Significant Fractional Anisotropy Reductions Research Articles

Diffusion tensor imaging of the auditory nerve in patients with long-term single-sided deafness

A cochlear implant (CI) can restore hearing in patients with profound sensorineural hearing loss by direct electrical stimulation of the auditory nerve. Therefore, the viability of the auditory nerve is vitally important in successful hearing recovery. However, the nerve typically degenerates following cochlear hair cell loss, and the amount of degeneration may considerably differ between the two ears, also in patients with bilateral deafness. A measure that reflects the nerve's condition would help to assess the best of both nerves and decide accordingly which ear should be implanted for optimal benefit from a CI. Diffusion tensor MRI (DTI) may provide such a measure, by allowing noninvasive investigations of the nerve's microstructure. In this pilot study, we show the first use of DTI to image the auditory nerve in five normal-hearing subjects and five patients with long-term profound single-sided sensorineural hearing loss. A specialized acquisition protocol was designed for a 3 T MRI scanner to image the small nerve bundle. The nerve was reconstructed using fiber tractography and DTI metrics – which reflect the nerve's microstructural properties – were computed per tract. Comparing DTI metrics from the deaf-sided with the healthy-sided nerves in patients showed no significant differences. There was a small but significant reduction in fractional anisotropy in both auditory nerves in patients compared with normal-hearing controls. These results are the first evidence of possible changes in the microstructure of the bilateral auditory nerves as a result of single-sided deafness. Our results also indicate that it is too early to assess the degenerative status of the auditory nerve of a subject-specific basis.

A longitudinal study investigating sub-threshold symptoms and white matter changes in individuals with an ‘at risk mental state’ (ARMS)

BackgroundEvidence supports disruption in white matter (WM) connectivity in established schizophrenia, however, it is unclear when these abnormalities occur during the course of illness and if they are progressive. Here we investigated whether WM abnormalities predate illness onset by examining a group of individuals with an ‘at risk mental state’ (ARMS) and assess whether there is evidence of progressive change. We hypothesized that WM abnormalities are associated with symptom change. MethodsSixteen healthy controls and 41 ARMS subjects at baseline underwent Diffusion Tensor Imaging (DTI). Sub-threshold positive symptoms were measured using the Scale of Prodromal Symptoms (SOPS). Imaging and symptoms were re-administered in the ARMS group after one year (52weeks). Fractional anisotropy (FA) value differences between ARMS and control groups at baseline were localized using the method of Tract-Based Spatial Statistics (TBSS). ResultsAt baseline, FA was significantly reduced in a sub-region of the corpus callosum (CC) in the ARMS group as a whole compared to controls. This reduction was also found in the 34 individuals who did not transition (ARMS-N) during the one-year follow-up. However, the ARMS-N group showed a significant improvement in sub-threshold positive symptoms at follow-up, which was correlated with an increase in FA in the same CC region (r=−0.664, p<0.001). DiscussionThere was a significant FA reduction in the CC in individuals at high risk for psychosis regardless of transition status at one year. This suggests that WM abnormalities in the CC may represent a biological vulnerability to psychosis. Improvement in sub-threshold positive symptoms was associated with improvement in measures of WM integrity in the CC. This may suggest that neurobiological ‘resilience’ is associated with improved outcomes, although this notion requires future study.

Voxel-based analysis of fractional anisotropy in post-stroke apathy.

ObjectiveTo explore the structural basis of post-stroke apathy by using voxel-based analysis (VBA) of fractional anisotropy (FA) maps.MethodsWe enrolled 54 consecutive patients with ischemic stroke during convalescence, and divided them into apathy (n = 31) and non-apathy (n = 23) groups. We obtained magnetic resonance images of their brains, including T1, T2 and DTI sequences. Age, sex, education level, Hamilton Depression Scale (HAMD) scores, Mini-Mental State Examination (MMSE) scores, National Institutes of Health Stroke Scale (NIHSS) scores, and infarct locations for the two groups were compared. Finally, to investigate the structural basis of post-stroke apathy, VBA of FA maps was performed in which we included the variables that a univariate analysis determined had P-values less than 0.20 as covariates.ResultsHAMD (P = 0.01) and MMSE (P<0.01) scores differed significantly between the apathy and non-apathy groups. After controlling for age, education level, HAMD scores, and MMSE scores, significant FA reduction was detected in four clusters with peak voxels at the genu of the corpus callosum (X = −16, Y = 30, Z = 8), left anterior corona radiata (−22, 30, 10), splenium of the corpus callosum (−24, −56, 18), and right inferior frontal gyrus white matter (52, 24, 18), after family-wise error correction for multiple comparisons.ConclusionsPost-stroke apathy is related to depression and cognitive decline. Damage to the genu of the corpus callosum, left anterior corona radiata, splenium of the corpus callosum, and white matter in the right inferior frontal gyrus may lead to apathy after ischemic stroke.

