Reasonability of Frequent Laboratory Analyses during Therapy with Nivolumab and Nivolumab+Ipilimumab in Patients with Advanced or Metastatic Renal Cell Carcinoma during the Phase 2 Clinical Trial TITAN-RCC.

In clinical trials, laboratory values are assessed with high frequency. This can be stressful for patients, resource intensive, and difficult to implement, for example in office-based settings. In the prospective, multicentre phase 2 TITAN-RCC trial (NCT02917772), we investigated how many relevant changes in laboratory values would have been missed if laboratory values had been assessed less frequently. Patients with metastatic renal cell carcinoma (n = 207) received a response-based approach with nivolumab and nivolumab+ipilimumab boosts for non-response. We simulated that laboratory values were obtained before every second dose instead of every dose of the study drug(s). We assessed elevated leukocyte counts, alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, amylase, lipase, and thyroid-stimulating hormone. Dose delay and discontinuation criteria were defined according to the study protocol. With the reduced frequency of laboratory analyses, dose delay criteria were rarely missed: in a maximum of <0.1% (3/4382) of assessments (1% [2/207] of patients) during nivolumab monotherapy and in a maximum of 0.2% (1/465) of assessments (1% [1/132] of patients) during nivolumab+ipilimumab boosts. An exception was lipase-related dose delay which would have been missed in 0.6% (25/4204) of assessments (7% [15/207] of patients) during nivolumab monotherapy and in 0.8% (4/480) of assessments (3% [4/134] of patients) during nivolumab+ipilimumab boosts, but would have required the presence of symptoms. Discontinuation criteria would have only been missed for amylase (<0.1% [1/3965] of assessments [0.5% (1/207) of patients] during nivolumab monotherapy, none during nivolumab+ipilimumab boosts) and lipase (0.1% [5/4204] of assessments [2% (4/207) of patients] during nivolumab monotherapy; 0.2% [1/480] of assessments [0.7% (1/134) of patients] during nivolumab+ipilimumab boosts). However, only symptomatic patients would have had to discontinue treatment due to amylase or lipase laboratory values. In conclusion, a reduced frequency of laboratory testing appears to be acceptable in asymptomatic patients with metastatic renal cell carcinoma treated with nivolumab or nivolumab+ipilimumab.

Machine-Learning-Based Detecting of Eyelid Closure and Smiling Using Surface Electromyography of Auricular Muscles in Patients with Postparalytic Facial Synkinesis: A Feasibility Study.

Surface electromyography (EMG) allows reliable detection of muscle activity in all nine intrinsic and extrinsic ear muscles during facial muscle movements. The ear muscles are affected by synkinetic EMG activity in patients with postparalytic facial synkinesis (PFS). The aim of the present work was to establish a machine-learning-based algorithm to detect eyelid closure and smiling in patients with PFS by recording sEMG using surface electromyography of the auricular muscles. Sixteen patients (10 female, 6 male) with PFS were included. EMG acquisition of the anterior auricular muscle, superior auricular muscle, posterior auricular muscle, tragicus muscle, orbicularis oculi muscle, and orbicularis oris muscle was performed on both sides of the face during standardized eye closure and smiling tasks. Machine-learning EMG classification with a support vector machine allowed for the reliable detection of eye closure or smiling from the ear muscle recordings with clear distinction to other mimic expressions. These results show that the EMG of the auricular muscles in patients with PFS may contain enough information to detect facial expressions to trigger a future implant in a closed-loop system for electrostimulation to improve insufficient eye closure and smiling in patients with PFS.

Influence of Prostate Artery Embolization on Different Qualities of Lower Urinary Tract Symptoms Due to Benign Prostatic Obstruction.

