Inferior Frontal Occipital Fasciculus Research Articles

Facial emotion recognition function and white matter microstructural alterations in drug-naive, comorbidity-free autism.

Individuals with autism spectrum disorder have deficits in facial emotion recognition and white matter microstructural alterations. Nonetheless, most previous studies were confounded by different variables, such as psychiatric comorbidities and psychotropic medications used by ASD participants. Also, it remains unclear how exactly FER deficits are related to white matter microstructural alterations in ASD. Accordingly, we aimed to investigate the FER functions, white matter microstructure, and their relationship in drug-naive and comorbidity-free ASD individuals. 59 ASD individuals and 59 typically developed individuals were included, where 46 ASD and 50 TD individuals completed FER tasks. Covariance analysis showed scores were lower in both basic and complex FER tasks in the ASD group. Tract-Based Spatial Statistics showed FA values in widespread white matter fibers were lower in the ASD group than in the TD group, including forceps major and forceps minor of the corpus callosum, anterior thalamic radiation, corticospinal tract, cingulum, inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus. Moreover, in the TD group but not the ASD group, the performance in the complex FER task was negatively correlated with the FA value in some white matter fibers, including forceps major of the corpus callosum, ATR, CT, cingulum, IFOF, ILF, SLF. Our study suggests children with ASD may experience deficits in facial emotion recognition and exhibit alterations in white matter microstructure. More importantly, our study indicates that white matter microstructural alterations may be involved in FER deficits in children with ASD.

The covariant structural and functional neuro-correlates of cognitive impairments in patients with end-stage renal diseases.

Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

Corpus callosum and cerebellum participate in semantic dysfunction of Parkinson's disease: a diffusion tensor imaging-based cross-sectional study.

Language dysfunction is common in Parkinson's disease (PD) patients, among which, the decline of semantic fluency is usually observed. This study aims to explore the relationship between white matter (WM) alterations and semantic fluency changes in PD patients. 127 PD patients from the Parkinson's Progression Markers Initiative cohort who received diffusion tensor imaging scanning, clinical assessment and semantic fluency test (SFT) were included. Tract-based special statistics, automated fiber quantification, graph-theoretical and network-based analyses were performed to analyze the correlation between WM structural changes, brain network features and semantic fluency in PD patients. Fractional anisotropy of corpus callosum, anterior thalamic radiation, inferior front-occipital fasciculus, and uncinate fasciculus, were positively correlated with SFT scores, while a negative correlation was identified between radial diffusion of the corpus callosum, inferior longitudinal fasciculus, and SFT scores. Automatic fiber quantification identified similar alterations with more details in these WM tracts. Brain network analysis positively correlated SFT scores with nodal efficiency of cerebellar lobule VIII, and nodal local efficiency of cerebellar lobule X. WM integrity and myelin integrity in the corpus callosum and several other language-related WM tracts may influence the semantic function in PD patients. Damage to the cerebellum lobule VIII and lobule X may also be involved in semantic dysfunction in PD patients.

Assessing the impact of infantile hydrocephalus on visuomotor integration through behavioural and neuroimaging studies

ABSTRACT Infantile hydrocephalus considerably impacts neurodevelopment, warranting attention to potential long-term consequences on visuomotor functions. The current study investigated the impact of infantile hydrocephalus on functional connectivity within the posterior cortex. Fourteen patients, who were treated for infantile hydrocephalus, were matched for age and sex with 14 typically-developing controls. Both groups had a mean age of 9 years old. Resting-state functional MRI was used to conduct a functional connectivity analysis within the visuomotor integration network, including the inferior frontal occipital fasciculus, superior longitudinal fasciculus, and frontal aslant tract. Patients had reduced functional connectivity in visuomotor pathways compared to typically-developing children with notable impact on the left and right fusiform gyrus and precuneus. Children with infantile hydrocephalus also performed significantly lower in tasks involving visuomotor integration, visual processing, visuospatial skills, motor coordination, and fine motor manipulation. This study enhances our understanding of the multifaceted impact of infantile hydrocephalus on both neural connectivity and considering behavioral outcomes.

