Integrity Of White Matter Tracts Research Articles

Age- and memory- related differences in hippocampal gray matter integrity are better captured by NODDI compared to single-tensor diffusion imaging

Single-tensor diffusion imaging (DTI) has traditionally been used to assess integrity of white matter. For example, we previously showed that integrity of limbic white matter tracts declines in healthy aging and relates to episodic memory performance. However, multi-compartment diffusion models may be more informative about microstructural properties of gray matter. The current study examined hippocampal gray matter integrity using both single-tensor and multi-compartment (neurite orientation dispersion and density imaging, NODDI) diffusion imaging. Younger (20–38 years) and older (59–84 years) adults also completed the Mnemonic Similarity Task to measure mnemonic discrimination performance. Results revealed age-related declines in both single-tensor (lower fractional anisotropy, higher mean diffusivity) and multi-compartment (higher restricted, hindered and free diffusion) measures of hippocampal gray matter integrity. As expected, NODDI measures (hindered and free diffusion) captured more age-related variance than DTI measures. Moreover, mnemonic discrimination of highly similar lure items in memory was related to hippocampal gray matter integrity in younger but not older adults. These findings support the notion that age-related differences in gray matter integrity are better captured by multi-compartment versus single-tensor diffusion models and show that the relationship between mnemonic discrimination and hippocampal gray matter integrity is moderated by age.

Hearing loss and microstructural integrity of the brain in a dementia-free older population.

As hearing loss has been identified as an important risk factor for dementia, we aimed to assess the association between hearing loss and microstructural integrity of the brain. A total of 1086 dementia-free participants (mean age=75.2 [standard deviation: 4.9], 61.4% female) of the population-based Atherosclerosis Risk in Communities (ARIC) study underwent hearing assessment (2016-2017) and magnetic resonance imaging of the brain (2011-2013). Microstructural integrity was determined with diffusion tensor imaging. Multivariable linear regression was used to investigate associations between hearing loss and microstructural integrity of different brain regions and white matter (WM) tracts. Hearing loss was associated with lower WM microstructural integrity in the temporal lobe, lower gray matter integrity of the hippocampus, and with lower WM microstructural integrity of the limbic tracts and the uncinate fasciculus. Our results demonstrate that hearing loss is indepedently associated with lower microstructural integrity in brain regions that are important for different cognitive processes.

Association of SBP and BMI with cognitive and structural brain phenotypes in UK Biobank.

To test for associations between SBP and BMI, with domain-specific cognitive abilities and examine which brain structural phenotypes mediate those associations. Using cross-sectional UK Biobank data (final N = 28 412), we examined SBP/BMI vs. cognitive test scores of pairs-matching, matrix completion, trail making test A/B, digit symbol substitution, verbal-numerical reasoning, tower rearranging and simple reaction time. We adjusted for potential confounders of age, sex, deprivation, medication, apolipoprotein e4 genotype, smoking, population stratification and genotypic array. We tested for mediation via multiple structural brain imaging phenotypes and corrected for multiple testing with false discovery rate. We found positive associations for higher BMI with worse reaction time, reasoning, tower rearranging and matrix completion tasks by 0.024-0.067 SDs per BMI SD (all P < 0.001). Higher SBP was associated with worse reasoning (0.034 SDs) and matrix completion scores (-0.024 SDs; both P < 0.001). Both BMI and SBP were associated with multiple brain structural metrics including total grey/white matter volumes, frontal lobe volumes, white matter tract integrity and white matter hyperintensity volumes: specific metrics mediated around one-third of the associations with cognition. Our findings add to the body of evidence that addressing cardiovascular risk factors may also preserve cognitive function, via specific aspects of brain structure.

