Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain

Objectives: The thickness of the brain’s cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. Methods: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age=47.9±13.2 years) recruited from 73 (9.7±9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. Results: Significant genetic correlationwas observed amongGMthickness and FA values. Significant logarithm of odds (LOD≥3.0) QTLs were localized within chromosome 15q22–23. More detailed localization reported no significant association (p <5·10−5) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p ≤10−3) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer’s disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p <0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p <0.05) but failed to show a significant correlation (p =0.09) with FA. Discussion: This study identified a novel, significant QTL at 15q22–23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influenceGM thickness and WM–FA values

Augmenting melodic intonation therapy with non-invasive brain stimulation to treat impaired left-hemisphere function: two case studies.

The purpose of this study was to investigate whether or not the right hemisphere can be engaged using Melodic Intonation Therapy (MIT) and excitatory repetitive transcranial magnetic stimulation (rTMS) to improve language function in people with aphasia. The two participants in this study (GOE and AMC) have chronic non-fluent aphasia. A functional Magnetic Resonance Imaging (fMRI) task was used to localize the right Broca's homolog area in the inferior frontal gyrus for rTMS coil placement. The treatment protocol included an rTMS phase, which consisted of 3 treatment sessions that used an excitatory stimulation method known as intermittent theta burst stimulation, and a sham-rTMS phase, which consisted of 3 treatment sessions that used a sham coil. Each treatment session was followed by 40 min of MIT. A linguistic battery was administered after each session. Our findings show that one participant, GOE, improved in verbal fluency and the repetition of phrases when treated with MIT in combination with TMS. However, AMC showed no evidence of behavioral benefit from this brief treatment trial. Post-treatment neural activity changes were observed for both participants in the left Broca's area and right Broca's homolog. These case studies indicate that a combination of MIT and rTMS applied to the right Broca's homolog has the potential to improve speech and language outcomes for at least some people with post-stroke aphasia

The effects of tDCS across the Spatial Frequencies and Orientations that comprise the Contrast Sensitivity Function

Trans-cranial Direct Current Stimulation (tDCS) has recently been employed in traditional psychophysical paradigms in an effort to measure direct manipulations on spatial frequency channel operations in the early visual system. However, the effects of tDCS on contrast sensitivity have only been measured at a single spatial frequency and orientation. Since contrast sensitivity is known to depend on spatial frequency and orientation, we ask how the effects of anodal and cathodal tDCS may vary according to these dimensions. We measured contrast sensitivity with sinusoidal gratings at four different spatial frequencies (0.5, 4, 8, and 12 cycles/°), two orientations (45° Oblique and Horizontal), and for two stimulus size conditions [fixed size (3 degrees) and fixed period (1.5 cycles)]. The results showed that only contrast sensitivity measured with a 45° oblique grating with a spatial frequency of 8 cycles/° (period = 1.5 cycles) demonstrated clear polarity specific effects of tDCS, whereby cathodal tDCS increased, and anodal tDCS decreased contrast sensitivity. Overall, effects of tDCS were largest for oblique stimuli presented at high spatial frequencies (i.e., 8 and 12 cycles/°), and were absent at lower spatial frequencies. Further, the modulatory effects of tDCS were dependent on the sensitivity of the observer to the stimulus, and its spatial characteristics. It therefore seems that the effects of tDCS are only found for high spatial frequency stimuli that generally elicit lower contrast sensitivity, while the effects are diminished, or absent to stimuli that elicit higher contrast sensitivity

The Multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) high performance computing infrastructure: Applications in neuroscience and neuroinformatics research

The Multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) is a national imaging and visualization facility established by Monash University, the Australian Synchrotron, the Commonwealth Scientific Industrial Research Organization (CSIRO), and the Victorian Partnership for Advanced Computing (VPAC), with funding from the National Computational Infrastructure and the Victorian Government. The MASSIVE facility provides hardware, software, and expertise to drive research in the biomedical sciences, particularly advanced brain imaging research using synchrotron x-ray and infrared imaging, functional and structural magnetic resonance imaging (MRI), x-ray computer tomography (CT), electron microscopy and optical microscopy. The development of MASSIVE has been based on best practice in system integration methodologies, frameworks, and architectures. The facility has: (i) integrated multiple different neuroimaging analysis software components, (ii) enabled cross-platform and cross-modality integration of neuroinformatics tools, and (iii) brought together neuroimaging databases and analysis workflows. MASSIVE is now operational as a nationally distributed and integrated facility for neuroinfomatics and brain imaging research