The Plasticity of Brain Gray Matter and White Matter following Lower Limb Amputation.

Accumulating evidence has indicated that amputation induces functional reorganization in the sensory and motor cortices. However, the extent of structural changes after lower limb amputation in patients without phantom pain remains uncertain. We studied 17 adult patients with right lower limb amputation and 18 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging. Cortical thickness and fractional anisotropy (FA) of white matter (WM) were investigated. In amputees, a thinning trend was seen in the left premotor cortex (PMC). Smaller clusters were also noted in the visual-to-motor regions. In addition, the amputees also exhibited a decreased FA in the right superior corona radiata and WM regions underlying the right temporal lobe and left PMC. Fiber tractography from these WM regions showed microstructural changes in the commissural fibers connecting the bilateral premotor cortices, compatible with the hypothesis that amputation can lead to a change in interhemispheric interactions. Finally, the lower limb amputees also displayed significant FA reduction in the right inferior frontooccipital fasciculus, which is negatively correlated with the time since amputation. In conclusion, our findings indicate that the amputation of lower limb could induce changes in the cortical representation of the missing limb and the underlying WM connections.

Diffusion tensor imaging parameters' changes of cerebellar hemispheres in Parkinson's disease.

Studies with diffusion tensor imaging (DTI) analysis have produced conflicting information about the involvement of the cerebellar hemispheres in Parkinson's disease (PD). We, thus, used a new approach for the analysis of DTI parameters in order to ascertain the involvement of the cerebellum in PD. We performed a fiber tract-based analysis of cerebellar peduncles and cerebellar hemispheres in 16 healthy subjects and in 16 PD patients with more than 5 years duration of disease, using a 3T MRI scanner and a constrained spherical deconvolution (CSD) approach for tractographic reconstructions. In addition, we performed statistical analysis of DTI parameters and fractional anisotropy (FA) XYZ direction samplings. We found a statistically significant decrement of FA values in PD patients compared to controls (p < 0.05). In addition, extrapolating and analyzing FA XYZ direction samplings for each patient and each control, we found that this result was due to a stronger decrement of FA values along the Y axis (antero-posterior direction) (p < 0.01); FA changes along X and Z axes were not statistically significant (p > 0.05). We confirmed also no statistically significant differences of FA and apparent diffusion coefficient (ADC) for cerebellar peduncles in PD patients compared to healthy controls. The DTI-based cerebellar abnormalities in PD could constitute an advance in the knowledge of this disease. We demonstrated a statistically significant reduction of FA in cerebellar hemispheres of PD patients compared to healthy controls. Our work also demonstrated that the use of more sophisticated approaches in the DTI parameter analysis could potentially have a clinical relevance.

Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: a multimodal brain imaging study.

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.

Short association fibres of the insula-temporoparietal junction in early psychosis: a diffusion tensor imaging study.

Evidence shows that there are reductions in gray matter volume (GMV) and changes in long association white matter fibres within the left insula-temporoparietal junction (TPJ) during the early stages of psychotic disorders but less is known about short association fibres (sAFs). In this study we sought to characterise the changes in sAFs and associated volumetric changes of the left insula-TPJ during the early stages of psychosis. Magnetic resonance imaging was obtained from a sample of young people with psychosis (n = 42) and healthy controls (n = 45), and cortical parcellations of the left insula-TPJ were used as seeding masks to reconstruct 13 sAFs. Compared to healthy counterparts, the psychosis group showed significant reductions in fractional anisotropy (FA) in the sAFs connecting the superior (STG) and middle temporal gyri (MTG) and as well as reduced GMV within the inferior temporal gyrus and increased white matter volume (WMV) within Heschl's gyrus (HG). Furthermore, adolescent-onset psychosis subjects (onset 18 year or earlier) showed FA reductions in the STG-HG sAF when compared to adult-onset subjects, but this was not associated with changes in GMV nor WMV of the STG or HG. These findings suggest that during the early stages of psychosis, changes in sAFs and associated cortical GMV and WMV appear to occur independently, however age of onset of a psychotic syndrome/disorder influences the pattern of neuroanatomical abnormalities.

