Identifying Depressed Essential Tremor Using Resting-State Voxel-Wise Global Brain Connectivity: A Multivariate Pattern Analysis

Background and Objective: Although depression is one of the most common non-motor symptoms in essential tremor (ET), its pathogenesis and diagnosis biomarker are still unknown. Recently, machine learning multivariate pattern analysis (MVPA) combined with connectivity mapping of resting-state fMRI has provided a promising way to identify patients with depressed ET at the individual level and help to reveal the brain network pathogenesis of depression in patients with ET.Methods: Based on global brain connectivity (GBC) mapping from 41 depressed ET, 49 non-depressed ET, 45 primary depression, and 43 healthy controls (HCs), multiclass Gaussian process classification (GPC) and binary support vector machine (SVM) algorithms were used to identify patients with depressed ET from non-depressed ET, primary depression, and HCs, and the accuracy and permutation tests were used to assess the classification performance.Results: While the total accuracy (40.45%) of four-class GPC was poor, the four-class GPC could discriminate depressed ET from non-depressed ET, primary depression, and HCs with a sensitivity of 70.73% (P < 0.001). At the same time, the sensitivity of using binary SVM to discriminate depressed ET from non-depressed ET, primary depression, and HCs was 73.17, 80.49, and 75.61%, respectively (P < 0.001). The significant discriminative features were mainly located in cerebellar-motor-prefrontal cortex circuits (P < 0.001), and a further correlation analysis showed that the GBC values of significant discriminative features in the right middle prefrontal gyrus, bilateral cerebellum VI, and Crus 1 were correlated with clinical depression severity in patients with depressed ET.Conclusion: Our findings demonstrated that GBC mapping combined with machine learning MVPA could be used to identify patients with depressed ET, and the GBC changes in cerebellar-prefrontal cortex circuits not only posed as the significant discriminative features but also helped to understand the network pathogenesis underlying depression in patients with ET.

Multivariate pattern analysis reveals location specific aftereffects of 10Hz motor cortex transcranial alternating current stimulation

Background: Transcranial alternating current stimulation (tACS) may induce frequency-specific aftereffects on brain oscillations in the stimulated location, which could serve as evidence for region-specific neuroplasticity. Aftereffects of tACS on the motor system remain unknown. Objective: To find evidence for aftereffects in short EEG segments following tACS to two critical nodes of the motor network, namely, left motor cortex (lMC) and right cerebellum (rCB). We hypothesized that aftereffects of lMC will be stronger in and around lMC compared to both active stimulation of rCB, as well as inactive (sham) control conditions. Methods: To this end, we employed multivariate pattern analysis (MVPA), and trained a classifier to distinguish between EEG signals following each of the three stimulation protocols. This method accounts for the multitude facets of the EEG signal and thus is more sensitive to subtle modulation of the EEG signal. Results: EEG signals in both theta (θ, 4-8Hz) and alpha (α, 8-13Hz) were better classified to lMC-tACS compared to rCB-tACS/sham, in and around lMC-tACS stimulation locations (electrodes FC3 and CP3). This effect was associated with a decrease in power following tACS. Source reconstruction revealed significant differences in premotor cortex but not in primary motor cortex as the computational model suggested. Correlation between classification accuracies in θ and α in lMC-tACS was stronger compared to rCB-tACS/sham, suggesting cross-frequency effects of tACS. Nonetheless, θ/α phase-coupling did not differ between stimulation protocols. Conclusions: Successful classification of EEG signals to left motor cortex using MVPA revealed focal tACS aftereffects on the motor cortex, indicative of region-specific neuroplasticity.

MEG cortical microstates: spatiotemporal characteristics, dynamic functional connectivity and stimulus-evoked responses

EEG microstate analysis is an approach to study brain states and their fast transitions in healthy cognition and disease. A key limitation of conventional microstate analysis is that it must be performed at the sensor level, and therefore gives limited anatomical insight. Here, we generalise the microstate methodology to be applicable to source-reconstructed electrophysiological data. Using simulations of a neural-mass network model, we first established the validity and robustness of the proposed method. Using MEG resting-state data, we uncovered ten microstates with distinct spatial distributions of cortical activation. Multivariate pattern analysis demonstrated that source-level microstates were associated with distinct functional connectivity patterns. We further demonstrated that the occurrence probability of MEG microstates were altered by auditory stimuli, exhibiting a hyperactivity of the microstate including the auditory cortex. Our results support the use of source-level microstates as a method for investigating brain dynamic activity and connectivity at the millisecond scale.

