White matter tracts and executive functions: a review of causal and correlation evidence.

Executive functions are high-level cognitive processes involving abilities such as working memory/updating, set-shifting and inhibition. These complex cognitive functions are enabled by interactions among widely distributed cognitive networks, supported by white matter tracts. Executive impairment is frequent in neurological conditions affecting white matter; however, whether specific tracts are crucial for normal executive functions is unclear. We review causal and correlation evidence from studies that used direct electrical stimulation during awake surgery for gliomas, voxel-based and tract-based lesion-symptom mapping, and diffusion tensor imaging to explore associations between the integrity of white matter tracts and executive functions in healthy and impaired adults. The corpus callosum was consistently associated with all executive processes, notably its anterior segments. Both causal and correlation evidence showed prominent support of the superior longitudinal fasciculus to executive functions, notably to working memory. More specifically, strong evidence suggested that the second branch of the superior longitudinal fasciculus is crucial for all executive functions, especially for flexibility. Global results showed left lateralization for verbal tasks and right lateralization for executive tasks with visual demands. The frontal aslant tract potentially supports executive functions, however, additional evidence is needed to clarify whether its involvement in executive tasks goes beyond the control of language. Converging evidence indicates that a right-lateralized network of tracts connecting cortical and subcortical grey matter regions supports the performance of tasks assessing response inhibition, some suggesting a role for the right anterior thalamic radiation. Finally, correlation evidence suggests a role for the cingulum bundle in executive functions, especially in tasks assessing inhibition. We discuss these findings in light of current knowledge about the functional role of these tracts, descriptions of the brain networks supporting executive functions and clinical implications for individuals with brain tumours.

rTMS concurrent with cognitive training rewires AD brain by enhancing GM-WM functional connectivity: a preliminary study.

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40 Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.

Development of white matter in young adulthood: The speed of brain aging and its relationship with changes in fractional anisotropy.

White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.

Functional role of area 8A in the posterior dorsolateral frontal region of the human brain: A single case study.

Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right-handed male patient underwent neuropsychological assessment and testing on two conditional associative-learning tasks: the motor hand conditional associative-learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative-learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high-level cognitive processes.

White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis.

BACKGROUND: Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. METHODS: Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. RESULTS: The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aß42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). CONCLUSION: Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aß42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.

Alterations in structural integrity of superior longitudinal fasciculus III associated with cognitive performance in cerebral small vessel disease.

BACKGROUND: This study aimed to investigate the alterations in structural integrity of superior longitudinal fasciculus subcomponents with increasing white matter hyperintensity severity as well as the relationship to cognitive performance in cerebral small vessel disease. METHODS: 110 cerebral small vessel disease study participants with white matter hyperintensities were recruited. According to Fazekas grade scale, white matter hyperintensities of each subject were graded. All subjects were divided into two groups. The probabilistic fiber tracking method was used for analyzing microstructure characteristics of superior longitudinal fasciculus subcomponents. RESULTS: Probabilistic fiber tracking results showed that mean diffusion, radial diffusion, and axial diffusion values of the left arcuate fasciculus as well as the mean diffusion value of the right arcuate fasciculus and left superior longitudinal fasciculus III in high white matter hyperintensities rating group were significantly higher than those in low white matter hyperintensities rating group (p < 0.05). The mean diffusion value of the left superior longitudinal fasciculus III was negatively related to the Montreal Cognitive Assessment score of study participants (p < 0.05). CONCLUSIONS: The structural integrity injury of bilateral arcuate fasciculus and left superior longitudinal fasciculus III is more severe with the aggravation of white matter hyperintensities. The structural integrity injury of the left superior longitudinal fasciculus III correlates to cognitive impairment in cerebral small vessel disease.

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.

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 impact of patient factors and tumor characteristics on language neuroplasticity in left hemispheric diffuse gliomas prior to surgical resection.

PURPOSE: Language networks are reorganized during glioma growth, leading to varying language performance in patients with gliomas located in or around language-eloquent areas. Therefore, pre-treated language performance reflects the neuroplasticity potential. Different domains of language processing, such as speech expression, repetition, and comprehension, involving different neural networks. We analyzed the effects of patient factors and tumor characteristics on the pre-treated performance to investigate neuroplastic potential of different language domains. METHODS: Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. The correlation with abnormal language performance was verified using univariate and multivariate logistic regression. RESULTS: In total, 104 left hemispheric glioma patients were enrolled in this study. 44% of patients had repetitive abnormalities, 34.9% had comprehensive abnormalities, and 32.1% had expressive abnormalities. The proportion of normal language performance was 60% in grade 2 and 3 gliomas and 16% in grade 4 gliomas. Tumor grade (p = 0.006) and T2 volume (p = 0.008) were associated with abnormal performance in the expressive domain, education level (p = 0.004) and T1 C+ volume (p = 0.049) in the repetitive domain, and education level (p = 0.013), T2 volume (p = 0.011), and tumor grade (p = 0.089) in the comprehensive domain. CONCLUSION: Different clinical and radiological factors affected the abnormal performance of the three language domains, indicating their functional connectivity and neuroplastic potential are inherently varied. The dynamic interactions between patient factors, tumor characteristics, and language processing should be considered when resecting left hemispheric gliomas.

