Differences In White Matter Connectivity Research Articles

Structural Connectivity Differences in People with Parkinson’s Disease With Visual Hallucinations (P6-11.011)

<h3>Objective:</h3> To investigate structural connectivity in people with Parkinson’s disease with or without visual hallucinations. <h3>Background:</h3> Up to 70% of people with Parkinson’s disease (PwP) experience visual hallucinations (VH) during the course of the disease. The mechanisms through which the PD neurodegenerative process leads to VH remain largely undetermined. The purpose of this study was to determine to what extent whole-brain structural connectivity is different in PwP experiencing VH (PD-VH+) from those not experiencing VH (PD-VH−). <h3>Design/Methods:</h3> Sixty-nine PwP and eighteen subjects with essential tremor (ET) participated in a neuropsychological evaluation and MRI imaging to determine eligibility for deep brain stimulation. As a part of the evaluation, participants were asked if they had experienced VH. Diffusion Kurtosis Imaging (DKI) scans were processed using a connectometry approach in DSI studio to determine whole-brain group differences in white-matter connectivity. <h3>Results:</h3> Sixty-nine PwP (mean age = 64 +/− 7.5 years, disease duration = 9.2 +/− 4.8 years) were included in the study. Twenty-four (35%) participants in the PD group reported VH. No subjects with ET reported VH. Relative to PD-VH+ and ET groups, the PD-VH− group had decreased structural connectivity within prefrontal white-matter fibers, including the bilateral anterior frontostriatal tracts and the corpus callosum-forceps minor (FDR corrected p=0.000082). Structural connectivity in these tracts did not differ between the PD-VH+ and ET groups. Analyses included correction for sex, age, handedness, and disease duration. <h3>Conclusions:</h3> These results suggest that the integrity of frontostriatal and callosal structural connectivity is necessary for the emergence of VH in PD. This aligns with the proposed top-down processing mechanisms of VH in PD. <b>Disclosure:</b> Emma Wetmore has nothing to disclose. Dr. Lench has nothing to disclose. The institution of Dr. Revuelta has received research support from NIH. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for VeraSci. Dr. Turner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Saccadous. Dr. Turner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. The institution of Dr. Turner has received research support from NIH. The institution of Dr. Turner has received research support from Aker BioMarine. An immediate family member of Dr. Rodriguez-Porcel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anmeal. Dr. Rodriguez-Porcel has received publishing royalties from a publication relating to health care.

Individual Differences in Corticostriatal White-matter Tracts Predict Successful Daily-life Routine Formation.

Despite good intentions, people often fail to cross the "intention-behavior gap," especially when goal achievement requires repeated action. To bridge this gap, the formation of automatized routines may be crucial. However, people may differ in the tendency to switch from goal-directed toward habitual control. To shed light on why some people succeed in forming routines while others struggle, the present study related the automatization of a novel, daily routine to individual differences in white-matter connectivity in corticostriatal networks that have been implicated in goal-directed and habitual control. Seventy-seven participants underwent diffusion-weighted imaging and formed the daily routine of taking a (placebo) pill for 3 weeks. Pill intake was measured by electronic pill boxes, and participants filled out a daily on-line questionnaire on the subjective automaticity of this behavior. Automatization of pill intake was negatively related to striatal (mainly caudate) connectivity with frontal goal-directed and cognitive control regions, namely, ventromedial pFC and anterior cingulate gyrus. Furthermore, daily pill intake was positively related to individual differences in striatal (mainly caudate) connectivity with cognitive control regions, including dorsolateral and anterior pFC. Therefore, strong control networks may be relevant for implementing a new routine but may not benefit its automatization. We also show that habit tendency (assessed with an outcome-devaluation task), conscientiousness, and daily life regularity were positively related to routine automatization. This translational study moves the field of habit research forward by relating self-reported routine automatization to individual differences in performance on an experimental habit measure and to brain connectivity.

