had higher FA than controls, occipital FA was positively associated with working memory and complex visuomotor sequencing, whereas FA in anterior regions was negatively associated with verbal memory performance.

Conclusions

Findings suggest differential influences of white matter development on cognition in MJ + ALC using adolescents than in non-using peers. Neuroadaptation may reflect additive and subtractive responses to substance use that are complicated by competing maturational processes.     

Transverse diffusivity of cerebral parenchyma predicts visual tracking performance in relapsing–remitting multiple sclerosis

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing–remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined in the cerebral parenchyma. Cognitive performance of the MS patients was assessed with the oral response format of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). A significant correlation was found between performance on the SDMT and the fractional anisotropy in the brain. This correlation was predominantly induced by transverse diffusivity. Transverse diffusivity refers to the diffusion across fibers rather than along the fibers and is believed to be a specific marker for axonal loss and demyelination associated with MS. No significant association between DTI-measures and PASAT performance was found and this negative finding was mainly attributed to psychometric qualities. These results indicate that diffusivity along the non-principal diffusion direction, a possible signature of MS-related white matter pathology, contributes to information processing speed as measured with the SDMT, a task that requires close visual tracking and a widely used clinical marker for cognitive decline in MS.     

Splenium development and early spoken language in human infants

The association between developmental trajectories of language‐related white matter fiber pathways from 6 to 24 months of age and individual differences in language production at 24 months of age was investigated. The splenium of the corpus callosum, a fiber pathway projecting through the posterior hub of the default mode network to occipital visual areas, was examined as well as pathways implicated in language function in the mature brain, including the arcuate fasciculi, uncinate fasciculi, and inferior longitudinal fasciculi. The hypothesis that the development of neural circuitry supporting domain‐general orienting skills would relate to later language performance was tested in a large sample of typically developing infants. The present study included 77 infants with diffusion weighted MRI scans at 6, 12 and 24 months and language assessment at 24 months. The rate of change in splenium development varied significantly as a function of language production, such that children with greater change in fractional anisotropy (FA) from 6 to 24 months produced more words at 24 months. Contrary to findings from older children and adults, significant associations between language production and FA in the arcuate, uncinate, or left inferior longitudinal fasciculi were not observed. The current study highlights the importance of tracing brain development trajectories from infancy to fully elucidate emerging brain–behavior associations while also emphasizing the role of the splenium as a key node in the structural network that supports the acquisition of spoken language.     

Smaller splenium in children with nonverbal learning disability compared to controls,high-functioning autism and ADHD

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.     

White-matter microstructure and language lateralization in left-handers: A whole-brain MRI analysis

Most people are left-hemisphere dominant for language. However the neuroanatomy of language lateralization is not fully understood. By combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we studied whether language lateralization is associated with cerebral white-matter (WM) microstructure. Sixteen healthy, left-handed women aged 20–25 were included in the study. Left-handers were targeted in order to increase the chances of involving subjects with atypical language lateralization. Language lateralization was determined by fMRI using a verbal fluency paradigm. Tract-based spatial statistics analysis of DTI data was applied to test for WM microstructural correlates of language lateralization across the whole brain. Fractional anisotropy and mean diffusivity were used as indicators of WM microstructural organization. Right-hemispheric language dominance was associated with reduced microstructural integrity of the left superior longitudinal fasciculus and left-sided parietal lobe WM. In left-handed women, reduced integrity of the left-sided language related tracts may be closely linked to the development of right hemispheric language dominance. Our results may offer new insights into language lateralization and structure–function relationships in human language system.     

MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain

As Norman Geschwind asserted in 1965, syndromes resulting from white matter lesions could produce deficits in higher-order functions and “disconnexion” or the interruption of connection between gray matter regions could be as disruptive as trauma to those regions per se. The advent of in vivo diffusion tensor imaging, which allows quantitative characterization of white matter fiber integrity in health and disease, has served to strengthen Geschwind’s proposal. Here we present an overview of the principles of diffusion tensor imaging (DTI) and its contribution to progress in our current understanding of normal and pathological brain function.     

Endogenous testosterone concentration, mental rotation, and size of the corpus callosum in a sample of young Hungarian women

In the present study brain laterality, hemispheric communication, and mental rotation performance were examined. A sample of 33 women were tested for a possible linear relationship of testosterone level and mental rotation with structural background of the brain. Subjects with a smaller splenial area of corpus callosum tended to have lower levels of testosterone (r =.37, p<.05). However, there were no significant differences in mean scores of mental rotation of object and hand between groups with high and low levels of testosterone. There was a significant difference in relative size of the 6th area (slice) of the corpus callosum between groups with good and poor scores on mental rotation of an object and also in relative size of the 4th and 5th slices of the corpus callosum between groups on mental rotation of the hand. The good and poor scorers' show different relations with the measures of the corpus. The mental rotation of hand was associated with the parietal areas of the corpus callosum, while the mental rotation of object was associated only with the occipital area. These observations suggest that higher testosterone levels may be associated with a larger splenial area, which represents an important connection between the parieto-occipitocortical areas involved in activation of mental images. Further srudy is encouraged.