Frontoparietal Anatomical Connectivity Predicts Second Language Learning Success.

There is considerable individual variability in second language (L2) learning abilities in adulthood. The inferior parietal lobule, important in L2 learning success, is anatomically connected to language areas in the frontal lobe via the superior longitudinal fasciculus (SLF). The second and third branches of the SLF (SLF II and III) have not been examined separately in the context of language, yet they are known to have dissociable frontoparietal connections. Studying these pathways and their functional contributions to L2 learning is thus of great interest. Using diffusion MRI tractography, we investigated individuals undergoing language training to explore brain structural predictors of L2 learning success. We dissected SLF II and III using gold-standard anatomical definitions and related prelearning white matter integrity to language improvements corresponding with hypothesized tract functions. SLF II properties predicted improvement in lexical retrieval, while SLF III properties predicted improvement in articulation rate. Finer grained separation of these pathways enables better understanding of their distinct roles in language, which is essential for studying how anatomical connectivity relates to L2 learning abilities.

White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder.

BACKGROUND: Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness. METHODS: A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects. RESULTS: Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF. CONCLUSIONS: Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

Association between Motor Planning and the Frontoparietal Network in Children: An Exploratory Multimodal Study.

OBJECTIVE: Evidence from adult literature shows the involvement of cortical grey matter areas of the frontoparietal lobe and the white matter bundle, the superior longitudinal fasciculus (SLF) in motor planning. This is yet to be confirmed in children. METHOD: A multimodal study was designed to probe the neurostructural basis of childhood motor planning. Behavioural (motor planning), magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) data were acquired from 19 boys aged 8-11 years. Motor planning was assessed using the one and two colour sequences of the octagon task. The MRI data were preprocessed and analysed using FreeSurfer 6.0. Cortical thickness and cortical surface area were extracted from the caudal middle frontal gyrus (MFG), superior frontal gyrus (SFG), precentral gyrus (PcG), supramarginal gyrus (SMG), superior parietal lobe (SPL) and the inferior parietal lobe (IPL) using the Desikan-Killiany atlas. The DWI data were preprocessed and analysed using ExploreDTI 4.8.6 and the white matter tract, the SLF was reconstructed. RESULTS: Motor planning of the two colour sequence was associated with cortical thickness of the bilateral MFG and left SFG, PcG, IPL and SPL. The right SLF was related to motor planning for the two colour sequence as well as with the left cortical thickness of the SFG. CONCLUSION: Altogether, morphology within frontodorsal circuity, and the white matter bundles that support communication between them, may be associated with individual differences in childhood motor planning.

Mendelian randomization studies of brain MRI yield insights into the pathogenesis of neuropsychiatric disorders.

BACKGROUND: Observational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown. RESULTS: Here, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10- 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer's disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10- 5). By combining all observations, we found that the overall p-value for DTI - Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI - Bipolar disorder (BP) (λ = 2.64) and DTI - AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10- 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation. CONCLUSIONS: As a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.

Isolating the white matter circuitry of the dorsal language stream: Connectome-Symptom Mapping in stroke induced aphasia.

The application of ℓ1-regularized machine learning models to high-dimensional connectomes offers a promising methodology to assess clinical-anatomical correlations in humans. Here, we integrate the connectome-based lesion-symptom mapping framework with sparse partial least squares regression (sPLS-R) to isolate elements of the connectome associated with speech repetition deficits. By mapping over 2,500 connections of the structural connectome in a cohort of 71 stroke-induced cases of aphasia presenting with varying left-hemisphere lesions and repetition impairment, sPLS-R was trained on 50 subjects to algorithmically identify connectomic features on the basis of their predictive value. The highest ranking features were subsequently used to generate a parsimonious predictive model for speech repetition whose predictions were evaluated on a held-out set of 21 subjects. A set of 10 short- and long-range parieto-temporal connections were identified, collectively delineating the broader circuitry of the dorsal white matter network of the language system. The strongest contributing feature was a short-range connection in the supramarginal gyrus, approximating the cortical localization of area Spt, with parallel long-range pathways interconnecting posterior nodes in supramarginal and superior temporal cortex with anterior nodes in both ventral and-notably-in dorsal premotor cortex, respectively. The collective disruption of these pathways indexed repetition performance in the held-out set of participants, suggesting that these impairments might be characterized as a parietotemporal disconnection syndrome impacting cortical area Spt and its associated white matter circuits of the frontal lobe as opposed to being purely a disconnection of the arcuate fasciculus.

The ipsilateral interhemispheric transprecuneal approach: microsurgical anatomy, indications, and neurosurgical applications.

