Abnormalities In White Matter Tracts Research Articles

Diffusion indices alteration in major white matter tracts of children with tic disorder using TRACULA

BackgroundTic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis.MethodsWe analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts.ResultsOur findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation.ConclusionThese results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis.

Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB. ClinicalTrials.gov: NCT02485808.

A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice

Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity—all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients.

Diffusion Tensor MR Imaging Evaluation in Children with Developmental Delay

Context: Developmental delay (DD) has a significant detrimental effect on the child’s quality of life. The critical time of diagnosis has a significant impact in preventing the decreased quality of life that the children with DD face, for which magnetic resonance imaging (MRI) with its new imaging techniques plays a pivotal role. Diffusion tensor imaging (DTI), a MRI technique, identifies microscopic features that are thought to be precursors to the ultimate stage of macroscopic tissue atrophy. Objectives: Spectrum of abnormal MRI brain findings was characterized, and role of DTI was evaluated in children with DD. Methods: Observational, descriptive study was performed on 80 children. Fifty cases of DD between the age of 1 month and 16 years, and 30 normal age-matched controls, underwent brain MRI with DTI for structural assessment of brain with measurement of fractional anisotropy (FA) of white matter tracts. “One sample t test” determined whether statistical significance existed between mean FA values of cases and controls. Results: Spectrum of hypoxic-ischemic insult and white matter abnormalities were the common findings seen in 21 (42%) and 19 (38%) children, respectively, amongst cases. On DTI, reduced FA was observed in white matter tracts of 24 (48%) children, most commonly in the corpus callosum of 13 (26%) children. Abnormal FA values in certain white matter tracts were observed in 6 (40%) out of 15 children with normal MRI brain. Conclusion: DTI exhibited the ability to pick up white matter tract abnormalities in the form of reduced FA values in children with DD, including some who showed structurally normal MRI.

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.

Abnormal Structural Network Communication Reflects Cognitive Deficits in Schizophrenia.

Schizophrenia has long been thought to be a disconnection syndrome and several previous studies have reported widespread abnormalities in white matter tracts in individuals with schizophrenia. Furthermore, reductions in structural connectivity may also impair communication between anatomically unconnected pairs of brain regions, potentially impacting global signal traffic in the brain. Therefore, we used different communication models to examine direct and indirect structural connections (polysynaptic) communication in large-scale brain networks in schizophrenia. Diffusion-weighted magnetic resonance imaging scans were acquired from 62 patients diagnosed with schizophrenia and 35 controls. In this study, we used five network communication models including, shortest paths, navigation, diffusion, search information and communicability to examine polysynaptic communication in large-scale brain networks in schizophrenia. We showed less efficient communication between spatially widespread brain regions particulary encompassing cortico-subcortical basal ganglia network in schizophrenia group relative to controls. Then, we also examined whether reduced communication efficiency was related to clinical symptoms in schizophrenia group. Among different measures of communication efficiency, only navigation efficiency was associated with global cognitive impairment across multiple cognitive domains including verbal learning, processing speed, executive functions and working memory, in individuals with schizophrenia. We did not find any association between communication efficiency measures and positive or negative symptoms within the schizophrenia group. Our findings are important for improving our mechanistic understanding of neurobiologicalprocess underlying cognitive symptoms in schizophrenia.

Examining Brain Structural Connectivity in Early-life Interpersonal Stress

IntroductionEarly-life interpersonal stress, particularly childhood maltreatment (CM), is associated with social cognition deficits as well as neurobiological abnormalities including alterations in brain structure and function and heightened inflammation. However, few studies have investigated whether peer victimisation (PV) has similar effects.ObjectivesThis study first examines the associations between white matter tract abnormalities and childhood interpersonal stress from carers (CM) and peers (PV). Next, it explores how the observed tract alterations are in terms related to cytokine IL-6 level and theory of mind (ToM) performance in the CM and PV groups.MethodsData were collected from 107 age-and gender-matched youths (34 CM, 35 PV and 38 controls). Tractography and whole-brain tract-based spatial statistics (TBSS) analyses were conducted.ResultsTractography showed that both CM and PV groups had smaller right inferior longitudinal fasciculus (ILF) tract volume than controls, which was furthermore associated with longer maltreatment duration within the CM group. At the microstructural level, the CM group had higher fractional anisotropy (FA) of bilateral anterior thalamic radiation (ATR) than both PV and control groups, which were associated with enhanced affective ToM performance in maltreated individuals only. Reduced left ATR FA, however, was associated with greater emotional and behavioural difficulties in the PV group. Using TBSS, the CM group had higher FA than both PV and control groups in predominantly right-hemispheric limbic tracts (UF, ATR, ILF, cingulum bundle and inferior fronto-occipital fasciculus), corpus callosum and corona radiata, which were furthermore associated with heightened cytokine IL-6 level within the CM group.ConclusionsEarly-life interpersonal stress, particularly from carers, is associated with widespread alterations of neural pathways connecting the frontal, temporal and occipital cortices involved in cognitive and affective control. The adverse caregiving experience may conceivably contribute to enhanced mental-state decoding but there exists a hidden cost of heightened inflammation in these seemingly healthy maltreated youths. Our findings thus underscore the need to further examine the mental and physical well-being of healthy individuals exposed to early-life stress as they may still be vulnerable to psychopathology later on.Disclosure of InterestNone Declared

