Background-Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. Methods and Results-We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to ingested arsenic, including the duration of consuming artesian well water, the average arsenic concentration in consumed artesian well water, and cumulative arsenic exposure, were all significantly associated with prevalence of carotid atherosclerosis in a dose-response relationship. The biological gradient remained significant after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was 3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of Ն20 mg/L-years compared with those without exposure to arsenic from drinking artesian well water. Conclusions-Carotid atherosclerosis is associated with ingested inorganic arsenic, showing a significant biological

The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN. In this study, we sought to identify constituents of the rat DMN using resting-state functional MRI (rs-fMRI) and diffusion tensor imaging. After identifying DMN using a group-level independent-component analysis on the rs-fMRI data, modularity analyses fractionated the DMN into an anterior and a posterior subsystem, which were further segregated into five modules. Diffusion tensor imaging tractography demonstrates a close relationship between fiber density and the functional connectivity between DMN regions, and provides anatomical evidence to support the detected DMN subsystems. Finally, distinct modulation was seen within and between these DMN subcomponents using a neurocognitive aging model. Taken together, these results suggest that, like the human DMN, the rat DMN can be partitioned into several subcomponents that may support distinct functions. These data encourage further investigation into the neurobiological mechanisms of DMN processing in preclinical models of both normal and disease states.default mode network | functional connectivity | modularity | rat brain | aging T he default mode network (DMN) of the brain, first demonstrated in humans (1) and then in nonhuman primates (2) and rodents (3-5), contains a set of distributed brain regions that are approximately analogous across the species. Anatomically, the human DMN includes medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and precuneus, bilateral inferior parietal cortex, temporal cortex, and hippocampus (HIPP) (6, 7). The human DMN is thought to support a variety of self-referential functions, including recollection and imagination, conceptual processing, and autobiographical memory (6,8,9). A reduction of DMN's activity (or deactivation) has been conceptualized as the suppression of brain activity responsible for processing introspective thinking and planning. In so doing, it supports the processing of events external to the individual, including such executive functions as working memory (10). Compared with healthy individuals, various neurological and psychiatric disorders including schizophrenia (11), Alzheimer's disease (12), autism (13), and addiction (14, 15) have been linked to DMN dysregulation.Based on distinct responses to various cognitive tasks and functional connectivity architecture, the human DMN has been fractionated using both graph theory (16) and independentcomponent analysis (ICA) methods (17) into a set of...