Altered White Matter Connectivity in Children with Prenatal Marijuana Exposure

&#x0D; &#x0D; &#x0D; Background:&#x0D; The potential health outcomes of cannabis use during pregnancy are currently not well-known. Several studies have shown an association between prenatal marijuana exposure (PME) and adverse neonatal outcomes. Specifically, cannabis use has been associated with an increased risk of cognitive deficits and neuropsychiatric disease. The aim of this project is to examine alterations in cerebral white matter connectivity of children with PME compared to unexposed controls based on diffusion tensor imaging (DTI). Identifying such microstructural alterations may help us better understand neurodevelopmental and cognitive effects of PME.&#x0D; Hypothesis:&#x0D; We hypothesize that there will be differences in white matter connectivity in children with PME compared to controls.&#x0D; Methods:&#x0D; DTI images for children with (n=88) and without (n=90) PME were obtained from the Adolescent Brain Cognitive Development (ABCD) Study database. Image quality assurance, preprocessing, and tractography were completed using DSI Studio. Fiber counts between 94 regions of interest were assessed. A groupwise comparison was performed to assess differences in structural connectivity in children with and without PME.&#x0D; Results:&#x0D; The PME group and control group had 35 and 37 males, respectively. The mean age for both groups was 9.9 years. First level comparative analysis revealed alterations in microstructural connectivity between PME and control groups. Increased connectivity was found in the PME group compared to the control group in 51 tracts, while decreased connectivity was indicated in 22 tracts. However, significance was not maintained when corrected for multiple comparisons.&#x0D; Conclusion/Impact:&#x0D; Although there were small alterations in brain structural connectivity in children with PME, these were not significant after correcting for multiple comparisons. It is possible that microstructural neuroplasticity in the developing brain lowers the impact of potential long-term adverse effects of marijuana exposure in utero. Further studies are required to understand longitudinal brain development and adverse neurodevelopmental and cognitive outcomes associated with PME.&#x0D; &#x0D; &#x0D;

QOL-09. WHOLE-BRAIN WHITE MATTER NETWORK CONNECTIVITY IS DISRUPTED BY PEDIATRIC BRAIN TUMOR TREATMENT

INTRODUCTIONTreatments for pediatric brain tumors (PBT) are neurotoxic and lead to long-term deficits that are driven by the perturbation of underlying white matter (WM). It is unclear if and how treatment may impair WM connectivity across the entire brain.METHODSMagnetic resonance images from 41 PBT survivors (mean age: 13.19 years, 53% M) and 41 typically developing (TD) children (mean age: 13.32 years, 51% M) were analyzed. Image reconstruction, segmentation, and node parcellation were completed in FreeSurfer. DTI maps and probabilistic streamline generation were completed in MRtrix3. Connectivity matrices were based on the number of streamlines connecting two nodes and the mean DTI (FA) index across streamlines. We used graph theoretical analyses to define structural differences between groups, and random forest (RF) analyses to identify hubs that reliably classify PBT and TD children.RESULTSFor survivors treated with radiation, betweeness centrality was greater in the left insular (p < 0.000) but smaller in the right pallidum (p < 0.05). For survivors treated without radiation (surgery-only), betweeness centrality was smaller in the right interparietal sulcus (p < 0.05). RF analyses showed that differences in WM connectivity from the right pallidum to other parts of the brain reliably classified PBT survivors from TD children (classification accuracy = 77%).CONCLUSIONSThe left insular, right pallidum, and right inter-parietal sulcus are structurally perturbed hubs in PBT survivors. WM connectivity from the right pallidum is vulnerable to the long-term effects of treatment for PBT.