Baseline symptom-related white matter tracts predict individualized treatment response to 12-week antipsychotic monotherapies in first-episode schizophrenia

There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks. Clinical symptoms were evaluated using the eight “core symptoms” selected from the Positive and Negative Syndrome Scale (PANSS-8). Follow-up assessments were conducted at the 4th, 8th, and 12th weeks by trained psychiatrists. LASSO regression model and cross-validation were conducted to examine the performance of baseline symptom-related alterations FA and MD of WM in the prediction of individualized treatment outcome. Fifty patients completed both clinical follow-up assessments by the 8th and 12th weeks. 30 patients were classified as responders, and 20 patients were classified as nonresponders. At baseline, the altered diffusion properties of fiber tracts in the anterior thalamic radiation, corticospinal tract, callosum forceps minor, longitudinal fasciculi (ILF), inferior frontal-occipital fasciculi (IFOF) and superior longitudinal fasciculus (SLF) were related to the severity of symptoms. These abnormal fiber tracts, especially the ILF, IFOF, and SLF, significantly predicted the response to antipsychotic treatment at the individual level (AUC = 0.828, P < 0.001). These findings demonstrate that early microstructural WM changes contribute to the pathophysiology of psychosis and may serve as meaningful individualized predictors of response to antipsychotics.

Moving towards an Understanding of the Role of the Inferior Fronto-Occipital Fasciculus in Language Processing

Evidence has been provided for a clear structural distinction between the dorsal and ventral portions of the inferior frontal occipital fasciculus (IFOF). As such, there is reason to propose that there might also be a functional differentiation of the dorsal and ventral components of the IFOF. Here, we explored three main hypotheses/schools of thought with regards to the functional frameworks of the dorsal and ventral components of the IFOF: (1) the phonological vs. semantic processing hypothesis, (2) the difficult vs. non-difficult task processing hypothesis and (3) the automatic vs. non-automatic processing hypothesis. Methods: Participants (N = 32) completed a series of behavioral tasks that aligned with each of the main hypotheses. Using a regression-based approach, we assessed the unique contribution of behavioral performance to dorsal and ventral IFOF white matter indicators (i.e., fractional anisotropy and mean diffusivity). Results: We found significant relationships between ventral IFOF indices and orthographic awareness (p = 0.018) and accuracy (p = 0.009). Overall, our results provide converging evidence that the IFOF primarily operates as a ventral language tract in adults. Thus, the structural distinction between dorsal and ventral IFOF does not manifest as a parallel functional distinction.

Ventral and dorsal aspects of the inferior frontal-occipital fasciculus support verbal semantic access and visually-guided behavioural control

The Inferior Frontal Occipital Fasciculus (IFOF) is a major anterior-to-posterior white matter pathway in the ventral human brain that connects parietal, temporal and occipital regions to frontal cortex. It has been implicated in a range of functions, including language, semantics, inhibition and the control of action. The recent research shows that the IFOF can be sub-divided into a ventral and dorsal branch, but the functional relevance of this distinction, as well as any potential hemispheric differences, are poorly understood. Using DTI tractography, we investigated the involvement of dorsal and ventral subdivisions of the IFOF in the left and right hemisphere in a response inhibition task (Go/No-Go), where the decision to respond or to withhold a prepotent response was made on the basis of semantic or non-semantic aspects of visual inputs. The task also varied the presentation modality (whether concepts were presented as written words or images). The results showed that the integrity of both dorsal and ventral IFOF in the left hemisphere were associated with participants’ inhibition performance when the signal to stop was meaningful and presented in the verbal modality. This effect was absent in the right hemisphere. The integrity of dorsal IFOF was also associated with participants’ inhibition efficiency in difficult perceptually guided decisions. This pattern of results indicates that left dorsal IFOF is implicated in the domain-general control of visually-guided behaviour, while the left ventral branch might interface with the semantic system to support the control of action when the inhibitory signal is based on meaning.

White matter tracts contribute selectively to cognitive functioning in patients with glioma.

