Automated Discrimination of Brain Pathological State Attending to Complex Structural Brain Network Properties: The Shiverer Mutant Mouse Case

Neuroimaging classification procedures between normal and pathological subjects are sparse and highly dependent of an expert's clinical criterion. Here, we aimed to investigate whether possible brain structural network differences in the shiverer mouse mutant, a relevant animal model of myelin related diseases, can reflect intrinsic individual brain properties that allow the automatic discrimination between the shiverer and normal subjects. Common structural networks properties between shiverer (C3Fe.SWV Mbpshi/Mbpshi, n = 6) and background control (C3HeB.FeJ, n = 6) mice are estimated and compared by means of three diffusion weighted MRI (DW-MRI) fiber tractography algorithms and a graph framework. Firstly, we found that brain networks of control group are significantly more clustered, modularized, efficient and optimized than those of the shiverer group, which presented significantly increased characteristic path length. These results are in line with previous structural/functional complex brain networks analysis that have revealed topologic differences and brain network randomization associated to specific states of human brain pathology. In addition, by means of network measures spatial representations and discrimination analysis, we show that it is possible to classify with high accuracy to which group each subject belongs, providing also a probability value of being a normal or shiverer subject as an individual anatomical classifier. The obtained correct predictions (e.g., around 91.6–100%) and clear spatial subdivisions between control and shiverer mice, suggest that there might exist specific network subspaces corresponding to specific brain disorders, supporting also the point of view that complex brain network analyses constitutes promising tools in the future creation of interpretable imaging biomarkers

Investigating the reliability of population receptive field size estimates using fMRI

In functional MRI (fMRI), population receptive field (pRF) models allow a quantitative description of the response as a function of the features of the stimuli that are relevant for each voxel. The most popular pRF model used in fMRI assumes a Gaussian shape in the features space (e.g., the visual field) reducing the description of the voxel's pRF to the Gaussian mean (the pRF preferred feature) and standard deviation (the pRF size). The estimation of the pRF mean has been proven to be highly reliable. However, the estimate of the pRF size has been shown not to be consistent within and between subjects. While this issue has been noted experimentally, here we use an optimization theory perspective to describe how the inconsistency in estimating the pRF size is linked to an inherent property of the Gaussian pRF model. When fitting such models, the goodness of fit is less sensitive to variations in the pRF size than to variations in the pRF mean. We also show how the same issue can be considered from a bias-variance perspective. We compare different estimation procedures in terms of the reliability of their estimates using simulated and real fMRI data in the visual (using the Human Connectome Project database) and auditory domain. We show that, the reliability of the estimate of the pRF size can be improved considering a linear combination of those pRF models with similar goodness of fit or a permutation based approach. This increase in reliability of the pRF size estimate does not affect the reliability of the estimate of the pRF mean and the prediction accuracy

Different and common brain signals of altered neurocognitive mechanisms for unfamiliar face processing in acquired and developmental prosopagnosia

Neuropsychological studies have shown that prosopagnosic individuals perceive face structure in an atypical way. This might preclude the formation of appropriate face representations and, consequently, hamper effective recognition. The present ERP study, in combination with Bayesian source reconstruction, investigates how information related to both external (E) and internal (I) features was processed by E.C. and I.P., suffering from acquired and developmental prosopagnosia, respectively. They carried out a face-feature matching task with new faces. E.C. showed poor performance and remarkable lack of early face-sensitive P1, N170 and P2 responses on right (damaged) posterior cortex. Although she presented the expected mismatch effect to target faces in the E-I sequence, it was of shorter duration than in Controls, and involved left parietal, right frontocentral and dorsofrontal regions, suggestive of reduced neural circuitry to process face configurations. In turn, I.P. performed efficiently but with a remarkable bias to give “match” responses. His face-sensitive potentials P1–N170 were comparable to those from Controls, however, he showed no subsequent P2 response and a mismatch effect only in the I-E sequence, reflecting activation confined to those regions that sustain typically the initial stages of face processing. Relevantly, neither of the prosopagnosics exhibited conspicuous P3 responses to features acting as primes, indicating that diagnostic information for constructing face representations could not be sufficiently attended nor deeply encoded. Our findings suggest a different locus for altered neurocognitive mechanisms in the face network in participants with different types of prosopagnosia, but common indicators of a deficient allocation of attentional resources for further recognition

Audiovisual Interactions Among Near-Threshold Oscillating Stimuli in the Far Periphery Are Phase-Dependent

Recent studies have highlighted the possible contributions of direct connectivity between early sensory cortices to audiovisual integration. Anatomical connections between the early auditory and visual cortices are concentrated in visual sites representing the peripheral field of view. Here, we aimed to engage early sensory interactive pathways with simple, far-peripheral audiovisual stimuli (auditory noise and visual gratings). Using a modulation detection task in one modality performed at an 84% correct threshold level, we investigated multisensory interactions by simultaneously presenting weak stimuli from the other modality in which the temporal modulation was barely-detectable (at 55 and 65% correct detection performance). Furthermore, we manipulated the temporal congruence between the cross-sensory streams. We found evidence for an influence of barely-detectable visual stimuli on the response times for auditory stimuli, but not for the reverse effect. These visual-to-auditory influences only occurred for specific phase-differences (at onset) between the modulated audiovisual stimuli. We discuss our findings in the light of a possible role of direct interactions between early visual and auditory areas, along with contributions from the higher-order association cortex. In sum, our results extend the behavioral evidence of audio-visual processing to the far periphery, and suggest – within this specific experimental setting – an asymmetry between the auditory influence on visual processing and the visual influence on auditory processing

Cross-validation and permutations in MVPA: validity of permutation strategies and power of cross-validation schemes

Multi-Voxel Pattern Analysis (MVPA) is a well established tool to disclose weak, distributed effects in brain activity patterns. The generalization ability is assessed by testing the learning model on new, unseen data. However, when limited data is available, the decoding success is estimated using cross-validation. There is general consensus on assessing statistical significance of cross-validated accuracy with non-parametric permutation tests. In this work we focus on the false positive control of different permutation strategies and on the statistical power of different cross-validation schemes.With simulations, we show that estimating the entire cross-validation error on each permuted dataset is the only statistically valid permutation strategy. Furthermore, using both simulations and real data from the HCP WU-Minn 3T fMRI dataset, we show that, among the different cross-validation schemes, a repeated split-half cross-validation is the most powerful, despite achieving slightly lower classification accuracy, when compared to other schemes. Our findings provide additional insights into the optimization of the experimental design for MVPA, highlighting the benefits of having many short runs

Fast Gaussian Naïve Bayes for searchlight classification analysis

The searchlight technique is a variant of multivariate pattern analysis (MVPA) that examines neural activity across large sets of small regions, exhaustively covering the whole brain. This usually involves application of classifier algorithms across all searchlights, which entails large computational costs especially when testing the statistical significance of the accuracies with permutation methods. In this article, a new implementation of the Gaussian Naive Bayes classifier is presented (henceforth massive-GNB). This approach allows classification in all searchlights simultaneously, and is faster than previously published searchlight GNB implementations, as well as other more complex classifiers including support vector machines (SVM). To ensure that the gain in speed in GNB would be useful in searchlight analysis, we compared the accuracies of massive-GNB and SVM in detecting the lateral occipital complex (LOC) in an fMRI localizer experiment (26 subjects). Moreover, this region as defined in a meta-analysis of many activation studies was used as a gold standard to compare error rates for both classifiers. In individual searchlights, SVM was somewhat more accurate than massive-GNB and more selective in detecting the meta-analytic LOC. However, with multiple comparison correction at the cluster-level the two classifiers performed equivalently. Thus for cluster-level analysis, massive-GNB produces an accuracy similar to more sophisticated classifiers but with a substantial gain in speed. Massive-GNB (available as a public Matlab toolbox) could facilitate the more widespread use of searchlight analysis