Microstructural differences in white matter tracts across middle to late adulthood: a diffusion MRI study on 7167 UK Biobank participants.

White matter fiber tracts demonstrate heterogeneous vulnerabilities to aging effects. Here, we estimated age-related differences in tract properties using UK Biobank diffusion magnetic resonance imaging data of 7167 47- to 76-year-old neurologically healthy people (3368 men and 3799 women). Tract properties in terms of generalized fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were sampled on 76 fiber tracts; for each tract, age-related differences were estimated by fitting these indices against age in a linear model. This cross-sectional study demonstrated 4 age-difference patterns. The dominant pattern was lower generalized fractional anisotropy and higher axial diffusivity, radial diffusivity, and mean diffusivity with age, constituting 45 of 76 tracts, mostly involving the association, projection, and commissure fibers connecting the prefrontal lobe. The other 3 patterns constituted only 14 tracts, with atypical age differences in diffusion indices, and mainly involved parietal, occipital, and temporal cortices. By analyzing the large volume of diffusion magnetic resonance imaging data available from the UK Biobank, the study has provided a detailed description of heterogeneous age-related differences in tract properties over the whole brain which generally supports the myelodegeneration hypothesis.

Generalization of diffusion magnetic resonance imaging-based brain age prediction model through transfer learning.

Brain age prediction models using diffusion magnetic resonance imaging (dMRI) and machine learning techniques enable individual assessment of brain aging status in healthy people and patients with brain disorders. However, dMRI data are notorious for high intersite variability, prohibiting direct application of a model to the datasets obtained from other sites. In this study, we generalized the dMRI-based brain age model to different dMRI datasets acquired under different imaging conditions. Specifically, we adopted a transfer learning approach to achieve domain adaptation. To evaluate the performance of transferred models, brain age prediction models were constructed using a large dMRI dataset as the source domain, and the models were transferred to three target domains with distinct acquisition scenarios. The experiments were performed to investigate (1) the tuning data size needed to achieve satisfactory performance for brain age prediction, (2) the feature types suitable for different dMRI acquisition scenarios, and (3) performance of the transfer learning approach compared with the statistical covariate approach. By tuning the models with relatively small data size and certain feature types, optimal transferred models were obtained with significantly improved prediction performance in all three target cohorts (p â€‹< â€‹0.001). The mean absolute error of the predicted age was reduced from 13.89 to 4.78 years in Cohort 1, 8.34 to 5.35 years in Cohort 2, and 8.74 to 5.64 years in Cohort 3. The test-retest reliability of the transferred model was verified using dMRI data acquired at two timepoints (intraclass correlation coefficient â€‹= â€‹0.950). Clinical sensitivity of the brain age prediction model was investigated by estimating the brain age in patients with schizophrenia. The prediction made by the transferred model was not significantly different from that made by the reference model. Both models predicted significant brain aging in patients with schizophrenia as compared with healthy controls (p â€‹< â€‹0.001); the predicted age difference of the transferred model was 4.63 and 0.26 years for patients and controls, respectively, and that of the reference model was 4.39 and -0.09 years, respectively. In conclusion, transfer learning approach is an efficient way to generalize the dMRI-based brain age prediction model. Appropriate transfer learning approach and suitable tuning data size should be chosen according to different dMRI acquisition scenarios.

Deficient visuospatial working memory functions and neural correlates of the default-mode network in adolescents with autism spectrum disorder.

