Brain Microstructure and Impulsivity Differ between Current and Past Methamphetamine Users.

Effects of estrogens on cognition and brain morphology: Involvement of the cerebellum

Cannabis use is a common risk factor for psychoses. But although prevalence of consumption as well as potency of cannabis increased, the incidence of schizophrenia remained stable. The discontinuation hypothesis suggests that a potential increase of psychoses incidence may be relativized by more frequent cessation of consumption due to higher rates of adverse psychosis-like intoxication effects (PLE), caused by stronger cannabis. A mixed methods online survey was administered to 441 current and past users to analyze the predictive impact of different acute intoxication effects regarding abstinence motivation/cessation of use. Our hypothesis was that PLE would be experienced as the most aversive intoxication effect and therefore have the highest predictive significance. Possible confounds were included (craving, patterns of consumption and sociodemographics). Further analyzes compared past versus current users regarding the quality of intoxication effects, suggesting that past users retrospectively experienced more unpleasant experiences than current users. Free-text data explored subjective reasons for abstinence. We found that paranoid/dysphoric intoxication effects were most predictive for abstinence motivation. Less predictive were psychosis-like intoxication effects such as hallucinations. Group comparisons revealed significant more unpleasurable and less positive intoxication effects in past users compared with current users. Current users with the intention to stop consumption showed significantly more paranoia/dysphoria intoxication compared to users with no intention to stop use. As a conclusion, different intoxication experiences have different effects on abstinence motivation and substance use behavior. They therefore provide a focus that should be increasingly integrated into treatment concepts.

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.

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.

Neuroimaging depression and anxiety in essential tremor: A diffusion tensor imaging study

Objective To characterize the brain microstructure changes of amyotrophic lateral sclerosis (ALS) patients with various levels of cognitive impairment as measured by diffusion tensor imaging (DTI). Methods A total of 55 ALS patients and 20 healthy controls (HC) were enrolled in the Department of Neurology of Peking Union Medical College Hospital From September 2013 to March 2017, and all participants underwent neuropsychological assessments and DTI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n=27), ALS with cognitive impairment (ALS-Ci, n=17) and ALS-frontotemporal dementia (ALS-FTD, n=11) subgroups. Comparisons of voxel-based and atlas-based fractional anisotropy (FA) and mean diffusivity (MD) data were conducted among the four subgroups. Results In the voxel-based analyses, the FA showed significant differences in cingulate gyrus, corpus callosum, brain stem and cerebellum, and MD showed significant differences in bilateral frontal lobe, temporal lobe, cingulate gyrus, corpus callosum, and cerebellum among the four subgroups. Besides, when compared to ALS-Ci, ALS-Cn and HC groups in the order, the areas of involvement were larger and differences were more significant in ALS-FTD group. In the atlas-based analyses, the FA and MD of the corticospinal tracts revealed no difference within the patients groups, but decreased FA and increased MD were found compared to HC group. The ALS-FTD patients manifested widespread white matter fiber integrity damage and microstructure impairment in the extramotor areas compared to other three groups. Conclusion The brain white matter structural patterns of ALS patients correlate with their cognitive function, and there is a gradient of alterations across the ALS-Cn, ALS-Ci and ALS-FTD continuum. Key words: Amyotrophic lateral sclerosis; Cognition disorders; Frontotemporal dementia; Diffusion tensor imaging

Hormone replacement therapy has been associated in some studies with reductions in breast cancer mortality among women who develop this disease. It is unclear whether this association reflects the biologic activity of the hormones or the earlier detection of tumors among hormone users. We examined breast cancer mortality among women who were diagnosed with axillary lymph node-negative and node-positive breast cancer according to the currency of estrogen use at diagnosis. Vital status through June 1995 was determined for 2614 patients with postmenopausal breast cancer diagnosed during the period from 1973 to January 1981. We estimated adjusted hazard-rate ratios (adjusting for tumor size, age, race, Quetelet [body mass] index, and number of positive lymph nodes in women with node-positive disease) and unadjusted cumulative probabilities of breast cancer death over time since diagnosis. Among patients with node-negative disease, rate ratios for breast cancer mortality associated with current use compared with nonuse at diagnosis were 0.5 (95% confidence interval [CI] = 0.3-0.8) until 144 months after diagnosis and 2.2 (95% CI = 0.9-5.2) thereafter. Mortality was not statistically significantly lower in past users. The cumulative probabilities of breast cancer mortality at the end of follow-up were 0.14, 0.14, and 0.09 in nonusers, past users, and current users, respectively. Among women with node-positive disease, the rate ratios associated with current and past use were both 0.5 until 48 months after diagnosis (95% CI = 0.3-0.8 for current users; 95% CI = 0.3-0.9 for past users) and were 1.1 (95% CI = 0.7-1.7) and 1.8 (95% CI = 1.2-2.7), respectively, thereafter. The cumulative probabilities of breast cancer mortality were 0.32, 0.39, and 0.27 in nonusers, past users, and current users, respectively. Patients with breast cancer who were using replacement estrogens at the time of diagnosis experienced reductions in breast cancer mortality, which waned with the time since diagnosis.

