Effects of covariates on brain perfusion.

<p>Regression coefficients refer to change in brain perfusion in mL/100 g/min per unit increase of covariate.</p><p>*Sex omitted due to co-linearity.</p>†<p>p<0.05, ^†† p<0.01 (p-values are not adjusted for multiple comparisons).</p><p>Abbreviations: LDL  =  low density lipoprotein, HDL  =  high density lipoprotein, ADMA  =  asymmetric dimethylarginine, Arg  =  L-arginine.</p

Subject characteristics.

<p>Abbreviations: MMSE  =  mini mental state examination, LDL  =  low density lipoprotein, HDL  =  high density lipoprotein, CV =  cardiovascular WML  =  white matter lesion, ADMA  =  asymmetric dimethylarginine, Arg =  L-arginine.</p

The relationship between homocysteine and global brain perfusion.

<p>Dashed line shows line of regression (r² = 0.17, p = 0.009).</p

Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

<div><p>Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial attention, especially in top-down (i.e., goal-oriented) attentional processing. This right hemisphere lateralization was partly, but not completely, explained by an increased grey matter volume in the right hemisphere of the early visual areas. Difference in activation of the superior parietal lobule was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual perception tasks.</p></div

Maximum intensity projections of the average activation and deactivation for all scan sessions (2 sessions with 2 different goggle positions in all eligible subjects).

<p>Due to the high power of the approach great expanses are activated, which creates the impression that activation and deactivation appear to overlap locally. Both maps are, however, exclusive.</p

Region of interest-based analysis showing absolute BOLD responses to visual stimulation in areas of lateralized activation from the voxel-wise analysis.

<p>Cluster numbers are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126477#pone.0126477.t002" target="_blank">Table 2</a>. Values on the y-axes of the boxplots are mean percentage BOLD signal changes.</p

Maximum intensity projections (“glass-brain”) presentations of the voxel-wise results from the interhemispheric comparison analyses.

<p>Right>Left activation is shown on the right hemisphere side (marked “R”) while Left>Right activation is shown on the left side. <b>(a)</b> Left-to-right activation differences corrected for six different parameters (See text). <b>(b)</b> and <b>(c)</b> Differences that correlate positively with age and grey matter volume, respectively.</p

Methods of the main experiment comparing activation of left hemispheres to right hemispheres.

<p><b>(a)</b> Two scan sessions were carried out in 54 subjects out during full-field visual stimulation: one with the stimulation goggles in the standard position and one with the goggles flipped 180 degrees. <b>(b)</b> Left-right mirrored copies of the acquired data were created for each scan session. <b>(c)</b> After processing the first-level fMRI results, data from the two scan sessions were averaged for each subject. <b>(d)</b> First-level results of mirrored data were subtracted from first-level results of data in the original orientation to produce left-right difference images that would allow for adding covariates to the model. The difference images have the same values in the right and left sides of image space but with opposite signs. To avoid this redundancy the left side of the image space was zeroed by a binary mask.</p

Significant voxel clusters of left-right interhemispheric differences from the voxel-wise general linear model analysis.

<p>Also shown are results from the co-variates “Age” and “Grey matter volume”. Voxels: number of voxels in significant cluster. Z-max: maximum Z value of most significant voxel. X, Y, Z: Montreal Neurological Institute coordinates of most significant voxel. LI: Laterality Index based on the region-of-interest analysis, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126477#sec002" target="_blank">Methods</a>. NA: Not applicable.</p

Maximum intensity projections (“glass-brain”) presentations of the voxel-wise results from the validation experiment.

<p>Results for “activated” > “non-activated” hemispheres in five subjects are shown on the right hemisphere side (marked with an R), a marked activation in the occipital lobe, peaking in the primary visual cortex, while results for “non-activated” > “activated” hemispheres, depicted on the left hemisphere side show no difference.</p