Integrity Of White Matter Tracts Research Articles

White matter microstructure alterations in systemic lupus erythematosus: A preliminary coordinate-based meta-analysis of diffusion tensor imaging studies.

Systemic lupus erythematosus is often accompanied with neuropsychiatric symptoms. Neuroimaging evidence indicated that microstructural white matter (WM) abnormalities play role in the neuropathological mechanism. Diffusion tensor imaging (DTI) studies allows the assessment of the microstructural integrity of WM tracts, but existing findings were inconsistent. This present study aimed to conduct a coordinate-based meta-analysis (CBMA) to identify statistical consensus of DTI studies in SLE. Relevant studies that reported the differences of fractional anisotropy (FA) between SLE patients and healthy controls (HC) were searched systematically. Only studies reported the results in Talairach or Montreal Neurological Institute (MNI) coordinates were included. The anisotropic effect size version of signed differential mapping (AES-SDM) was applied to detect WM alterations in SLE. Totally, five studies with seven datasets which included 126 patients and 161 HC were identified. The pooled meta-analysis demonstrated that SLE patients exhibited significant FA reduction in the left striatum and bilateral inferior network, mainly comprised the corpus callosum (CC), bilateral inferior fronto-occipital fasciculus (IFOF), bilateral anterior thalamic projections, bilateral superior longitudinal fasciculus (SLF), left inferior longitudinal fasciculus (ILF), and left insula. No region with higher FA was identified. Disorders of the immune system might lead to subtle WM microstructural alterations in SLE, which might be related with cognitive deficits or emotional distress symptoms. This provides a better understanding of the pathological mechanism of microstructural brain abnormalities in SLE.

Decreases in Dorsal Cervical Spinal Cord White Matter Tract Integrity Are Associated with Elevated Levels of Serum MicroRNA Biomarkers in NCAA Division I Collegiate Football Players.

This prospective, controlled, observational cohort study assessed the performance of a novel panel of serum microRNA (miRNA) biomarkers relative to findings on cervical spinal cord magnetic resonance imaging (MRI) in collegiate football players. There were 44 participants included in the study: 30 non-athlete control subjects and 14 male collegiate football athletes participating in a Division I Football Bowl Subdivision of the National Collegiate Athletic Association. Diffuse tensor MRI and blood samples were acquired within the week before the athletic season began and within the week after the last game of the season. All miRNAs were significantly higher in athletes regardless of their fractional anisotropy (FA) values (p < 0.001), even those considered to be in the “normal” range of FA for white and gray matter integrity in the cervical spinal cord. miRNA biomarkers were most significantly correlated with FA of the white matter (WM) tracts of the dorsal (posterior) spinal cord; particularly, the fasciculus gracilis, fasciculus cuneatus, lateral corticospinal tract, rubrospinal tract, lateral reticulospinal tract, spinal lemniscus, and spinothalamic and -reticular tracts. Areas under the curve for miRNA biomarkers predicting lower FA of WM dorsal (posterior) cervical spinal tracts, therefore lower white matter integrity (connectivity), were miR-505* = 0.75 (0.54–0.96), miR-30d = 0.74 (0.52–0.95), and miR-92a = 0.75 (0.53–0.98). Should these findings be replicated in a larger cohort of athletes, these markers could potentially serve as measures of neuroimaging abnormalities in athletes at risk for concussion and subconcussive injuries to the cervical spinal cord.

Aberrant White Matter Microstructure in Depressed Patients with Suicidality.