Change in Right Inferior Longitudinal Fasciculus Integrity Is Associated With Naming Recovery in Subacute Poststroke Aphasia

Background. Despite progress made in understanding functional reorganization patterns underlying recovery in subacute aphasia, the relation between recovery and changes in white matter structure remains unclear. Objective. To investigate changes in dorsal and ventral language white matter tract integrity in relation to naming recovery in subacute poststroke aphasia. Methods. Ten participants with aphasia after left-hemisphere stroke underwent language testing and diffusion tensor imaging twice within 3 months post onset, with a 1-month interval between sessions. Deterministic tractography was used to bilaterally reconstruct the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MdLF), and uncinate fasciculus (UF). Per tract, the mean fractional anisotropy (FA) was extracted as a measure of microstructural integrity. Naming accuracy was assessed with the Boston Naming Test (BNT). Correlational analyses were performed to investigate the relationship between changes in FA values and change in BNT score. Results. A strong positive correlation was found between FA change in the right ILF within the ventral stream and change on the BNT (r = 0.91, P < .001). An increase in FA in the right ILF was associated with considerable improvement of naming accuracy (range BNT change score: 12-14), a reduction with limited improvement or slight deterioration. No significant correlations were found between change in naming accuracy and FA change in any of the other right or left ventral and dorsal language tracts. Conclusions. Naming recovery in subacute aphasia is associated with change in the integrity of the right ILF.

Diffusion Kurtosis Imaging Reveals Optic Tract Damage That Correlates with Clinical Severity in Glaucoma.

Glaucoma is a neurodegenerative disease of the visual system and is the leading cause of irreversible blindness worldwide. To date, its pathophysiological mechanisms remain unclear. This study evaluated the feasibility of advanced diffusion magnetic resonance imaging techniques for examining the microstructural environment of the visual pathway in glaucoma. While conventional diffusion tensor imaging (DTI) showed lower fractional anisotropy and higher directional diffusivities in the optic tracts of glaucoma patients than healthy controls, diffusion kurtosis imaging (DKI) and the extended white matter tract integrity (WMTI) model indicated lower radial kurtosis, higher axial and radial diffusivities in the extra-axonal space, lower axonal water fraction, and lower tortuosity in the same regions in glaucoma patients. These findings suggest glial involvements apart from compromised axonal integrity in glaucoma. In addition, DKI and WMTI but not DTI parameters significantly correlated with clinical ophthalmic measures via optical coherence tomography and visual field perimetry testing. Taken together, DKI and WMTI provided sensitive and comprehensive imaging biomarkers for quantifying glaucomatous damage in the white matter tract across clinical severity complementary to DTI.

Predictive value of fractional anisotropy changes of the corticospinal tract in the acute phase of ischemic stroke

Objective To evaluate the role of reduction in fractional anisotropy (FA) of the ipsilesional corticospinal tract detected by diffusion tensor imaging (DTI) as a prognostic tool to predict the outcome following an acute ischemic stroke. Background There are high costs and concerns about postischemic stroke disability worldwide. DTI is an emerging neuroimaging technique that allows us to measure the integrity of white matter tracts. The reduction of FA value detected by DTI can predict residual neurological deficit in the acute phase of ischemic stroke after 3 months. Patients and methods A nonrandomized, retrospective cohort study was conducted on 40 patients with acute ischemic stroke for the first time and 40 controls of healthy individuals. We assessed our patients according to the size of the infarction, stroke severity using the National Institute of Health and Stroke Scale (NIHSS), and degree of reduction of FA detected by DTI. Patients were followed up clinically using NIHSS after 3 months for residual neurological deficits. Results We observed a good association between reduction of FA value measured by DTI and clinical findings of acute ischemic stroke assessed by NIHSS at the time of onset and after 3 months (P = 0.004, 0.007), respectively. The reduction of FA value was measured by DTI, which is also correlated with the size of the infarction of ischemic stroke (P Conclusion Reduction of FA of the corticospinal tract was measured by DTI. The image could be used as a useful tool for predicting long-term poststroke disability after 3 months.

Assessing changes in microstructural integrity of white matter tracts in children with leukaemia following exposure to chemotherapy.