15 * Early pharmacological enhancement of gap junction coupling with rotigaptide reduces arrhythmia vulnerability and modulates structural remodelling in reperfused myocardial infarction

Introduction: Survivors of myocardial infarction (MI) are at increased risk of late ventricular arrhythmias and sudden cardiac death with infarct size and scar heterogeneity as key determinants of arrhythmic risk. Current preventative strategies are limited to few, select antiarrhythmic drugs or an implantable cardioverter-defibrillator. Cardiac gap junctions (GJ) have a key role in allowing the passage of small molecules between cells and may mediate the spread of acute myocardial infarction. We hypothesised that enhancing GJ coupling in the acute phase of MI may beneficially modify the extent and pattern of necrosis and infarction acutely, thus affording a protective effect against late arrhythmogenesis. Methods: A small-animal model of infarction-reperfusion, mimicking clinical reperfusion, was used to study the effects of Rotigaptide on arrhythmogenicity and structural remodelling in a four-week healed model of MI. Male Sprague-Dawley rats (250–300g) underwent infarction-reperfusion surgery with either Rotigaptide (n=15) or Saline (n=15) via minipump. The arrhythmia phenotype was characterised at four-weeks with in-vivo telemetry, 6-lead ECG, ex-vivo arrhythmia provocation studies and dual optical mapping. Structural changes post-MI were studied with diffusion-weighted MRI (DWI) and Masson's Trichrome histology. Results: Rotigaptide resulted in a significant reduction in arrhythmias induced by programmed stimulation (arrhythmia score ROT 3.2 vs. CON 1.4, p<0.05), driven by a reduction in sustained VT (20% vs. 53%, p<0.06). Rotigaptide had no effect on mortality or the incidence of spontaneous arrhythmias or ECG parameters. Remodelling of the optical action potential (AP) was similar between groups a reduction in conduction velocity at the border zone and slowing of the AP upstroke. DWI provided quantifiable measures of structural remodelling in the remote, IBZ and infarct. In control hearts, the infarct demonstrated a significant reduction in fractional anisotropy, and a significant increase in mean diffusivity, compared to remote, partially reversed by Rotigaptide (FA: CON -15% vs. ROT -5%, p<0.05, MD: 6% vs. 2%, p<0.05). The 3D laminar structure of the IBZ was remodelled by Rotigaptide, with a reduction in mean (ROT 16 degrees vs. CON 19 degrees, p<0.05) and dispersion (9 degrees vs. 12 degrees, p<0.05) of the transverse angle. There was no remodelling of helix or transverse angle in remote of either treatment group. Conclusions: Pharmacological GJ enhancement in the early healing phase in reperfused infarction modifies the infarct scar morphology to render myocardium less vulnerable to arrhythmias during programmed stimulation, without affecting the properties of the cardiac action potential or calcium transient. The effects of Rotigaptide were limited to at-risk regions with attenuation of remodelling in the infarct and reduced fibre dispersion in the IBZ offering potential mechanistic explanations for the reduced arrhythmic risk.

White matter integrity and late-life depression in community-dwelling individuals: diffusion tensor imaging study using tract-based spatial statistics.

Late-life depression has been associated with white matter changes in studies using the regions of interest approach. To investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling individuals using diffusion tensor imaging with tract-based spatial statistics. The sample comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression. Individuals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up. Reduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.

Diffusion abnormalities of the corpus callosum in patients with malformations of cortical development and epilepsy

Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can characterize white matter (WM) architecture and microstructure. DTI has demonstrated extensive WM changes in patients with several epileptic syndromes, but few studies have focused on patients with malformations of cortical development (MCD). Our aim was to investigate the quantitative diffusion properties of the corpus callosum (CC), a major commissural bundle critical in inter-hemispheric connectivity, in a large group of patients with MCD. Thirty-two MCD patients and 32 age and sex-matched control subjects were evaluated with DTI at 3.0 T. We analyzed the three major subdivisions of the CC (genu, body, and splenium) with deterministic tractography to yield fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ||) and perpendicular diffusivity (λ⊥). We further assessed the CC with region of interest (ROI)-based analyses and evaluated different subgroups of MCD (polymicrogyria/schizencephaly, heterotopia, and cortical dysplasia). Partial correlations between diffusion changes and clinical parameters (epilepsy duration and age at disease onset) were also queried. There were significant reductions of FA, accompanied by increases in MD and λ⊥ in all segments of the CC in the patients group with both analytical methods. The absolute differences in FA were greater on ROI-analyses. There were no significant differences between the MCD subgroups, and no correlations between clinical parameters of epilepsy and FA. Our study indicates DTI abnormalities consistent with microstructural changes in the corpus callosum of MCD patients. The findings support the idea that patients with epilepsy secondary to cortical malformations present widespread WM changes that extend beyond the macroscopic MRI-visible lesions.

Altered corticomotor-cerebellar integrity in young ataxia telangiectasia patients.

Magnetic resonance imaging (MRI) research in identifying altered brain structure and function in ataxia-telangiectasia, an autosomal recessive neurodegenerative disorder, is limited. Diffusion-weighted MRI were obtained from 11 ataxia telangiectasia patients (age range, 7-22 years; mean, 12 years) and 11 typically developing age-matched participants (age range, 8-23 years; mean, 13 years). Gray matter volume alterations in patients were compared with those of healthy controls using voxel-based morphometry, whereas tract-based spatial statistics was employed to elucidate white matter microstructure differences between groups. White matter microstructure was probed using quantitative fractional anisotropy and mean diffusivity measures. Reduced gray matter volume in both cerebellar hemispheres and in the precentral-postcentral gyrus in the left cerebral hemisphere was observed in ataxia telangiectasia patients compared with controls (P < 0.05, corrected for multiple comparisons). A significant reduction in fractional anisotropy in the cerebellar hemispheres, anterior/posterior horns of the medulla, cerebral peduncles, and internal capsule white matter, particularly in the left posterior limb of the internal capsule and corona radiata in the left cerebral hemisphere, was observed in patients compared with controls (P < 0.05). Mean diffusivity differences were observed within the left cerebellar hemisphere and the white matter of the superior lobule of the right cerebellar hemisphere (P < 0.05). Cerebellum-localized gray matter changes are seen in young ataxia telangiectasia patients along with white matter tract degeneration projecting from the cerebellum into corticomotor regions. The lack of cortical involvement may reflect early-stage white matter motor pathway degeneration within young patients.

Alteration of fractional anisotropy and mean diffusivity in glaucoma: novel results of a meta-analysis of diffusion tensor imaging studies.

ObjectivesWe hypothesized that a meta-analysis of existing studies may help to reveal significant changes on diffusion tensor imaging (DTI) in patients with glaucoma. Therefore, a meta-analysis was utilized to investigate the possibility that DTI can detect white matter damage in patients with glaucoma.MethodsThe study design and report adhered to the PRISMA Statement guidelines. DTI studies that compared glaucoma patients and controls were surveyed using PubMed, Web of Science and EMBASE (January 2008 to September 2013). Stata was used to analyze the decrease in fractional anisotropy (FA) and increase in mean diffusivity (MD) in the optic nerve and optic radiation in patients with glaucoma.ResultsEleven DTI studies were identified through a comprehensive literature search, and 10 independent DTI studies of glaucoma patients were eligible for the meta-analysis. A random effects model revealed a significant FA reduction in the optic nerve and optic radiation, as well as a significant MD increase in the tracts. A heterogeneity analysis suggested that FA may be related to glaucoma severity.ConclusionsOur findings revealed that the optic nerve and optic radiation were vulnerable regions in patients with glaucoma and that FA may be correlated with glaucoma severity and age. Furthermore, this study suggests that magnetic resonance imaging in patients with glaucoma may help to provide objective evidence to aid in the diagnosis and management of glaucoma.

Diffusion tensor imaging in blepharospasm and blepharospasm-oromandibular dystonia.

Patterns of white matter (WM) abnormalities and correlation with clinical features in patients with blepharospasm (BSP) and patients with blepharospasm-oromandibular dystonia (BOM) remain unknown. Using voxel-based analysis, diffusion behaviors of WM including fractional anisotropy (FA), mean diffusivity (MD) and eigenvalues were compared between 20 BSP patients vs. 11 healthy controls (HCs) and 11 patients with BOM vs. 11 HCs. Correlation analyses were performed to assess possible association between diffusion behaviors of significantly different areas and clinical measures. Compared with HCs, BSP patients showed significant FA reductions in the left anterior lobe of cerebellum. Significant increases of MD and radial diffusivity (RD) were detected in right lentiform nucleus and thalamus. Significantly decreased FA in the right precuneus of parietal lobe, increased MD in the right lentiform nucleus and insula, and increased axial diffusivity in the right insula were observed in BOM patients. The FA values in the WM of left cerebellum negatively correlated with disease severity in BSP patients measured by JRS (r=-0.655, p=0.002). The FA values in the right parietal WM negatively correlated with disease duration in BOM patients (r=-0.745, p=0.008). Both BSP and BOM are related to microstructural abnormalities of WM in the basal ganglia. WM changes outside the basal ganglia may present trait features that are specific for individual dystonia phenotype. The correlation between FA abnormalities and symptom severity suggests that DTI parameters might be of clinical value in assessing and following disability in BSP patients.

Early Detection of Widespread Progressive Brain Injury after Cardiac Arrest: A Single Case DTI and Post-Mortem Histology Study

ObjectiveWe tested the hypothesis in sense of a proof of principle that white matter (WM) degeneration after cardiopulmonary arrest (CPA) can be assessed much earlier by diffusion tensor imaging (DTI) than by conventional MRI.MethodsWe performed DTI and T2-weighted FLAIR imaging over four serial acquisitions of a 76-year-old man with unresponsive wakefulness syndrome at day 41, 75, 173 and 284 after CPA. DTI was also performed in ten healthy control subjects. Fractional anisotropy (FA) derived from DTI was assessed in eleven regions of interest within the cerebral white matter (WM) and compared with post-mortem neuropathological findings.ResultsIn contrast to conventional FLAIR images that revealed only circumscribed WM damage, the first DTI demonstrated significant reduction of FA across the whole WM. The following FLAIR images (MRI 2-4) revealed increasing atrophy and leukoaraiosis paralleled by clinical deterioration with reduction of wakefulness and intractable seizures. Neuropathological findings confirmed the widespread and marked brain injury following CPA.ConclusionDTI may help to evaluate microstructural brain damage following CPA and may have predictive value for further evolution of cerebral degeneration in the chronic phase after CPA.

Pseudo-continuous arterial spin labeling MRI study of schizophrenic patients

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a novel noninvasive technique that can measure regional cerebral blood flow (rCBF). To our knowledge, few studies have examined rCBF in patients with schizophrenia by ASL-MRI. Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in schizophrenic patients, taking the regional cerebral gray matter volume into account. The subjects were 36 patients with schizophrenia and 42 healthy volunteers who underwent 3-tesla MRI, diffusion tensor imaging (DTI), and pCASL. We evaluated the gray matter volume imaging, DTI, and pCASL imaging data in a voxel-by-voxel statistical analysis. The schizophrenia patients showed reduced rCBF in the left prefrontal and bilateral occipital cortices compared to the healthy volunteers. There was a significant reduction of gray matter volume in the left inferior frontal cortex in the schizophrenia patients. With respect to the fractional anisotropy (FA) values in the DTI, there were significant FA reductions in the left superior temporal, left external capsule, and left inferior prefrontal regions in the patients compared to the controls. ConclusionOur pCASL study with partial volume effect correction together with volumetry and DTI data demonstrated hypoactivity in the left prefrontal area beyond structural abnormalities in schizophrenia patients. There were also hypofunction areas in bilateral occipital cortices, although structural abnormalities were not apparent.

Bilateral white matter abnormality in children with frontal lobe epilepsy

In frontal lobe epilepsy (FLE), interictal discharges and seizures are more likely to spread to contralateral hemisphere and become secondarily generalized. The aim of this study was to assess white matter (WM) integrity in children with FLE using diffusion tensor imaging (DTI). Children with FLE and normal MRI, and healthy controls with no neurological or psychiatric disorders underwent DTI on 3T MRI. Whole brain fractional anisotropy (FA) and mean diffusivity (MD) maps were compared between right and left FLE with controls. 43 children with FLE, consisting of 28 left and 15 right FLE, and 44 healthy controls were recruited. Patients with left FLE had significant FA reductions in left (p=0.002) and right (p=0.003 and p=0.034) superior longitudinal fasciculi (SLF), genu/body (p=0.0002) and splenium (p=0.011) of corpus callosum. Patients with right FLE had significant FA reductions in left (p=0.016) and right (p=0.033) SLF, genu (p=0.001) and body of corpus callosum (p=0.001 and p=0.008), and significant MD elevation in right thalamus (p=0.032). There was no significant association between FA or MD and clinical seizure parameters. The abnormal WM both ipsilateral and contralateral to seizure focus may be due to seizure activity or abnormal brain development.

