Abnormalities In White Matter Tracts Research Articles

Abnormalities in white matter tracts in the fronto-striatal-thalamic circuit are associated with verbal performance in 22q11.2DS

BackgroundAbnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating 22q11.2 deletion syndrome (22q11DS), a genetic syndrome associated with a 30% risk for developing schizophrenia in adulthood and a decline in Verbal IQ (VIQ) preceding psychosis onset. Here, we examined white matter (WM) tracts in FST sub-circuits, especially those in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC) sub-circuits, and their associations with VIQ in young adults with 22q11DS. MethodsDiffusion MRI scans were acquired from 21 individuals with 22q11DS with prodromal symptoms of schizophrenia, 30 individuals with 22q11DS without prodromal symptoms, and 30 healthy controls (mean age: 21 ± 2 years). WM tracts were reconstructed between striatum and thalamus with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. Fractional anisotropy (FA) and radial diffusivity (RD) were used for group comparisons. VIQ was assessed and associations with the diffusion measures were evaluated. ResultsFA was significantly increased and RD decreased in most tracts of the DLPFC and VLPFC sub-circuits in 22q11DS. Verbal IQ scores correlated negatively with FA and, at trend level, positively with RD in the right thalamus-IFG tract in 22q11DS with prodromal symptoms. ConclusionsWhile abnormalities in FST sub-circuits are associated with schizophrenia, we observed that these abnormalities are also present in 22q11DS individuals with prodromal symptoms and are associated with verbal performance in the right thalamus-IFG tract.

The correlation between white matter integrity and pragmatic language processing in first episode schizophrenia

Objective: Higher-order language disturbances could be the result of white matter tract abnormalities. The study explores the relationship between white matter and pragmatic skills in first-episode schizophrenia. Methods: Thirty-four first-episode patients with schizophrenia and 32 healthy subjects participated in a pragmatic language and Diffusion Tensor Imaging study, where fractional anisotropy of the arcuate fasciculus, corpus callosum and cingulum was correlated with the Polish version of the Right Hemisphere Language Battery. Results: The patients showed reduced fractional anisotropy in the right arcuate fasciculus, left anterior cingulum bundle and left forceps minor. Among the first episode patients, reduced understanding of written metaphors correlated with reduced fractional anisotropy of left forceps minor, and greater explanation of written and picture metaphors correlated with reduced fractional anisotropy of the left anterior cingulum. Conclusions: The white matter dysfunctions may underlie the pragmatic language impairment in schizophrenia. Our results shed further light on the functional neuroanatomical basis of pragmatic language use by patients with schizophrenia.

Neuroanatomical Changes in Leber's Hereditary Optic Neuropathy: Clinical Application of 7T MRI Submillimeter Morphometry.

Leber’s hereditary optic neuropathy (LHON) is one of the mitochondrial diseases that causes loss of central vision, progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In recent years, diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts, such as the optic tract, and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect other subcortical areas of the brain. This study aimed to improve our understanding of morphometric changes in subcortical brain areas and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. For all individuals, quantitative analysis of the morphometric results was performed. Furthermore, morphometric characteristics which differentiated the groups were correlated with variables covering selected aspects of the LHON clinical picture. Compared to healthy controls (HC), LHON carriers showed significantly lower volume of both palladiums (left p = 0.023; right p = 0.018), the right accumbens area (p = 0.007) and the optic chiasm (p = 0.014). Additionally, LHON patients have significantly higher volume of both lateral ventricles (left p = 0.034; right p = 0.02), both temporal horns of the lateral ventricles (left p = 0.016; right p = 0.034), 3rd ventricle (p = 0.012) and 4th ventricle (p = 0.002). Correlation between volumetric results and clinical data showed that volume of both right and left lateral ventricles significantly and positively correlated with the duration of the illness (left R = 0.841, p = 0.002; right R = 0.755, p = 0.001) and the age of the LHON participants (left R = 0.656, p = 0.007; right R = 0.691, p = 0.004). The abnormalities in volume of the LHON patients’ subcortical structures indicate that the disease can cause changes not only in the white matter areas constituting visual tracts, but also in the other subcortical brain structures. Furthermore, the correlation between those results and the illness duration suggests that the disease might have a neurodegenerative nature; however, to fully confirm this observation, longitudinal studies should be conducted.