Intrathecal and intravenous chemotherapy, specifically methotrexate, might contribute to neural microstructural damage. To assess, by diffusion tensor imaging, microstructural integrity of white matter in paediatric patients with acute lymphoblastic leukaemia (ALL) following intrathecal and intravenous chemotherapy. Eleven children diagnosed with de novo ALL underwent MRI scans of the brain with diffusion tensor imaging (DTI) prior to commencement of chemotherapy and at 12months after diagnosis, using a 3-tesla (T) MRI scanner. We investigated the changes in DTI parameters in white matter tracts before and after chemotherapy using tract-based spatial statistics overlaid on the International Consortium of Brain Mapping DTI-81 atlas. All of the children underwent formal neurodevelopmental assessment at the two study time points. Whole-brain DTI analysis showed significant changes between the two time points, affecting several white matter tracts. The tracts demonstrated longitudinal changes of decreasing mean and radial diffusivity. The neurodevelopment of the children was near compatible for age at the end of ALL treatment. The quantification of white matter tracts changes in children undergoing chemotherapy showed improving longitudinal values in DTI metrics (stable fractional anisotropy, decreasing mean and radial diffusivity), which are incompatible with deterioration of microstructural integrity in these children.

Investigation of structure-function correlation among the young offspring of patients with bipolar disorder

Bipolar disorder (BD) has been associated with impaired executive functioning and integrity of fronto-limbic white matter tracts. The evaluation of these factors in young offspring of patients with BD (BDoff) as a high-risk group offers an opportunity to investigate factors that could predict vulnerability to the disorder. This study aims to examine the correlation between neurocognition and neuroimaging findings to evaluate the potential for these findings as biomarkers for the early recognition of BD. We enrolled BDoff (n = 16) who were aged between 12 and 18. Participants were assessed using clinical and neurocognitive tests. In addition, structural brain magnetic resonance and diffusion tensor imaging data were obtained. Mean fractional anisotropy (FA) and mean diffusivity (MD) values of the superior longitudinal fasciculus (SLF) and cingulum were extracted and correlations with neuropsychological data were analyzed. FA values in the SLF were negatively correlated with Stroop interference, the Wisconsin Card Sorting Test, and the Trail Making Test (B-A) scores. MD values in the cingulum were inversely correlated with the Child and Youth Resilience Measure and positively correlated with higher scores on the Barratt Impulsiveness Scale-Attentional. These findings provide a link between features of the brain and cognitive dysfunction in BDoff.

Individual differences in white and grey matter structure associated with verbal habits of thought

Modality specific encoding habits account for a significant portion of individual differences reflected in functional activation during cognitive processing. Yet, little is known about how these habits of thought influence long-term structural changes in the brain. Traditionally, habits of thought have been assessed using self-report questionnaires such as the visualizer-verbalizer questionnaire. Here, rather than relying on subjective reports, we measured habits of thought using a novel behavioral task assessing attentional biases toward picture and word stimuli. Hypothesizing that verbal habits of thought are reflected in the structural integrity of white matter tracts and cortical regions of interest, we used diffusion tensor imaging and volumetric analyses to assess this prediction. Using a whole-brain approach, we show that word bias is associated with increased volume in several bilateral language regions, in both white and grey matter parcels. Additionally, connectivity within white matter tracts within an a priori speech production network increased as a function of word bias. These results demonstrate long-term structural and morphological differences associated with verbal habits of thought.