The functional organization of white matter (WM) tracts is not well characterized, especially in patients with intrinsic brain tumors where complex patterns of tissue injury, compression, and neuroplasticity may be present. This study uses diffusion tensor imaging (DTI) to investigate the relationships between WM tract disruption and cognitive deficits in glioma patients. Seventy-nine patients with glioma underwent preoperative DTI and neuropsychological testing. Thirteen WM tracts were reconstructed bilaterally. Fractional anisotropy and streamline number were obtained for each tract as indices of connectivity. Univariate regression models were used to model the association between WM tract connectivity and neuropsychological outcomes. Glioma patients exhibited variable injury to WM tracts and variable cognitive deficits on validated neuropsychological tests. We identified 16 age-adjusted associations between WM tract integrity and neuropsychological function. The left inferior frontal-occipital fasciculus (IFOF) predicted list learning and dominant-hand fine motor dexterity. The right IFOF predicted non-dominant-hand fine motor dexterity and visuospatial index scores. The left inferior longitudinal fasciculus (ILF) predicted immediate memory list learning and index scores. The right ILF predicted non-dominant-hand fine motor dexterity and backward digit span scores. The left superior longitudinal fasciculus (SLF) I predicted processing speed. The left SLF III predicted list learning, immediate memory index scores, phonemic fluency, and verbal abstract reasoning. The left cingulum predicted processing speed. The right anterior AF predicted verbal abstract reasoning. WM tract disruption predicts cognitive dysfunction in glioma patients. By improving knowledge of WM tract organization, this analysis may guide maximum surgical resection and functional preservation in glioma patients.

Deficits in naming pictures of objects are associated with glioma infiltration of the inferior longitudinal fasciculus: A study with diffusion MRI tractography, volumetric MRI, and neuropsychology.

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.

White matter tract abnormalities are associated with executive dysfunction in temporal lobe epilepsy and hippocampal sclerosis (P12-1.010)

<h3>Objective:</h3> To evaluate the role of white-matter tract involvement in executive dysfunction in patients with temporal lobe epilepsy and unilateral hippocampal sclerosis (TLE-HS). <h3>Background:</h3> TLE-HS patients frequently display executive dysfunction (ED). The neuroanatomical substrate of ED in TLE-HS remains poorly understood. In this study, we investigated the role of white-matter tract involvement in ED in TLE-HS. <h3>Design/Methods:</h3> Patients with unilateral TLE-HS, aged 17–55, education&gt;=8 years, IQ&gt;=70, EEG findings of unilateral or bilateral temporal discharges were studied. Patients and healthy controls fulfilling the same inclusion criteria underwent the Stroop Color and Word Test (SCWT) and a 3T MRI with DTI sequences. DTI Fractional Anisotropy (FA) data was extracted and analyzed using FSL. FA maps were compared with Tract-Based Spatial Statistics (TBSS) voxel-wise analysis. Patients were classified as ED if performance in the SCWT was below minus 1.5 (−1.5) Standard Deviations of the mean performance of healthy controls. <h3>Results:</h3> 49 patients (30 left and 19 right HS) underwent the SCWT. Performance did not differ between right and left HS. Patients with normal and impaired executive function did not differ in disease duration, antiseizure medication load, and seizure frequency. Both patient groups showed diffuse FA decrease when compared to healthy controls. Compared to TLE-HS patients with normal SCWT performance, patients with ED had more pronounced FA alterations, showing statistically significant decreased FA in the superior longitudinal fasciculi, body of the corpus callosum, forceps major, corona radiata, inferior frontal-occipital fasciculus, uncinate fasciculus and corticospinal tract, and right thalamic radiations. <h3>Conclusions:</h3> In this TLE-HS patient population, executive dysfunction was associated with more pronounced widespread WM tract damage, in comparison with TLE-HS patients with preserved executive function. This finding underscores the role of microstructural WM damage in executive dysfunction in TLE-HS. <b>Disclosure:</b> Miss Solti has nothing to disclose. Mr. Mahler Ferreira Oliveira has nothing to disclose. Carla Adda has nothing to disclose. Rosa Valerio has nothing to disclose. Dr. Jorge has nothing to disclose. Katarina Lyra has nothing to disclose. Mr. Pastorello has nothing to disclose. Claudia Leite has nothing to disclose. Maria Otaduy has nothing to disclose. Dr. Castro has nothing to disclose.

Alterations in white matter integrity and network topological properties are associated with a decrease in global motion perception in older adults.