The Relation between Persistent Post-Traumatic Headache and PTSD: Similarities and Possible Differences.

Post-traumatic headache (PTH) may be considered a secondary headache, which is linked to severe disability and psychosocial impairment. Interestingly, nearly 30% of subjects with persistent post-traumatic headache (PPTH) also suffer from post-traumatic stress disorder (PTSD). Although existing studies demonstrated the existence of common pathophysiological characteristics in subjects with migraine and PPTH, the differences and similarities between these complex diseases are currently poorly understood and are yet to be comprehensively elucidated. Thus, the present review aimed to systematically investigate the nature of PPTH in the effort to better identify both the neurobiological and clinical aspects underlying this condition. Overall, the included studies reported that: (1) the predictors for persistent acute traumatic injury to the head were female gender, persistent symptoms related to mild post-traumatic brain injury (mTBI), PTSD, elevated inflammatory markers, prior mild traumatic brain injury, being injured while suffering from alcohol abuse; (2) static/dynamic functional connectivity differences, white matter tract abnormalities, and morphology changes were found between PPTH and migraine in brain regions involved in pain processing; and (3) clinical differences which were most prominent at early time points when they were linked to the increased risk of PPTH. Based on the selected reports, the relation between migraine and PPTH needs to be considered bidirectionally, but PTSD may play a critical role in this relation. The main implications of these findings, with a specific focus on PTSD, are discussed. Further longitudinal studies are needed to reveal the exact nature of this relation, as well as to clarify the distinct clinical characteristics of migraine, PPTH, and PTSD.

Abnormalities in the white matter tracts in patients with Parkinson disease and psychosis.

The objective of the current study was to compare the microstructural integrity of the white matter (WM) tracts in patients having Parkinson disease (PD) with and without psychosis (PD-P and PD-NP) through diffusion tensor imaging (DTI). This cross-sectional study involved 48 PD-NP and 42 PD-P who were matched for age, sex, and education. Tract-based spatial statistics (TBSS) was used to compare several DTI metrics from the diffusion-weighted MRIs obtained through a 3-Tesla scanner. A set of neuropsychological tests was used for the cognitive evaluation of all patients. The severity and stage of PD were not statistically different between the groups. The PD-P group performed poorly in all the neuropsychological domains compared with the PD-NP group. TBSS analysis revealed widespread patterns of abnormality in the fractional anisotropy (FA) in the PD-P group, which also correlated with some of the cognitive scores. These tracts include inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, right parieto-occipital WM, body of the corpus callosum, and corticospinal tract. This study provides novel insights into the putative role of WM tract abnormalities in the pathogenesis of PD-P by demonstrating significant alterations in several WM tracts. Additional longitudinal studies are warranted to confirm the findings of our research.

Functional connectivity and microstructural changes of the brain in primary Sjögren syndrome: the relationship with depression.

Fatigue and depression are among the most common manifestations of primary Sjögren syndrome (pSS), but information is lacking on the relationship with brain function and microstructural changes. To investigate microstructural changes and brain connectivity in pSS, and to evaluate their relationship with fatigue and depression. The study included 29 patients with pSS (mean age 61.2 ± 12.1 years; disease duration 10.5 ± 5.9 years) and 28 controls (mean age 58.4 ± 9.2 years). All the patients completed the Beck's depression and Fatigue Assessment Scale questionnaires. The imaging protocol consisted of: (i) standard magnetic resonance imaging (MRI) pulse sequences (FLAIR, 3D T1W); (ii) a diffusion tensor imaging pulse sequence; and (iii) a resting state functional MRI pulse sequence. Resting state brain networks and maps of diffusion metrics were calculated and compared between patients and controls. Compared with the controls, the patients with pSS and depression showed increased axial, radial, and mean diffusivity and decreased fractional anisotropy; those without depression showed decreased axial diffusivity in major white matter tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, anterior thalamic radiation, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, and forceps minor-major). Decreased brain activation in the sensorimotor network was observed in the patients with pSS compared with the controls. No correlation was found between fatigue and structural or functional changes of the brain. pSS is associated with functional connectivity abnormalities of the somatosensory cortex and microstructural abnormalities in major white matter tracts, which are more pronounced in depression.

Recent neuro-imaging findings with respect to conduct disorder, callous-unemotional traits and psychopathy.