M175. BRAIN STRUCTURAL CORRELATES OF FUNCTIONAL CAPACITY IN FIRST-EPISODE PSYCHOSIS

BackgroundImpaired functional capacity is a core feature of schizophrenia and present even in first episode psychosis (FEP) patients. Impairments in daily functioning tend to persist despite antipsychotic therapy but their neural basis is not clear. Previous studies suggest that volume loss in frontal cortex might be an important contributor but findings are inconsistent. We aimed to comprehensively investigate the brain structural correlates of functional capacity in first episode psychosis using MRI and a reliable objective measure of functioning (University of California, San Diego Performance-Based Skills Assessment (UPSA))MethodsIn FEP and a well-matched control group, we measured cortical thickness, gray matter volume, and white matter tract integrity (fractional anisotropy, FA) in specific regions implicated by previous work. Between-group differences in these parameters were assessed first. We then examined correlations between MRI measures and UPSA scores in the FEP group while controlling for negative symptomology and medication use.ResultsThe FEP group had thinner cortex in various frontal regions, fusiform, and insula, and reduced FA in inferior longitudinal fasciculus. In FEP, poorer functioning (UPSA) correlated with reduced superior frontal volume and lower FA in inferior longitudinal fasciculus.DiscussionIn accordance with previous findings, FEP exhibited widespread brain structural differences compared to controls. Importantly, frontal brain volumes and integrity of the inferior longitudinal fasciculus were identified as the structural correlates of functional capacity in FEP, after controlling for other relevant factors. These findings enhance mechanistic understanding of functional capacity deficits in schizophrenia by specifying the underlying neural correlates. In future, this could help inform intervention strategies.

T169. SEMANTIC PROCESSING IN RELATION TO ANATOMICAL INTEGRITY OF THE VENTRAL LANGUAGE STREAM IN SCHIZOPHRENIA SPECTRUM DISORDERS

BackgroundSemantic processing anomalies, clinically reflected by disorganized speech are a core symptom of schizophrenia. In the light of accumulating evidence on its prominent role in semantic processing, aberrant structural integrity of the ventral language stream may reflect impaired semantic processing in schizophrenia spectrum disorders (SSD).MethodsComparison of white matter tract integrity in SSD patients and healthy controls using diffusion tensor imaging combined with probabilistic fiber tractography. For the ventral language stream, we assessed the inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus, and uncinate fasciculus. The arcuate fasciculus and corticospinal tractwere used as control tracts. In SSD patients, the relationship between semantic processing impairments and tract integrity was analyzed separately. Three-dimensional tract reconstructions were performed in 45/44 SSD patients/controls (“Bern sample”) and replicated in an independent sample of 24/24 SSD patients/controls (“Basel sample”).ResultsMultivariate analyses of fractional anisotropy, mean, axial, and radial diffusivity of the left IFOF showed significant differences between SSD patients and controls (p<0.001, ηp2=0.23) in the Bern sample. In SSD, axial diffusivity of the left IFOF was inversely correlated with semantic processing impairments (r=-0.579, p<0.0001). In the Basel sample, significant group differences for the left IFOF were replicated (p<0.01, ηp2=0.29), while the correlation between axial diffusivity of the left IFOF and semantic processing decline (r=-0.376, p=0.09) showed a statistical trend. No significant effects were found for the dorsal language stream.DiscussionThis work provides direct evidence for the importance of the integrity of the ventral language stream, in particular the left IFOF, in semantic processing deficits in SSD.

Alterations of white matter integrity associated with cognitive deficits in patients with glioma.

ObjectiveThis study aimed to investigate the characteristic of brain structural connections in glioma patients and further evaluate the relationship between changes in the white matter tracts and cognitive decline.MethodsThis retrospective study included a total of 35 subjects with glioma and 14 demographically matched healthy controls, who underwent diffusion tensor imaging scans and formal neuropsychological assessment tests. Fractional anisotropy (FA) values of white matter tracts were derived from atlas‐based analysis to compare group differences. Furthermore, subgroup‐level analysis was performed to differentiate the effects of tumor location on white matter tracts. Partial correlation analysis was used to examine the associations between neurocognitive assessments and the integrity of tracts. Region of interest‐based network analysis was performed to validate the alteration of structural brain network in subjects with glioma.ResultsCompared with controls, subjects with glioma exhibited reduced FA values in the right uncinate fasciculus. Besides, subjects with glioma exhibited worse performance in several cognitive assessments. Partial correlation analysis indicated that the FA value in the right superior longitudinal fasciculus temporal part was significantly positively correlated with scores of visual–spatial abilities in subjects with glioma in the right temporal lobe (r = .932, p = .002). Region of interest‐based network analysis revealed that subjects with glioma exhibited reduced FA, fiber length (FL), and fiber number (FN) between specific brain regions compared with controls.ConclusionThe present study demonstrated the reduced integrity of white matter tracts and altered structural connectivity in brain networks in patients with glioma. Notably, white matter tracts in the right hemisphere might be vulnerable to the effects of a frontal or temporal lesion and might be associated with deficient cognitive function.

