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Here we highlight an emerging trend in the use of machine learning classifiers to test for abstraction across patterns of neural activity. When a classifier algorithm is trained on data from one cognitive context, and tested on data from another, conclusions can be drawn about the role of a given brain region in representing information that abstracts across those cognitive contexts. We call this kind of analysis Multivariate Cross-Classification (MVCC), and review several domains where it has recently made an impact. MVCC has been important in establishing correspondences among neural patterns across cognitive domains, including motor-perception matching and cross-sensory matching. It has been used to test for similarity between neural patterns evoked by perception and those generated from memory. Other work has used MVCC to investigate the similarity of representations for semantic categories across different kinds of stimulus presentation, and in the presence of different cognitive demands. We use these examples to demonstrate the power of MVCC as a tool for investigating neural abstraction and discuss some important methodological issues related to its application.

A small physical change in the eye influences the entire neural information process along the visual pathway, causing perceptual errors and behavioral changes. Astigmatism, a refractive error in which visual images do not evenly focus on the retina, modulates visual perception, and the accompanying neural processes in the brain. However, studies on the neural representation of visual stimuli in astigmatism are scarce. We investigated the relationship between retinal input distortions and neural bias in astigmatism and how modulated neural information causes a perceptual error. We induced astigmatism by placing a cylindrical lens on the dominant eye of human participants, while they reported the orientations of the presented Gabor patches. The simultaneously recorded electroencephalogram activity revealed that stimulus orientation information estimated from the multivariate electroencephalogram activity was biased away from the neural representation of the astigmatic axis and predictive of behavioral bias. The representational neural dynamics underlying the perceptual error revealed the temporal state transition; it was transiently dynamic and unstable (approximately 350 ms from stimulus onset) that soon stabilized. The biased stimulus orientation information represented by the spatially distributed electroencephalogram activity mediated the distorted retinal images and biased orientation perception in induced astigmatism. In this study, we investigated the neural sources of perceptual error induced by the astigmatic distortion of the retinal image. We found a systematic distortion in the neural orientation representation estimated from the multivariate analysis of the electroencephalogram recordings, which supports the observed patterns of perceptual error.

Background: Electroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients. Methods: This study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response. Results: A total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response. Conclusions: The FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to explore the mechanisms underlying ECT's effects on depression and explore the specific predictors of the effects of ECT based on the pre-ECT treatment magnetic resonance imaging.

Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these results, the combination of naturalistic movie stimuli and classification analysis in fMRI experiments may prove to be a sensitive tool for the assessment of changes in natural cognitive processes under experimental manipulation.

Multivariate decoding methods were developed originally as tools to enable accurate predictions in real-world applications. The realization that these methods can also be employed to study brain function has led to their widespread adoption in the neurosciences. However, prior to the rise of multivariate decoding, the study of brain function was firmly embedded in a statistical philosophy grounded on univariate methods of data analysis. In this way, multivariate decoding for brain interpretation grew out of two established frameworks: multivariate decoding for predictions in real-world applications, and classical univariate analysis based on the study and interpretation of brain activation. We argue that this led to two confusions, one reflecting a mixture of multivariate decoding for prediction or interpretation, and the other a mixture of the conceptual and statistical philosophies underlying multivariate decoding and classical univariate analysis. Here we attempt to systematically disambiguate multivariate decoding for the study of brain function from the frameworks it grew out of. After elaborating these confusions and their consequences, we describe six, often unappreciated, differences between classical univariate analysis and multivariate decoding. We then focus on how the common interpretation of what is signal and noise changes in multivariate decoding. Finally, we use four examples to illustrate where these confusions may impact the interpretation of neuroimaging data. We conclude with a discussion of potential strategies to help resolve these confusions in interpreting multivariate decoding results, including the potential departure from multivariate decoding methods for the study of brain function. •We highlight two sources of confusion that affect the interpretation of multivariate decoding results.•Confusion 1: The dual use of multivariate decoding for real-world predictions and interpretation in terms of brain function.•Confusion 2: A mixture of statistical and conceptual frameworks of classical univariate analysis and multivariate decoding.•We show six differences between univariate analysis and multivariate decoding and a different meaning of signal and noise.•We use four illustrative examples to reveal these confusions and the assumptions of multivariate decoding for interpretation.

The multivariate analysis of brain signals has recently sparked a great amount of interest, yet accessible and versatile tools to carry out decoding analyses are scarce. Here we introduce The Decoding Toolbox (TDT) which represents a user-friendly, powerful and flexible package for multivariate analysis of functional brain imaging data. TDT is written in Matlab and equipped with an interface to the widely used brain data analysis package SPM. The toolbox allows running fast whole-brain analyses, region-of-interest analyses and searchlight analyses, using machine learning classifiers, pattern correlation analysis, or representational similarity analysis. It offers automatic creation and visualization of diverse cross-validation schemes, feature scaling, nested parameter selection, a variety of feature selection methods, multiclass capabilities, and pattern reconstruction from classifier weights. While basic users can implement a generic analysis in one line of code, advanced users can extend the toolbox to their needs or exploit the structure to combine it with external high-performance classification toolboxes. The toolbox comes with an example data set which can be used to try out the various analysis methods. Taken together, TDT offers a promising option for researchers who want to employ multivariate analyses of brain activity patterns.

