Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Analyses Steps for the lGI-Values and Correlations with Anatomical Parameters (GM/WM-volume, Cortical Surface Area and Cortical Thickness).

<p>Analyses Steps for the lGI-Values and Correlations with Anatomical Parameters (GM/WM-volume, Cortical Surface Area and Cortical Thickness).</p

Comparison of Age-Related Changes between GM-Volume, Cortical Thickness, Cortical Surface Area and Gyrification.

<p>Age effects in a vertex-by-vertex analyses on GM-volume (GMV), cortical thickness (CT), lGI and cortical surface area (SA) presented on an average template brain. Left hemisphere from lateral view in the first row, from medial view in the second row. Right hemisphere is viewed from lateral view in the third row; medial view in the fourth row. The analyses for all parameters (lGI, cortical thickness, GM-volume and cortical surface area) were corrected for multiple comparisons with a false discovery rate (FDR) of q at 0.05 and to increase the signal to noise ratio, a 20 mm full-width at half maximum (FWHM) smoothing was employed. Blue colors indicate a significant decrease of lGI-, cortical thickness-, GM-volume- and cortical surface area- values with increasing age, whereas warmer colors are coded for age-related increases. Cortical thickness reductions showed the largest age-dependent effects in frontal, temporal and parietal regions (left hemisphere (effect sizes, Cohen's d): superior-frontal cortex: d = 2.27, rostral-middle frontal cortex: 1.84, pericalcarine: d = 1.29, middle-temporal gyrus: d = 1.01; right hemisphere: precentral cortex: d = 1.07, cuneus: d = 1.07, inferior temporal cortex: d = 1.15, superior frontal gyrus: d = 0.56) which overlapped with decreased GM-volume (left hemisphere (effect sizes, Cohen's d): superior-frontal: d = 0.78, superior-temporal: 1.46, lingual gyrus: d = 0.48, post-central gyrus: d = 0.81; right hemisphere: pars orbitalis: d = 0.59, inferior parietal: d = 1.39, paracentral gyrus: d = 0.82, superior frontal: d = 1.12). Cortical surface area decreased most prominently in parietal, precentral, supramarginal and caudal-middle frontal cortices (left hemisphere (effect sizes, Cohens'd): precentral cortex: d = 0.7, caudal-middle-frontal: d = 0.34, supramarginal: d = 0.45; right hemisphere: precentral cortex: d = 0.67, superior parietal: d = 0.69 and inferior parietal: d = 1.01).</p

Correlations between mean lGI-Values with Thickness, WM-, GM-Volume and Surface Area.

<p>r. values with p<0.05.</p><p>p<0.01.</p><p>p<0.001.</p

Whole-Brain Analyses of the Local Gyrification Index (lGI) during Adolescence.

<p>Effects of age on the local gyrification index (lGI) in a whole brain, vertex-by-vertex analyses projected onto an average template brain. Left panel: left hemisphere from lateral (top), medial (middle), frontal (left bottom) and occipital (right bottom) view. Right panel: right hemisphere from lateral (up), medial (middle), frontal (left bottom) and occipital (right bottom) view. Blue colors indicate a significant decrease of lGI-values with increasing age, whereas warmer colors are coded for an increase in lGI. Age-dependent effects were corrected for multiple comparisons with a false discovery rate (FDR) of q at 0.005 and a smoothing of 5 mm was used. lGI-values showed the largest age-dependent effects in precentral, frontal and parietal regions (left hemisphere (effect sizes, Cohen's d): precentral cortex: d = 1.61, superior-frontal cortex: 1.83, lateral-orbitofrontal cortex: d = 1.06, superior parietal cortex: d = 1.20; right hemisphere: precentral cortex: d = 1.57, rostral-middle frontal gyrus: d = 1.79, pars triangularis: d = 1.36, inferior parietal cortex: d = 1.58).</p

Scatter plots for the nine brain areas with significant correlations between age and lGI-values.

<p>All trajectories were best represented with cubic fits. The explained variance (R²) values are: left Precentral = 0.396, left Inferior-temporal = 0.218, left Superior-frontal = 0.298, left Lateral-orbitofrontal = 0.196; right Precental = 0.382, right Pars triangularis = 0.228, right Superior-parietal = 0.217, right Rostral-middlefrontal = 0.311, right Caudal-anterior (a.) Cingulate = 0.161.</p

Age-Related Decreases in Gyrification.

<p>Note: Reported are cluster number, maximum p-value within a cluster, maximum vertex, area size of the cluster (in mm²), Talairach coordinates of the vertex, number of vertices, FreeSurfers anatomical region, Brodman area (BA). Note some clusters span more than one anatomical region or BA. Neuroanatomical classifications were done by Talairach Client v.2.4.2 (<a href="http://www.talairach.org/client.html" target="_blank">http://www.talairach.org/client.html</a>) and FreeSurfers Desikan gyral based atlas (Desikan et al., 2006).</p

Based on the FreeSurfers Desikan labeling, eight regions of interest (ROI's) were selected to analyze the relationships between lGI, Cortical Thickness, GM-volume, Cortical Surface Area and WM-volume.

<p>ROI's in the left hemisphere (lateral view): 1) precentral gyrus (blue), 2) superior frontal gyrus (red), 3) lateral-orbitofrontal cortex (violet) and 4) inferior temporal cortex (brown). ROI's right hemisphere (lateral view): 1) precentral gyrus (blue), 2) rostral-middle-frontal gyrus (yellow), 3) pars triangularis gyrus (green) and 4) superior-parietal cortex (light blue). Note the relative good spatial orientation in comparison to brain areas, which lGI's are significant correlated with age from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084914#pone-0084914-g004" target="_blank">Figure 4</a>.</p