To review recent neuro-imaging findings with respect to conduct disorder and callous-unemotional traits in childhood and comparable psychopathy in adult-hood that deepen the literature in important ways. Recent structural findings particularly bring clarity to the literature. First, they reinforce previous work indicating that severity of psychopathy is positively associated with extent of cavum septum pellucidum. This suggests psychopathy is associated with early neurodevelopmental disruption within limbic structures. Second, they clarify the direction of the association between conduct disorder and particularly callous-unemotional traits and white matter tract abnormalities even if it remains less transparent exactly which tracts are disrupted. However, conclusions based on recent functional imaging studies are more equivocal with inconsistencies in direction of emotional (albeit with notably more work confirming the previous reports of hypo-responsiveness in limbic regions) and reward responsiveness. The recent data are, for the most part, consistent with a view that callous-unemotional traits/psychopathy represents an early appearing neuro-developmental disorder particularly associated with compromised emotional (limbic) functioning. However, some patients presenting with severe antisocial behavior may also show hyper-threat sensitivity, perhaps reflecting trauma exposure, and require different clinical interventions.

Structure-function abnormalities in cortical sensory projections in embouchure dystonia

BackgroundEmbouchure dystonia (ED) is a task-specific focal dystonia in professional brass players leading to abnormal orofacial muscle posturing/spasms during performance. Previous studies have outlined abnormal cortical sensorimotor function during sensory/motor tasks and in the resting state as well as abnormal cortical sensorimotor structure. Yet, potentially underlying white-matter tract abnormalities in this network disease are unknown. ObjectiveTo delineate structure-function abnormalities within cerebral sensorimotor trajectories in ED. MethodProbabilistic tractography and seed-based functional connectivity analysis were performed in 16/16 ED patients/healthy brass players within a simple literature-informed network model of cortical sensorimotor processing encompassing supplementary motor, superior parietal, primary somatosensory and motor cortex as well as the putamen. Post-hoc grey matter volumetry was performed within cortices of abnormal trajectories. ResultsED patients showed average axial diffusivity reduction within projections between the primary somatosensory cortex and putamen, with converse increases within projections between supplementary motor and superior parietal cortex in both hemispheres. Increase in the mode of anisotropy in patients was accompanying the latter left-hemispheric projection, as well as in the supplementary motor area’s projection to the left primary motor cortex. Patient’s left primary somatosensory functional connectivity with the putamen was abnormally reduced and significantly associated with the axial diffusivity reduction. Left primary somatosensory grey matter volume was increased in patients. ConclusionCorrelates of abnormal tract integrity within primary somatosensory cortico-subcortical projections and higher-order sensorimotor projections support the key role of dysfunctional sensory information propagation in ED pathophysiology. Differential directionality of cortico-cortical and cortico-subcortical abnormalities hints at non-uniform sensory system changes.

White matter integrity differences associated with post-traumatic stress disorder are not normalized by concurrent marijuana use

Marijuana (MJ) use and post-traumatic stress disorder (PTSD) have both been associated with abnormalities in brain white matter tracts, including the cingulum and the anterior thalamic radiations (ATR), which project from subcortical regions to frontal cortex. Studies have not assessed the integrity of these tracts in patients with comorbid PTSD and MJ use. To examine effects of PTSD and MJ use on brain structure, we performed diffusion tensor imaging scans on seventy-two trauma-exposed participants, categorized into four groups: those with PTSD who used MJ at least weekly (PTSD+MJ; n = 20), those with PTSD with no regular MJ use (PTSD; n = 19), trauma-exposed controls without PTSD who used MJ (TEC+MJ; n = 14) and trauma-exposed controls with no PTSD or MJ use (TEC; n = 19). White matter integrity was evaluated by calculating fractional anisotropy (FA). Results showed that while FA values in the right ATR and the cingulum differed across groups, there were no significant interactions between PTSD and MJ in any white matter tracts, indicating that MJ exposure neither normalizes nor worsens white matter abnormalities in those with PTSD. Further study is needed to evaluate the impact of MJ use on other neurobiological markers of PTSD.

Pre- and Post-therapy Assessment of Clinical Outcomes and White Matter Integrity in Autism Spectrum Disorder: Pilot Study.