BACKGROUND: Prostate artery embolization (PAE) is an increasingly used minimally invasive treatment for lower urinary tract symptoms secondary to benign prostatic obstruction (BPO) OBJECTIVE: To analyze the impact of PAE on voiding and storage symptoms. DESIGN, SETTING, AND PARTICIPANTS: Between July 2014 and May 2019, 351 consecutive men with BPO who underwent PAE were included in a single-center study. INTERVENTION: PAE is an interventional radiological procedure embolizing the prostatic arteries with microspheres. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint represented assessment of the International Prostatic Symptom Score (IPSS) at baseline and at 1, 3, 6, 12, and 24 mo after PAE. Secondary endpoints comprised assessment of IPSS quality of life (QoL), International Index of Erectile Function, peak urinary flow rate, postvoid residual volume, prostate volume, and prostate-specific antigen at the same time points. Data were analyzed using standard statistical methods, generalized estimating equations (symptom improvement over time as odds ratios), and McNemar-Bowker test (degree of improvement compared between symptoms). RESULTS AND LIMITATIONS: Clinical success rates for PAE were 68%, 73%, and 66% at 1, 12, and 24 mo, respectively. The median IPSS improved significantly from 22 to 10 points after 2 yr (p < 0.001). Storage (-50%) and voiding (-58%) symptoms improved similarly (each p < 0.001), with nocturia decreasing least frequently but significantly (p < 0.001). After 1 and 2 yr, 35% (95% confidence interval [CI] 29-41%) and 30% (95% CI 21-40%) of patients reported alleviated storage, and 39% (95% CI 33-45%) and 38% (95% CI 29-49%) reported alleviated voiding symptoms, respectively. QoL improved from 5 to 2 points (p < 0.001). The main limitation is the number of patients lost during follow-up. CONCLUSIONS: PAE significantly improved voiding and storage symptoms to a similar extent. This study may aid in counseling patients about this minimally invasive BPO treatment. PATIENT SUMMARY: Prostate artery embolization (PAE) is a minimally invasive treatment option for patients with voiding and storage symptoms from benign prostate enlargement. Our analysis shows that PAE improves relevant lower urinary tract symptoms.

The Right Hemisphere Is Responsible for the Greatest Differences in Human Brain Response to High-Arousing Emotional versus Neutral Stimuli: A MEG Study.

Studies investigating human brain response to emotional stimuli-particularly high-arousing versus neutral stimuli-have obtained inconsistent results. The present study was the first to combine magnetoencephalography (MEG) with the bootstrapping method to examine the whole brain and identify the cortical regions involved in this differential response. Seventeen healthy participants (11 females, aged 19 to 33 years; mean age, 26.9 years) were presented with high-arousing emotional (pleasant and unpleasant) and neutral pictures, and their brain responses were measured using MEG. When random resampling bootstrapping was performed for each participant, the greatest differences between high-arousing emotional and neutral stimuli during M300 (270-320 ms) were found to occur in the right temporo-parietal region. This finding was observed in response to both pleasant and unpleasant stimuli. The results, which may be more robust than previous studies because of bootstrapping and examination of the whole brain, reinforce the essential role of the right hemisphere in emotion processing.

Automated emotion classification in the early stages of cortical processing: An MEG study.

PURPOSE: Here we aimed to automatically classify human emotion earlier than is typically attempted. There is increasing evidence that the human brain differentiates emotional categories within 100-300 ms after stimulus onset. Therefore, here we evaluate the possibility of automatically classifying human emotions within the first 300 ms after the stimulus and identify the time-interval of the highest classification performance. METHODS: To address this issue, MEG signals of 17 healthy volunteers were recorded in response to three different picture stimuli (pleasant, unpleasant, and neutral pictures). Six Linear Discriminant Analysis (LDA) classifiers were used based on two binary comparisons (pleasant versus neutral and unpleasant versus neutral) and three different time-intervals (100-150 ms, 150-200 ms, and 200-300 ms post-stimulus). The selection of the feature subsets was performed by Genetic Algorithm and LDA. RESULTS: We demonstrated significant classification performances in both comparisons. The best classification performance was achieved with a median AUC of 0.83 (95 %- CI [0.71; 0.87]) classifying brain responses evoked by unpleasant and neutral stimuli within 100-150 ms, which is at least 850 ms earlier than attempted by other studies. CONCLUSION: Our results indicate that using the proposed algorithm, brain emotional responses can be significantly classified at very early stages of cortical processing (within 300 ms). Moreover, our results suggest that emotional processing in the human brain occurs within the first 100-150 ms.

Classification of facial movements in chronic facial palsy based on intramuscular EMG signals recorded from the paretic side.