Age-related differences in white matter diffusion measures in autism spectrum condition

BackgroundAutism spectrum condition (ASC) is accompanied by developmental differences in brain anatomy and connectivity. White matter differences in ASC have been widely studied with diffusion imaging but results are heterogeneous and vary across the age range of study participants and varying methodological approaches. To characterize the neurodevelopmental trajectory of white matter maturation, it is necessary to examine a broad age range of individuals on the autism spectrum and typically developing controls, and investigate age × group interactions.MethodsHere, we employed a spatially unbiased tract-based spatial statistics (TBSS) approach to examine age-related differences in white matter connectivity in a sample of 41 individuals with ASC, and 41 matched controls between 7–17 years of age.ResultsWe found significant age-related differences between the ASC and control group in widespread brain regions. This included age-related differences in the uncinate fasciculus, corticospinal tract, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior longitudinal fasciculus and forceps major. Measures of fractional anisotropy (FA) were significantly positively associated with age in both groups. However, this relationship was significantly stronger in the ASC group relative to controls. Measures of radial diffusivity (RD) were significantly negatively associated with age in both groups, but this relationship was significantly stronger in the ASC group relative to controls.LimitationsThe generalisability of our findings is limited by the restriction of the sample to right-handed males with an IQ > 70. Furthermore, a longitudinal design would be required to fully investigate maturational processes across this age group.ConclusionsTaken together, our findings suggest that autistic males have an altered trajectory of white matter maturation relative to controls. Future longitudinal analyses are required to further characterize the extent and time course of these differences.

Disruption of white matter connectivity in chronic obstructive pulmonary disease.

BackgroundMild cognitive impairment is a common systemic manifestation of chronic obstructive pulmonary disease (COPD). However, its pathophysiological origins are not understood. Since, cognitive function relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity.MethodsStructural networks were constructed for 30 COPD patients (aged 54–84 years, 57% male, FEV1 52.5% pred.) and 23 controls (aged 51–81 years, 48% Male). Networks comprised 90 grey matter regions (nodes) interconnected by white mater fibre tracts traced using deterministic tractography (edges). Edges were weighted by the number of streamlines adjusted for a) streamline length and b) end-node volume. White matter connectivity was quantified using global and nodal graph metrics which characterised the networks connection density, connection strength, segregation, integration, nodal influence and small-worldness. Between-group differences in white matter connectivity and within-group associations with cognitive function and disease severity were tested.ResultsCOPD patients’ brain networks had significantly lower global connection strength (p = 0.03) and connection density (p = 0.04). There was a trend towards COPD patients having a reduction in nodal connection density and connection strength across the majority of network nodes but this only reached significance for connection density in the right superior temporal gyrus (p = 0.02) and did not survive correction for end-node volume. There were no other significant global or nodal network differences or within-group associations with disease severity or cognitive function.ConclusionCOPD brain networks show evidence of damage compared to controls with a reduced number and strength of connections. This loss of connectivity was not sufficient to disrupt the overall efficiency of network organisation, suggesting that it has redundant capacity that makes it resilient to damage, which may explain why cognitive dysfunction is not severe. This might also explain why no direct relationships could be found with cognitive measures. Smoking and hypertension are known to have deleterious effects on the brain. These confounding effects could not be excluded.

White matter microstructural differences between right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is a chronic focal epileptic disorder characterized by recalcitrant seizures often necessitating surgical intervention. Identifying the laterality of seizure focus is crucial for pre-surgical planning. We implemented diffusion MRI (DMRI) connectometry to identify differences in white matter connectivity in patients with left and right mTLE relative to healthy control subjects. We enrolled 12 patients with right mTLE, 12 patients with left mTLE, and 12 age/sex matched healthy controls (HCs). We used DMRI connectometry to identify local connectivity patterns of white matter tracts, based on quantitative anisotropy (QA). We compared QA of white matter to reconstruct tracts with significant difference in connectivity between patients and HCs and then between patients with left and right mTLE. Right mTLE patients show higher anisotropy in left inferior longitudinal fasciculus (ILF) and forceps minor and lower QA in genu of corpus callosum (CC), bilateral corticospinal tracts (CSTs), and bilateral middle cerebellar peduncles (MCPs) compared to HCs. Left mTLE patients show higher anisotropy in genu of CC, bilateral CSTs, and right MCP and decreased anisotropy in forceps minor compared to HCs. Compared to patients with right mTLE, left mTLE patients showed increased and decreased connectivity in some major tracts. Our study showed the pattern of microstructural disintegrity in mTLE patients relative to HCs. We demonstrated that left and right mTLE patients have discrepant alternations in their white matter microstructure. These results may indicate that left and right mTLE have different underlying pathologic mechanisms.

White Matter Network Disruption and Cognitive Dysfunction in Neuromyelitis Optica Spectrum Disorder.

Background: In neuromyelitis optica spectrum disorder (NMOSD), brain involvement is common and cognitive dysfunction is frequently found. The study investigated alterations of white matter (WM) connectivity using graph theory and correlations with cognitive dysfunction in patients with NMOSD.Methods: We prospectively enrolled patients with NMOSD (N = 14) and age- and sex-matched healthy controls (N = 21). Structural connections between any pair of the 90 cortical and subcortical regions were established using diffusion tensor imaging and graph theory. Network-based statistics was employed to assess differences in WM connectivity between the NMOSD and healthy control groups. We further investigated the relationship between the topological network characteristics and cognitive test performances.Results: WM network analysis showed decreased total strength of brain networks and two disrupted sub-networks in patients with NMOSD. The first featured six hub nodes in the rectus, hippocampus, calcarine, cuneus, and precuneus with the left-sided predominance. The second had six hub nodes in the orbitomiddle frontal, post-central, superior parietal, superior, and middle temporal, and caudate with the right-sided predominance. Compared to healthy controls, NMOSD patients showed poor performance on tests for attention/working memory and processing speed, visuospatial processing, and executive function, which were associated with significant decreases in nodal clustering coefficient, local efficiency, and regional efficiency in the disrupted sub-networks (all p < 0.05).Conclusions: The data show the overall WM disruption and the relationship between poor cognitive function and sub-network alterations identified by the network analysis in NMOSD patients. We suggest that cognitive dysfunction is related to dysconnectivity of WM network including default mode network in NMOSD.

Differences in white matter connectivity between treatment-resistant and treatment-responsive subtypes of schizophrenia

Schizophrenia is a heterogeneous disorder exhibiting variable responsiveness to treatment between individuals. Previous work demonstrated that white matter abnormalities may relate to antipsychotic response but no study to date has examined differences between first-line treatment responders (FLR) and clozapine-eligible individuals receiving first-line antipsychotics. The current study aimed to establish whether differences in white matter structure exist between these two cohorts. Diffusion-weighted images were acquired for 15 clozapine-eligible and 10 FLR participants. Measures of fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) were obtained and between-group t-tests interrogating differences in FA were conducted. To investigate the neural basis of a decrease in FA, the significant cluster from FA analysis was masked and used to obtain mean RD and AD measures for that region. Those who were clozapine-eligible had significantly lower FA in the body of the corpus callosum (p < 0.05), associated with a significant increase in mean RD compared with FLR (p < 0.001). No difference in mean AD was observed for this region. These data reveal differences in diffusion measures between FLR and those eligible for clozapine and suggest that lower FA and greater RD in the corpus callosum could exist as a biomarker of treatment resistance in people with schizophrenia.

Cerebral white matter sex dimorphism in alcoholism: a diffusion tensor imaging study.

Excessive alcohol consumption is associated with brain aberrations, including abnormalities in frontal and limbic brain regions. In a prior diffusion tensor magnetic resonance imaging (dMRI) study of neuronal circuitry connecting the frontal lobes and limbic system structures, we demonstrated decreases in white matter fractional anisotropy in abstinent alcoholic men. In the present study, we examined sex differences in alcoholism-related abnormalities of white matter connectivity and their association with alcoholism history. The dMRI scans were acquired from 49 abstinent alcoholic individuals (26 women) and 41 nonalcoholic controls (22 women). Tract-based spatial statistical tools were used to estimate regional FA of white matter tracts and to determine sex differences and their relation to measures of alcoholism history. Sex-related differences in white matter connectivity were observed in association with alcoholism: Compared to nonalcoholic men, alcoholic men had diminished FA in portions of the corpus callosum, the superior longitudinal fasciculi II and III, and the arcuate fasciculus and extreme capsule. In contrast, alcoholic women had higher FA in these regions. Sex differences also were observed for correlations between corpus callosum FA and length of sobriety. Our results suggest that sexual dimorphism in white matter microstructure in abstinent alcoholics may implicate underlying differences in the neurobehavioral liabilities for developing alcohol abuse disorders, or for sequelae following abuse.

Dissociable frontostriatal white matter connectivity underlies reward and motor impulsivity

Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry.

White Matter Integrity in Genetic High-Risk Individuals and First-Episode Schizophrenia Patients: Similarities and Disassociations.

White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC), anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR-SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus (SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA was significantly positively correlated with hallucinations, and right SLF II was positively correlated with thought disorder. The presence of shared WM deficits in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ, while the disparate FA changes in the FE-SZ group may represent symptom-generating circuitry that mediates perceptual and cognitive disturbances of SZ and ultimately culminates in the onset of psychotic episodes.

Differential White Matter Connectivity in Early Mild Cognitive Impairment According to CSF Biomarkers

Mild cognitive impairment (MCI) is a heterogeneous group and certain MCI subsets eventually convert to dementia. Cerebrospinal fluid (CSF) biomarkers are known to predict this conversion. We sought evidence for the differences in white matter connectivity between early amnestic MCI (EMCI) subgroups according to a CSF phosphorylated tau181p/amyloid beta1–42 ratio of 0.10. From the Alzheimer's Disease Neuroimaging Initiative database, 16 high-ratio, 25 low-ratio EMCI patients, and 20 normal controls with diffusion tensor images and CSF profiles were included. Compared to the high-ratio group, radial diffusivity significantly increased in both sides of the corpus callosum and the superior and inferior longitudinal fasciculus in the low-ratio group. In widespread white matter skeleton regions, the low-ratio group showed significantly increased mean, axial, and radial diffusivity compared to normal controls. However, the high-ratio group showed no differences when compared to the normal group. In conclusion, our study revealed that there were significant differences in white matter connectivity between EMCI subgroups according to CSF phosphorylated tau181p/amyloid beta1–42ratios.

Diffusion Tensor Imaging in Bipolar Disorder with Cocaine Dependence vs. a Healthy Control: Preliminary Findings

Diffusion Tensor Imaging (DTI) has been a useful technology to examine brain anomalies in relation to white matter atrophy in neurologically impaired patient populations. Of particular interest is using DTI to better characterize brain structure in patients with mental illness or addiction. To that end, the available data show white matter atrophy in brain areas that underlie executive functioning, emotion, and memory in those with bipolar disorder. In those with substance use disorders, the current data illustrate white matter atrophy in the corpus callosi. However, studies examining white matter connectivity and atrophy in those with co-occurring bipolar and cocaine use disorders are lacking. Here, an exploratory case series illustrating differences in white matter connectivity among two subjects with co-occurring bipolar and cocaine use disorders in comparison to a healthy control are shown.

Sexually Dimorphic White Matter Geometry Abnormalities in Adolescent Onset Schizophrenia

The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

Investigating connectivity between the cerebellum and thalamus in schizophrenia using diffusion tensor tractography: A pilot study

Connections of the cortical–thalamic–cerebellar–cortical regions provide a framework for studying the neural substrates of schizophrenia. A novel diffusion tensor tractography method was used to evaluate the differences in white matter connectivity between 12 patients with schizophrenia and 10 controls. For the tract tracing, we focused on the connection between the cerebellum and the thalamus. Fractional anisotropy (FA) measures along the fiber tracks were compared between patients and the control sample. Fiber tracts located between the cerebellar white matter and the thalamus exhibit a reduced FA in patients with schizophrenia in comparison with controls. The FA values along the defined fiber tracts were not overall reduced but exhibited a reduction in the anisotropy in the region in the superior cerebellar peduncles projecting towards the red nucleus.

328. Differences in white matter connectivity in men and women with and without schizophrenia

328. Differences in white matter connectivity in men and women with and without schizophrenia