Posterior Quadrantic Dysplasia: An Uncommon Cause of Childhood Seizures with Brief Review of Literature

ABSTRACT Posterior quadrantic dysplasia (PQD) is a rare cause of medically refractory seizures among the paediatric population. We are reporting a case study of a 14-year-old female child with refractory seizures with seizure onset since birth. She was diagnosed with Posterior quadrantic dysplasia in left temporo-occipito-parietal lobes on magnetic resonance imaging. Our case report highlights the diffusion tensor imaging (DTI) and tractography along with routine magnetic resonance imaging findings in a classical presentation of PQD. DTI helps in proper delineation of white matter tract abnormalities and consequently in the approach for the surgical management. It is vital for radiologists to be familiar with these imaging findings for early diagnosis and treatment of PQD.

White Matter Characteristics of Damage Along Fiber Tracts in Patients with Type 2 Diabetes Mellitus

PurposeThe white matter (WM) of the brain of type 2 diabetes mellitus (T2DM) patients is susceptible to neurodegenerative processes, but the specific types and positions of microstructural lesions along the fiber tracts remain unclear.MethodsIn this study 61 T2DM patients and 61 healthy controls were recruited and underwent diffusion spectrum imaging (DSI). The results were reconstructed with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). WM microstructural abnormalities were identified using tract-based spatial statistics (TBSS). Pointwise WM tract differences were detected through automatic fiber quantification (AFQ). The relationships between WM tract abnormalities and clinical characteristics were explored with partial correlation analysis.ResultsTBSS revealed widespread WM lesions in T2DM patients with decreased fractional anisotropy and axial diffusivity and an increased orientation dispersion index (ODI). The AFQ results showed microstructural abnormalities in T2DM patients in specific portions of the right superior longitudinal fasciculus (SLF), right arcuate fasciculus (ARC), left anterior thalamic radiation (ATR), and forceps major (FMA). In the right ARC of T2DM patients, an aberrant ODI was positively correlated with fasting insulin and insulin resistance, and an abnormal intracellular volume fraction was negatively correlated with fasting blood glucose. Additionally, negative associations were found between blood pressure and microstructural abnormalities in the right ARC, left ATR, and FMA in T2DM patients.ConclusionUsing AFQ, together with DTI and NODDI, various kinds of microstructural alterations in the right SLF, right ARC, left ATR, and FMA can be accurately identified and may be associated with insulin and glucose status and blood pressure in T2DM patients.

Histologic lesion type correlates of magnetic resonance imaging biomarkers in four-repeat tauopathies