Objective: This pilot study aims to identify white matter (WM) tract abnormalities in Autism Spectrum Disorders (ASD) toddlers and pre-schoolers by Diffusion Tensor Imaging (DTI), and to correlate imaging findings with clinical improvement after early interventional and Applied Behavior Analysis (ABA) therapies by Verbal Behavior Milestones Assessment and Placement Program (VB-MAPP).Methods: DTI scans were performed on 17 ASD toddlers/pre-schoolers and seven age-matched controls. Nine ASD patients had follow-up MRI 12 months following early intervention and ABA therapy. VB-MAPP was assessed and compared at diagnosis, 6 and 12 months after therapies. Tract-Based Spatial Statistics (TBSS) was used to measure fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial (RD) diffusivity.Results: VB-MAPP scores improved at 6 and 12 months after early intervention and ABA therapy compared to scores at baseline. TBSS analysis showed significant FA decrease and/or RD increase in ASD patients before therapy vs. controls in inferior fronto-occipital fasciculi, uncinate fasciculi, left superior fronto-occipital fasciculus, forceps minor, left superior fronto-occipital fasciculus, right superior longitudinal fasciculus, corona radiate bilaterally, and left external capsule. A significantly FA increase in 21 tracts and ROIs is reported in post- vs. pre-therapy DTI analysis.Conclusion: DTI findings highlighted ASD patient WM abnormalities at diagnosis and confirmed the benefits of 12 months of early intervention and ABA therapy on clinical and neuro imaging outcomes.

Altered white matter connectivity in young people exposed to childhood abuse: a tract-based spatial statistics (TBSS) and tractography study

Childhood abuse is associated with structural brain abnormalities. Few studies have investigated white matter tract abnormalities in medication-naive, drug-free individuals who experienced childhood abuse. We examined the association between childhood abuse and abnormalities in white matter tracts in that population, controlling for psychiatric comorbidities. We collected diffusion tensor imaging data for age- and sex-matched youth with childhood abuse, psychiatric controls (matched for psychiatric diagnoses) and healthy controls. Tract-specific analysis was conducted using tractography. Tract-based spatial statistics (TBSS) was used to assess group differences in fractional anisotropy (FA) at the whole-brain level. We included 20 youth who experienced childhood abuse, 18 psychiatric controls and 25 healthy controls in our analysis. Tractography analysis showed abuse-specific reduced tract volume in the inferior longitudinal fasciculus (ILF) and inferior frontal-occipital fasciculus (IFoF) in the abuse group relative to both healthy and psychiatric controls. Furthermore, abnormalities in the left IFoF were associated with greater abuse severity. The TBSS analysis showed significantly reduced FA in a left-hemispheric cluster comprising the ILF, IFoF and corpus callosum splenium in the abuse group relative to healthy and psychiatric controls. It is unclear to what extent pubertal development, malnutrition and prenatal drug exposure may have influenced the findings. Childhood abuse is associated with altered structure of neural pathways connecting the frontal, temporal and occipital cortices that are known to mediate affect and cognitive control. The abuse-specific deficits in the ILF and IFoF suggest that fibre tracts presumably involved in conveying and processing the adverse abusive experience are specifically compromised in this population.

Molecular Senescence Is Associated With White Matter Microstructural Damage in Late-Life Depression

ObjectivesThe authors aim to investigate the association between white matter integrity and accelerated brain aging in late-life depression. MethodsThe authors measured senescence-associated secretory phenotype (SASP) index proteins, cognitive performance, and MRI diffusion tensor imaging (DTI) measures of fractional anisotropy and mean diffusivity-based indices of white matter microstructure measures in 56 older adults with remitted late-life depression. ResultsHigher SASP index was significantly correlated with older age (r = 0.42, p = 0.001) and worse executive function performance (r = −0.27, p = 0.04). After controlling for the effect of age, overall cognitive performance, and white matter hyperintensities, the association between SASP and left and right cingulate bundle mean diffusivity remained statistically significant. ConclusionsOur data suggest that, in the context of late-life depression, SASP proteins are associated with microstructural abnormalities in white matter tracts in brain and worse executive function performance.

Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder.

Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as "disconnection syndromes," with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

A preliminary investigation of impulsivity, aggression and white matter in patients with bipolar disorder and a suicide attempt history

BackgroundImpulsivity and aggression may be associated with suicide attempts in bipolar disorder (BD), but findings have been inconsistent. Abnormalities in anterior white matter tracts that project to the frontal lobes mediate top-down regulation of emotion and may contribute to this clinical phenomenology. MethodsWe assessed white matter (i.e., fractional anisotropy) in anterior and posterior brain regions using diffusion tensor imaging in 18 patients with BD and no prior suicide attempt (BD-S), 12 patients with BD and a prior suicide attempt (BD+S), and 12 healthy volunteers. Patients completed the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behavior Scale and Impulsive Premeditated Aggression Scale (IPAS). All individuals completed the Barratt Impulsiveness Scale (BIS-11). ResultsPatients with BD+S had higher overall impulsivity (assessed using both the UPPS-P Impulsive Behavior Scale and BIS-11) and premeditated aggression compared to patients with BD-S. There were no significant group differences on measures of fractional anisotropy (FA). In patients with BD+S, however, higher FA in the anterior (but not the posterior) brain regions correlated with greater overall impulsivity on the UPPS-P Impulsive Behavior Scale. There were no significant correlations between either anterior or posterior brain regions with clinical measures in patients with BD-S. LimitationsCross-sectional study, sample size and possible contribution of psychotropic medications. ConclusionImpulsivity and aggression may be risk factors for a suicide attempt in BD. White matter in the anterior limb of the internal capsule and anterior corona radiata may play a role in this phenomenology.

Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome.

To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome. Eight families with DMJD were studied by whole-exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression. All patients showed biallelic mutations in the nonclustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth. DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions. Ann Neurol 2018;84:646-655.

Cerebral White Matter Changes in Young Healthy Individuals With High Trait Anxiety: A Tract-Based Spatial Statistics Study

Background: Abnormalities in prespecified and empirical white matter tracts in young patients with anxiety-related disorders have been reported in some diffusion tensor imaging (DTI) studies. However, with few literatures examining the association between the integrity of whole brain white matter and trait anxiety levels in the non-clinical populations, whether white matter changes arise in young healthy individuals with high trait anxiety remains unknown.Methods: We examined whole brain white matter alterations in young healthy individuals with high anxiety but without history of neurological or psychiatric disorders via DTI technology. Group comparison of tract-based spatial statistics (TBSS) was performed to investigate the microstructural diffusion alterations in 38 high anxious subjects in comparison with 34 low anxious subjects matched with age, gender, and degree of education. These analyses controlled for depression to establish specificity to trait anxiety.Results: Young healthy subjects with high trait anxiety had significantly decreased fractional anisotropy (FA) values in multiple clusters, including corona radiate (CR), anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), bilaterally, body, genu, and splenium of corpus callosum (CC) and forceps minor, compared with low trait anxious subjects. For the abnormal FA regions, the other diffusion metrics were also altered slightly.Conclusions: Non-clinical individuals with high anxiety already have white matter alterations in the thalamus-cortical circuit and some emotion-related areas that were widely reported in anxiety-related disorders. The altered white matter may be a vulnerability marker in individuals at high risk of clinical anxiety. These findings can deepen our understanding of the pathological mechanism of anxiety and further support the need for preventive interventions in high anxiety individuals.

The Role of Diffusion Tensor Imaging (DTI) in Developmental Brain Anomalies in Pediatric Age Group

AbstractBackground: Neurodevelopmental disorders are complex processes with underlying abnormalities of white matter tracts. DTI is an advanced neuroimaging technique that can delineate the underlying abnormal white matter tracts in these disorders.Purpose: To demonstrate the role of diffusion tensor imaging and the tarctography techniques in the diagnosis of brain developmental anomalies in pediatric age group.Patients and Methods: This is a prospective study carried out in Radio-Diagnosis Department, Faculty of Medicine, Cairo University between March 2014 and October 2015. It included eleven patients (1 day-15 years) having neurological dysfunctional symptoms and ten control subjects of the same age group. Conventional MRI images and tractography maps were used. The examined tracts were Corpus Callosum (CC), corticospinal tract (Cst), superior and inferior longitudinal fasciculi (SLF, ILF). Fractional Anisotropy (FA) was measured at bilateral frontal, parietal and occipital white matters regions.Results: Nine cases out of eleven cases with positive conventional MRI findings showed additional DTI findings. e.g tract disruption, absent or attenuated fibers Altered FA values in the white matter tracts were also found.Conclusion: This study emphasis the feasibility of applying DTI technique in the evaluation of developmental brain anomalies to demonstrate additional findings not clearly visualized in conventional MR images to increase the diag-nostic accuracy.