Surgical treatment of intraventricular lesions is challenging because of their deep location, vascularization, and their complex relationships with white matter fibers. The authors undertook this study to describe the microsurgical anatomy of the white matter fibers covering the lateral wall of the atrium and temporal horn and to demonstrate how the ipsilateral interhemispheric transprecuneal approach can be safely used to remove lesions of this region sparing the anatomo-functional integrity of the fibers themselves. A detailed description of the approach including operative measurements is also given. The Klingler' technique with progressive identification of white matter fibers covering the lateral wall of the atrium and temporal horn was performed on ten formalin-fixed human hemispheres. Then, ten fresh, non-formalin-fixed non-silicon-injected adult cadaveric heads were analyzed for the simulation of the ipsilateral interhemispheric transprecuneal approach. Three illustrative cases are presented. The simulation of the interhemispheric transprecuneal approach on ten fresh non-formalin-fixed specimens showed that a 10 to 20 mm corticotomy perpendicular to the parieto-occipital sulcus at the junction with the cingulum allows a wide corridor for the exposure of the entire atrial cavity and the posterior third of the temporal horn. The ipsilateral interhemispheric transprecuneus approach represents a safe and effective option for tumors involving the atrium and the posterior third of the temporal horn.

Intra- and interhemispheric white matter tract associations with auditory spatial processing: Distinct normative and aging effects.

Declining auditory spatial processing is hypothesized to contribute to the difficulty older adults have detecting, locating, and selecting a talker from among others in noisy listening environments. Though auditory spatial processing has been associated with several cortical structures, little is known regarding the underlying white matter architecture or how age-related changes in white matter microstructure may affect it. The arcuate fasciculus is a target for understanding age-related differences in auditory spatial attention based on normative spatial attention findings in humans. Similarly, animal and human clinical studies suggest that the corpus callosum plays a role in the cross-hemispheric integration of auditory spatial information important for spatial localization and attention. The current investigation used diffusion imaging to examine the extent to which age-group differences in the identification of spatially cued speech were accounted for by individual differences in the white matter microstructure of the right arcuate fasciculus and the corpus callosum. Higher right arcuate and callosal fractional anisotropy (FA) predicted better segregation and identification of spatially cued speech across younger and older listeners. Further, individual differences in callosal microstructure mediated age-group differences in auditory spatial processing. Follow-up analyses suggested that callosal tracts connecting left and right pre-frontal and posterior parietal cortex are particularly important for auditory spatial processing. The results are consistent with previous work in animals and clinical human samples and provide a cortical mechanism to account for age-related deficits in auditory spatial processing. Further, the results suggest that both intrahemispheric and interhemispheric mechanisms are involved in auditory spatial processing.

Chronic disorders of consciousness: a case report with longitudinal evaluation of disease progression using 7 T magnetic resonance imaging.

BACKGROUND: Outcome prediction for patients with disorders of consciousness (DOC) is essential yet challenging. Evidence showed that patients with DOC lasting 1 year or longer after a brain injury were less likely to recover. However, the reasons why outcomes of DOC patients differ greatly remain unclear. With a variety of analytical methods and through quantitative behavioral assessments, we aimed to track the progression of a patient with severe brain injury, in order to advance our understanding of the underlying mechanisms of DOC. CASE PRESENTATION: We performed a longitudinal study for a 52-year-old male DOC patient who has remained in the state for 1.5 years with comprehensive rehabilitative therapies. The patient underwent 3 times of assessments of Coma Recovery Scale-Revised (CRS-R) and ultra-high-field 7 T magnetic resonance imaging (MRI). Both topologic properties and brain microstructure were analyzed to track disease progression. We observed dynamic increases of fiber densities with measurements at three time points (t1:1.5 M, t2:7.5 M t3:17.5 M). Specifically, fiber densities of the superior longitudinal fasciculus and arcuate fasciculus nerve fiber bundles improved mostly in the visual, verbal, and auditory subscales, which was consistent with the CRS-R scores. Moreover, the graph-theory analyses demonstrated that network topologic properties showed an improvement although the disease duration exceeded 1 year. CONCLUSIONS: DOC patients with a course longer than 1 year remain possible to improve, and including evaluation methods such as WM connectome analysis and graph theory could be potentially valuable for a more precise assessment of patients with a longer course of DOC.

Altered White Matter Organization in the TUBB3 E410K Syndrome.

Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.

Tractography and the connectome in neurosurgical treatment of gliomas: the premise, the progress, and the potential.

The ability of diffusion tensor MRI to detect the preferential diffusion of water in cerebral white matter tracts enables neurosurgeons to noninvasively visualize the relationship of lesions to functional neural pathways. Although viewed as a research tool in its infancy, diffusion tractography has evolved into a neurosurgical tool with applications in glioma surgery that are enhanced by evolutions in crossing fiber visualization, edema correction, and automated tract identification. In this paper the current literature supporting the use of tractography in brain tumor surgery is summarized, highlighting important clinical studies on the application of diffusion tensor imaging (DTI) for preoperative planning of glioma resection, and risk assessment to analyze postoperative outcomes. The key methods of tractography in current practice and crucial white matter fiber bundles are summarized. After a review of the physical basis of DTI and post-DTI tractography, the authors discuss the methodologies with which to adapt DT image processing for surgical planning, as well as the potential of connectomic imaging to facilitate a network approach to oncofunctional optimization in glioma surgery.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition.