Lateralization of the arcuate fasciculus from childhood to adulthood and its relation to cognitive abilities in children

The arcuate fasciculus is a major white matter tract involved in language processing that has also been repeatedly implicated in intelligence and reasoning tasks. Language in the human brain is lateralized in terms of both function and structure, and while the arcuate fasciculus reflects this asymmetry, its pattern of lateralization is poorly understood in children and adolescents. We used diffusion tensor imaging (DTI) and tractography to examine arcuate fasciculus lateralization in a large (n = 183) group of healthy right‐handed volunteers aged 5–30 years; a subset of 68 children aged 5–13 years also underwent cognitive assessments. Fractional anisotropy and number of streamlines of the arcuate fasciculus were both significantly higher in the left hemisphere than the right hemisphere in most subjects, although some subjects (10%) were right lateralized. Age and gender effects on lateralization were not significant. Children receiving cognitive assessments were divided into three groups: a “left‐only” group in whom only the left side of the arcuate fasciculus could be tracked, a left‐lateralized group, and a right‐lateralized group. Scores on the Peabody Picture Vocabulary Test (PPVT) and NEPSY Phonological Processing task differed significantly among groups, with left‐only subjects outperforming the right‐lateralized group on the PPVT, and the left‐lateralized children scoring significantly better than the right‐lateralized group on phonological processing. In summary, DTI tractography demonstrates leftward arcuate fasciculus lateralization in children, adolescents, and young adults, and reveals a relationship between structural white matter lateralization and specific cognitive abilities in children. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Whiter matter abnormalities in medication-naive subjects with a single short-duration episode of major depressive disorder

Convergent studies have implicated white matter abnormalities in the pathophysiology of major depressive disorder (MDD). In this study, diffusion tensor imaging (DTI) was used to examine white matter abnormalities in 23 single-episode, medication-naive MDD participants versus 21 healthy control participants. Voxel-based analysis was used to investigate whole brain white matter abnormalities in the MDD group. Fractional anisotropy was significantly lower and apparent diffusion coefficient was significantly higher in the right superior longitudinal fasciculus (SLF) within the frontal lobe, right middle frontal and left parietal white matter in the MDD group compared with the healthy group.     

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

Background

In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence.

Methods

DTI was performed in 78 healthy subjects aged 8–21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence.

Results

In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age.

Conclusions

These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.     

Structural connectivity of the frontal lobe in children with drug-resistant partial epilepsy

The superior longitudinal fasciculus (SLF) II and cingulum are two white matter tracts important for attention and other frontal lobe functions. These functions are often disturbed in children with drug-resistant (DR) partial epilepsy, even when no abnormalities are seen on conventional MRI. We set out to determine whether abnormalities in these structures might be depicted on diffusion tensor imaging (DTI) studies in the absence of abnormalities on conventional MRI. We compared the DTI findings of 12 children with DR partial epilepsy with those of 12 age- and gender-matched controls. We found that the SLF II fractional anisotropy (FA) values of the patients were significantly lower than those of the controls (means: 0.398±0.057 and 0.443±0.059, respectively, P=0.002). Similarly, apparent diffusion coefficient (ADC) and parallel diffusivity values for SLF II were also significantly lower in the patients. There were no differences in the FA and ADC values of the cingulum. Our findings are consistent with abnormal structural connectivity of the frontal lobe in children with DR partial epilepsy and provide a possible explanation for the previously reported functional abnormalities related to the SLF II in these patients.     

Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia

BACKGROUND: The fornix is a major projection of the hippocampus to and from other brain regions. A previous diffusion tensor imaging (DTI) study has reported disrupted integrity of the fornix in patients with schizophrenia. However, functional significance of the DTI abnormalities of the fornix in schizophrenia has not been fully studied yet. We investigated an association between DTI abnormalities of the fornix and impairment of memory organization in schizophrenia. METHODS: Thirty-one patients with schizophrenia and 65 age- and gender-matched healthy controls underwent DTI, and fractional anisotropy (FA) and mean diffusivity (MD) were measured in cross-sections of fornix tractography. In addition, all of the patients and 32 controls performed a verbal learning task specialized for evaluating memory organization, the verbal memory subscale of the Wechsler Memory Scale-Revised, the category- and letter fluency tests, and the Japanese version of National Adult Reading Test. RESULTS: Statistically significant reduction of FA and increase of MD were found in the fornix of patients with schizophrenia compared with controls with no significant lateralization. A significant patients-specific correlation was found between increased MD in the left fornix and lower scores on utilization of semantic organization in the verbal learning task. In addition, increased MD in the right fornix showed a patients-specific association with poorer performance on the category fluency test, which indexes organization of long-term semantic memory. These patients-specific correlations, however, were not statistically lateralized to either hemisphere. CONCLUSIONS: These results indicate that disrupted integrity of the fornix contributes to impaired memory organization in schizophrenia.     

The anatomy of the callosal and visual-association pathways in high-functioning autism: A DTI tractography study

There is increasing recognition that many of the core behavioral impairments that characterize autism potentially emerge from poor neural synchronization across nodes comprising dispersed cortical networks. A likely candidate for the source of this atypical functional connectivity in autism is an alteration in the structural integrity of intra- and inter-hemispheric white matter (WM) tracts that form large-scale cortical networks. To test this hypothesis, in a group of adults with high-functioning autism (HFA) and matched control participants, we used diffusion tensor tractography to compare the structural integrity of three intra-hemispheric visual-association WM tracts, the inferior longitudinal fasciculus (ILF), the inferior fronto-occipito fasciculus (IFOF) and the uncinate fasciculus (UF), with the integrity of three sub-portions of the major inter-hemispheric fiber tract, the corpus callosum. Compared with the control group, the HFA group evinced an increase in the volume of the intra-hemispheric fibers, particularly in the left hemisphere, and a reduction in the volume of the forceps minor (F-Mi) and body of the corpus callosum. The reduction in the volume of the F-Mi also correlated with an increase in repetitive and stereotypical behavior as measured by the Autism Diagnostic Interview. These findings suggest that the abnormalities in the integrity of key inter- and intra-hemispheric WM tracts may underlie the atypical information processing observed in these individuals.     

Clustering and switching processes in semantic verbal fluency in the course of Alzheimer's disease subjects: results from the PAQUID longitudinal study

Reduced semantic fluency performances have been reported in the preclinical phase of Alzheimer's disease (AD). To investigate the cognitive processes underlying this early deficit, this study analyzed the verbal production of predemented subjects for the animals category with the qualitative parameters related to clustering (i.e. the ability to generate words belonging to semantic subcategories of animals) and switching (i.e. the ability to shift from one subcategory to another) proposed by Troyer. This qualitative analysis was applied to the PAQUID (Personnes Agées QUID) cohort, a 17-year longitudinal population-based study. The performances on the animal verbal fluency task of 51 incident cases of possible and probable AD were analyzed at the onset of dementia, 2 years and 5 years before dementia onset. Each case was matched for age, sex and education to two control subjects leading to a sample of 153 subjects. The mean cluster size and the raw number of switches were compared in the two samples. The results revealed a significantly lower switching index in the future AD subjects than in the elderly controls including 5 years before dementia incidence. A significant decline in this parameter was evidenced all along the prodromal phase until the clinical diagnosis of dementia. In contrast, the mean cluster size could not discriminate the two groups. Therefore the results support the hypothesis that impaired shifting abilities - rather than semantic memory storage degradation - could explain the early decline in semantic fluency performance occurring in the predementia phase of AD.     

Facial affect recognition linked to damage in specific white matter tracts in traumatic brain injury

Emotional processing deficits have recently been identified in individuals with traumatic brain injury (TBI), specifically in the domain of facial affect recognition. However, the neural networks underlying these impairments have yet to be identified. In the current study, 42 individuals with moderate to severe TBI and 23 healthy controls performed a task of facial affect recognition (Facial Emotion Identification Test (FEIT)) in order to assess their ability to identify and discriminate six emotions: happiness, sadness, anger, surprise, shame, and fear. These individuals also underwent structural neuroimaging including diffusion tensor imaging to examine white matter (WM) integrity. Correlational analyses were performed to determine where in the brain WM damage was associated with performance on the facial affect recognition task. Reduced performance on the FEIT was associated with reduced WM integrity (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) in the inferior longitudinal fasciculus and inferior-fronto-occipital fasciculus in individuals with TBI. Poor performance on the task was additionally associated with reduced gray matter (GM) volume in lingual gyrus and parahippocampal gyrus. The results implicate a pattern of WM and GM damage in TBI that may play a role in emotional processing impairments.     