Previous studies have mainly explored the effects of structural and functional aging of cortical regions on global motion sensitivity in older adults, but none have explored the structural white matter (WM) substrates underlying the age-related decrease in global motion perception (GMP). In this study, random dot kinematogram and diffusion tensor imaging were used to investigate the effects of age-related reductions in WM fiber integrity and connectivity across various regions on GMP. We recruited 106 younger adults and 94 older adults and utilized both tract-based spatial statistics analysis and graph theoretical analysis to comprehensively investigate group differences in WM microstructural and network connections between older and younger adults at the microscopic and macroscopic levels. Moreover, partial correlation analysis was used to explore the relationship between alterations in WM and the age-related decrease in GMP. The results showed that decreased GMP in older adults was related to decreased fractional anisotropy (FA) of the inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and cingulum cingulate gyrus. Decreased global efficiency of the WM structural network and increased characteristic path length were closely associated with decreased global motion sensitivity. These results suggest that the reduced GMP in older adults may stem from reduced WM integrity in specific regions of WM fiber tracts as well as decreased efficiency of information integration and communication between distant cortical regions, supporting the "disconnection hypothesis" of cognitive aging.

Association between childhood trauma and white matter deficits in first-episode schizophrenia

ObjectiveThis study aimed to investigate the relationship between childhood trauma (ChT) and white matter (WM) deficits in first-episode schizophrenia (FES). MethodsA total of 103 individuals with FES and 206 healthy control individuals (HCs) were enrolled and assessed based on ChT Questionnaire (CTQ) and Positive and Negative Symptoms Scale (PANSS). Diffusion tensor imaging was acquired on a Signa 3.0 T scanner. Map of fractional anisotropy (FA) was analyzed using Tract-Based Spatial Statistics. Hierarchical logistic regression analyses were used to examine associations of sociodemographic characteristics, total CTQ scores, and WM deficits. ResultsCompared with the HCs group, the FES group showed significantly lower FA in several WM bundles (left anterior thalamic radiation, left inferior frontal-occipital fasciculus, left cingulum, forceps major, and forceps minor), and the mean FA value in these WM bundles was inversely related to the total CTQ score. In addition, a higher CTQ score may increase the risk of schizophrenia, while higher FA values may decrease the risk of schizophrenia. ConclusionThis study demonstrates that individuals with FES evince widespread cerebral WM abnormalities and that these abnormalities were associated with ChT. These results provide clues about the neural basis and potential biomarkers of schizophrenia.

Directional and general impairments in initiating motor responses after stroke.

Visuospatial neglect is a disorder characterized by an impairment of attention, most commonly to the left side of space in individuals with stroke or injury to the right hemisphere. Clinical diagnosis is largely based on performance on pen and paper examinations that are unable to accurately measure the speed of processing environmental stimuli-important for interacting in our dynamic world. Numerous studies of impairment after visuospatial neglect demonstrate delayed reaction times when reaching to the left. However, little is known of the visuospatial impairment in other spatial directions and, further, the influence of the arm being assessed. In this study, we quantify the ability of a large cohort of 204 healthy control participants (females = 102) and 265 individuals with stroke (right hemisphere damage = 162, left hemisphere damage = 103; mean age 62) to generate goal-directed reaches. Participants used both their contralesional and ipsilesional arms to perform a centre-out visually guided reaching task in the horizontal plane. We found that the range of visuospatial impairment can vary dramatically across individuals with some individuals displaying reaction time impairments restricted to a relatively small portion of the workspace, whereas others displayed reaction time impairments in all spatial directions. Reaction time impairments were observed in individuals with right or left hemisphere lesions (48% and 30%, respectively). Directional impairments commonly rotated clockwise when reaching with the left versus the right arms. Impairment in all spatial directions was more prevalent in right than left hemisphere lesions (32% and 12%, respectively). Behavioral Inattention Test scores significantly correlated (r = -0.49, P < 0.005) with reaction time impairments but a large portion of individuals not identified as having visuospatial neglect on the Behavioral Inattention Test still displayed reaction time impairments (35%). MRI and CT scans identified distinct white matter and cortical regions of damage for individuals with directional (insula, inferior frontal-occipital fasciculus and inferior longitudinal fasciculus) and general (superior and middle temporal gyri) visuospatial impairment. This study highlights the prevalence and diversity of visuospatial impairments that can occur following stroke.