Representational similarity analysis (RSA) is a computational technique that uses pairwise comparisons of stimuli to reveal their representation in higher-order space. In the context of neuroimaging, mass-univariate analyses and other multivariate analyses can provide information on what and where information is represented but have limitations in their ability to address how information is represented. Social neuroscience is a field that can particularly benefit from incorporating RSA techniques to explore hypotheses regarding the representation of multidimensional data, how representations can predict behavior, how representations differ between groups and how multimodal data can be compared to inform theories. The goal of this paper is to provide a practical as well as theoretical guide to implementing RSA in social neuroscience studies.

In multivariate pattern analysis of neuroimaging data, ‘second-level’ inference is often performed by entering classification accuracies into a t-test vs chance level across subjects. We argue that while the random-effects analysis implemented by the t-test does provide population inference if applied to activation differences, it fails to do so in the case of classification accuracy or other ‘information-like’ measures, because the true value of such measures can never be below chance level. This constraint changes the meaning of the population-level null hypothesis being tested, which becomes equivalent to the global null hypothesis that there is no effect in any subject in the population. Consequently, rejecting it only allows to infer that there are some subjects in which there is an information effect, but not that it generalizes, rendering it effectively equivalent to fixed-effects analysis. This statement is supported by theoretical arguments as well as simulations. We review possible alternative approaches to population inference for information-based imaging, converging on the idea that it should not target the mean, but the prevalence of the effect in the population. One method to do so, ‘permutation-based information prevalence inference using the minimum statistic’, is described in detail and applied to empirical data. •A second level t-test applied to accuracies in MVPA does not provide population inference.•The same holds for other measures used in information-based imaging.•The reason is that the true value of ‘information-like’ measures cannot be below chance level.•This is in contrast to the use of the t-test in univariate analysis which does support generalization.•Population inference in MVPA can be achieved by targeting the effect prevalence instead of the mean.

Numerous studies have examined the neural substrates of intertemporal decision‐making, but few have systematically investigated separate neural representations of the two attributes of future rewards (i.e., the amount of the reward and the delay time). More importantly, no study has used the novel analytical method of representational connectivity analysis (RCA) to map the two dimensions' functional brain networks at the level of multivariate neural representations. This study independently manipulated the amount and delay time of rewards during an intertemporal decision task. Both univariate and multivariate pattern analyses showed that brain activity in the dorsomedial prefrontal cortex (DMPFC) and lateral frontal pole cortex (LFPC) was modulated by the amount of rewards, whereas brain activity in the DMPFC and dorsolateral prefrontal cortex (DLPFC) was modulated by the length of delay. Moreover, representational similarity analysis (RSA) revealed that even for the regions of the DMPFC that overlapped between the two dimensions, they manifested distinct neural activity patterns. In terms of individual differences, those with large delay discounting rates (k) showed greater DMPFC and LFPC activity as the amount of rewards increased but showed lower DMPFC and DLPFC activity as the delay time increased. Lastly, RCA suggested that the topological metrics (i.e., global and local efficiency) of the functional connectome subserving the delay time dimension inversely predicted individual discounting rate. These findings provide novel insights into neural representations of the two attributes in intertemporal decisions, and offer a new approach to construct task‐based functional brain networks whose topological properties are related to impulsivity. DMPFC represented both amount and delay‐time with distinct activation patterns. RCA‐based amount‐related and time‐related networks topological properties can predict k.

•We propose a pipeline for MEG research making analysis steps and parameters explicit.•The FLUX pipeline is developed to be used with MNE Python and FieldTrip and it includes the associated documented code.•The pipeline includes the state-of-the-art suggestions for noise cancellation as well as source modelling including pre-whitening and handling of rank-deficient data.•To facilitate pre-registration and precise reporting we provide concrete suggestions on parameters and text to document.•An example data set allows for the pipeline to be used in educational settings. Magnetoencephalography (MEG) allows for quantifying modulations of human neuronal activity on a millisecond time scale while also making it possible to estimate the location of the underlying neuronal sources. The technique relies heavily on signal processing and source modelling. To this end, there are several open-source toolboxes developed by the community. While these toolboxes are powerful as they provide a wealth of options for analyses, the many options also pose a challenge for reproducible research as well as for researchers new to the field. The FLUX pipeline aims to make the analyses steps and setting explicit for standard analysis done in cognitive neuroscience. It focuses on quantifying and source localization of oscillatory brain activity, but it can also be used for event-related fields and multivariate pattern analysis. The pipeline is derived from the Cogitate consortium addressing a set of concrete cognitive neuroscience questions. Specifically, the pipeline including documented code is defined for MNE Python (a Python toolbox) and FieldTrip (a Matlab toolbox), and a data set on visuospatial attention is used to illustrate the steps. The scripts are provided as notebooks implemented in Jupyter Notebook and MATLAB Live Editor providing explanations, justifications and graphical outputs for the essential steps. Furthermore, we also provide suggestions for text and parameter settings to be used in registrations and publications to improve replicability and facilitate pre-registrations. The FLUX can be used for education either in self-studies or guided workshops. We expect that the FLUX pipeline will strengthen the field of MEG by providing some standardization on the basic analysis steps and by aligning approaches across toolboxes. Furthermore, we also aim to support new researchers entering the field by providing education and training. The FLUX pipeline is not meant to be static; it will evolve with the development of the toolboxes and with new insights. Furthermore, with the anticipated increase in MEG systems based on the Optically Pumped Magnetometers, the pipeline will also evolve to embrace these developments.