Brain White Matter Abnormalities Research Articles

Joint Assessment of Structural, Perfusion, and Diffusion MRI in Alzheimer′s Disease and Frontotemporal Dementia

Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4 Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD.

Whiter matter abnormalities in medication-naive subjects with a single short-duration episode of major depressive disorder

Convergent studies have implicated white matter abnormalities in the pathophysiology of major depressive disorder (MDD). In this study, diffusion tensor imaging (DTI) was used to examine white matter abnormalities in 23 single-episode, medication-naive MDD participants versus 21 healthy control participants. Voxel-based analysis was used to investigate whole brain white matter abnormalities in the MDD group. Fractional anisotropy was significantly lower and apparent diffusion coefficient was significantly higher in the right superior longitudinal fasciculus (SLF) within the frontal lobe, right middle frontal and left parietal white matter in the MDD group compared with the healthy group.

The microstructural integrity of the corpus callosum and associated impulsivity in alcohol dependence: A tractography-based segmentation study using diffusion spectrum imaging

Previous post-mortem and structural magnetic resonance imaging (MRI) studies in patients with alcohol dependence have demonstrated abnormalities of brain white matter. The present study investigated the microstructural integrity in the corpus callosum and the associations of this integrity with neurobehavioral assessments. Twenty-five male cases fulfilling the DSM-IV diagnosis of alcohol dependence and 15 male control subjects were scanned using a 3T MRI system. Callosal fiber tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into seven functionally distinct segments. The microstructural integrity was quantified in terms of generalized fractional anisotropy (GFA). Compared with normal subjects, men with alcohol dependence showed lower GFA values on all segments of the corpus callosum. The segment interconnecting the bilateral orbitofrontal cortices was the most affected. The score on the Barratt Impulsivity Scale showed an inverse relationship with GFA on the callosal fiber tracts connecting the bilateral orbitofrontal cortices. Furthermore, the duration of regular use was negatively associated with GFA on the callosal fiber tracts connecting the bilateral temporal and parietal cortices. Our findings suggest that a high self-rated impulsivity level was associated with low anisotropy in white matter of corpus callosum sectors extending to the orbitofrontal cortex.

Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome

We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. Female patients with interstitial cystitis/painful bladder syndrome and controls with no interstitial cystitis/painful bladder syndrome completed a biopsychosocial phenotyping questionnaire battery which included demographics/history form, self-reported history of associated conditions, and 10 validated questionnaires focused on symptoms, suffering/coping and behavioral/social factors. Questionnaires were completed by 205 patients with interstitial cystitis/painful bladder syndrome and 117 controls matched for age. Prevalence of self-reported associated condition diagnosis in interstitial cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p <0.001). In the interstitial cystitis/painful bladder syndrome cohort 50.3% reported no other associated condition, 24.4% had interstitial cystitis/painful bladder syndrome + irritable bowel syndrome only, 2.5% had interstitial cystitis/painful bladder syndrome + fibromyalgia only, 1.5% had interstitial cystitis/painful bladder syndrome + chronic fatigue syndrome only, while 20.2% had multiple associated conditions. As the number of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated with this apparent phenotypic progression. Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact. There are at least 3 distinct clinical phenotypes based on identification of overlapping syndrome patterns. A suggestion that remains to be proven with longitudinal studies is that there may be progression over time from an organ centric to a regional and finally to a systemic pain syndrome with progression of symptom severity, and deterioration of cognitive and psychosocial parameters.

Neurodevelopmental disorders in children with severe to profound sensorineural hearing loss: a clinical study

The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation between these additional disabilities and the aetiology of deafness. One hundred children with severe/profound SNHL (60 males, 40 females; mean age 5 y 7 mo, SD 3 y 6 mo, range 8 mo-16 y) were investigated using a diagnostic protocol including neurodevelopmental, genetic, neurometabolic, and brain magnetic resonance imaging (MRI) assessment. Forty-eight per cent of the sample exhibited one or more additional disabilities, with cognitive, behavioural-emotional, and motor disorders being the most frequent. The risk of additional disabilities varied according to the type of aetiology. Thirty-seven out of 80 individuals with available MRIs showed signal abnormalities, in particular brain malformations (46%) and white matter abnormalities (54%). Frequency and type of disability were associated with aetiology (p=0.015) and MRI data (p<0.001). A multidimensional evaluation, including aetiological, neurodevelopmental, and MRI investigation, is needed for planning therapeutic intervention, such as cochlear implantation in children with severe to profound hearing impairment. The aetiology of deafness is a relevant risk indicator for the presence of an associated disorder.

