Objective classification biomarkers that are developed using resting-state functional magnetic resonance imaging (rs-fMRI) data are expected to contribute to more effective treatment for psychiatric disorders. Unfortunately, no widely accepted biomarkers are available at present, partially because of the large variety of analysis pipelines for their development. In this study, we comprehensively evaluated analysis pipelines using a large-scale, multi-site fMRI dataset for major depressive disorder (MDD). We explored combinations of options in four sub-processes of the analysis pipelines: six types of brain parcellation, four types of functional connectivity (FC) estimations, three types of site-difference harmonization, and five types of machine-learning methods. A total of 360 different MDD classification biomarkers were constructed using the SRPBS dataset acquired with unified protocols (713 participants from four sites) as the discovery dataset, and datasets from other projects acquired with heterogeneous protocols (449 participants from four sites) were used for independent validation. We repeated the procedure after swapping the roles of the two datasets to identify superior pipelines, regardless of the discovery dataset. The classification results of the top 10 biomarkers showed high similarity, and weight similarity was observed between eight of the biomarkers, except for two that used both data-driven parcellation and FC computation. We applied the top 10 pipelines to the datasets of other psychiatric disorders (autism spectrum disorder and schizophrenia), and eight of the biomarkers exhibited sufficient classification performance for both disorders. Our results will be useful for establishing a standardized pipeline for classification biomarkers.

Humans have the amazing ability to learn the dynamics of the body and environment to develop motor skills. Traditional motor studies using arm reaching paradigms have viewed this ability as the process of 'internal model adaptation'. However, the behaviors have not been fully explored in the case when reaches fail to attain the intended target. Here we examined human reaching under two force fields types; one that induces failures (i.e., target errors), and the other that does not. Our results show the presence of a distinct failure-driven adaptation process that enables quick task success after failures, and before completion of internal model adaptation, but that can result in persistent changes to the undisturbed trajectory. These behaviors can be explained by considering a hierarchical interaction between internal model adaptation and the failure-driven adaptation of reach direction. Our findings suggest that movement failure is negotiated using hierarchical motor adaptations by humans.

An increasing number of projects in neuroscience require statistical analysis of high-dimensional data, as, for instance, in the prediction of behavior from neural firing or in the operation of artificial devices from brain recordings in brain-machine interfaces. Although prevalent, classical linear analysis techniques are often numerically fragile in high dimensions due to irrelevant, redundant, and noisy information. We developed a robust Bayesian linear regression algorithm that automatically detects relevant features and excludes irrelevant ones, all in a computationally efficient manner. In comparison with standard linear methods, the new Bayesian method regularizes against overfitting, is computationally efficient (unlike previously proposed variational linear regression methods, is suitable for data sets with large numbers of samples and a very high number of input dimensions) and is easy to use, thus demonstrating its potential as a drop-in replacement for other linear regression techniques. We evaluate our technique on synthetic data sets and on several neurophysiological data sets. For these neurophysiological data sets we address the question of whether EMG data collected from arm movements of monkeys can be faithfully reconstructed from neural activity in motor cortices. Results demonstrate the success of our newly developed method, in comparison with other approaches in the literature, and, from the neurophysiological point of view, confirms recent findings on the organization of the motor cortex. Finally, an incremental, real-time version of our algorithm demonstrates the suitability of our approach for real-time interfaces between brains and machines.

An increasing number of projects in neuroscience requires the sta- tistical analysis of high dimensional data sets, as, for instance, in predicting behavior from neural firing or in operating artificial de- vices from brain recordings in brain-machine interfaces. Linear analysis techniques remain prevalent in such cases, but classical linear regression approaches are often numerically too fragile in high dimensions. In this paper, we address the question of whether EMG data collected from arm movements of monkeys can be faith- fully reconstructed with linear approaches from neural activity in primary motor cortex (M1). To achieve robust data analysis, we develop a full Bayesian approach to linear regression that auto- matically detects and excludes irrelevant features in the data, reg- ularizing against overfitting. In comparison with ordinary least squares, stepwise regression, partial least squares, LASSO regres- sion and a brute force combinatorial search for the most predictive input features in the data, we demonstrate that the new Bayesian method offers a superior mixture of characteristics in terms of reg- ularization against overfitting, computational efficiency and ease of use, demonstrating its potential as a drop-in replacement for other linear regression techniques. As neuroscientific results, our anal- yses demonstrate that EMG data can be well predicted from M1 neurons, further opening the path for possible real-time interfaces between brains and machines.