Depression is a common psychiatric disorder affecting 264 million people globally, and the worst outcome is suicide. While regional brain alterations in depressed suicidal brain have previously been reported, knowledge about white matter (WM) microstructure is limited. Automated fiber quantification (AFQ) acquired by magnetic resonance imaging was used to calculate diffusion properties of fiber tracks to explore the structural alteration of WM associated with suicidality in depressive patients. Cross-sectional. Forty-five depressive patients without suicidality (DS- group, 60.00% females), 53 depressed patients with suicidality (DS+ group, 66.04% females), and 59 healthy controls (HC group, 67.80% females). 3.0 T; single-shot echo-planar imaging sequence. The point-wise group difference of the fiber tracts was determined by diffusion properties including fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of 18 specific WM tracts. Analysis of covariance (ANCOVA) and partial correlation analysis were used. A threshold of P < 0.05 was considered statistically significant. The significantly different diffusion properties were found in callosum forceps, left inferior fronto-occipital fasciculus (IFOF), right anterior thalamic radiation (ATR), and left cingulum cingulate in DS- and DS+ groups. The correlation analysis results showed that MD of right ATR was significantly positively correlated with Hamilton Depression Rating Scale (HAMD) scores (r=0.363). In addition, AD of right ATR (r=0.372), MD of callosum forceps minor (r=0.511), RD of left IFOF (r=0.429), and RD of callosum forceps minor (r=0.515) were significantly positively correlated with suicide item scores of HAMD. Our demonstration of decreased WM tract integrity including callosum forceps, IFOF, and ATR confirms the central involvement of the frontal cortex and limbic system with suicidality in depression. 3 TECHNICAL EFFICACY STAGE: 3.

Who benefits most from expectancy effects? A combined neuroimaging and antidepressant trial in depressed older adults

Depressed patients’ expectations of improvement drive placebo effects in antidepressant clinical trials, yet there is considerable heterogeneity in the magnitude of expectancy effects. The present study seeks to identify those individuals who benefit most from expectancy effects using baseline neuroimaging and cognitive measures. Older adult outpatients diagnosed with major depressive disorder (MDD) participated in a prospective, 8-week clinical trial in which expectancy was experimentally manipulated and its effects on depression outcome measured. Based on the literature, we selected a priori 12 cognitive and brain-based variables linked to depression and expectancy, together with demographic variables, and incorporated them into a combined moderator. The combined moderator was developed as a weighted combination of the individual moderators, and was used to identify individuals who benefited most from expectancy effects. The combined moderator was found to predict differential change in depression severity scores between the high- vs. low-expectancy groups with a medium-size effect (Spearman effect size: 0.28). While at the sample level no expectancy effect was found, the combined moderator divided older adults with MDD into those who did and those who did not improve as the result of expectancy manipulation, with those benefiting from the manipulation showing greater processing speed, executive function, and frontostriatal white matter tract integrity. The findings suggest that it is possible to identify a subgroup of older adult individuals with MDD for whom expectancy manipulation results in greater antidepressant treatment response, supporting a precision medicine approach. This subgroup is characterized by distinct cognitive dysfunction and neuroimaging impairments profiles.

Global Fractional Anisotropy: Effect on Resting-state Neural Activity and Brain Networking in Healthy Participants

The global fractional anisotropy (gFA) is a structural marker of white matter myelination and integrity. Previous studies already evidenced that aging-related reduced integrity of specific white matter tracts is associated with decreased functional connectivity in several hubs. However, the correlations between gFA and functional brain connectivity remain unknown. In this cross-sectional study, we analyzed structural and functional MR datasets of 79 healthy participants from the Leipzig Study for Mind–Body–Emotion Interactions. DTI model-based method was used to quantify gFA values. We tested associations between gFA, age, and gender. The fractional amplitude of low-frequency fluctuations (fALFF) and ROI-to-ROI connectivity were analyzed in a regression model for evaluating the effects of gFA on brain activity and networking, respectively. A negative correlation was found between gFA and age (ρ = −0.343; p = 0.002). No statistically significant correlation as found between gFA and gender (p = 0.229). Higher values of gFA were associated with increased brain regional activity, including areas of the default mode network. There was a higher degree of correlation between some regions, particularly those that conform to the limbic system. Our study demonstrates that gFA influences regional neural activity and brain networking on resting, particularly the limbic system.