Psychosis risk is associated with decreased white matter integrity in limbic network corticostriatal tracts

It is thought that altered connectivity between the striatum and the cortex could contribute to psychosis. However, whether psychosis risk is associated with altered white matter connectivity between the striatum and any cortical region is still unclear. Further, no previous study has directly examined whether psychosis risk is associated with altered striatal connectivity with specific cortical networks. The current study examined the integrity of corticostriatal white matter tracts in psychosis risk (n=18) and in non-psychosis risk comparison participants (n=19). We used probabilistic tractography to identify white matter tracts connecting each of four different striatal subregions with their most functionally connected cortical network: limbic, default mode, frontoparietal, and motor networks. We then compared groups on fractional anisotropy in these four tracts. Psychosis risk was associated with decreased fractional anisotropy in white matter tracts connecting the limbic striatum with the limbic cortical network, especially in an anterior right external capsule segment and in tracts specifically connected to the right prefrontal cortex. In contrast, psychosis risk was not associated with decreased white matter integrity in other corticostriatal tracts. Hence, the current research suggests that psychosis risk is especially associated with decreased corticostriatal white matter integrity involved in processing emotional and personally relevant information.

The relationship between physical activity, apolipoprotein E \u03b54 carriage, and brain health

BackgroundNeuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon.MethodThe relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated.ResultsA relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory).ConclusionsPA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ε4 carriers.

Structural integrity of white matter tracts as a predictor of acute ischemic stroke outcome.

Clinical assessment scores in acute ischemic stroke are only moderately correlated with lesion volume since lesion location is an important confounding factor. Many studies have investigated gray matter indicators of stroke severity, but the understanding of white matter tract involvement is limited in the early phase after stroke. This study aimed to measure and model the involvement of white matter tracts with respect to 24-h post-stroke National Institutes of Health Stroke Scale (NIHSS). A total of 96 patients (50 females, mean age 66.4 ± 14.0 years, median NIHSS 5, interquartile range: 2-9.5) with follow-up fluid-attenuated inversion recovery magnetic resonance imaging data sets acquired one to seven days after acute ischemic stroke onset due to proximal anterior circulation occlusion were included. Lesions were semi-automatically segmented and non-linearly registered to a common reference atlas. The lesion overlap and tract integrity were determined for each white matter tract in the AALCAT atlas and used to model NIHSS outcomes using a supervised linear-kernel support vector regression method, which was evaluated using leave-one-patient-out cross validation. The support vector regression model using the tract integrity and tract lesion overlap measurements predicted the 24-h NIHSS score with a high correlation value of r = 0.7. Using the tract overlap and tract integrity feature improved the modeling accuracy of NIHSS significantly by 6% (p < 0.05) compared to using overlap measures only. White matter tract integrity and lesion load are important predictors for clinical outcome after an acute ischemic stroke as measured by the NIHSS and should be integrated for predictive modeling.

The assessment of cerebral white matter microstructure in cerebral small vessel disease based on the diffusion-weighted magnetic resonance imaging