Patients suffering from chronic facial palsy are frequently impaired by severe life-long dysfunctions. Thus, the loss of the ability to close eyes rapidly and completely bears the risk of corneal damages. Moreover, the loss of smile and an altered facial expression imply psychological stress and impede a healthy social life. Since surgical and conservative treatments frequently do not solve many problems sufficiently, closed-loop neural prosthesis are considered as feasible approach. For it, amongst others a reliable detection of the currently executed facial movement is necessary. In our proof of concept study, we propose a data-driven feature extraction for classifying eye closures and smile based on intramuscular EMGs from orbicularis oculi and zygomaticus muscles of the patient's palsy side. The data-adaptive nature of the approach enables a flexible applicability to different muscles and subjects without patient-or muscle-specific adaptations.

The Temporal and Spatial Dynamics of Cortical Emotion Processing in Different Brain Frequencies as Assessed Using the Cluster-Based Permutation Test: An MEG Study.

The processing of emotions in the human brain is an extremely complex process that extends across a large number of brain areas and various temporal processing steps. In the case of magnetoencephalography (MEG) data, various frequency bands also contribute differently. Therefore, in most studies, the analysis of emotional processing has to be limited to specific sub-aspects. Here, we demonstrated that these problems can be overcome by using a nonparametric statistical test called the cluster-based permutation test (CBPT). To the best of our knowledge, our study is the first to apply the CBPT to MEG data of brain responses to emotional stimuli. For this purpose, different emotionally impacting (pleasant and unpleasant) and neutral pictures were presented to 17 healthy subjects. The CBPT was applied to the power spectra of five brain frequencies, comparing responses to emotional versus neutral stimuli over entire MEG channels and time intervals within 1500 ms post-stimulus. Our results showed significant clusters in different frequency bands, and agreed well with many previous emotion studies. However, the use of the CBPT allowed us to easily include large numbers of MEG channels, wide frequency, and long time-ranges in one study, which is a more reliable alternative to other studies that consider only specific sub-aspects.

Abnormal Emotional Processing and Emotional Experience in Patients with Peripheral Facial Nerve Paralysis: An MEG Study.

Abnormal emotional reactions of the brain in patients with facial nerve paralysis have not yet been reported. This study aims to investigate this issue by applying a machine-learning algorithm that discriminates brain emotional activities that belong either to patients with facial nerve paralysis or to healthy controls. Beyond this, we assess an emotion rating task to determine whether there are differences in their experience of emotions. MEG signals of 17 healthy controls and 16 patients with facial nerve paralysis were recorded in response to picture stimuli in three different emotional categories (pleasant, unpleasant, and neutral). The selected machine learning technique in this study was the logistic regression with LASSO regularization. We demonstrated significant classification performances in all three emotional categories. The best classification performance was achieved considering features based on event-related fields in response to the pleasant category, with an accuracy of 0.79 (95% CI (0.70, 0.82)). We also found that patients with facial nerve paralysis rated pleasant stimuli significantly more positively than healthy controls. Our results indicate that the inability to express facial expressions due to peripheral motor paralysis of the face might cause abnormal brain emotional processing and experience of particular emotions.

Exploring intrinsic triggers for functional facial electrostimulation based on intramuscular electromyography recordings.

Based on univariate intramuscular electromyography (EMG) recordings of facial muscles of patients suffering from chronic idiopathic facial palsy we propose a data-driven feature selection process for the discrimination of different mimic maneuvers. Following fundamental ideas of automatic EMG decompositions based on templates defined by motor unit action potentials, the proposed approach relies on a multiple template matching. Yet, the novel methodology utilizes templates derived from the intramuscular EMG signal itself without any supervisor interaction or a priori information by identifying abundant short signal sections (motifs). Focusing on motifs as individual, characteristical graphoelements of an EMG recording implies a high level of flexibility. In connection with facial palsy such a flexibility is necessary, since unique individual, also pathological, EMG patterns can be expected due to the high spatial variability of intramuscular recordings combined with random patterns of aberrant reinnervation. The proposed methodology is applied to EMG data of frontalis, zygomaticus, and orbicularis oculi muscle without patient- or muscle-specific adaptations.

Signal-Adaptive Denoising Of Event-Related Potentials.