Longitudinal Structural and Diffusion-Weighted Neuroimaging of Young Children Born Preterm

BackgroundChildren born preterm are at risk for diffuse injury to subcortical gray and white matter. MethodsWe used a longitudinal cohort study to examine the development of subcortical gray matter and white matter volumes, and diffusivity measures of white matter tracts following preterm birth. Our participants were 47 children born preterm (24 to 32 weeks gestational age) and 28 children born at term. None of the children born preterm had significant neonatal brain injury. Children received structural and diffusion weighted magnetic resonance imaging scans at ages five, six, and seven years. We examined volumes of amygdala, hippocampus, caudate nucleus, putamen, thalamus, brainstem, cerebellar white matter, intracranial space, and ventricles, and volumes, fractional anisotropy, and mean diffusivity of anterior thalamic radiation, cingulum, corticospinal tract, corpus callosum, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, temporal and parietal superior longitudinal fasciculus, and uncinate fasciculus. ResultsChildren born preterm had smaller volumes of thalamus, brainstem, cerebellar white matter, cingulum, corticospinal tract, inferior frontal occipital fasciculus, uncinate fasciculus, and temporal superior longitudinal fasciculus, whereas their ventricles were larger compared with term-born controls. We found no significant effect of preterm birth on diffusivity measures. Despite developmental changes and growth, group differences were present and similarly strong at all three ages. ConclusionEven in the absence of significant neonatal brain injury, preterm birth has a persistent impact on early brain development. The lack of a significant term status by age interaction suggests a delayed developmental trajectory.

The regional relationship between CSF VEGF and white matter microstructural integrity in older adults: A voxelwise DTI study

AbstractBackgroundBoth white matter (WM) micro‐ and macro‐ structural abnormalities occur in Alzheimer’s disease (AD) with micro‐structural abnormalities likely preceding macrostructural changes in the AD cascade. Diffusion tensor imaging (DTI) fractional anisotropy (FA) ‐ which is sensitive to factors such as myelination, fiber coherence, and fiber density‐ within an MRI voxel may be used to detect AD‐specific deficits. However, mechanisms driving loss of WM microstructural integrity in AD are poorly understood. Vascular endothelial growth factor (VEGF) is a multi‐function vascular protein linked to early AD brain and cognition biomarkers. VEGF provides neurotrophic support via glia and is also secreted by glial cells essential for maintaining myelin. However, in humans, the relationship between VEGF and WM microstructural integrity has yet to be mapped. We evaluated whether cerebrospinal fluid (CSF) VEGF levels were associated with voxelwise WM FA in older adults without dementia.MethodWe evaluated 72 older adults without dementia from the USC Alzheimer’s Disease Research Center (ADRC) (mean age 65.7; 47‐82 years old) with a clinical dementia rating (CDR) score of 0 (n=56) or 0.5 (n=16) who had both CSF VEGF‐A levels and a 3 T diffusion MRI scan (64‐direction (b=1000 s/mm2) DWI volumes). MRI scans were pre‐processed to reduce artifacts related to motion, distortion, eddy currents, bias field, and susceptibility artifacts. Tract‐based spatial statistics, using FSL software, was implemented to derive skeletonized FA maps along WM tracts. The association between VEGF and voxelwise FA WM integrity was evaluated using FSL’s general linear model tool. We covaried for age, sex, and CDR. FA significance cluster maps were corrected for voxelwise multiple comparisons.ResultHigher CSF VEGF levels were associated with lower DTI FA, indicative of poorer WM microstructural integrity, in the left and right superior longitudinal fasciculus, left anterior thalamic radiation, and left inferior frontal occipital fasciculus (p&lt;0.05) (Figure 1).ConclusionThese results demonstrate for the first time in humans that VEGF levels are related to WM microstructure in older adults without dementia, primarily in long range association fibers connecting temporal, parietal, and frontal lobes. These pathways are essential for memory, language, attention and emotional control.

White matter tract changes in pediatric posterior fossa brain tumor survivors after surgery and chemotherapy.