Hippocampal and thalamic diffusion abnormalities in children with temporal lobe epilepsy

PURPOSE: Previous studies using diffusion MRI in patients with temporal lobe epilepsy have shown abnormal water diffusion in the hippocampus. Because thalamus and lentiform nuclei are considered important for the regulation of cortical excitability and seizure propagation, we analyzed diffusion tensor imaging (DTI) abnormalities in these subcortical structures and in hippocampus of children with partial epilepsy with and without secondary generalization. METHODS: Fourteen children with partial epilepsy involving the temporal lobe underwent MRI including a DTI sequence. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained in the hippocampus, thalamus, and lentiform nucleus, and compared with DTI data of 14 control children with no epilepsy, as well as glucose positron emission tomography (PET) findings. RESULTS: Decreased FA (p < 0.001) and increased ADC (p = 0.003) values were found in the hippocampi ipsilateral to the seizure focus. Significant FA decreases (p = 0.002) also were seen in the contralateral hippocampi, despite unilateral seizure onset and excellent surgical outcome in patients who underwent surgery. ADC values showed a trend for increase in the thalami ipsilateral to the epileptic focus in the seven children with secondarily generalized seizures (p = 0.09). No group differences of ADC or FA were found in the lentiform nuclei. The DTI variables did not correlate with regional glucose metabolism in any of the structures analyzed. CONCLUSIONS: Increased ADC values in hippocampus can assist in lateralizing the seizure focus, but decreased FA in the contralateral hippocampus suggests that it too may be dysfunctional despite unilateral seizure onset. Less-robust thalamic abnormalities of water diffusion in patients with secondarily generalized seizures suggest secondary involvement of the thalamus, perhaps due to recruitment of this structure into the epileptic network; however, this must be confirmed in a larger population. DTI appears to be a sensitive method for detection abnormalities in children with partial epilepsy, even in structures without apparent changes on conventional MRI.     

Lateralization of the arcuate fasciculus and its differential correlation with reading ability between young learners and experienced readers: a diffusion tensor tractography study in a Chinese cohort

As Chinese reading engages a different neural network from alphabetic language reading, we investigate whether leftward lateralization of the arcuate fasciculus (AF), as observed in the Western population, is also present in the Chinese population and if it does, whether it is associated with better reading ability. Diffusion tensor tractography analysis on 75 Chinese subjects of three age groups (first graders, fourth graders, and college students) showed that 70-83% of them had leftward lateralization of the AF. The pattern of lateralization did not differ significantly among the three groups, suggesting that lateralization of the AF is formed at an early age and before one enters first grade. Among the first graders, who had just started to learn to read, subjects with strongly leftward lateralized AF scored significantly higher than those with other defined lateralization patterns in Chinese (P = 0.001) and English (P = 0.036) reading tasks. This association was not observed among the fourth graders and college students who were experienced Chinese readers. Among the fourth graders, females were found to obtain significantly higher Chinese (P = 0.033) and English reading scores than males (P = 0.002). Our study suggests a differential effect of leftward lateralization of the AF on reading ability at different stages of reading development in the Chinese population.     

White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study

Diffusion tensor imaging was used to evaluate cerebral white matter in eight patients (ages 10-17), with myotonic dystrophy type 1 (3 congenital-onset, 5 juvenile-onset) compared to eight controls matched for age and sex. Four regions of interest were examined: inferior frontal, superior frontal, supracallosal, and occipital. The myotonic dystrophy group showed white matter abnormalities compared to controls in all regions. All indices of white matter integrity were abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. With no evidence of regional variation, correlations between whole cerebrum white matter fractional anisotropy and neurocognitive functioning were examined in the patients. Strong correlations were observed between whole cerebrum fractional anisotropy and full-scale intelligence and a measure of executive functioning. Results indicate that significant white matter abnormality is characteristic of young patients with myotonic dystrophy type 1 and that the white matter abnormality seen with neuroimaging has implications for cognitive functioning.     

Association between white matter microstructure and cognitive function in patients with methamphetamine use disorder

