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 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.     

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.     

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。     

Sex differences in the IQ-white matter microstructure relationship: A DTI study

Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men.     

Mapping brain maturation and cognitive development during adolescence

Non-invasive mapping of brain structure and function with magnetic resonance imaging (MRI) has opened up unprecedented opportunities for studying the neural substrates underlying cognitive development. There is an emerging consensus of a continuous increase throughout adolescence in the volume of white matter, both global and local. There is less agreement on the meaning of asynchronous age-related decreases in the volume of grey matter in different cortical regions; these might equally represent loss ("pruning") or gain (intra-cortical myelination) of tissue. Functional MRI studies have so far focused mostly on executive functions, such as working memory and behavioural inhibition, with very few addressing questions regarding the maturation of social cognition. Future directions for research in this area are discussed in the context of processing biological motion and matching perceptions and actions.     

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.     

Electrophysiological changes during adolescence: A review

While psychological research has long shown that adolescence is a period of major cognitive and affective transition, recent neurophysiological research has shown that adolescence is also accompanied by observable maturational changes in the brain, both in terms of structure and neurotransmitter function. Given this situation, we would expect that there should be observable and perhaps major changes in electrocortical activity and responses. In this review, we discuss developmental reductions in EEG power and alterations in the dominant band of EEG oscillation frequency, moderated by developmental factors such as growth-related changes in grey and white matter, and in the developmental history of cognitive and sociocultural stressors. Similarly, we summarize alterations in event-related potential components reflecting stimulus processing, response monitoring, and response anticipation. We review the literature on such changes in EEG and event-related potentials during the adolescent period and summarize some of the new developments in the field as well as interpretative difficulties.     

Growth of white matter in the adolescent brain: Myelin or axon?

White matter occupies almost half of the human brain. It contains axons connecting spatially segregated modules and, as such, it is essential for the smooth flow of information in functional networks. Structural maturation of white matter continues during adolescence, as reflected in age-related changes in its volume, as well as in its microstructure. Here I review recent observations obtained with magnetic resonance imaging in typically developing adolescents and point out some of the known variations in structural properties of white matter vis-à-vis brain function in health and disease. I conclude by re-focusing the interpretations of MR-based studies of white matter from myelin to axon.     

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.     

基于神经成像技术的青少年大脑发育研究

大脑成熟是一个动态过程, 高级神经活动的发育主要集中于个体发展的第二个10年：青少年时期。青少年时期是行为、认知和脑迅速发展的时期。青少年普遍表现出来的注意、冲动控制、计划、决策等认知能力的提高都是基于神经系统的成熟发展起来的。运用神经成像等技术的研究指出, 大脑在青少年时期的发展经历着突触精简以及髓鞘化的过程; 白质、灰质在青少年时期的成熟有不同的发展轨迹。青少年大脑皮层的成熟顺序与认知功能的发展相联系, 人脑的高级认知功能在青少年时期发展完成。在这一过程中, 脑的发展会受到情绪、环境以及经验等因素的影响。     

Exposure to severe urban air pollution influences cognitive outcomes, brain volume and systemic inflammation in clinically healthy children

Exposure to severe air pollution produces neuroinflammation and structural brain alterations in children. We tested whether patterns of brain growth, cognitive deficits and white matter hyperintensities (WMH) are associated with exposures to severe air pollution. Baseline and 1 year follow-up measurements of global and regional brain MRI volumes, cognitive abilities (Wechsler Intelligence Scale for Children-Revised, WISC-R), and serum inflammatory mediators were collected in 20 Mexico City (MC) children (10 with white matter hyperintensities, WMH⁺, and 10 without, WMH⁻) and 10 matched controls (CTL) from a low polluted city. There were significant differences in white matter volumes between CTL and MC children - both WMH⁺ and WMH⁻ - in right parietal and bilateral temporal areas. Both WMH⁻ and WMH⁺ MC children showed progressive deficits, compared to CTL children, on the WISC-R Vocabulary and Digit Span subtests. The cognitive deficits in highly exposed children match the localization of the volumetric differences detected over the 1 year follow-up, since the deficits observed are consistent with impairment of parietal and temporal lobe functions. Regardless of the presence of prefrontal WMH, Mexico City children performed more poorly across a variety of cognitive tests, compared to CTL children, thus WMH⁺ is likely only partially identifying underlying white matter pathology. Together these findings reveal that exposure to air pollution may perturb the trajectory of cerebral development and result in cognitive deficits during childhood.     

