Polymicrogyria (PMG) is a malformation of cortical development characterized by an irregular gyral pattern and its diagnosis and severity have been qualitatively judged by visual inspection of imaging features. We aimed to provide a quantitative description of abnormal sulcal patterns for individual PMG brains using our sulcal graph-based analysis and examined the association with language impairment. The sulcal graphs were constructed from magnetic resonance images in 26 typical developing and 18 PMG subjects and the similarity between sulcal graphs was computed by using their geometric and topological features. The similarities between typical and PMG groups were significantly lower than the similarities measured within the typical group. Furthermore, more lobar regions were determined to be abnormal in most patients when compared with the visual diagnosis of PMG involvement, suggesting that PMG may have more global effects on cortical folding than previously expected. Among the PMG, the group with intact language development showed sulcal patterns more closely matched with the typical than the impaired group in the left parietal lobe. Our approach shows the potential to provide a quantitative means for detecting the severity and extent of involvement of cortical malformation and a greater understanding of genotype-phenotype and clinical-imaging features correlations.

Prior studies have shown that patients with AD have decreased functional or structural connectivity between the hippocampus and other brain areas. To the best of our knowledge, however, there have been no studies investigating the topography of cortical thinning areas and correlations with HA using surface based morphometry of three-dimensional (3D) T1-weighted magnetic resonance (MR) images. Cortical thickness was measured using SBM, and hippocampal volume was measured using an automated method, in 219 patients with AD and 54 subjects with no cognitive impairment (NCI). A partial correlation model was used in analysis of cortical thinning related to HA. Cortical thinning areas related to HA were found mostly within areas associated with polysynaptic or direct pathways of the hippocampus, a finding consistent with the disconnection hypothesis. Therefore, the cortical atrophy related to HA in patients with AD may represent disrupted cortical brain networks in connection with HA. However, since the topography of HA-related cortical thinning in groups with Clinical Dementia Ratings (CDR) of 0.5 and 1 corresponded to the stages I-II and III-IV of Braak and Braak staging, respectively, we could not exclude the possibility of the "concomitant hypothesis," i.e. that these areas are affected concomitantly with the hippocampus.

Cardiovascular risk factors are associated with cognitive impairments. However, the effects of cardiovascular risk factors on the topography of cortical thinning have not yet been studied in patients with mild cognitive impairment (MCI) or dementia. Thus, we aimed to evaluate the topography of cortical thinning related to cardiovascular risk factors and the relationships among cardiovascular risk factors, white matter hyperintensities (WMH), and cortical atrophy. Participants included 226 patients with Alzheimer disease or subcortical vascular dementia and 135 patients with amnestic MCI or subcortical vascular MCI. We automatically measured the volume of WMH and cortical thickness. Hypertension was associated with cortical thinning in the frontal and perisylvian regions, and cortical thinning related to diabetes mellitus (DM) occurred in the frontal region. In path analyses, hypertension accounted for 0.04 of the frontal thinning with the mediation of WMH and 0.16 without the mediation of WMH. In case of DM, it accounted for 0.02 of the frontal thinning with the mediation of WMH and 0.13 without the mediation of WMH. Hypertension and DM predominantly affected frontal thinning both with and without the mediation of WMH, where the effects without the mediation of WMH were greater than those with the mediation of WMH.

Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimer's disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction.

Patients with probable Alzheimer's disease (AD) and the amnesic form of mild cognitive impairment (aMCI) often demonstrate several types of neuropsychological deficits. These deficits are often related to cortical atrophy, induced by neuronal degradation. The purpose of this study is to investigate whether different anatomic patterns of cortical atrophy are associated with specific neuropsychological deficits. The participants were 170 patients with AD and 99 patients with aMCI. All participants underwent the Seoul Neuropsychological Screening Battery (SNSB), which includes tests that assess attention, language, visuospatial functions, verbal and visual memory, and frontal/executive functions. Cortical atrophy (thinning) was quantified by measuring the thickness of the cortical mantle across the entire brain using automated, three-dimensional magnetic resonance imaging. The relationship between cortical thickness and neuropsychological performance was analysed using stepwise multiple linear regression analyses. These analyses (corrected P.001) showed that several specific brain regions with cortical thinning were associated with cognitive dysfunction including: digit span backward, verbal and picture recall, naming and fluency, drawing-copying, response inhibition and selective attention. Some of the other functions, however, were not associated with specific foci of cortical atrophy (digit span forward, the word reading portion of the Stroop test, word and picture recognition). Our study, involving a large sample of participants with aMCI and AD, provides support for the postulate that cortical thinning-atrophy in specific anatomic loci are pathological markers for specific forms of cognitive dysfunction.