Methamphetamine use disorder (MUD) has been associated with broad neurocognitive impairments. While the cognitive impairments of MUD have been demonstrated, the neuropathological underpinnings remain inadequately understood. To date, the published human diffusion tensor imaging (DTI) studies involving the correlation between diffusion parameters and neurocognitive function in MUD are limited. Hence, the present study aimed to examine the association between cognitive performance and white matter microstructure in patients with MUD. Forty‐five patients with MUD and 43 healthy controls (HCs) completed their demographic information collection, cognitive assessments, and DTI imaging. DTI images were preprocessed to extract fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of various fiber tracts. Univariate tests were used to examine group differences in cognitive assessments and DTI metrics. Linear regression was used to examine the relationship between these two metrics. The results revealed that patients with MUD had lower subset scores of the MATRICS Consensus Cognitive Battery (MCCB), which reflects five cognitive domains: processing speed, attention, verbal learning, visual learning, problem‐solving. Patients with MUD also had significantly higher AD, MD, and RD values of the left superior longitudinal fasciculus than HCs. Furthermore, the RD value of the left superior longitudinal fasciculus was a significant predictor of processing speed and problem‐solving ability, as shown by the digit‐symbol coding test and NAB‐Mazes scores, respectively. Findings extended our understanding of white matter microstructure that is related to neurocognitive deficits in MUD and provided potential targets for the prevention and treatment of this chronic disorder.     

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi‐modal neuroimaging analyses on a group of patients with low‐grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region‐of‐interests and voxel‐level whole‐brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.     

White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study

Background

Some gray and white matter regions of the brain are sexually dimorphic. The best MRI technique for identifying subtle differences in white matter is diffusion tensor imaging (DTI). The purpose of this paper is to investigate whether white matter patterns in female to male (FtM) transsexuals before commencing cross-sex hormone treatment are more similar to that of their biological sex or to that of their gender identity.

Method

DTI was performed in 18 FtM transsexuals and 24 male and 19 female heterosexual controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter fibers of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics.

Results

In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal tract.

Conclusions

Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.     

Abnormal white matter integrity in young children with autism

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism.     

Developmental trajectories of white matter structure in children with and without reading impairments

Left temporal-parietal white matter structure is consistently associated with reading abilities in children. A small number of longitudinal studies show that development of this area over time is altered in children with impaired reading. However, it remains unclear how brain developmental patterns relate to specific reading skills such as fluency, which is a critical part of reading comprehension. Here, we examined white matter development trajectories in children with dysfluent reading (20 dysfluent and inaccurate readers, 36 dysfluent and accurate readers) compared to non-impaired readers (n = 14) over 18 months. We found typical age-related increases of fractional anisotropy (FA) in bilateral temporal-parietal areas in non-impaired readers, but a lack of similar changes in dysfluent readers. We also found steeper decreases of mean diffusivity (MD) in the right corona radiata and left uncinate fasciculus in dysfluent inaccurate readers compared to dysfluent accurate readers. Changes in diffusion parameters were correlated with changes in reading scores over time. These results suggest delayed white matter development in dysfluent readers, and show maturational differences between children with different types of reading impairment. Overall, these results highlight the importance of considering developmental trajectories, and demonstrate that the window of plasticity may be different for different children.     

The arcuate fasciculus and the disconnection theme in language and aphasia: history and current state

Few themes have been more central to neurological models of aphasia than the disconnection paradigm and the role of the arcuate fasciculus. Introduced by luminaries of 19th Century neurology and resurrected by the charismatic work of Norman Geschwind, the disconnection theme has triggered spectacular advances of modern understanding of language and aphasia. But the disconnection paradigm had alternate fortunes, ranging from irrational exuberance to benign neglect, and its followers have not always shared the same view on its functional consequences and anatomical correlates. Our goal in this paper is, first, to survey the 19th Century roots of the connectionist approach to aphasia and, second, to describe emerging imaging technologies based on diffusion tensor imaging (DTI) that promise to consolidate and expand the disconnection approach to language and its disorders.     

Language exposure during infancy is negatively associated with white matter microstructure in the arcuate fasciculus

Decades of research have established that the home language environment, especially quality of caregiver speech, supports language acquisition during infancy. However, the neural mechanisms behind this phenomenon remain under studied. In the current study, we examined associations between the home language environment and structural coherence of white matter tracts in 52 typically developing infants from English speaking homes in a western society. Infants participated in at least one MRI brain scan when they were 3, 6, 12, and/or 24 months old. Home language recordings were collected when infants were 9 and/or 15 months old. General linear regression models indicated that infants who heard the most adult words and participated in the most conversational turns at 9 months of age also had the lowest fractional anisotropy in the left posterior parieto-temporal arcuate fasciculus at 24 months. Similarly, infants who vocalized the most at 9 months also had the lowest fractional anisotropy in the same tract at 6 months of age. This is one of the first studies to report significant associations between caregiver speech collected in the home and white matter structural coherence in the infant brain. The results are in line with prior work showing that protracted white matter development during infancy confers a cognitive advantage.