Diffusion tensor imaging and decision making in cocaine dependence.

BackgroundChronic stimulant abuse is associated with both impairment in decision making and structural abnormalities in brain gray and white matter. Recent data suggest these structural abnormalities may be related to functional impairment in important behavioral processes.Methodology/Principal FindingsIn 15 cocaine-dependent and 18 control subjects, we examined relationships between decision-making performance on the Iowa Gambling Task (IGT) and white matter integrity as measured by diffusion tensor imaging (DTI). Whole brain voxelwise analyses showed that, relative to controls, the cocaine group had lower fractional anisotropy (FA) and higher mean of the second and third eigenvalues (λ⊥) in frontal and parietal white matter regions and the corpus callosum. Cocaine subjects showed worse performance on the IGT, notably over the last 40 trials. Importantly, FA and λ⊥ values in these regions showed a significant relationship with IGT performance on the last 40 trials.ConclusionsCompromised white matter integrity in cocaine dependence may be related to functional impairments in decision making.

Microstructural changes and atrophy in brain white matter tracts with aging

Diffusion tensor (DT) magnetic resonance imaging (MRI) tractography was used to investigate microstructural and volumetric abnormalities of the major brain white matter (WM) tracts with aging in 84 healthy subjects. Linear relationships were found between age and mean diffusivity (MD) increase and fractional anisotropy (FA) decrease in all WM tracts, except the right cingulum and bilateral uncinate, where a linear correlation with age was found for FA only. Quadratic model fitted better MD and FA values of several tracts, including the corpus callosum, limbic pathways, and bilateral association, and corticospinal tracts. Age-related MD and FA abnormalities were associated with radial diffusivity increase in all WM tracts, while axial diffusivity changes were characterized by a considerable variation from a tract to another. A linear negative relationship with age was found for the volumes of the left cingulum and fornix, while the quadratic model fitted better age-related volume loss of corpus callosum and right inferior fronto-occipital fasciculus. Diffusion tensor magnetic resonance imaging may shed light into the complex pathological substrates of WM changes with aging.

Cortical and subcortical white matter abnormalities in adults with remitted first‐episode mania revealed by Tract‐Based Spatial Statistics

Abnormalities of brain white matter have been noted in structural magnetic resonance imaging and diffusion tensor imaging (DTI) studies of bipolar disorder, but there are fewer investigations specifically examining white matter integrity early in the course of illness. In this study, we employed DTI to elucidate white matter changes in adult patients with remitted first-episode mania and hypothesized that first-episode mania was associated with decreased fractional anisotropy in cortical (frontal) and subcortical (thalamus, striatum) white matter as well as white matter tracts (cingulum, corpus callosum). Diffusion tensor images were acquired from 16 patients with remitted first-episode mania and 16 healthy controls matched for age, gender, handedness, and years of education. Fractional anisotropy and radial and axial diffusivities were analyzed using Tract-Based Spatial Statistics. Patients had lower fractional anisotropy and higher radial diffusivity in the left anterior frontal white matter, right posterior thalamic radiation, left cingulum, and bilateral sagittal striatum. In addition, increased radial diffusivity was found in the left corpus callosum. Our findings highlighted that white matter abnormalities were present by the time of remission of first-episode mania. The widespread occurrence of these white matter abnormalities both in first-episode mania and chronic bipolar disorder suggested that disruption of white matter cortical-subcortical networks as well as projection, associative, and commissural tracts is a hallmark of the illness.

Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia

Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.