Neurobiological underpinnings of rapid white matter plasticity during intensive reading instruction

Diffusion MRI is a powerful tool for imaging brain structure, but it is challenging to discern the biological underpinnings of plasticity inferred from these and other non-invasive MR measurements. Biophysical modeling of the diffusion signal aims to render a more biologically rich image of tissue microstructure, but the application of these models comes with important caveats. A separate approach for gaining biological specificity has been to seek converging evidence from multi-modal datasets. Here we use metrics derived from diffusion kurtosis imaging (DKI) and the white matter tract integrity (WMTI) model along with quantitative MRI measurements of T1 relaxation to characterize changes throughout the white matter during an 8-week, intensive reading intervention (160 total hours of instruction). Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7–12 years old), and over the same period in an age-matched non-intervention control group. Throughout the white matter, mean 'extra-axonal' diffusivity was inversely related to intervention time. In contrast, model estimated axonal water fraction (AWF), overall diffusion kurtosis, and T1 relaxation time showed no significant change over the intervention period. Both diffusion and quantitative T1 based metrics were correlated with pre-intervention reading performance, albeit with distinct anatomical distributions. These results are consistent with the view that rapid changes in diffusion properties reflect phenomena other than widespread changes in myelin density. We discuss this result in light of recent work highlighting non-axonal factors in experience-dependent plasticity and learning.

Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants.

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro‐ and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term‐equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3–4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole‐brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel‐based (FB) analysis to compute fiber density (FD), fiber‐bundle cross‐section (FC), and combined fiber density and cross‐section (FDC) for each tract. Of 223 VPT infants with high‐quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.

Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank

Anhedonia is a core symptom of multiple psychiatric disorders and has been associated with alterations in brain structure. Genome-wide association studies suggest that anhedonia is heritable, with a polygenic architecture, but few studies have explored the association between genetic loading for anhedonia—indexed by polygenic risk scores for anhedonia (PRS-anhedonia)—and structural brain imaging phenotypes. Here, we investigated how anhedonia and PRS-anhedonia were associated with brain structure within the UK Biobank cohort. Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness (CT) and white matter integrity) were analysed using linear mixed models in relation to anhedonia and PRS-anhedonia in 19,592 participants (9225 males; mean age = 62.6 years, SD = 7.44). We found that state anhedonia was significantly associated with reduced total grey matter volume (GMV); increased total white matter volume (WMV); smaller volumes in thalamus and nucleus accumbens; reduced CT within the paracentral cortex, the opercular part of inferior frontal gyrus, precentral cortex, insula and rostral anterior cingulate cortex; and poorer integrity of many white matter tracts. PRS-anhedonia was associated with reduced total GMV; increased total WMV; reduced white matter integrity; and reduced CT within the parahippocampal cortex, superior temporal gyrus and insula. Overall, both state anhedonia and PRS-anhedonia were associated with individual differences in multiple brain structures, including within reward-related circuits. These associations may represent vulnerability markers for psychopathology relevant to a range of psychiatric disorders.

Striatal Acetylcholine-Dopamine Imbalance in Parkinson Disease: InVivo Neuroimaging Study with Dual-Tracer PET and Dopaminergic PET-Informed Correlational Tractography.

Previous studies of animal models of Parkinson disease (PD) suggest an imbalance between striatal acetylcholine and dopamine, although other studies have questioned this. To our knowledge, there are no previous invivo neuroimaging studies examining striatal acetylcholine-dopamine imbalance in PD patients. Using cholinergic and dopaminergic PET (18F-fluoroethoxybenzovesamicol [18F-FEOBV] and 11C-dihydrotetrabenazine [11C-DTBZ], respectively) and correlational tractography, our aim was to investigate the acetylcholine-dopamine interaction at 2 levels of dopaminergic loss in PD subjects: integrity loss of the nigrostriatal dopaminergic white matter tract and loss at the presynaptic-terminal level. Methods: The study involved 45 subjects with mild to moderate PD (36 men, 9 women; mean age, 66.3 ± 6.3 y, disease duration, 5.8 ± 3.6 y; Hoehn and Yahr stage, 2.2 ± 0.6) and 15 control subjects (9 men, 6 women; mean age, 69.1 ± 8.6 y). PET imaging was performed using standard protocols. We first estimated the integrity of the dopaminergic nigrostriatal white matter tracts in PD subjects by incorporating molecular information from striatal 11C-DTBZ PET into the fiber tracking process using correlational tractography (based on quantitative anisotropy [QA], a measure of tract integrity). Subsequently, we used voxel-based correlation to test the association of the mean QA of the nigrostriatal tract of each cerebral hemisphere with the striatal 18F-FEOBV distribution volume ratio (DVR) in PD subjects. The same analysis was performed for 11C-DTBZ DVR in 12 striatal subregions (presynaptic-terminal level). Results: Unlike 11C-DTBZ DVR in striatal subregions, the mean QA of the nigrostriatal tract of the most affected hemisphere showed a negative correlation with a striatal cluster of 18F-FEOBV DVR in PD subjects (corrected P = 0.039). We also found that the mean 18F-FEOBV DVR within this cluster was higher in the PD group than in the control group (P = 0.01). Cross-validation analyses confirmed these findings. We also found an increase in bradykinesia ratings associated with increased acetylcholine-dopamine imbalance in the most affected hemisphere (r = 0.41, P = 0.006). Conclusion: Our results provide evidence for the existence of striatal acetylcholine-dopamine imbalance in early PD and may provide an avenue for testing invivo effects of therapeutic strategies aimed at restoring striatal acetylcholine-dopamine balance in PD.

Anterior cingulate cortex metabolites and white matter microstructure: a multimodal study of emergent alcohol use disorder.

Multimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.

Evaluation of White Matter Tracts in Autistic Individuals: A Review of Diffusion Tensor Imaging Studies

Introduction: Many cognitive and social deficits in autism are caused by abnormal functional connections between brain networks, which are manifested by impaired integrity of white matter tracts. White matter tracts are like the "highways" of the brain, which allow fast and efficient communication in different areas of the brain. The purpose of this article is to review the results of autism studies that have used diffusion tensor images (DTI). Diffusion tensor images is a neuroimaging technique to examine the integrity of tracts. Conclusion: The results of these studies suggest that neural tracts can be abnormal in people with Autism spectrum disorder (ASD) due to impaired white matter integrity. Thus, changes in these tracts in the brains of people with ASD are helpful in identifying individual differences. Although most studies have reported decreased FA and increased MD, RD, and AD in white matter tracts, some studies have reported increased FA or no significant difference between the control and autistic groups.

Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype

Intellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders and are characterized by substantial impairment in intellectual and adaptive functioning, with their genetic and molecular basis remaining largely unknown. Here, we identify biallelic variants in the gene encoding one of the Elongator complex subunits, ELP2, in patients with ID and ASD. Modelling the variants in mice recapitulates the patient features, with brain imaging and tractography analysis revealing microcephaly, loss of white matter tract integrity and an aberrant functional connectome. We show that the Elp2 mutations negatively impact the activity of the complex and its function in translation via tRNA modification. Further, we elucidate that the mutations perturb protein homeostasis leading to impaired neurogenesis, myelin loss and neurodegeneration. Collectively, our data demonstrate an unexpected role for tRNA modification in the pathogenesis of monogenic ID and ASD and define Elp2 as a key regulator of brain development.

Evidence That Neighborhood Threat and Brain Volume Mediate the Relationship Between Neighborhood Poverty and Children’s Psychopathology

Increased rates of internalizing and externalizing behaviors have been observed in children from more impoverished neighborhoods. Correlates of neighborhood poverty (NP) such as increased crime rates or altered brain structure may contribute to this relationship. The goal of this project is to examine the extent to which NP relates to children’s mental health outcomes independent of household socioeconomic status, and to determine whether neighborhood threat, brain volume, and the structural integrity of white matter tracts mediate this relationship.

Aberrant Levels of Cortical Myelin Distinguish Individuals With Unipolar Depression From Healthy Controls

Evidence implicates lower white matter tract integrity in unipolar depression (UD) relative to healthy controls (HC), yet cortical myelin in UD has remained largely underexamined.

White matter microstructural integrity correlates of emotion dysregulation in children with ADHD: A diffusion imaging tractography study

BackgroundEmotion dysregulation (ED) is prevalent in youths with attention-deficit hyperactivity disorder (ADHD) and causes more social impairment and poor adaptive function. Alterations in the integrity of white matter (WM) tracts might have important implications for affective processing related to ED. However, little is known about the WM correlates underpinning ED in ADHD. MethodsUsing diffusion spectrum image tractography, we obtained generalized fractional anisotropy (GFA) values of 76 WM tracts in 77 children with ADHD and 105 typically developing controls (TDC). ED severity was defined by the dysregulation profile from the child behavior checklist. Canonical correlation analysis (CCA) was performed to identify modes that relate WM microstructural property to ED severity and cognitive measures. ResultsThe application of CCA identified one significant mode (r = 0.638, FWE-corrected p = 0.046) of interdependencies between WM property patterns and diagnosis, ADHD total symptom levels, dysregulation by diagnosis interaction, and full-scale intellectual quotient (FIQ). GFA values of 19 WM tracts that were linked to affective-processing, sensory-processing and integration, and cognitive control circuitry were positively correlated with ED severity in TDC but negatively correlated with ED severity in ADHD. ADHD symptom severity and diagnosis were negatively associated with the GFA patterns of this set of tract bundles. In contrast, FIQ was positively correlated with this set of tract bundles. ConclusionsThis study used the CCA to show that children with ADHD and TDC had distinct multivariate associations between ED severity (diagnosis by ED interaction) and microstructural property in a set of WM tracts. These tracts interconnect the cortical regions that are principally involved in emotion processing, integration, and cognitive control in multiple brain systems. The WM microstructure integrity impairment might be an essential correlate of emotion dysregulation in ADHD.

Surgical planning in patients with brain glioma using diffusion tensor MR imaging and tractography

BackgroundDiffusion-tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that depicts the integrity of white matter (WM) tracts. This study was conducted to assess the utility of DTI tractography as an imaging technique in assessment of brain gliomas and planning of the surgical corridor.ResultsTwenty adult patients with brain gliomas were included. Neurological examination and conventional MRI and DTI scans were performed before and after surgery. Low-grade and high-grade tumors were found in 30% and 70% of patients, respectively. Preoperative DTI demonstrated five patterns of WM tract involvement: non-affected (10%), displaced (75%), edematous (55%), infiltrated (60%), and disrupted (20%). The obtained DTI scans were used for preoperative planning of the surgical corridor and extent of resection to achieve the maximum resection while preserving the WM tracts. Total resection was achieved in 40%, while 60% underwent subtotal resection. Postoperative neurological examination showed deterioration of cognitive function, motor power, and vision in 15%, 10%, and 5% of patients, respectively. Headache persisted in 15%, while motor power improved in 35% of patients. High-grade tumors were significantly associated with higher percentage of subtotal resection (p=0.018) and pattern IV (p=0.018). There was a significant association between the preoperative pattern of WM tract involvement and the postoperative DTI changes (p<0.001).ConclusionDTI enables assessment of displaced and infiltrated WM tracts in the vicinity of brain tumors. Preoperative planning of tumor resection and surgical corridor should include DTI scan to achieve the balance between maximum resection of tumor and maximal preservation of function.

Fast qualitY conTrol meThod foR derIved diffUsion Metrics (YTTRIUM) in big data analysis: U.K. Biobank 18,608 example

Deriving reliable information about the structural and functional architecture of the brain in vivo is critical for the clinical and basic neurosciences. In the new era of large population‐based datasets, when multiple brain imaging modalities and contrasts are combined in order to reveal latent brain structural patterns and associations with genetic, demographic and clinical information, automated and stringent quality control (QC) procedures are important. Diffusion magnetic resonance imaging (dMRI) is a fertile imaging technique for probing and visualising brain tissue microstructure in vivo, and has been included in most standard imaging protocols in large‐scale studies. Due to its sensitivity to subject motion and technical artefacts, automated QC procedures prior to scalar diffusion metrics estimation are required in order to minimise the influence of noise and artefacts. However, the QC procedures performed on raw diffusion data cannot guarantee an absence of distorted maps among the derived diffusion metrics. Thus, robust and efficient QC methods for diffusion scalar metrics are needed. Here, we introduce Fast qualitY conTrol meThod foR derIved diffUsion Metrics (YTTRIUM), a computationally efficient QC method utilising structural similarity to evaluate diffusion map quality and mean diffusion metrics. As an example, we applied YTTRIUM in the context of tract‐based spatial statistics to assess associations between age and kurtosis imaging and white matter tract integrity maps in U.K. Biobank data (n = 18,608). To assess the influence of outliers on results obtained using machine learning (ML) approaches, we tested the effects of applying YTTRIUM on brain age prediction. We demonstrated that the proposed QC pipeline represents an efficient approach for identifying poor quality datasets and artefacts and increases the accuracy of ML based brain age prediction.

Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making.

Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.

CX3CR1 deficiency aggravates brain white matter injury and affects expression of the CD36/15LO/NR4A1 signal

ObjectiveTo study the effects of CX3CR1 on white matter injury, neurofunction, recognition, and expression of the CD36/15LO/NR4A1 signal in mice with traumatic brain injury (TBI). MethodsCX3CR1GFP/GFP, CX3CR1GFP/+ and C57BL/6 male mice were randomly divided into 3 groups. We used a controlled cortical impact (CCI) to establish a TBI model and T2wt MRI to detect the TBI lesion. FA and DTI allowed for quantitative evaluation of the structural integrity of white matter tracts. Several behavior tests were used to investigate nerve function; a computer-based tracing system was used to trace and analyze dendrites and cell bodies of microglia and astrocytes in the peri-lesional brain areas. We also used RT-PCR and western blot to detect the effect of CX3CL1/CX3CR1 axis on CD36/15LO/NR4A1 signal. ResultsThe fractional anisotropy (FA) at the corpus callosum area of brain was decreased at 3 days post TBI, the average lesion volume CX3CR1GFP/GFP group was increased, and the neurologic deficit scores of mice of Cx3Cr1GFP/+ and wild-type groups were significantly increased compared to Cx3Cr1GFP/GFP group mice. In the Corner turn test, TBI induced impairments in forelimb function that were more severe than Cx3Cr11GFP/+ and wild-type TBI mice. We operated the Y-maze at 3 days post-TBI and the NOR test at 28 days after TBI. There was a significant TBI effect induced in decreased percentage entries into the novel arm in Cx3Cr1GFP/+ and wild-type TBI mice, compared with Cx3Cr1GFP/GFP; Cx3Cr1GFP/+. Wild-type mice showed decreased exploration time in new objects compared with Cx3Cr1GFP/GFP. Those two behavior tests demonstrated that Cx3Cr1 knock-out increased the damage caused by TBI to memory. In the tail suspension and force swimming tests, there was no significant difference between those three groups. CD36 increased in Cx3Cr1GFP/GFP compared with the other three groups at 3 days after TBI. TBI inhibited the expression of NR4A1 at 3 d after damage. Cx3Cr1 deficiency can induce high expression of 15LO, this was unaffected by TBI. ConclusionCX3CR1 deletion can enhance white matter injury. It increased the expression of CD36 and 15LO and increased expression of NR4A1. The lack of CX3CR1 can affect the recovery of nerve function.

Abstract P366: High Burden of Tract-Specific White Matter Hyperintensities Relates to Impaired Microstructural Integrity of Distal White Matter Tracts in Community-Dwelling Elders

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.