Material hardship, prefrontal cortex-amygdala structure, and internalizing symptoms in children.

White matter tract integrity and intelligence in patients with mental retardation and healthy adults

Background: Apathy, the major manifestation of impaired goal-directed behavior (GDB), is the most common neuropsychiatric syndrome associated with behavioral variant frontotemporal degeneration (bvFTD). The behavioral and biological mechanisms of apathy, however, are not well understood. We hypothesized that GDB has multiple components—including at least initiation, planning and motivation—and that GDB is supported by a network of multiple frontal brain regions. In this study, we examined this hypothesis by evaluating the selective breakdown of GDB in bvFTD, and relating these deficits to gray matter (GM) atrophy and white matter (WM) integrity.Methods: Eighteen apathetic bvFTD participants and 17 healthy controls completed the Philadelphia Apathy Computerized Test (PACT). This test quantifies each of three components of GDB hypothesized to contribute to apathy. We then used regression analyses to relate PACT scores to GM atrophy and reduced white matter (WM) fractional anisotropy (FA) in bvFTD.Results: Compared to controls, bvFTD participants demonstrated significant impairments in each of the three hypothesized components of GDB that contribute to apathy. Regression analyses related each component to disease in specific GM structures and associated WM tracts. Poor initiation thus was related to GM atrophy in anterior cingulate and reduced FA in the cingulum. Planning impairment was related to GM atrophy in dorsolateral prefrontal cortex and reduced FA in superior longitudinal fasciculus. Poor motivation was related to GM atrophy in orbitofrontal cortex (OFC) and reduced FA in uncinate fasciculus (UNC).Conclusions: bvFTD patients have difficulty with initiation, planning and motivation components of GDB. These findings are consistent with the hypotheses that GDB encompasses at least three processes, that these are supported by a large-scale neural network within specific portions of the frontal lobe, and that degradation of any one of these prefrontal regions in bvFTD may contribute to apathy.

ROI-based diffusion tensor analysis for the differential diagnosis of mild cognitive impairment and Alzheimer's disease

Diffusion tensor imaging with tractography to predict memory deficits in patient groups with temporal lobe lesions.

Objective To study the changes of fractional anisotropy (FA) value of white matter of brain and temporal stem in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients as well as normal cognitive (NC) aged people with diffusion tensor imaging (DTI), and explore the damage mechanism of temporal stem and its diagnostic value on AD and aMCI. Methods Ten patients with AD, 10 patients with aMCI and 10 NC volunteers as control group were scanned by routine MRI and DTI. FA values were calculated by post-processing software (DTIstudio) in temporal stem (including anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus), and white matter in anterior frontal, temperal, parietal and occipital lobes. The data were analyzed by SPSS 13.0. If bilateral differences of FA values were not statistically significant (P > 0.05), the average values of bilateral FA were selected and compared among 3 groups. If bilateral differences of FA values were statistically significant (P 0.05, for all). 2) There was significant difference of FA values in anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus between AD and aMCI groups (P 0.05, for all). Conclusions The significant difference of FA values in temporal stem among AD, aMCI and NC groups suggests that temporal stem fiber bundles are of great significance in the white matter damage of AD, and DTI is helpful for the differential diagnosis of AD, aMCI and NC. The abnormal changes of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal and parietal lobes are of great diagnostic value in AD. doi: 10.3969/j.issn.1672-6731.2014.03.011

Abnormal frontal cortex white matter connections in bipolar disorder: A DTI tractography study

Purpose: The purpose of this study was to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of normal adult brain tissue and tumors, and to compare the differences. Materials and Methods: Eight normal adults and ten patients in whom intracranial tumors had been diagnosed were included. Imaging was performed using a 1.5 T MR unit and a single-shot spin-echo EPI pulse sequence (TR/TE=4024/94 msec, 128 acquisition/256 reconstruction, 23 cm FOV, 5 mm thickness, 2 mm interslice gap, 4 NSA), six different direction gradients (x, y, z, xy, yz, xz), and 2 b-values (0, 1000). Isotropic ADC (D) was obtained from seven images per slice, and fractional anisotropy (FA) was calculated from the isotropic ADC and eigenvalues of three directions. A region of interest was drawn at frontal gray and white matter, periventricular white matter, the corpus callosum, internal capsule, caudate nucleus and center of the tumor mass, and for each region, fractional anisotropy readings were obtained. Results: In normal adults, the findings were as follows: frontal gray matter: D=0.810.06, FA=0.320.03; frontal white matter: D=0.790.04, FA=0.560.09, periventricular white matter: D=0.770.02, FA=0.51 0.04; corpus callosum: D=0.790.07, FA=0.820.07; internal capsule: D=0.730.04, FA=0.770.05; caudate nucleus: D=0.760.05, FA=0.350.05. High anisotropy was demonstrated in white matter, especially in the corpus callosum and internal capsule, and the degree of anisotropy was similar in gray and deep gray matter. For most brain tumors, isotropic ADC was similar to that of white matter, but fractional anisotropy was lower. A low-grade astrocytoma showed higher isotropic ADC and lower fractional anisotropy than normal white matter, and at the center of a meningioma, fractional anisotropy was high. Conclusion: For the classification of brain tumors and determination of the extent of disease, comparison between the apparent diffusion coefficient and fractional anisotropy is useful.