The amnestic form of mild cognitive impairment (aMCI) is likely a precursor of Alzheimer disease (AD). Both verbal and visual memory tests are used in the diagnosis of aMCI; however, it is unknown which type of test is superior at predicting the underlying pathologic changes associated with AD. In this study, we compared the topography of cortical thinning among 3 subtypes of patients with aMCI: 33 patients with predominant verbal memory impairment (verbal-aMCI), 35 with predominant visual memory impairment (visual-aMCI), and 56 with both verbal and visual memory-predominant impairment (both-aMCI), and 143 patients with normal cognition. As a result, patients with verbal-aMCI showed cortical thinning in the left anterior and medial temporal regions compared with individuals with normal cognition, while those with visual-aMCI did not show significant cortical thinning. The cortical thinning areas of both-aMCI group overlapped those of verbal-aMCI but were more widespread involving the bilateral temporal regions. These findings suggest that the verbal-aMCI and both-aMCI are more likely to be a precursor of AD than visual-aMCI, and that both-aMCI may be more advanced subtype than verbal-aMCI on the spectrum from MCI to AD.

In this paper, we deal with a subcortical surface registration problem. Subcortical structures including hippocampi and caudates have a small number of salient features such as heads and tails unlike cortical surfaces. Therefore, it is hard, if not impossible, to perform subcortical surface registration with only such features. It is also non-trivial for neuroanatomical experts to select landmarks consistently for subcortical surfaces of different subjects. We therefore present a landmark-free approach for subcortical surface registration by measuring the amount of mesh distortion between subcortical surfaces assuming that the surfaces are represented by meshes. The input meshes can be constructed using any surface modeling tool available in the public domain since our registration method is independent of a surface modeling process. Given the source and target surfaces together with their representing meshes, the vertex positions of the source mesh are iteratively displaced while preserving the underlying surface shape in order to minimize the distortion to the target mesh. By representing each surface mesh as a point on a high-dimensional Riemannian manifold, we define a distance metric on the manifold that measures the amount of distortion from a given source mesh to the target mesh, based on the notion of isometry while penalizing triangle flipping. Under this metric, we reduce the distortion minimization problem to the problem of constructing a geodesic curve from the moving source point to the fixed target point on the manifold while satisfying the shape-preserving constraint. We adopt a multi-resolution framework to solve the problem for distortion-minimizing mapping between the source and target meshes. We validate our registration scheme through several experiments: distance metric comparison, visual validation using real data, robustness test to mesh variations, feature alignment using anatomic landmarks, consistency with previous clinical findings, and comparison with a surface-based registration method, LDDMM-surface.

The global pattern of cortical sulci provides important information on brain development and functional compartmentalization. Sulcal patterns are routinely used to determine fetal brain health and detect cerebral malformations. We present a quantitative method for automatically comparing and analyzing the sulcal pattern between individuals using a graph matching approach. White matter surfaces were reconstructed from volumetric T1 MRI data and sulcal pits, the deepest points in local sulci, were identified on this surface. The sulcal pattern was then represented as a graph structure with sulcal pits as nodes. The similarity between graphs was computed with a spectral-based matching algorithm by using the geometric features of nodes (3D position, depth and area) and their relationship. In particular, we exploited the feature of graph topology (the number of edges and the paths between nodes) to highlight the interrelated arrangement and patterning of sulcal folds. We applied this methodology to 48 monozygotic twins and showed that the similarity of the sulcal graphs in twin pairs was significantly higher than in unrelated pairs for all hemispheres and lobar regions, consistent with a genetic influence on sulcal patterning. This novel approach has the potential to provide a quantitative and reliable means to compare sulcal patterns.

Sulcal pits are hypothesized to form early during development and be under tighter genetic control than other regions of the cortex. We investigated the relationship between the presence of sulcal pits and intellectual ability, estimated with the full-scale, verbal, and performance intelligence quotient (IQ), in the brains of 78 healthy young adults. We automatically extracted sulcal pits from magnetic resonance images and developed a method for their automatic labeling. The difference in the number of sulcal pits between high and average IQ groups for each labeled region was statistically analyzed. We found that in the high verbal IQ group a sulcal pit was more frequently present in the left posterior inferior frontal sulcus (70% in the high IQ group vs. 40% in the average IQ group) and the right posterior inferior temporal sulcus (70% vs. 43%), which have been reported to be regions of language function. Greater mean curvature of the deep sulcal areas in these regions was shown for the high verbal IQ group. This provides the complementary morphological information about the presence of more sulcal pits. These findings suggest that factors influencing verbal intelligence may emerge in the language areas early during cortical development and may be under tight genetic control.

The aim of this study was to investigate the effect of demographic factors (age of onset, sex and years of education) on the distribution of cortical thickness in a large sample of patients with Alzheimer's disease (AD). The study participants consisted of 193 AD patients and 142 controls with no cognitive impairment (NCI) that were measured with cortical thickness across the entire brain. The effects of demographic factors on cortical thickness were analyzed by applying linear regression after controlling confounding factors. Older individuals in NCI group showed more cortical thinning in frontal, temporal association cortices and insula than younger participants. Early onset AD was associated with cortical thinning in the parietal lobe, whereas late onset AD was associated with cortical thinning in the medial temporal region. The NCI group demonstrated sex-related differences in cortical thickness, although those differences were not present in the AD group. While the education effect was absent in NCI individuals, high levels of education in the AD group correlated with cortical thinning in the frontal and temporoparietal association cortices. Our results show that AD with earlier onset and higher education had suffered more pronounced cortical atrophy in specific parts of the brain than their counterparts, which may be related to cognitive reserve theory.