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Tohka, J.

Publications and source records attributed to Tohka, J..

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Comparing fMRI inter-subject correlations between groups

Inter-subject correlation (ISC) based analysis is a conceptually simple approach to analyze functional magnetic resonance imaging (fMRI) data acquired under naturalistic stimuli such as a movie. We describe and validate the statistical approaches for comparing ISCs between two groups of subjects implemented in the ISC toolbox, which is an open source software package for ISC-based analysis of fMRI data. The approaches are based on permutation tests. We validated the approaches using five different data sets from the ICBM functional reference battery tasks. First, we created five null datasets (one for each task) by dividing the subjects into two matched groups and assumed that no group difference exists. Second, based on one null dataset, we created datasets with simulated ISC differences of varying size between the two groups. Based on the experiments with these two types of data, we recommend the use of subject-wise permutations, instead of element-wise permutations. The tests based on subject-wise permutations led to correct false positive rates. We observed that the null-distributions should be voxel-specific and not based on pooling all voxels across the brain as is typical in fMRI. This was the case even if studentized permutation tests were used. Additionally, we experimented with an fMRI dataset acquired using a dance movie stimulus for comparison of a group of adult males on the autism spectrum to a matched typically developed group. The experiment confirmed the differences between voxel-based permutation tests and global model based permutation tests.

neuroscience

3D Axonal Morphometry of White Matter

Axonal structure underlies white matter functionality and plays a major role in brain connectivity. The current literature on the axonal structure is based on the analysis of two-dimensional (2D) cross-sections, which, as we demonstrate, is precarious. To be able to quantify three-dimensional (3D) axonal morphology, we developed a novel pipeline for automated 3D segmentation and morphometric analysis (ACSON) of the white matter ultrastructure. The automated pipeline eliminates the need for time-consuming manual segmentation of 3D datasets. ACSON segments myelin, myelinated and unmyelinated axons, mitochondria, cells and vacuoles, and analyzes the morphology of axons. We applied the pipeline to serial block-face scanning electron microscopy images of the corpus callosum of sham-operated (n = 2) and brain injured (n = 3) rats 5 months after the injury. The 3D morphometry showed that axonal cross-sections were elliptic rather than spherical, and their diameter varied substantially along axons. It also showed a significant reduction in the axonal diameter of the ipsilateral corpus callosum of rats 5 months after brain injury, indicating ongoing axonal alterations even at this chronic time-point.

neuroscience

Comparison of feature representations in MRI-based MCI-to-AD conversion prediction

Alzheimers Disease (AD) is a progressive neurological disorder in which the death of brain cells causes memory loss and cognitive decline. The identifica-tion of at-risk subjects yet showing no dementia symptoms but who will later convert to AD can be crucial for the effective treatment of AD. For this, Magnetic Resonance Imaging (MRI) is expected to play a crucial role. During recent years, several Machine Learning (ML) approaches to AD-conversion prediction have been proposed using different types of MRI features. However, few studies comparing these different feature representations exist, and the existing ones do not allow to make definite conclusions. We evaluated the performance of various types of MRI features for the conversion prediction: voxel-based features extracted based on voxel-based morphometry, hippocampus volumes, volumes of the entorhinal cortex, and a set of regional volumetric, surface area, and cortical thickness measures across the brain. Regional features consistently yielded the best performance over two classifiers (Support Vector Machines and Regularized Logistic Regression), and two datasets studied. However, the performance difference to other features was not statistically significant. There was a consis-tent trend of age correction improving the classification performance, but the improvement reached statistical significance only rarely.

neuroscience

T1 white/gray contrast as a predictor of chronological age, and an index of cognitive performance

The maturational schedule of human brain development appears to be narrowly confined. The chronological age of an individual can be predicted from brain images with considerable accuracy, and deviation from the typical pattern of brain maturation has been related to cognitive performance. Methods using multi-modal data, or complex measures derived from voxels throughout the brain have shown the greatest accuracy, but are difficult to interpret in terms of the biology. Measures based on the cortical surface(s) have yielded less accurate predictions, suggesting that perhaps developmental changes related to cortical gray matter are not strongly related to chronological age, and that perhaps development is more strongly related to changes in subcortical regions or in deep white matter. We show that a simple metric based on the white/gray contrast at the inner border of the cortical gray-matter is a comparably good predictor of chronological age, and our usage of an elastic net penalized linear regression model reveals the brain regions which contribute most to age-prediction. We demonstrate this in two large datasets: the NIH Pediatric Data, with 832 scans of typically developing children, adolescents, and young adults; and the Pediatric Imaging, Neurocognition, and Genetics data, with 760 scans of individuals in a similar age-range. Moreover, we show that the residuals of age-prediction based on this white/gray contrast metric are more strongly related to IQ than are those from cortical thickness, suggesting that this metric is more sensitive to aspects of brain development that reflect cognitive performance.

neuroscience

Sign-Consistency Based Variable Importance For Machine Learning In Brain Imaging

An important problem that hinders the use of supervised classification algorithms for brain imaging is that the number of variables per single subject far exceeds the number of training subjects available. Deriving multivariate measures of variable importance becomes a challenge in such scenarios. This paper proposes a new measure of variable importance termed sign-consistency bagging (SCB). The SCB captures variable importance by analyzing the sign consistency of the corresponding weights in an ensemble of linear support vector machine (SVM) classifiers. Further, the SCB variable importances are enhanced by means of transductive conformal analysis. This extra step is important when the data can be assumed to be heterogeneous. Finally, the proposal of these SCB variable importance measures is completed with the derivation of a parametric hypothesis test of variable importance. The new importance measures were compared with a t-test based univariate and an SVM-based multivariate variable importances using anatomical and functional magnetic resonance imaging data. The obtained results demonstrated that the new SCB based importance measures were superior to the compared methods in terms of reproducibility and classification accuracy.

neuroscience