BackgroundAnalyses of spoken discourse (speech beyond single words or sentences) can detect cognitive impairment in cerebrovascular disease (CVD) [Roberts, 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 visible white matter damage detected using structural magnetic resonance imaging (MRI) and potential early‐stage damage in normal‐appearing white matter (NAWM) detected using diffusion tensor imaging (DTI) to better define the link between CVD‐related neurodegeneration and altered speech.MethodSpoken discourse and 3T MRI data were obtained from the CVD cohort of the Ontario Neurodegenerative Disease Research Initiative (n = 127). Spoken discourse analyses were completed previously [Roberts et al., 2021]. White matter hyperintensities (WMH) and the NAWM portions of the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus – parietal (SLFp) and temporal (SLFt) endings, and uncinate fasciculus (UNC) were segmented in each hemisphere (Figure 1). Mean values of fractional anisotropy (FA) and mean diffusivity (MD) within NAWM, and normalized WMH volume were calculated for each of the white matter tracts. Three canonical correlation analyses examined associations between 10 spoken discourse measures and the imaging metrics (WMH volume, FA, MD) in each tract.ResultCanonical correlations were significant for FA (rc = 0.51, p<0.05) and MD (rc = 0.56, p<0.05) but not WMH volume (rc = 0.42, p = 0.69). Among the white matter tracts, the strongest canonical loadings were seen for FA and MD in the left SLFp (FA: 0.80; MD: ‐0.61) and left SLFt (FA: 0.60; MD: ‐0.40) (Figure 2). Higher FA and lower MD in the left SLFp and left SLFt were associated with fluency, information content, and syntax performance.ConclusionSpoken discourse performance was associated with microstructural integrity of NAWM but not visible white matter damage. These results suggest that DTI metrics provide a more relevant assessment of white matter tract function in relation to speech than a volumetric measure of tract lesion load. Of the white matter tracts investigated in this study, spoken discourse performance in CVD was most strongly linked to white matter microstructure in the parietal and temporal endings of the left superior longitudinal fasciculus.

White matter disruptions in patients with bipolar disorder

The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients.

Objective: To study the alteration of the optic radiations in patients with primary open-angle glaucoma (POAG) by diffusion tensor imaging (DTI) and tractography, and to reveal the correlation between the DTI derived parameters and the severity of the disease. Methods: A total of 24 patients with POAG and 20 age- and gender-matched healthy controls were enrolled in this study from January 2011 to June 2013.All subjects underwent ophthalmoscopy, standard automatic perimetry, intraocular pressure measurement and MRI scanning.All the eyes of POAG patients were evaluated by Hodapp-Anderson-Parrish (HAP) system.Then the stages of bilateral eyes were added together to evaluate the disease severity.Tractography was used to measure the fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) of the optic radiations of these subjects.The results of the two groups were compared.Partial correlation was then used to reveal the correlation between these derived DTI parameters and the severity of POAG. Results: Compared with health controls, POAG patients showed significant decreased FA (t=-3.299, P=0.002) and AD (t=-2.485, P=0.013), increased RD (t=2.365, P=0.018) in optic radiation .The alteration of MD was not significant (t=0.719, P=0.454). Mean FA values of the optic radiations were negatively correlated with POAG stages (r=-0.643, P= 0.001), while mean RD values (r=0.570, P= 0.004) and mean MD values (r= 0.448, P= 0.028) were positively correlated with POAG stages.No correlation between AD values and severity of POAG was found. Conclusion: In the optic radiations of POAG patients, the FA values and AD values decrease, while RD values increase, indicating the fiber integrity changes.The alterations of FA, RD and MD are correlated with disease severity.

For humans and non-human primates, the alteration of the visual pathway’s white matter fibers after visual deprivation has been partially explored. However, the changes in the optic tracts after the transection of the optic nerve have not been well characterized. In the current study, we attempted to investigate the differences in optic tracts between normal and unilateral optic nerve transected macaque monkeys using diffusion tensor imaging (DTI). Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Group A served as a control group, and Group B underwent unilateral (right eye) optic nerve transection to produce monocular blindness. Sixteen months (Group B16M) and thirty-two months (Group B32M) after optic nerve transection, diffusion tensor imaging was performed on all monkeys. Then, we compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in bilateral optic tracts between Group A and Group B and between Group B16M and Group B32M. In both Group B16M and Group B32M, when compared with normal monkeys in Group A, FA was decreased and MD, AD and RD were increased in the bilateral optic tracts of monkeys with monocular blindness. Furthermore, compared with Group B16M, FA was reduced and MD, AD, RD were more obviously increased in the bilateral optic tracts of Group B32M, and noticeable differences in MD, AD and RD were found between the left and right optic tracts in group B32M. We believe that the results of this study would be helpful in investigation of the histological abnormalities of the integrity damage, axonal degeneration and demyelination of optic tracts in macaque monkeys with monocular blindness by DTI parameters in noninvasively and quantitatively.

Diffusion tensor imaging of rectal carcinoma: Clinical evaluation and its correlation with histopathological findings

BackgroundWe hypothesized that the integrity of white matter might be related to the severity of freezing of gait in age-related white matter changes.MethodsTwenty subjects exhibiting excessive hyperintensities in the periventricular and deep white matter were recruited. The subjects underwent the Freezing of Gait Questionnaire, computerized gait analyses, and diffusion tensor magnetic resonance imaging. Images of axial, radial and mean diffusivity, and fractional anisotropy were calculated as indices of white matter integrity and analyzed with tract-based spatial statistics.ResultsThe fractional anisotropy, mean, axial and radial diffusivity averaged across the whole white matter structure were all significantly correlated with Freezing of Gait Questionnaire scores. Regionally, a negative correlation between Freezing of Gait Questionnaire scores and fractional anisotropy was found in the left superior longitudinal fasciculus beneath the left premotor cortex, right corpus callosum, and left cerebral peduncle. The scores of the Freezing of Gait Questionnaire were positively correlated with mean diffusivity in the left corona radiata and right corpus callosum, and with both axial and radial diffusivity in the left corona radiata. The white matter integrity in these tracts (except the corpus callosum) showed no correlation with cognitive or other gait measures, supporting the specificity of those abnormalities to freezing of gait.ConclusionDivergent pathological lesions involved neural circuits composed of the cerebral cortex, basal ganglia and brainstem, suggesting that freezing of gait has a multifactorial nature.