In the present study we propose a data-driven, fully unsupervised denoising approach for multi-trial univariate signals. The proposed methodology is based on Empirical Mode Decomposition (EMD) and hence also applicable for transient or non-stationary signals. The rationale of the presented method is that different realizations (multiple trials) of the same underlying process have also similar intrinsic signal components. These components may be extracted by EMD for each single realization and finally, the entirety of all signal components forms clusters of corresponding components with similar spectral characteristics. A denoising is then tantamount to identifying the cluster(s) containing high-frequency noise components. The effectiveness of the proposed methodology is demonstrated on the basis of visual event-related potentials (ERPs) of dyslexic and normal control children. We could show that the novel method allows for a reliable ERP estimation and that it provides a tool for an objective extraction of ERPs on both a single-subject as well as on a single-trial basis.

Influence of imputation strategies on the identification of brain functional connectivity networks.

Whenever neurophysiological data, such as EEG data are recorded, occurring artifacts pose an essential problem. This study addresses this issue by using imputation methods whereby whole data sets of a trial, or distinct electrodes, are not removed from the analysis of the EEG data but are replaced. We present different imputation strategies but use only two which are optimal for this particular study; predictive mean matching and data augmentation. The study addresses the as of yet unresolved question if the quality of derived brain functional networks is improved by imputation methods compared to traditional exclusion techniques which drop data, and will finally assesses the differences between the two imputation methods themselves used here. In this study, EEG data from a study evaluating dyslexia-specific therapy on a neurophysiological level were used to investigate imputation strategies in research of cortical interaction. Several recorded values were artificially declared as 'missing'. This enables the comparison of networks based on the complete data set without any missing values (pseudo ground truth) and those derived from imputation approaches in a realistic situation of disturbed data. Functional connectivity was quantified by time-variant partial directed coherence, providing a directed, temporally varying and frequency-selective connectivity measure. Based on the comparison between pseudo ground truth and networks of data with excluded missing values and data with imputed values, we found that any imputation strategy is preferable to the entire exclusion of data. The study also showed that the choice of the applied imputation algorithm impacts the resulting networks only marginally.

Identifying HIV Associated Neurocognitive Disorder Using Large-Scale Granger Causality Analysis on Resting-State Functional MRI.

We investigate the applicability of large-scale Granger Causality (lsGC) for extracting a measure of multivariate information flow between pairs of regional brain activities from resting-state functional MRI (fMRI) and test the effectiveness of these measures for predicting a disease state. Such pairwise multivariate measures of interaction provide high-dimensional representations of connectivity profiles for each subject and are used in a machine learning task to distinguish between healthy controls and individuals presenting with symptoms of HIV Associated Neurocognitive Disorder (HAND). Cognitive impairment in several domains can occur as a result of HIV infection of the central nervous system. The current paradigm for assessing such impairment is through neuropsychological testing. With fMRI data analysis, we aim at non-invasively capturing differences in brain connectivity patterns between healthy subjects and subjects presenting with symptoms of HAND. To classify the extracted interaction patterns among brain regions, we use a prototype-based learning algorithm called Generalized Matrix Learning Vector Quantization (GMLVQ). Our approach to characterize connectivity using lsGC followed by GMLVQ for subsequent classification yields good prediction results with an accuracy of 87% and an area under the ROC curve (AUC) of up to 0.90. We obtain a statistically significant improvement (p<0.01) over a conventional Granger causality approach (accuracy = 0.76, AUC = 0.74). High accuracy and AUC values using our multivariate method to connectivity analysis suggests that our approach is able to better capture changes in interaction patterns between different brain regions when compared to conventional Granger causality analysis known from the literature.

Exploring connectivity with large-scale Granger causality on resting-state functional MRI.

