Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia

Background Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. Methods Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. Results Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)–left inferior temporal gyrus (ITG), right IFG–left ITG, right IFG–left middle frontal gyrus (MFG), and right IFG–right MFG in the FES group. Conclusion Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Reduced White Matter Integrity in Patients With End-Stage and Non-end-Stage Chronic Kidney Disease: A Tract-Based Spatial Statistics Study

Background and Purpose: Reduced white matter (WM) integrity has been implicated in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD). However, whether the differences in WM abnormalities exist in ESRD and non-end-stage CKD (NES-CKD) remains unclear. Hence, this study aimed to investigate the WM microstructural changes between the two stages using diffusion tensor imaging (DTI) and explore the related influencing factors.Methods: Diffusion tensor imaging’ images were prospectively acquired from 18 patients with ESRD, 22 patients with NES-CKD, and 19 healthy controls (HCs). Tract-based spatial statistics (TBSS) was performed to assess the voxel-wise differences in WM abnormalities among the three groups. The relationships between DTI parameters and biochemical data were also analyzed.Results: Compared with NES-CKDs, FA value was significantly decreased, and AD value increased in ESRDs mainly in brain regions of bilateral anterior thalamic radiation (ATR), the genu and body of corpus callosum (CC), bilateral anterior corona radiata, superior corona radiata, and superior longitudinal fasciculus. Besides, extensive and symmetrical deep WM damages were observed in patients with ESRD, accompanied by increased MD and RD values. Multiple regression analysis revealed that uric acid and serum phosphorus level can be used as independent predictors of WM microstructural abnormalities in clusters with statistical differences in DTI parameters between ESRD and NES-CKD groups.Conclusion: In the progression of CKD, patients with ESRD have more severe WM microstructural abnormalities than NES-CKDs, and this progressive deterioration may be related to uric acid and phosphate levels.

Study of white matter integrity in fathers of children with attention deficit hyperactivity disorder

Background Attention deficit hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder that can extend into adulthood with multiple reported neuroimaging abnormalities. The focus of this research was to assess white matter impairments in ADHD children’s fathers with and without potential adult ADHD to see if these differences are connected with the persistence of ADHD into adulthood. Results The occurrence rate of the potential adult ADHD diagnosis among fathers of children with ADHD was 60%. There were statistically significant differences between fathers with ADHD and the non-ADHD population, due to the fact that the mean FA of the left superior corona radiata and the right posterior corona radiata were lower in the ADHD group than in the non-ADHD group, while the FA of the ADHD group was significantly greater than that of the non-ADHD group in terms of the left and right anterior thalamic radiations, the right superior longitudinal fasciculus and the left anterior corona radiata. Conclusions We observed an increased prevalence of ADHD in fathers of children diagnosed with ADHD. Fathers with potential adult ADHD have a variety of white matter abnormalities that reflect the neurobiological basis of ADHD, even in sub-threshold cases. This may provide insight into the neuroanatomical locations associated with the maintenance of ADHD throughout adulthood.

Reorganizations of latency structure within white matter from wakefulness to sleep

Previous studies based on resting-state fMRI (rsfMRI) data have revealed the existence of highly reproducible latency structure, reflecting the propagation of BOLD fMRI signals, in white matter (WM). Here, based on simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data collected from 35 healthy subjects who were instructed to sleep, we explored the alterations of propagations in WM across wakefulness and nonrapid eye movement (NREM) sleep stages. Lagged cross-covariance was computed among voxel-wise time series, followed by parabolic interpolation to determine the actual latency value in-between. In WM, regions including cerebellar peduncle, internal capsule, posterior thalamic radiation, genu of corpus callosum, and corona radiata, were found to change their temporal roles drastically, as revealed by applying linear mixed-effect model on voxel-wise latency projections across wakefulness and NREM sleep stages. Using these regions as seeds, further seed-based latency analysis revealed that variations of latency projections across different stages were underlain by inconsistent temporal shifts between each seed and the remaining part of WM. Finally, latency analysis on resting-state networks (RSNs), obtained by applying k-means clustering technique on group-level functional connectivity matrix, identified a path of signal propagations similar to previous findings in EEG during wakefulness, which propagated mainly from the brainstem upward to internal capsule and further to corona radiata. This path showed inter-RSN temporal reorganizations depending on the paired stages between which the brain transitioned, e.g., it changed, between internal capsule and corona radiata, from mainly unidirectional to clearly reciprocal when the brain transitioned from wakefulness to N3 stage. These findings suggested the functional role of BOLD signals in white matter as a slow process, dynamically modulated across wakefulness and NREM sleep stages, and involving in maintaining different levels of consciousness and cognitive processes.