Moderate–severe traumatic brain injury causes delayed loss of white matter integrity: Evidence of fornix deterioration in the chronic stage of injury

Objectives: To examine structural integrity loss in the fornix from 5–30 months after moderate and severe traumatic brain injury (TBI) using diffusion tensor imaging.Methods: MRIs were prospectively undertaken in 29 adults with moderate and severe TBI at two time points. Fractional anisotropy (FA) was calculated for the fornix (column/body, right crux and left crux) at 5 and 30 months post-injury.Results: Paired t-tests revealed significant FA reductions with large effect sizes across time in the column/body, p < 0.001, right crux, p < 0.001 and left crux, p < 0.001.Conclusions: These data contribute to the growing body of evidence that loss of white matter continues in moderate and severe TBI even after the acute neurological effects of TBI have resolved. As the fornix plays a critical role in memory, this may be a contributing factor to the poor clinical outcomes observed in these patients.

Impaired empathic abilities and reduced white matter integrity in schizophrenia

Empathic abilities are impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, the relationship between empathic disabilities and altered white matter in the disorder remains unclear. The present study tested associations between empathic disabilities and white matter integrity in order to investigate the neural basis of impaired empathy in schizophrenia. Sixty-nine patients with schizophrenia and 69 age-, gender-, handedness-, education- and IQ level-matched healthy controls underwent diffusion-weighted imaging. Empathic abilities were assessed using the Interpersonal Reactivity Index (IRI). Using tract-based spatial statistics (TBSS), the associations between empathic abilities and white matter fractional anisotropy (FA), a measure of white matter integrity, were examined in the patient group within brain areas that showed a significant FA reduction compared with the controls. The patients with schizophrenia reported lower perspective taking and higher personal distress according to the IRI. The patients showed a significant FA reduction in bilateral deep white matter in the frontal, temporal, parietal and occipital lobes, a large portion of the corpus callosum, and the corona radiata. In schizophrenia patients, fantasy subscales positively correlated with FA in the left inferior fronto-occipital fasciculi and anterior thalamic radiation, and personal distress subscales negatively correlated with FA in the splenium of the corpus callosum. These results suggest that disrupted white matter integrity in these regions constitutes a pathology underpinning specific components of empathic disabilities in schizophrenia, highlighting that different aspects of empathic impairments in the disorder would have, at least partially, distinct neuropathological bases.

Microstructural white-matter abnormalities associated with treatment resistance, severity and duration of illness in major depression

Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established. The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate. Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = -0.49, p = 0.04) and higher depression severity (at a trend level: β = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = -0.28, p = 0.04; and β = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered. Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.

Effects of chemotherapy on the brain in childhood: diffusion tensor imaging of subtle white matter damage

With reducing mortality in children with hematological malignancies, the survivors' quality of life regarding development of chronic neurological disturbances is important. We aimed to determine whether chemotherapy affects white matter (WM). Using brain diffusion tensor imaging, we evaluated 17 patients (15 with acute lymphoblastic leukemia, 2 with non-Hodgkin's lymphoma; 9 male, 8 female; age, 1.6-13years) before and after chemotherapy. We measured the quantitative values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at the regions of interest (ROIs) such as periventricular WM, corona radiata, posterior limb of the internal capsule, and corpus callosum. We assessed sensorimotor and callosal tracts by tractography. Reduction in FA and increase in ADC were significant at the ROIs of the left and right anterior periventricular WM and corona radiata and at the tract passing through the genu. A significant reduction in FA with a nonsignificant increase in ADC was seen at the ROI of the genu and at the tracts passing through the body and isthmus. Chemotherapy in children with hematological malignancies predominantly affects the frontal WM. This finding might indicate a negative effect of chemotherapy on neurological development in children with hematological malignancies.