Survivors of pediatric posterior fossa brain tumors are susceptible to the adverse effects of treatment as they grow into adulthood. While the exact neurobiological mechanisms of these outcomes are not yet understood, the effects of treatment on white matter (WM) tracts in the brain can be visualized using diffusion tensor (DT) imaging. We investigated these WM microstructural differences using the statistical method tract-specific analysis (TSA). We applied TSA to the DT images of 25 children with a history of posterior fossa tumor (15 treated with surgery, 10 treated with surgery and chemotherapy) along with 21 healthy controls. Between these 3 groups, we examined differences in the most used DTI metric, fractional anisotropy (FA), in 11 major brain WM tracts. Lower FA was found in the splenium of the corpus callosum (CC), the bilateral corticospinal tract (CST), the right inferior frontal occipital fasciculus (IFOF) and the left uncinate fasciculus (UF) in children with brain tumors as compared to healthy controls. Lower FA, an indicator of microstructural damage to WM, was observed in 4 of the 11 WM tracts examined in both groups of children with a history of posterior fossa tumor, with an additional tract unique to children who received surgery and chemotherapy (left UF). Our findings indicate that a history of tumor in the posterior fossa and surgical resection may have effects on the WM in other parts of the brain.

Longer screen time utilization is associated with the polygenic risk for Attention-deficit/hyperactivity disorder with mediation by brain white matter microstructure.

SummaryBackgroundAttention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset.MethodsLeveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9–11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses.FindingsChildren with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU.InterpretationThese findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU.FundingThis study was mainly supported by NSFC and National Key R&D Program of China.

An investigation of white matter properties as they relate to spelling behaviour in skilled and impaired readers

ABSTRACT We examined the extent to which white matter is related to spelling behaviour in adults with skilled vs. impaired literacy skills. Adults (N = 30; 17 skilled) completed a battery of spelling tasks and underwent a brain scan to measure diffusion properties of white matter tracts, namely the arcuate fasciculus, inferior longitudinal fasciculus, inferior frontal occipital fasciculus and uncinate fasciculus. Regression analyses and between groups tests of correlation strength were run. Results While the inferior longitudinal fasciculus was more strongly related to spelling behaviour in skilled adults, the uncinate fasciculus was more strongly related to spelling behaviour in impaired adults. We found strong left lateralization of the arcuate fasciculus and inferior longitudinal fasciculus in both groups. However, lateralization of the inferior frontal occipital fasciculus was more strongly related to spelling response time behaviour in skilled adults, whereas lateralization of the uncinate fasciculus was more strongly related to spelling accuracy behaviour in the impaired adults. Conclusion This study provides some useful information for understanding the underlying white matter pathways that support spelling in skilled and impaired adults and underscore the advantage of adopting multiple spelling tasks and outcomes (i.e., response time and accuracy) to better characterize brain-behaviour relationships in skilled and impaired adults.

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders.

ObjectiveTuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI).MethodsA total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers.ResultsThe TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC.ConclusionThe disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.

Microstructural changes of white matter fiber tracts induced by insular glioma revealed by tract-based spatial statistics and automatic fiber quantification

Gliomas typically grow along white matter fiber tracts, yet their invasion patterns remain unclear. This study assessed the effect of insular glioma on large white matter fiber tracts and the microstructural subcortical changes associated with clinical outcomes in patients with insular glioma. Twenty-five patients with insular glioma were enrolled and divided into left and right groups according to tumor lateralization. The control group comprised 14 healthy volunteers. Subjects in both the glioma and control groups underwent diffusion tensor magnetic resonance imaging at 3.0 T. The characteristics of white matter fiber bundles were analyzed using tract-based spatial statistics and automatic fiber quantification. Both Automatic Fiber Quantification and Tract-Based Spatial Statistics revealed that patients with insular glioma had significantly lower fractional anisotropy (FA) values in the inferior frontal-occipital fasciculus and uncinate fasciculus ipsilateral to the tumor, than the controls. Fractional anisotropy associated with mean diffusivity values several large fiber tracts showed potential on tumor-grade distinguishing. Diffusion metrics can sensitively detect microstructural changes in tumor progression. Insular glioma significantly affects the microstructure of white matter fibers proximal to the tumor. The range of white matter fiber bundles affected differs according to the grade of the glioma. These changes are mainly associated with early-stage tumor invasion.