Tract-specific analysis of white matter integrity disruption in schizophrenia

Posttraumatic stress symptoms (PTSS) are commonly experienced in people with chronic pain. Reduced white matter microstructural integrity in the uncinate fasciculus and the cingulum has separately been reported in chronic pain and posttraumatic stress disorder (PTSD) studies. However, the relationship between chronic pain, PTSS and white matter integrity remains unclear. This study aims to disentangle the relationship between PTSS severity and white matter microstructural integrity common across different chronic pain conditions. Thirty-six subjects with chronic pain and 20 without chronic pain (controls) underwent diffusion weighted imaging and completed the civilian version of the PTSD CheckList (PCL-C). Average fractional anisotropy (FA) values were extracted from the uncinate fasciculus, and the cingulate and hippocampal portions of the cingulum. A series of multiple linear regressions determined the main effects of group, PTSS severity (PCL-C total score) and their interactions on each region separately. The group-by-PTSS interaction was significantly associated with uncinate fasciculus FA variations. Moderation analysis indicated that increasing PTSS severity was significantly associated with reduced uncinate fasciculus FA in the control group, but not in the chronic pain group. No other significant association was found for any other ROI FA values. Consistent with previous studies, increasing PTSS levels were associated with reduced FA of the uncinate fasciculus in controls, but not in people with chronic pain. Other mechanisms may be at play in chronic pain, including the interplay with other psychopathological problems or specific pain type effects.

Through learning and practice, we can acquire numerous skills, ranging from the simple (whistling) to the complex (memorizing operettas in a foreign language). It has been proposed that complex learning requires a network of brain regions that interact with one another via white matter pathways. One candidate white matter pathway, the uncinate fasciculus (UF), has exhibited mixed results for this hypothesis: some studies have shown UF involvement across a range of memory tasks, while other studies report null results. Here, we tested the hypothesis that the UF supports associative memory processes and that this tract can be parcellated into sub-tracts that support specific types of memory. Healthy young adults performed behavioral tasks (two face-name learning tasks, one word pair memory task) and underwent a diffusion-weighted imaging scan. Our results revealed that variation in UF microstructure was significantly associated with individual differences in performance on both face-name tasks, as well as the word association memory task. A UF sub-tract, functionally defined by its connectivity between face-selective regions in the anterior temporal lobe and orbitofrontal cortex, selectively predicted face-name learning. In contrast, connectivity between the fusiform face patch and both anterior face patches had no predictive validity. These findings suggest that there is a robust and replicable relationship between the UF and associative learning and memory. Moreover, this large white matter pathway can be subdivided to reveal discrete functional profiles.

White Matter Correlates of Adolescent Depression: Structural Evidence for Frontolimbic Disconnectivity

Global White Matter Changes and Associations with Cognition in Pediatric Sickle Cell Disease

This thesis aimed to investigate the feasibility of two diffusion imaging techniques, Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI), on detecting subtle physiological or pathological microstructural changes in normal-appearing neural tissues of human central nervous system. 
\n At first, ten patients with neuromyelitis optica (NMO) and twelve age- and gender-matched healthy subjects were recruited. DTI-derived indices including fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivities were quantified in the lateral and dorsal columns of cervical spinal cord. Based on the regions of interest (ROIs) measurement, NMO patients showed reduced FA, increased MD and radial diffusivity compared to control subjects, while axial diffusivity did not show any significant difference. The three former DTI metrics also showed significant correlations with disability scores, and especially FA was found to be sensitive to mild NMO. Our results show that DTI-derived indices can quantitatively assess the white matter (WM) abnormalities with seemingly normal appearance in conventional MRI, and are associated with the level of clinical disability, suggesting that DTI may have great potential as a useful diagnostic tool in the clinical setting.
\n DKI is an extension of conventional DTI to probe the non-Gaussian diffusion property in biological tissues. Besides the four conventional DTI-derived metrics, DKI also provide three additional kurtosis metrics (mean kurtosis (MK), axial and radial kurtosis). In the second study, ROI-based analysis was used to characterize age-related microstructural changes in WM, cortical and subcortical gray matter (GM) of 27 healthy adults (21~59 yrs). Though the volumes of GM and WM were still preserved, DTI-derived metrics can detect the subtle changes in WM and GM. Meanwhile, MK and radial kurtosis significantly increased in both caudate nucleus and putamen while Thalamus showed little aging effect in the diffusivity and kurtosis metrics but significantly decreased only in FA. Our results demonstrated that DKI is sensitive to detect the age-related alterations in neural microstructures at the stage of early aging.
\n In addition, DKI has been applied to detect the pathological changes in the normal-appearing neural tissues of 18 patients with multiple sclerosis (MS), compared to 22 healthy controls. Diffuse WM abnormalities have been observed extensively in the brain, revealed by DKI-derived metrics. Though the volumetric and voxel-wise analysis revealed no significant changes in the volume of cortical GM, decreased FA and kurtoses with increased diffusivities in MS group were sensitive to disclose the subtle alterations in global and regional cortical GM tissues. Significant correlations have been found between FA in the global, frontal and temporal cortical GM in relapsing-remitting MS patients and their disability scores, suggesting FA as an important biomarker to monitor the disease progress in cortical GM. Moreover, elevated kurtosis indices in MS patients did not correlate with diffusivities in caudate nucleus, putamen and thalamus, suggesting these metrics may be vulnerable to different pathologic aspects of the disease.
\n In conclusion, DKI is sensitive to neural alterations during normal aging and in MS pathologies, and can provide complementary information to conventional MRI and DTI.