Individualized diagnosis of major depressive disorder via multivariate pattern analysis of thalamic sMRI features

Background Magnetic resonance imaging (MRI) studies have found thalamic abnormalities in major depressive disorder (MDD). Although there are significant differences in the structure and function of the thalamus between MDD patients and healthy controls (HCs) at the group level, it is not clear whether the structural and functional features of the thalamus are suitable for use as diagnostic prediction aids at the individual level. Here, we were to test the predictive value of gray matter density (GMD), gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) in the thalamus using multivariate pattern analysis (MVPA). Methods Seventy-four MDD patients and 44 HC subjects were recruited. The Gaussian process classifier (GPC) was trained to separate MDD patients from HCs, Gaussian process regression (GPR) was trained to predict depression scores, and Multiple Kernel Learning (MKL) was applied to explore the contribution of each subregion of the thalamus. Results The primary findings were as follows: [1] The balanced accuracy of the GPC trained with thalamic GMD was 96.59% (P < 0.001). The accuracy of the GPC trained with thalamic GMV was 93.18% (P < 0.001). The correlation between Hamilton Depression Scale (HAMD) score targets and predictions in the GPR trained with GMD was 0.90 (P < 0.001, r2 = 0.82), and in the GPR trained with GMV, the correlation between HAMD score targets and predictions was 0.89 (P < 0.001, r2 = 0.79). [2] The models trained with ALFF and fALFF in the thalamus failed to discriminate MDD patients from HC participants. [3] The MKL model showed that the left lateral prefrontal thalamus, the right caudal temporal thalamus, and the right sensory thalamus contribute more to the diagnostic classification. Conclusions The results suggested that GMD and GMV, but not functional indicators of the thalamus, have good potential for the individualized diagnosis of MDD. Furthermore, the thalamus shows the heterogeneity in the structural features of thalamic subregions for predicting MDD. To our knowledge, this is the first study to focus on the thalamus for the prediction of MDD using machine learning methods at the individual level.

Multivariate pattern analysis of brain structure predicts functional outcome after auditory-based cognitive training interventions

Cognitive gains following cognitive training interventions are associated with improved functioning in people with schizophrenia (SCZ). However, considerable inter-individual variability is observed. Here, we evaluate the sensitivity of brain structural features to predict functional response to auditory-based cognitive training (ABCT) at a single-subject level. We employed whole-brain multivariate pattern analysis with support vector machine (SVM) modeling to identify gray matter (GM) patterns that predicted higher vs. lower functioning after 40 h of ABCT at the single-subject level in SCZ patients. The generalization capacity of the SVM model was evaluated by applying the original model through an out-of-sample cross-validation analysis to unseen SCZ patients from an independent validation sample who underwent 50 h of ABCT. The whole-brain GM volume-based pattern classification predicted higher vs. lower functioning at follow-up with a balanced accuracy (BAC) of 69.4% (sensitivity 72.2%, specificity 66.7%) as determined by nested cross-validation. The neuroanatomical model was generalizable to an independent cohort with a BAC of 62.1% (sensitivity 90.9%, specificity 33.3%). In particular, greater baseline GM volumes in regions within superior temporal gyrus, thalamus, anterior cingulate, and cerebellum predicted improved functioning at the single-subject level following ABCT in SCZ participants. The present findings provide a structural MRI fingerprint associated with preserved GM volumes at a single baseline timepoint, which predicted improved functioning following an ABCT intervention, and serve as a model for how to facilitate precision clinical therapies for SCZ based on imaging data, operating at the single-subject level.

Spatiotemporally Resolved Multivariate Pattern Analysis for M/EEG

An emerging goal in neuroscience is tracking what information is represented in brain activity over time as a participant completes some task. Whilst EEG and MEG offer millisecond temporal resolution of how activity patterns emerge and evolve, standard decoding methods present significant barriers to interpretability as they obscure the underlying spatial and temporal activity patterns. We instead propose the use of a generative encoding model framework that simultaneously infers the multivariate spatial patterns of activity and the variable timing at which these patterns emerge on individual trials. An encoding model inversion allows predictions to be made about unseen test data in the same way as in standard decoding methodology. These SpatioTemporally Resolved MVPA (STRM) models can be flexibly applied to a wide variety of experimental paradigms, including classification and regression tasks. We show that these models provide insightful maps of the activity driving predictive accuracy metrics; demonstrate behaviourally meaningful variation in the timing of pattern emergence on individual trials; and achieve predictive accuracies that are either equivalent or surpass those achieved by more widely used methods. This provides a new avenue for investigating the brain's representational dynamics and could ultimately support more flexible experimental designs in future.