Introduction. Multidimensional or biophysical modelling approaches are actively used to examine the complex microstructure of brain matter in diffusion-weighted MRI, where tissue structures are schematically simplified and divided into separate regions to calculate the diffusion values. This approach demonstrates greater specificity when compared with the widely used diffusion tensor MRI (DT-MRI) and its metrics. The aim of the study was to compare DT-MRI and the biophysical diffusion models, and to evaluate their possible use in a more precise studying of the affected white matter in cerebral small vessel disease (CSVD). Materials and methods. We examined 96 patients (including 65 women; mean age 61.0±6.6 years) with CSVD and 23 healthy volunteers, comparable in age and gender (including 15 women; mean age 58±6 years). The patients were divided into 3 groups according to the severity of white matter disease as measured using the Fazekas scale. All study subjects underwent a brain MRI (3 T) with diffusion-weighted MRI (b = 0, 1000 and 2500 sec/mm 2 , 64 gradient directions) followed by the data processing; we obtained DT-MRI metric maps, as well as white matter tract integrity model and model using the spherical mean technique. Results. Significant differences were found between the study groups (except groups F0 and F1) in all metrics when the overall value of the white matter skeleton was examined ( p £ 0.05): there was a decrease in tissue anisotropy and axonal density in the white matter, as well as increased intra- and extra-axonal coefficients with more severe white matter disease. Analysis of individual white matter regions showed that the radial diffusion values had greater intergroup differences than the axial diffusion values in the corpus callosum (particularly, in the body and splenium). Conclusion. Biophysical models allow us to evaluate white matter disease in patients with CSVD using structural tissue features and indirect measures of intra- and extracellular diffusion. To clarify and increase the statistical significance of the obtained results, it is necessary to analyse the diffusion metrics using data from a larger patient sample.

Evidence for wakefulness-related changes to extracellular space in human brain white matter from diffusion-weighted MRI

Recently, several magnetic resonance imaging (MRI) studies have reported time-of-day effects on brain structure and function. Due to the possibility that time-of-day effects reflect mechanisms of circadian regulation, the aim of this prospective study was to assess these effects while under strict experimental control of variables that might influence biological clocks, such as caffeine intake and exposure to blue-emitting light. In addition, the current study assessed whether time-of-day effects were driven by changes to extracellular space, by including estimations of non-Gaussian diffusion metrics obtained from diffusion kurtosis imaging, white matter tract integrity and the spherical mean technique, in addition to conventional diffusion tensor imaging -derived parameters. Participants were 47 healthy adults who underwent diffusion-weighted imaging in the morning and evening of the same day. Morning and evening scans were compared using voxel-wise tract based spatial statistics and permutation testing. A day of wakefulness was associated with widespread increases in fractional anisotropy, indices of kurtosis and indices of the axonal water fraction. In addition, wakefulness was associated with widespread decreases in radial diffusivity, both in the single compartment and in extra-axonal space. These results suggest that an increase in the intra-axonal space relative to the extra-axonal volume underlies time-of-day effects in human white matter, which is in line with activity-induced reductions to the extracellular volume. These findings provide important insight into possible mechanisms driving time-of-day effects in MRI.

Regional callosal integrity and bilaterality of limb weakness in amyotrophic lateral sclerosis

Background and Objectives: The corpus callosum is a site of pathological involvement in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The corpus callosum shows widespread cortical connectivity topographically distributed along its length. Initial limb weakness in ALS is typically unilateral, becoming bilateral with disease progression. The precise anatomical substrate for this spread is uncertain. The present study investigated sub-regional variations in corpus callosum integrity in ALS, and whether these reflect a relationship with the development of unilateral or bilateral limb weakness. Methods: Sporadic ALS patients were categorized into unilateral (n = 14) or bilateral (n = 25) limb weakness at the time of assessment and underwent diffusion tensor imaging. Probabilistic bundle-specific tracking was carried out using MRtrix and TractSeg to parcellate the corpus callosum into seven anatomical segments (rostrum; genu; rostral body; anterior midbody; posterior midbody; isthmus; splenium). White matter tract integrity was assessed in all segments and compared with MRI data acquired from 25 healthy controls. Results: In the combined patient group, the most prominent differences in diffusivity metrics were in the rostral body, posterior midbody and isthmus of the corpus callosum (p < 0.04). Loss of corpus callosum integrity was most prominent in the sub-group with unilateral limb weakness at the time of scanning (p < 0.05). Conclusions: Corpus callosum involvement in ALS is detectable across multiple segments, in keeping with a widespread cortical distribution of pathology. The association of unilateral limb weakness with greater loss of corpus callosum integrity informs connectivity-based hypotheses of symptom propagation in ALS.