Primary four-repeat tauopathies are characterized by depositions of the four-repeat isoform of the microtubule binding protein, tau. The two most common sporadic four-repeat tauopathies are progressive supranuclear palsy and corticobasal degeneration. Because tau PET tracers exhibit poor binding affinity to four-repeat pathology, determining how well in vivo MRI findings relate to underlying pathology is critical to evaluating their utility as surrogate markers to aid in diagnosis and as outcome measures for clinical trials. We studied the relationship of cross-sectional imaging findings, such as MRI volume loss and diffusion tensor imaging white matter tract abnormalities, to tau histopathology in four-repeat tauopathies. Forty-seven patients with antemortem 3 T MRI volumetric and diffusion tensor imaging scans plus post-mortem pathological diagnosis of a four-repeat tauopathy (28 progressive supranuclear palsy; 19 corticobasal degeneration) were included in the study. Tau lesion types (pretangles/neurofibrillary tangles, neuropil threads, coiled bodies, astrocytic lesions) were semiquantitatively graded in disease-specific cortical, subcortical and brainstem regions. Antemortem regional volumes, fractional anisotropy and mean diffusivity were modelled using linear regression with post-mortem tau lesion scores considered separately, based on cellular type (neuronal versus glial), or summed (total tau). Results showed that greater total tau burden was associated with volume loss in the subthalamic nucleus (P = 0.001), midbrain (P < 0.001), substantia nigra (P = 0.03) and red nucleus (P = 0.004), with glial lesions substantially driving the associations. Decreased fractional anisotropy and increased mean diffusivity in the superior cerebellar peduncle correlated with glial tau in the cerebellar dentate (P = 0.04 and P = 0.02, respectively) and red nucleus (P < 0.001 for both). Total tau and glial pathology also correlated with increased mean diffusivity in the midbrain (P = 0.02 and P < 0.001, respectively). Finally, increased subcortical white matter mean diffusivity was associated with total tau in superior frontal and precentral cortices (each, P = 0.02). Overall, results showed clear relationships between antemortem MRI changes and pathology in four-repeat tauopathies. Our findings show that brain volume could be a useful surrogate marker of tau pathology in subcortical and brainstem regions, whereas white matter integrity could be a useful marker of tau pathology in cortical regions. Our findings also suggested an important role of glial tau lesions in the pathogenesis of neurodegeneration in four-repeat tauopathies. Thus, development of tau PET tracers selectively binding to glial tau lesions could potentially uncover mechanisms of disease progression.

Role of White Matter Abnormalities in the Relationship Between Microbleed Burden and Cognitive Impairment in Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline. We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA. This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aβ+ CAA) and patients with Alzheimer's disease (Aβ+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition. We analyzed 30 patients with Aβ+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aβ+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aβ+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aβ+ AD group(family-wise error-corrected p < 0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition. This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA.

Abnormal white matter structure in hoarding disorder

Although preliminary neuroimaging research suggests that patients with hoarding disorder (HD) show widespread abnormal task-related activity in the brain, there has been no research on alterations in the white matter tracts in these patients. The aim of this study was to investigate the characteristics of the major white matter tracts in patients with HD. Tract-based spatial statistics were used to search for white matter tract abnormalities throughout the brain in 25 patients with HD and 36 healthy controls. Post hoc analysis of regions of interest was performed to detect correlations with clinical features. Compared with the controls, patients with HD showed decreased fractional anisotropy and increased radial diffusivity in anatomically widespread white matter tracts. Post hoc analysis of regions of interest revealed a significant negative correlation between the severity of hoarding symptoms and fractional anisotropy in the left anterior limb of the internal capsule and a positive correlation between the severity of these symptoms and radial diffusivity in the right anterior thalamic radiation. Patients with HD showed a broad range of alterations in the frontal white matter tracts, including the frontothalamic circuit, frontoparietal network, and frontolimbic pathway. The findings of this study indicate associations between frontal white matter abnormalities related to the severity of hoarding symptoms in HD and the cortical regions involved in cognitive dysfunction. The insights provided would be useful for understanding the neurobiological basis of HD.

Disrupted White Matter Functional Connectivity With the Cerebral Cortex in Migraine Patients.

Background: In attempts to understand the migraine patients’ overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine.Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson’s correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t-tests were performed on the Pearson’s correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region.Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex.Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts.

Role of white matter alteration in the relationship between regional microbleeds and cognitive impairment in cerebral amyloid angiopathy

AbstractBackgroundPathophysiology of cognitive decline in CAA is multifactorial, because microbleeds, white matter hyperintensities, and combined concomitant parenchymal Alzheimer’s disease (AD) pathology have been suggested to cause cognitive impairment. The mechanism by which microbleeds affect cognitive impairment is still under investigation. We aimed to investigate the mechanism of how microbleeds contribute to cognitive impairment, in association with white matter tract abnormalities or cortical thickness in CAA with significant amyloid deposition.MethodWe retrospectively investigated 30 patients with probable CAA according to Boston criteria and 30 patients with Alzheimer’s disease (AD), all of whom showed severe amyloid deposition on amyloid PET (Aβ+). Age, sex, and clinical deteriorating scale were matched. Using MRI, cortical thickness and white matter tract abnormalities as fractional anisotropy (FA) were obtained. We compared cortical thickness, FA, and cognitive scores of five domains between Aβ+ CAA and Aβ+ AD. Using path analysis, we investigated the correlation between number of regional microbleeds, cortical thickness, FA, and cognitive impairments.ResultBoth CAA and AD group showed similar cortical amyloid deposition in AD related regions such as precuneus, and posterior cingulate cortex suggesting that CAA in this study might have AD pathology. Patients with Aβ+ CAA presented with significantly lower FA in clusters of posterior area than patients with Aβ+ AD (FWE‐corrected p value &lt;0.05) Importantly, total number of microbleeds were associated with decreased FA in tapetum of corpus callosum (r=‐0.429, p&lt;0.001), which were consequently associated with visuospatial function (r=0.466, p&lt;0.001). Cortical thickness was not significantly different between CAA and AD, and it did not mediate the association between regional microbleeds and cognition.ConclusionThis study suggests that lobar microbleeds may impact cognitive decline through the mediation of white matter tract abnormalities in CAA.

Neurovisualization features of brain anatomy in children with spastic cerebral palsy revealed by magnetic resonance tractography

Aim. To perform quantitative evaluation of the degree of white matter tract abnormalities in children with spastic cerebral palsy by magnetic resonance tractography to determine severity of the disease, as well as to carry out a dynamic assessment of treatment effectiveness.Materials and methods. The study included 46 children (32 males, 14 females; average age 5.4 ± 1.1 years). The participants were divided into two groups. The experimental group consisted of 23 children with spastic cerebral palsy. The control group included 23 children without any neurological disorder. Examination of the brain was performed on the Siemens Essenza 1,5 Т system (Siemens, Germany) and included magnetic resonance tractography to reconstruct the major white matter tracts. The number of fibers, average fractional anisotropy value, apparent diffusion coefficient, and coefficient of myelination of major white matter tracts in the brain were calculated and analyzed.Results. We found a significant difference in the above-stated parameters between the groups. The experimental group showed a decrease in the absolute number of fibers at the central and posterior segments of the corpus callosum, corticospinal tracts, and left inferior longitudinal fasciculus. Besides, we detected a decrease in fractional anisotropy at 2–5 segments of the corpus callosum and right lateral corticospinal tract, an increase in the apparent diffusion coefficient at 2, 4, and 5 segments of the corpus callosum and left lateral corticospinal tract, and a decrease in the myelination coefficient in all the examined tracts, except for superior longitudinal fasciculus. We revealed a positive correlation between the intensity of the motor disturbance and the coefficient of myelination at the anterior corpus callosum and inferior longitudinal fasciculus.Conclusion. Magnetic resonance tractography is an informative technique for unbiased evaluation of white matter tract anatomy, as well the level and degree of motor tract damage. The most useful characteristics of white matter tract anatomy are the absolute number of fibers in the tract, fractional anisotropy, and coefficient of myelination. Some of them correlated with the intensity of motor disturbance, so they can be regarded as potential predictors of rehabilitation potential.

Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.

SHANK3 Genotype Mediates Speech and Language Phenotypes in a Nonclinical Population

Mutations affecting the synaptic-scaffold gene SHANK3 represent the most common genetic causes of autism with intellectual disability, accounting for about 1-2% of cases. Rare variants of this gene have also been associated with schizophrenia, and its deletion results in the autistic condition known as Phelan–McDermid syndrome. Despite the importance of SHANK3 as a paradigmatic gene mediating neurodevelopmental disorders, its psychological effects in nonclinical populations have yet to be studied. We genotyped the nonsynonymous, functional SHANK3 SNP rs9616915 in a large population of typical individuals scored for autism spectrum traits (the Autism Quotient, AQ) and schizotypy spectrum traits (the Schizotypal Personality Questionnaire, SPQ-BR). Males, but not females, showed significant genotypic effects for the SPQ-BR subscale associated with speech and language: Odd Speech. These findings, in conjunction with animal model studies showing vocalization and auditory effects of SHANK3 mutations, and studies indicating severe language alterations and speech-associated white matter tract abnormalities in Phelan–McDermid syndrome, suggest that SHANK3 differentially affects the development and expression of human language and speech. Imaging genetic and speech-language studies of typical individuals carrying different genotypes of rs9616915 should provide novel insights into the neurological and psychological bases of speech and language alterations among individuals with SHANK3 mutations and Phelan–McDermid syndrome.

Possible Neuroprotective Effects of l-Carnitine on White-Matter Microstructural Damage and Cognitive Decline in Hemodialysis Patients.

Although l-carnitine alleviated white-matter lesions in an experimental study, the treatment effects of l-carnitine on white-matter microstructural damage and cognitive decline in hemodialysis patients are unknown. Using novel diffusion magnetic resonance imaging (dMRI) techniques, white-matter microstructural changes together with cognitive decline in hemodialysis patients and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent dMRI and laboratory and neuropsychological tests, which were compared across seven patients each in two groups according to duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment (NSTLC), and (2) long-term l-carnitine treatment (LTLC). Ten age- and sex-matched controls were enrolled. Compared to controls, microstructural disorders of white matter were widely detected on dMRI of patients. An autopsy study of one patient in the NSTLC group showed rarefaction of myelinated fibers in white matter. With LTLC, microstructural damage on dMRI was alleviated along with lower levels of high-sensitivity C-reactive protein and substantial increases in carnitine levels. The LTLC group showed better achievement on trail making test A, which was correlated with amelioration of disorders in some white-matter tracts. Novel dMRI tractography detected abnormalities of white-matter tracts after hemodialysis. Long-term treatment with l-carnitine might alleviate white-matter microstructural damage and cognitive impairment in hemodialysis patients.

Abstract P349: Neuroprotective Effects of L-Carnitine on Vascular Dementia in Hemodialysis Patients

Background and purpose: L-carnitine alleviated oxidative stress and white matter lesions in an experimental study. Cognitive decline is not uncommon in hemodialysis patients, the pathogenesis of which has not been elucidated. Methods: Using novel diffusion magnetic resonance imaging techniques, white matter microstructural changes and cognitive decline in hemodialysis patients, and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent diffusion tensor imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging, and laboratory and neuropsychological tests, which were compared between two groups based on the duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment; and (2) long-term l-carnitine treatment. Ten age and sex-matched controls were enrolled. Results: On neuropsychological testing, the majority of hemodialysis patients were categorized as having mild cognitive impairment. Seven patients were classified into the no or short-term l-carnitine treatment and long-term l-carnitine treatment groups. Compared to controls, microstructural disorders of white matter were widely detected in no or short-term l-carnitine treatment on diffusion magnetic resonance imaging. An autopsy study from the no or short-term l-carnitine treatment group showed rarefaction of myelinated fibers in white matter. In long-term l-carnitine treatment, microstructural damage on diffusion magnetic resonance imaging was alleviated along with lower levels of high-sensitivity C-reactive protein ( P &lt;0.001) and substantial increases of carnitine levels ( P &lt;0.001). The long-term l-carnitine treatment group showed better achievement in Trail Making Test-A ( P =0.017), which was correlated with amelioration of disorders in bilateral anterior thalamic radiations, the left cingulum in the cingulate gyrus, the right superior longitudinal fasciculus, and the forceps major ( P &lt;0.05). Conclusion: Novel diffusion magnetic resonance imaging tractography detected abnormalities of white matter tracts in hemodialysis patients. Long-term treatment with l-carnitine alleviated white matter microstructural damage and cognitive impairment.

Cingulate white matter volume and associated cognitive and behavioral impulsivity in Veterans with a history of suicide behavior

BackgroundSuicide is one of the leading causes of death for military personnel and Veterans. Neuroimaging studies have revealed abnormalities in white matter tracts and brain connectivity in suicide behavior (SB); however, reports of alterations in white matter volume and its association with related behaviors are limited. The current study examined the relationship between cingulate white matter volume (WMV), impulsivity, and SB in Veterans. MethodsFifty-two Veterans, ages 18 to 65, underwent magnetic resonance imaging on a 3T Siemens Verio scanner. Morphometric analysis of brain images was performed to evaluate differences in WMV in cingulate regions of interest. Participants completed the Columbia Suicide Severity Rating Scale to assess lifetime suicide behavior and the Barratt Impulsivity Scale (BIS) and the Continuous Performance Test (CPT) to assess impulsivity. ResultsTwenty-nine Veterans had a history of suicidal ideation (SI) and 23 had a history of suicide attempts (SA). Controlling for age, sex, handedness and total white matter volume, reduced WMV was observed in the left rostral anterior cingulate cortex (rACC) in Veterans with SA relative to Veterans with SI, p = .008. Additionally, non-planning on the BIS was negatively correlated with left rACC WMV for Veterans with a history of SA, p = .04. Other subregions of the ACC WMV were negatively correlated with planning and attention impulsivity (BIS) and omission and commission errors (CPT) for attempters. ConclusionsReduction in rACC WMV in Veterans with SA was negatively correlated with nonplanning measures. These findings are consistent with ACC involvement in inhibitory processes and build on evidence that SB is associated with neurobiological abnormalities and suggest that white matter changes may be related to actual attempts.