Cognitive correlates of medial temporal lobe development across adolescence: a magnetic resonance imaging study

Adolescent development involves progressive changes in brain structure and cognitive function, but relatively few studies have documented the cognitive correlates of differences in structural brain volumes in this age group. We examined the relations among age, cognitive processing, and mesial temporal lobe volume in 37 children and adolescents. Participants completed a brief cognitive assessment battery and underwent volumetric structural magnetic resonance imaging. For the sample as a whole, amygdala volume correlated positively with age, and larger volumes of both the left and right amygdala were significantly associated with better performance on several cognitive tasks assessing academic skills and acquired knowledge in long-term memory. In contrast, hippocampal volumes did not correlate with adolescents' age and were less frequently correlated with cognitive performance. Amygdala volumes were most predictive of cognitive abilities in boys, whereas for girls, the volume of the hippocampus contributed more frequently to the prediction of cognitive abilities. These data suggest that measurable differences in mesial temporal volumes during adolescence are reliably associated with long-term cognitive abilities, particularly academic skills and the acquisition of intellectual knowledge, and that these relationships may differ as a function of the sex of the child.     

Altered lateralization of dorsal language tracts in 6‐week‐old infants at risk for autism

Altered structural connectivity has been identified as a possible biomarker of autism spectrum disorder (ASD) risk in the developing brain. Core features of ASD include impaired social communication and early language delay. Thus, examining white matter tracts associated with language may lend further insight into early signs of ASD risk and the mechanisms that underlie language impairments associated with the disorder. Evidence of altered structural connectivity has previously been detected in 6‐month‐old infants at high familial risk for developing ASD. However, as language processing begins in utero, differences in structural connectivity between language regions may be present in the early infant brain shortly after birth. Here we investigated key white matter pathways of the dorsal language network in 6‐week‐old infants at high (HR) and low (LR) risk for ASD to identify atypicalities in structural connectivity that may predict altered developmental trajectories prior to overt language delays and the onset of ASD symptomatology. Compared to HR infants, LR infants showed higher fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF); in contrast, in the right SLF, HR infants showed higher FA than LR infants. Additionally, HR infants showed more rightward lateralization of the SLF. Across both groups, measures of FA and lateralization of these pathways at 6 weeks of age were related to later language development at 18 months of age as well as ASD symptomatology at 36 months of age. These findings indicate that early differences in the structure of language pathways may provide an early predictor of future language development and ASD risk.     

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.     

Stability of self-esteem across the life span

Two studies examined the rank-order stability of self-esteem from age 6 to 83: Study 1 was a meta-analysis of 50 published articles (N = 29,839) and Study 2 analyzed data from 4 large national studies (N = 74,381). Self-esteem showed substantial continuity over time (disattenuated correlations ranged from the .50s to .70s), comparable to the stability found for personality traits. Both studies provided evidence for a robust developmental trend: Self-esteem stability was low during childhood, increased throughout adolescence and young adulthood, and declined during midlife and old age. This trend could not be explained by age differences in the reliability of self-esteem measures, and generally replicated across gender, ethnicity, self-esteem scale, nationality (U.S. vs. non-U.S.), and year of publication.     

Differential brain shrinkage over 6 months shows limited association with cognitive practice

The brain shrinks with age, but the timing of this process and the extent of its malleability are unclear. We measured changes in regional brain volumes in younger (age 20–31) and older (age 65–80) adults twice over a 6 months period, and examined the association between changes in volume, history of hypertension, and cognitive training. Between two MRI scans, 49 participants underwent intensive practice in three cognitive domains for 100 consecutive days, whereas 23 control group members performed no laboratory cognitive tasks. Regional volumes of seven brain structures were measured manually and adjusted for intracranial volume. We observed significant mean shrinkage in the lateral prefrontal cortex, the hippocampus, the caudate nucleus, and the cerebellum, but no reliable mean change of the prefrontal white matter, orbital-frontal cortex, and the primary visual cortex. Individual differences in change were reliable in all regions. History of hypertension was associated with greater cerebellar shrinkage. The cerebellum was the only region in which significantly reduced shrinkage was apparent in the experimental group after completion of cognitive training. Thus, in healthy adults, differential brain shrinkage can be observed in a narrow time window, vascular risk may aggravate it, and intensive cognitive activity may have a limited effect on it.     

Neuroanatomical substrates of age-related cognitive decline

There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and diffusion tensor imaging measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerning measurement and methodology that may lead to stronger conclusions in the future.     

Between-individual variability and interpretation of associations between neurophysiological and behavioral measures in aging populations: comment on Salthouse (2011)

Salthouse (2011) argued that (a) variance between individuals on cognitive test scores remains constant between 20 and 90 years of age and (b) widely recognized problems of deducing functional relationships from patterns of correlations between measurements become especially severe for neuropsychological indices, especially for gross indices of age-related brain changes (e.g., losses of brain volume or increases in white matter lesions). I argue that between-individual variability on cognitive tests does increase with age and provides useful information on causes of age-related cognitive decline. I suggest that problems of inference from correlations are just as difficult for behavioral as for neurophysiological indices and that inclusion, in analyses, of even gross measures of brain status such as loss of volume and white matter lesions can correct misinterpretations that occur when only behavioral data are examined.