The aim of the study was to evaluate connectivity modifications in the Default Mode Network (DMN) in patients with cerebral glioma, and to correlate these modifications to tumor characteristics. Twenty-four patients with a left-hemisphere cerebral tumor (14 grade II and 10 grade IV gliomas) and 14 healthy age-matched right-hand volunteers were enrolled in the study. Subjects underwent fMRI while performing language tasks for presurgical mapping. Data was analyzed with independent component analysis in order to identify the DMN. DMN group maps were produced by random-effect analysis (p<0.001, FDR-corrected). An analysis of variance across the three groups (p<0.05) and post-hoc t-test contrasts between pairs of groups were calculated (p<0.05, FDR-corrected). All three groups showed typical DMN areas. However, reduced DMN connectivity was detected in tumor patients with respect to controls. A significantly increased and reduced integration of DMN areas was observed in the hippocampal and prefrontal regions, respectively. Modifications were closely related to tumor grading. Moreover, the DMN lateralized to the hemisphere contralateral to tumor in the low-grade, but not in the high-grade tumor patients. Modifications of DMN connectivity were induced by gliomas and differed for high and low grade tumors.

BACKGROUND AND PURPOSE: Investigation of the anatomy, patency, and blood flow of arterial and venous vessels in small animal models of cerebral ischemia, venous thrombosis, or vasospasm is of major interest. However, due to their small caliber, in vivo examination of these vessels is technically challenging. Using micro-CT, we compared the feasibility of in vivo DSA and CTA of the murine cerebrovasculature using an intra-arterial route of contrast administration. MATERIALS AND METHODS: The ECA was catheterized in 5 C57BL/6J mice. During intra-arterial injection of an iodized contrast agent (30 μL/1 sec), DSA of the intra- and extracranial vessels was performed in mice breathing room air and repeated in hypoxic/hypercapnic mice. Micro-CTA was performed within 20 seconds of intra-arterial contrast injection (220 μL/20 sec). Image quality of both methods was compared. Radiation dose measurements were performed with thermoluminescence dosimeters. RESULTS: Both methods provided high-resolution images of the murine cerebrovasculature, with the smallest identifiable vessel calibers of ≤50 μm. Due to its high temporal resolution of 30 fps, DSA allowed identification of anastomoses between the ICA and ECA by detection of retrograde flow within the superficial temporal artery. Micro-CTA during intra-arterial contrast injection resulted in a reduced injection volume and a higher contrast-to-noise ratio (19.0 ± 1.0) compared with DSA (10.0 ± 1.8) or micro-CTA when using an intravenous injection route (1.3 ± 0.4). CONCLUSIONS: DSA of the murine cerebrovasculature is feasible using micro-CT and allows precise and repeated measurements of the vessel caliber, and changes of the vessel caliber, while providing relevant information on blood flow in vivo.

Aging is a major co-risk factor in many neurodegenerative diseases. Cognitive enrichment positively affects the structural plasticity of the aging brain. In this study, we evaluated effects of a set of structured multimodal activities (Combination Training; CT) on cognitive performances, functional connectivity, and cortical thickness of a group of healthy elderly individuals. CT lasted six months. Neuropsychological and occupational performances were evaluated before and at the end of the training period. fMRI was used to assess effects of training on resting state network (RSN) functional connectivity using Independent Component Analysis (ICA). Effects on cortical thickness were also studied. Finally, we evaluated whether specific dopamine-related genes can affect the response to training. Results of the study indicate that CT improves cognitive/occupational performances and reorganizes functional connectivity. Intriguingly, individuals responding to CT showed specific dopamine-related genotypes. Indeed, analysis of dopamine-related genes revealed that carriers of DRD3 ser9gly and COMT Val158Met polymorphisms had the greatest benefits from exposure to CT. Overall, our findings support the idea that exposure to a set of structured multimodal activities can be an effective strategy to counteract aging-related cognitive decline and also indicate that significant capability of functional and structural changes are maintained in the elderly.

There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306. Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed. Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306.