White matter change with apathy and impulsivity in frontotemporal lobar degeneration syndromes.

ObjectiveTo identify the white matter correlates of apathy and impulsivity in the major syndromes associated with frontotemporal lobar degeneration, using diffusion-weighted imaging and data from the PiPPIN (Pick's Disease and Progressive Supranuclear Palsy: Prevalence and Incidence) study. We included behavioral and language variants of frontotemporal dementia, corticobasal syndrome, and progressive supranuclear palsy.MethodsSeventy patients and 30 controls underwent diffusion tensor imaging at 3-tesla after detailed assessment of apathy and impulsivity. We used tract-based spatial statistics of fractional anisotropy and mean diffusivity, correlating with 8 orthogonal dimensions of apathy and impulsivity derived from a principal component analysis of neuropsychological, behavioral, and questionnaire measures.ResultsThree components were associated with significant white matter tract abnormalities. Carer-rated change in everyday skills, self-care, and motivation correlated with widespread changes in dorsal frontoparietal and corticospinal tracts, while carer observations of impulsive–apathetic and challenging behaviors revealed disruption in ventral frontotemporal tracts. Objective neuropsychological tests of cognitive control, reflection impulsivity, and reward responsiveness were associated with focal changes in the right frontal lobe and presupplementary motor area. These changes were observed across clinical diagnostic groups, and were not restricted to the disorders for which diagnostic criteria include apathy and impulsivity.ConclusionThe current study provides evidence of distinct structural network changes in white matter associated with different neurobehavioral components of apathy and impulsivity across the diverse spectrum of syndromes and pathologies associated with frontotemporal lobar degeneration.

White matter tractography of the neural network for speech-motor control in children who stutter

Stuttering is a neurodevelopmental speech disorder with a phenotype characterized by speech sound repetitions, prolongations and silent blocks during speech production. Developmental stuttering affects 1% of the population and 5% of children. Neuroanatomical abnormalities in the major white matter tracts, including the arcuate fasciculus, corpus callosum, corticospinal, and frontal aslant tracts (FAT), are associated with the disorder in adults who stutter but are less well studied in children who stutter (CWS). We used deterministic tractography to assess the structural connectivity of the neural network for speech production in CWS and controls. CWS had higher fractional anisotropy and axial diffusivity in the right FAT than controls. Our findings support the involvement of the corticostriatal network early in persistent developmental stuttering.

Pain-related white matter tract abnormalities in mild traumatic brain injury patients with persistent headache.

BackgroundThe occurrence of debilitating chronic persistent (24/7) headache after mild traumatic brain injury represents a central neuropathic pain state. Previous studies suggest that this chronic headache state can be attributed to altered supraspinal modulatory functional connectivity in both resting and evoked pain states. Abnormalities in the myelin sheaths along the supraspinal superior longitudinal fasciculus and anterior thalamic radiation are frequently associated with alteration in pain modulation related to functional connectivity deficit with the prefrontal cortex. This study assessed the correlated axonal injury-related white matter tract abnormality underlying these previously observed prefrontal functional connectivity deficits by comparing the fractional anisotropy, axial diffusivity, and radial diffusivity of brain white matter in patients with mild traumatic brain injury-related headache to healthy controls.ResultDiffusion tensor imaging data from patients (N = 12, average age ± SD = 35.0 ± 8.0 years old, 10 male) with mild traumatic brain injury-headache were compared with images acquired from healthy controls. The mild traumatic brain injury cohort demonstrated two areas of significant (P < 0.01, F value >16, cluster size >50 voxels) white matter tract abnormalities closely related to pain affective and modulatory functions in (1) the left superior longitudinal fasciculus which connects the prefrontal cortices with the parietal cortices and (2) the right anterior thalamic radiation connecting the prefrontal cortices with the anterior cingulate cortex. In addition, a significant (P < 0.01) decrease in axial diffusivity and increase in radial diffusivity at the superior longitudinal fasciculus cluster were noted in the mild traumatic brain injury cohort.ConclusionThe identified white matter tract abnormalities may represent a state of Wallerian degeneration which correlates with the functional connectivity deficit in pain modulation and can contribute to the development of the chronic persistent headache in the patients with mild traumatic brain injury.