Objectives. Maternal prenatal stress is associated with elevated risk of adverse behavioural outcomes in offspring. This association may involve developmental disruption to limbic-prefrontal white matter circuitry, of which the uncinate fasciculus is the major tract. One potential candidate for modulating brain development is maternal prenatal stress. We provide the first prospective study of prenatal stress and white matter microstructure in children. Methods. A total of 22 healthy children (mean age 7 years) of mothers recruited in pregnancy underwent diffusion tensor magnetic resonance imaging. We examined correlations between prenatal stressful life events and white matter microstructural organisation indices (fractional anisotropy (FA) and perpendicular diffusivity (Dperp)) of the uncinate fasciculus and a “control” tract. Results. Maternal prenatal stressful life events were correlated positively with right uncinate fasciculus FA, and negatively with right uncinate fasciculus Dperp in their child, with a similar trend with left uncinate fasciculus Dperp. Prenatal stress was not associated with control tract properties; sociodemographic/obstetric variables were not associated with FA/Dperp of either tract. Conclusions. Variation in maternal prenatal stress may be associated with differences in the development of white matter within brain networks underlying child social behaviour.

BackgroundSpoken discourse (language beyond single words or sentences) performance can be used to detect cognitive impairment in cerebrovascular disease (CVD) [Roberts A, et al. (2021). Top Lang Disord 41(1):73‐98]. However, the neurological basis for altered spoken discourse in CVD is poorly defined. This study examined the association between spoken discourse and indicators of white matter microstructural integrity provided by diffusion tensor imaging (DTI) to better define the link between CVD‐related neurodegeneration and altered spoken discourse.MethodSpoken discourse and 3T DTI data (30‐32 directions, b=1000) were obtained from the CVD cohort of the Ontario Neurodegenerative Disease Research Initiative (n=133). Spoken discourse analyses were completed previously [Roberts, 2021]. A DTI analysis pipeline [Hassan SMH, et al. (2019) PLoS One 14(12):e0226715] was used to generate brain maps of fractional anisotropy (FA) and mean diffusivity (MD) and calculate mean FA and MD values for the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus – parietal (SLFp) and temporal (SLFt) endings, and uncinate fasciculi (UNC) in each hemisphere. Canonical correlation analyses examined associations between DTI metrics and 10 spoken discourse measures separately for FA in left hemisphere, MD in left hemisphere, FA in right hemisphere, MD in right hemisphere.ResultCanonical correlations were significant in the left hemisphere (FA: r=0.47, p<0.05; MD: r=0.51, p<0.01) but not the right (FA: r=0.34, p=0.90; MD: r=0.40, p=0.15)(Figure 1). Among the white matter tracts, the strongest canonical loadings were seen for the SLFp (FA: 0.81; MD: ‐0.59) and SLFt (FA: 0.71; MD: ‐0.40) compared to the ILF (FA: 0.44; MD: 0.03) and UNC (FA: ‐0.34; MD: 0.10). Higher FA in the SLFp and SLFt was associated with better performance on measures of fluency and information content. Lower MD in these tracts was associated with better performance on measures of fluency, information content, and syntax.ConclusionSpoken discourse performance was associated with white matter microstructural integrity in the left hemisphere of the brain. Of the white matter tracts investigated in this study, impaired spoken discourse performance in CVD was most strongly linked to altered tissue microstructure in the parietal and temporal endings of the superior longitudinal fasciculus.