In addition to the essential features of autism spectrum disorder (ASD), namely social communication deficits and repetitive behaviors, individuals with ASD may suffer from working memory deficits and an altered default-mode network (DMN). We hypothesized that an altered DMN is related to working memory deficits in those with ASD. A total of 37 adolescents with ASD and 36 age- and IQ-matched typically developing (TD) controls were analyzed. Visuospatial working memory performance was assessed using pattern recognition memory (PRM), spatial recognition memory (SRM), and paired-associates learning (PAL) tasks. The intrinsic functional connectivity (iFC) of the DMN was indexed by the temporal correlations between the resting-state functional magnetic resonance imaging signals of pairs of DMN regions, including those between the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) and between the PCC and parahippocampi (PHG). The corresponding structural connectivity of the DMN was indexed by the generalized fractional anisotropy (GFA) of the dorsal and ventral cingulum bundles on the basis of diffusion spectrum imaging data. The results showed that ASD adolescents exhibited delayed correct responses in PRM and SRM tasks and committed more errors in the PAL task than the TD controls did. The delayed responses during the PRM and SRM tasks were negatively correlated with bilateral PCC-mPFC iFCs, and PAL performance was negatively correlated with right PCC-PHG iFC in ASD adolescents. Furthermore, ASD adolescents showed significant lower GFA in the right cingulum bundles than the TD group did; the GFA value was negatively correlated with SRM performance in ASD. Our results provide empirical evidence for deficient visuospatial working memory and corresponding neural correlates within the DMN in adolescents with ASD. Autism Res 2016, 9: 1058-1072. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Primary and secondary alterations of white matter connectivity in schizophrenia: A study on first-episode and chronic patients using whole-brain tractography-based analysis.

Schizophrenia is a debilitating mental disorder that is associated with an impaired connection of cerebral white matter. Studies on patients with chronic and first-episode schizophrenia have found widespread white matter abnormalities. However, it is unclear whether the altered connections are inherent in or secondary to the disease. Here, we sought to identify white matter tracts with altered connections and to distinguish primary or secondary alterations among 74 fiber tracts across the whole brain using an automatic tractography-based analysis method. Thirty-one chronic, 25 first-episode patients with schizophrenia and 31 healthy controls were recruited to receive diffusion spectrum magnetic resonance imaging at 3T. Seven tracts were found to exhibit significant differences between the groups; they included the right arcuate fasciculus, bilateral fornices, left superior longitudinal fasciculus I, and fibers of the corpus callosum to the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral temporal poles, and bilateral hippocampi. Post-hoc between-group analyses revealed that the connection of the callosal fibers to the bilateral DLPFC was significantly decreased in chronic patients but not in first-episode patients. In a stepwise regression analysis, the decline of the tract connection was significantly predicted by the duration of illness. In contrast, the remaining six tracts showed significant alterations in both first-episode and chronic patients and did not associate with clinical variables. In conclusion, reduced white matter connectivity of the callosal fibers to the bilateral DLPFC may be a secondary change that degrades progressively in the chronic stage, whereas alterations in the other six tracts may be inherent in the disease.

NTU-DSI-122: A diffusion spectrum imaging template with high anatomical matching to the ICBM-152 space.

A diffusion-weighted (DW) template in a standard coordinate system is often necessary for the analysis of white matter (WM) structures using DW images. Although several DW templates have been constructed in the ICBM-152 space, a template for diffusion spectrum imaging (DSI) is still lacking. In this study, we developed a DSI template in the ICBM-152 space from 122 healthy adults. This high quality template, NTU-DSI-122, was built through incorporating the macroscopic anatomical information using high-resolution T1 -weighted images and the microscopic structural information obtained from DSI datasets. Two evaluations were conducted to examine the quality of NTU-DSI-122. The first evaluation examined the anatomical consistency of NTU-DSI-122 in matching to the ICBM-152 coordinate system. The results showed that this template matched to the ICBM-152 templates very well across the whole brain, not only in the deep white matter regions as other DW templates but also in the superficial white matter regions. In the second evaluation, a large number of independent diffusion tensor imaging (DTI) datasets were registered to the DTI template derived from NTU-DSI-122. The examination was performed by quantifying the anatomical consistency among the registered DTI datasets. The results showed that using NTU-DSI-122 as the registration template the registered DTI datasets can achieve high anatomical alignment. Both evaluations demonstrate that NTU-DSI-122 is a useful high quality DW template. Therefore, NTU-DSI-122 can serve as a representative DSI dataset for a healthy adult population, and will be of potential value for brain research and clinical applications. The NTU-DSI-122 template is available at http://www.nitrc.org/projects/ntu-dsi-122/.