Reduced density of ADAM 12-immunoreactive oligodendrocytes in the anterior cingulate white matter of patients with schizophrenia

Objectives. Abnormalities of brain white matter and oligodendroglia are replicated findings in schizophrenia research. The largely oligodendroglia-associated enzyme ADAM (A disintegrin and metalloprotease) 12 might be involved in the patho-physiology of schizophrenia, because the gene coding for human ADAM12 is located on chromosome 10q26.3, a gene locus which has been linked to schizophrenia, and some of its putative substrates are altered in schizophrenia. Methods. We studied the numerical density of ADAM12 expressing oligodendrocytes in post-mortem prefrontal brains of patients with haloperidol treated, chronic schizophrenia and matched controls. Results. A significantly reduced numerical density of ADAM12 immunoreactive oligodendrocytes was found in the white matter of the anterior cingulate cortex of schizophrenic patients. Conclusions. Although the pathophysiological implications of this finding are currently unknown, it is well conveyable that reduced ADAM12 protein contributes to a deviant metabolism of some of its substrates. These substrates are either parts of important signalling cascades (EGF, betacellulin, TGF-beta) or chemical components of myelin (neurofascin-ankyrin) known to be compromised in schizophrenia.

White matter abnormalities in adolescent-onset and adult-onset schizophrenia: new directions in research

Evaluation of: Kyriakopoulos M, Perez-Iglesias R, Woolley JB et al.: Effect of age at onset of schizophrenia on white matter abnormalities. Br. J. Psychiatry 195(4), 346–353 (2009). This study demonstrated that brain white matter abnormalities in schizophrenia may depend on developmental stage at the time of the illness. The authors reported different patterns of fractional anisotropy reductions in adolescent-onset compared with adult-onset schizophrenia. In addition, the effect of schizophrenia on fractional anisotropy is modulated by age-at-onset in bilateral prefrontal white matter. These white matter abnormalities appear to mirror the progression of gray matter volume deficits described in previous research. This study raises important questions regarding the progression of such abnormalities and highlights the need for longitudinal studies to investigate the staging of the appearance of structural and connectivity brain abnormalities in schizophrenia.

Schizophrenia patients and their healthy siblings share disruption of white matter integrity in the left prefrontal cortex and the hippocampus but not the anterior cingulate cortex

Healthy siblings of schizophrenia patients have an almost 9-fold higher risk for developing the illness than the general population. Disruption of white matter (WM) integrity as indicated by reduced fractional anisotropy (FA) derived from diffusion tensor imaging (DTI), is believed to be the key substrate of schizophrenia. However, it remains unclear whether schizophrenia patients and their healthy siblings share a specific pattern of disruption of WM integrity that may be related to the disease risk. The objective of this study is to determine whether a specific brain regional pattern of disruption of WM integrity is shared by schizophrenia patients and their healthy siblings. We investigated brain white matter abnormalities by voxel-based analysis of white matter FA data acquired from diffusion tensor imaging in 34 pairs of schizophrenia patients and their healthy siblings, as well as in 32 healthy controls. Both schizophrenia patients and their healthy siblings showed reduced white matter FA in the left prefrontal cortex and the hippocampus in comparison to healthy controls, without significant difference between patients and siblings. In marked contrast, only schizophrenia patients exhibited reduced white matter FA in the left anterior cingulate cortex in comparison to both siblings and controls, without significant difference between siblings and controls. Thus, schizophrenia patients and their healthy siblings share disruption of WM integrity in the left prefrontal cortex and the hippocampus that may be related to higher risk of healthy siblings to develop schizophrenia, which may be eventually attributed to additional disruption of WM integrity in the left anterior cingulate cortex.

Downregulation of oligodendrocyte transcripts is associated with impaired prefrontal cortex function in rats

Abnormalities of brain white matter and oligodendroglia are among the most consistent findings in schizophrenia (Sz) research. Various gene expression microarray studies of post-mortem Sz brains showed a downregulation of myelin transcripts, while imaging and microscopy studies demonstrated decreases in prefrontal cortical (PFC) white matter volume and oligodendroglia density. Currently, the extent to which reduced oligodendrocyte markers contribute to pathophysiological domains of Sz is unknown.We exposed adolescent rats to cuprizone (CPZ), a copper chelator known to cause demyelination in mice, and examined expression of oligodendrocyte mRNA transcripts and PFC-mediated behavior. Rats on the CPZ diet showed decreased expression of mRNA transcripts encoding oligodendroglial proteins within the medial PFC, but not in the hippocampus or the striatum. These rats also displayed a specific deficit in the ability to shift between perceptual dimensions in the attentional set-shifting task, a PFC-mediated behavioral paradigm modeled after the Wisconsin Card Sorting Test (WCST). The inability to shift strategies corresponds to the deficits exhibited by Sz patients in the WCST. The results demonstrate that a reduction in oligodendrocyte markers is associated with impaired PFC-mediated behaviors. Thus, CPZ exposure of rats can serve as a model to examine the contribution of oligodendrocyte perturbation to cognitive deficits observed in Sz.

6 Brain white matter abnormalities in patients with Myotonic dystrophy type 1: is this multiple sclerosis?

6 Brain white matter abnormalities in patients with Myotonic dystrophy type 1: is this multiple sclerosis?

Leukoencephalopathy in 21-β hydroxylase deficiency: Report of a family

21-Hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an autosomal recessive disorder characterized by impaired synthesis of cortisol from cholesterol by the adrenal cortex. Subclinical involvement of brain white matter has been reported in subjects with congenital adrenal hyperplasia. Here we report a woman with a genetically assessed classic congenital adrenal hyperplasia and brain white matter abnormalities. Both the carrier parents also showed signs of leucoencephalopathy. Common causes of leukoencephalopathy were excluded by appropriate analyses. Our observation suggests that white matter anomalies may also be present in carriers of a mutation in the CYP21 gene . We therefore suggest performing CYP21 gene analysis in subjects with brain MRI evidence of white matter abnormalities that cannot otherwise be explained.

White matter abnormalities in schizophrenia patients with tardive dyskinesia: A diffusion tensor image study

Objective Tardive dyskinesia (TD) is a severe side effect of antipsychotics. While increasing evidence suggests that damaged brain microcircuitry of white matter (WM) is responsible for the clinical symptoms in schizophrenia, no reports of WM abnormality associated with TD were noted. Method Brain white matter abnormalities were investigated among 20 schizophrenia patients with TD (Schizophrenia with TD group), 20 age-, gender-, and handedness-matched schizophrenic patients without TD (Schizophrenia without TD group), and 20 matched healthy subjects with magnetic resonance imaging and diffusion tensor imaging analysis. Voxel-wise analysis was used to compare fractional anisotropy (FA) maps of the white matter following intersubject registration to Talairach space. Clinical ratings included the Positive and Negative Symptoms Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS). Results The study subjects were 75% female with average of 40.1 ± 9. 8 years. The Schizophrenia with TD group had significantly higher PANSS total scores ( p = 0.024), PANSS negative score ( p = 0.001), SAS ( p < 0.001) and AIMS ( p < 0.001) scores; and demonstrated more widespread FA decreases than the Schizophrenia without TD group, especially over the inferior frontal gyrus, temporal sublobar extranuclear WM (around the basal ganglion), parietal precuneus gyrus WM (around somatosensory cortex), and medial frontal gyrus WM (around dorsolateral prefrontal cortex). The AIMS ( p < 0.01) and SAS ( p < 0.01) score positively correlated with decreased FA over these areas, and PANSS negative score positively correlated with FA decrease over medial frontal gyrus WM ( p < 0.01). Conclusions More widespread abnormality of white matter was noted among schizophrenia patients than those without, especially involved cortico-basal ganglion circuits with clinical symptom correlation of involuntary movements and negative symptoms. Further studies with larger sample size are required to validate the findings.

Application of a multifractal analysis to study brain white matter abnormalities of schizophrenia on T2-weighted magnetic resonance imaging

Multifractal analysis provides a precise quantitative description of the structural complexity of white matter (WM) on magnetic resonance imaging (MRI). To test this new technique as an aid to elucidating the pathology of schizophrenia, we examined a multifractal dimension (i.e. Δ α) of WM in schizophrenia patients and their relations to clinical variables. We examined 16 patients with schizophrenia and 16 controls matched for age, sex and handedness. Delta α value of WM in the prefrontal and frontoparietal lobes and the corpus callosum (genu and splenium) on T2-weighted MRI was calculated. Delta α was not significantly different between groups in either region of interest. However, group-by-side interaction for Δ α was found in the frontoparietal WM; post-hoc analysis revealed normal left dominant asymmetry in Δ α for frontoparietal WM in control subjects, which was absent in schizophrenia patients. Furthermore, the patients with schizophrenia had a lower asymmetry coefficient ([ R − L]/[ R + L]) for Δ α in frontoparietal WM. Relations to clinical symptoms from the Positive and Negative Syndrome Scale, Δ α in corpus callosum, and the asymmetry coefficient in prefrontal WM were correlated with negative and general psychopathology symptom scores. Our results support the left-sided dysfunction hypothesis of schizophrenia and its relation to schizophrenic symptoms. Multifractal analysis reveals abnormal patterns of WM structures in schizophrenia that could be implicated in the disorder's etiology.

WHITE MATTER ABNORMALITIES IN PATIENTS WITH SCHIZOPHRENIA AND OBSESSIVE-COMPULSIVE DISORDER

Introduction:Schizophrenia and OCD have a high comorbidity. Structural brain abnormalities in patients with schizophrenia and OCD are common. Furthermore, in clinical practice, both disorders present with motor abnormalities, neurological soft signs and cognitive deficits stemming from possibly similar brain etiology. Our aim was to investigate whole brain grey and white matter abnormalities and total brain volume in patients with schizophrenia with and without comorbidity with OCD. Methods:Voxel-based and volumetric analysis of high resolution structural T1-weighted 3 Tesla MRI images was used in 10 male patients with schizophrenia and OCD and 15 age and education matched patients with schizophrenia without OCD symptoms. Results:Schizophrenic patients with OCD had significantly reduced white matter density of the cerebellum, bilaterally, compared to schizophrenic patients without OCD symptoms. Furthermore, reduced total white matter volume was found in schizophrenic patients with OCD, which correlated significantly with the Yale Brown Obsessive Compulsive Scale total score. Conclusions:Patients with schizophrenia and OCD had reduced cerebellar white matter and a smaller total mean white matter volume, compared to schizophrenic patients without OCD symptoms. Cerebellar white matter abnormalities could be the underlying pathology for neurological soft signs, motor deficits and cognitive difficulties found in the population of schizophrenic patients with OCD. References

Diffusion tensor imaging in schizophrenia

Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that is increasingly being used for the non-invasive evaluation of brain white matter abnormalities. In this review, we discuss the basic principles of DTI, its roots and the contribution of European centres in its development, and we review the findings from DTI studies in schizophrenia. We searched EMBASE, PubMed, PsychInfo, and Medline from February 1998 to December 2006 using as keywords ‘schizophrenia’, ‘diffusion’, ‘tensor’, and ‘DTI’. Forty studies fulfilling the inclusion criteria of this review were included and systematically reviewed. White matter abnormalities in many diverse brain regions were identified in schizophrenia. Although the findings are not completely consistent, frontal and temporal white matter seems to be more commonly affected. Limitations and future directions of this method are discussed.

White Matter Abnormalities in First-Episode, Treatment-Naive Young Adults With Major Depressive Disorder

Objective: The aim of this study was to explore the microstructural integrity of whole-brain white matter by diffusion tensor imaging in first-episode, treatment-naive young adults with major depressive disorder. Method: Diffusion tensor imaging scans were obtained from 14 first-episode, treatment-naive young adult patients with major depressive disorder and 14 healthy comparison subjects. A voxel-based method was used to analyze the scans. Results: The patient group exhibited significantly lower fractional anisotropy values than healthy comparison subjects in the white matter of the right middle frontal gyrus, the left lateral occipitotemporal gyrus, and the subgyral and angular gyri of the right parietal lobe. There were no regions of significantly higher fractional anisotropy values in patients compared with healthy comparison subjects. Conclusions: These findings suggest that abnormalities of brain white matter may be present early in the course of major depressive disorder. They also support the idea that white matter lesions may disrupt the neural circuits involved in mood regulation and thus contribute to the neuropathology of major depressive disorder.