Fluid intelligence is associated with cortical volume and white matter tract integrity within multiple-demand system across adult lifespan

BackgroundFluid intelligence (Gf) is the innate ability of an individual to respond to complex and unexpected situations. Although some studies have considered that the multiple-demand (MD) system of the brain was the biological foundation for Gf, further characterization of their relationships in the context of aging is limited. The present study hypothesized that the structural metrics of the MD system, including cortical thickness, cortical volumes, and white matter (WM) tract integrity, was the brain correlates for Gf across the adult life span. Partial correlation analysis was performed to investigate whether the MD system could still explain Gf independent of the age effect. Moreover, the partial correlations between Gf and left/right structural metrics within the MD regions were compared to test whether the correlations displayed distinct lateralization. MethodsThe participants were recruited from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) databank, comprising the images of 603 healthy participants aged 18–88 years acquired on a 3-T system. The MRI data included high-resolution T1-weighted and diffusion-weighted images, from which gray matter and WM structural metrics of the MD system were analyzed, respectively. The structural metrics of gray matter were quantified in terms of cortical volume/thickness of five pairs of cortical regions, and those of WM were quantified in terms of the mean axial diffusivity (DA), radial diffusivity (DR), mean diffusivity (DM), and generalized fractional anisotropy (GFA) on five pairs of tracts. Partial correlation controlling for age and sex effects, was performed to investigate the associations of Gf scores with the mean DA, DR, DM and GFA of all tracts in the MD system, those of left and right hemispheric tracts, and those of each tract. Fisher’s exact test was used to compare the partial correlations between left and right MD regions. ResultsThe linear relationship between cortical volumes and Gf was evident across all levels of the MD system even after controlling for age and sex. For the WM integrity, diffusion indices including DA, DR, DM and GFA displayed linear relationships with Gf scores at various levels of the MD system. Among the 10 WM tracts connecting the MD regions, bilateral superior longitudinal fasciculus I and bilateral frontal aslant tracts exhibited the strongest and significant associations. Our results did not show significant inter-hemispheric differences in the associations between structural metrics of the MD system and Gf. ConclusionOur results demonstrate significant associations between Gf and both cortical volumes and tract integrity of the MD system across the adult lifespan in a population-based cohort. We found that the association remained significant in the entire adult lifespan despite simultaneous decline of Gf and the MD system. Our results suggest that the MD system might be a structural underpinning of Gf and support the fronto-parietal model of cognitive aging. However, we did not find hemispheric differences in the Gf-MD correlations, not supporting the hemi-aging hypothesis.

Reduced White Matter Integrity and Deficits in Neuropsychological Functioning in Adults With Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is currently viewed as a disorder of cortical systems connectivity, with a heavy emphasis being on the structural integrity of white matter tracts. However, the majority of the literature to date has focused on children with ASD. Understanding the integrity of white matter tracts in adults may help reveal the nature of ASD pathology in adulthood and the potential contributors to cognitive impairment. This study examined white matter water diffusion using diffusion tensor imaging in relation to neuropsychological measures of cognition in a sample of 45 adults with ASD compared to 20 age, gender, and full-scale-IQ-matched healthy volunteers. Tract-based spatial statistics were used to assess differences in diffusion along white matter tracts between groups using permutation testing. The following neuropsychological measures of cognition were assessed: processing speed, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Results indicated that fractional anisotropy (FA) was significantly reduced in adults with ASD in the anterior thalamic radiation (P = 0.022) and the right cingulum (P = 0.008). All neuropsychological measures were worse in the ASD group, but none of the measures significantly correlated with reduced FA in either tract in the adults with ASD or in the healthy volunteers. Together, this indicates that the tracts that are the most impacted in autism may not be (at least directly) responsible for the behavioral deficits in ASD. Autism Res 2020, 13: 702-714. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long-range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.