Abnormalities of Brain White Matter in Type 2 Diabetes Mellitus: A Meta-Analysis of Diffusion Tensor Imaging

Aims: The study aimed to conduct a meta-analysis to determine the abnormalities of white matter in patients with type 2 diabetes mellitus (T2DM) by identifying the consistency of diffusion tensor imaging (DTI).Method: The literature for DTI comparing patients with T2DM with controls published before October 30, 2020, were reviewed in PubMed, Web of Science, Embase, CNKI, and Wan Fang databases. The meta-analysis was performed using the activation likelihood estimation (ALE) method, including 12 reports and 381 patients with T2DM.Results: The meta-analysis identified 10 white matter regions that showed a consistent reduction of fractional anisotropy (FA) in patients with T2DM, including genu of the corpus callosum, the body of corpus callosum, bilateral anterior corona radiata, bilateral superior corona radiata, bilateral cingulum, and bilateral superior fronto-occipital fasciculus.Conclusion: This study revealed the abnormal characteristics of white matter in T2DM, which would be helpful to understand the underlying neuropathological and physiological mechanisms of T2DM and provide evidence for clinical diagnosis and treatment.

White Matter Integrity Underlies the Physical-Cognitive Correlations in Subjective Cognitive Decline

Objective: Although previous studies postulated that physical and cognitive decline codeveloped in preclinical dementia, the interconnected relationship among subjective cognitive complaints (SCCs), objective cognitive performance, and physical activity remained hazy. We investigated the mediating roles of physical activity between subjective and objective cognition. Diffusion tensor imaging (DTI) was utilized to test our hypothesis that brain white matter microstructural changes underlie the physical-cognitive decline in subjective cognitive decline (SCD).Methods: We enrolled cognitively normal older adults aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital during 2017–2020. Regression models analyzed mediation effects of physical activity between subjective and objective cognition. The self-reported AD8 questionnaire assessed SCCs. The SCD group, defined by AD8 score ≥ 2, further underwent diffusion MRI scans. Those who agreed to record actigraphy also wore the SOMNOwatch™ for 72 h. Spearman's correlation coefficients evaluated the associations of diffusion indices with physical activity and cognitive performance.Results: In 95 cognitively normal older adults, the AD8 score and the Montreal Cognitive Assessment (MoCA) score were mediated partially by the metabolic equivalent of the International Physical Activity Questionnaire-Short Form (IPAQ-SF MET) and fully by the sarcopenia score SARC-F. That is, the relation between SCCs and poorer cognitive performance was mediated by physical inactivity. The DTI analysis of 31 SCD participants found that the MoCA score correlated with mean diffusivity at bilateral inferior cerebellar peduncles and the pyramids segment of right corticospinal tract [p < 0.05, false discovery rate (FDR) corrected]. The IPAQ-SF MET was associated with fractional anisotropy (FA) at the right posterior corona radiata (PCR) (p < 0.05, FDR corrected). In 15 SCD participants who completed actigraphy recording, the patterns of physical activity in terms of intradaily variability and interdaily stability highly correlated with FA of bilateral PCR and left superior corona radiata (p < 0.05, FDR corrected).Conclusions: This study addressed the role of physical activity in preclinical dementia. Physical inactivity mediated the relation between higher SCCs and poorer cognitive performance. The degeneration of specific white matter tracts underlay the co-development process of physical-cognitive decline in SCD.