BACKGROUND: Large-scale Granger causality (lsGC) is a recently developed, resting-state functional MRI (fMRI) connectivity analysis approach that estimates multivariate voxel-resolution connectivity. Unlike most commonly used multivariate approaches, which establish coarse-resolution connectivity by aggregating voxel time-series avoiding an underdetermined problem, lsGC estimates voxel-resolution, fine-grained connectivity by incorporating an embedded dimension reduction. NEW METHOD: We investigate application of lsGC on realistic fMRI simulations, modeling smoothing of neuronal activity by the hemodynamic response function and repetition time (TR), and empirical resting-state fMRI data. Subsequently, functional subnetworks are extracted from lsGC connectivity measures for both datasets and validated quantitatively. We also provide guidelines to select lsGC free parameters. RESULTS: Results indicate that lsGC reliably recovers underlying network structure with area under receiver operator characteristic curve (AUC) of 0.93 at TR=1.5s for a 10-min session of fMRI simulations. Furthermore, subnetworks of closely interacting modules are recovered from the aforementioned lsGC networks. Results on empirical resting-state fMRI data demonstrate recovery of visual and motor cortex in close agreement with spatial maps obtained from (i) visuo-motor fMRI stimulation task-sequence (Accuracy=0.76) and (ii) independent component analysis (ICA) of resting-state fMRI (Accuracy=0.86). COMPARISON WITH EXISTING METHOD(S): Compared with conventional Granger causality approach (AUC=0.75), lsGC produces better network recovery on fMRI simulations. Furthermore, it cannot recover functional subnetworks from empirical fMRI data, since quantifying voxel-resolution connectivity is not possible as consequence of encountering an underdetermined problem. CONCLUSIONS: Functional network recovery from fMRI data suggests that lsGC gives useful insight into connectivity patterns from resting-state fMRI at a multivariate voxel-resolution.

Nonlinear Directed Interactions Between HRV and EEG Activity in Children With TLE.

OBJECTIVE: Epileptic seizure activity influences the autonomic nervous system (ANS) in different ways. Heart rate variability (HRV) is used as indicator for alterations of the ANS. It was shown that linear, nondirected interactions between HRV and EEG activity before, during, and after epileptic seizure occur. Accordingly, investigations of directed nonlinear interactions are logical steps to provide, e.g., deeper insight into the development of seizure onsets. METHODS: Convergent cross mapping (CCM) investigates nonlinear, directed interactions between time series by using nonlinear state space reconstruction. CCM is applied to simulated and clinically relevant data, i.e., interactions between HRV and specific EEG components of children with temporal lobe epilepsy (TLE). In addition, time-variant multivariate Autoregressive model (AR)-based estimation of partial directed coherence (PDC) was performed for the same data. RESULTS: Influence of estimation parameters and time-varying behavior of CCM estimation could be demonstrated by means of simulated data. AR-based estimation of PDC failed for the investigation of our clinical data. Time-varying interval-based application of CCM on these data revealed directed interactions between HRV and delta-related EEG activity. Interactions between HRV and alpha-related EEG activity were visible but less pronounced. EEG components mainly drive HRV. The interaction pattern and directionality clearly changed with onset of seizure. Statistical relevant interactions were quantified by bootstrapping and surrogate data approach. CONCLUSION AND SIGNIFICANCE: In contrast to AR-based estimation of PDC CCM was able to reveal time-courses and frequency-selective views of nonlinear interactions for the further understanding of complex interactions between the epileptic network and the ANS in children with TLE.

A Multivariate Granger Causality Concept towards Full Brain Functional Connectivity.

Detecting changes of spatially high-resolution functional connectivity patterns in the brain is crucial for improving the fundamental understanding of brain function in both health and disease, yet still poses one of the biggest challenges in computational neuroscience. Currently, classical multivariate Granger Causality analyses of directed interactions between single process components in coupled systems are commonly restricted to spatially low- dimensional data, which requires a pre-selection or aggregation of time series as a preprocessing step. In this paper we propose a new fully multivariate Granger Causality approach with embedded dimension reduction that makes it possible to obtain a representation of functional connectivity for spatially high-dimensional data. The resulting functional connectivity networks may consist of several thousand vertices and thus contain more detailed information compared to connectivity networks obtained from approaches based on particular regions of interest. Our large scale Granger Causality approach is applied to synthetic and resting state fMRI data with a focus on how well network community structure, which represents a functional segmentation of the network, is preserved. It is demonstrated that a number of different community detection algorithms, which utilize a variety of algorithmic strategies and exploit topological features differently, reveal meaningful information on the underlying network module structure.

Detecting spatially highly resolved network modules: a multi subject approach.

The connectivity analysis of spatially highly resolved data results in networks comprising an immense number of nodes and edges which makes it hard or even impossible to investigate the high-dimensional (HD) network as a whole. A solution to this problem is offered by a connectivity-based segmentation of the HD networks into subsets of functionally similar nodes (network modules) that exhibit pronounced interaction. However, an investigation of the results at group level is problematic as identified modules are not assigned to each other across different subjects. In this work, we propose a rearrangement of the subject-specific networks into an integrative tensor which is subsequently decomposed into additive factors. This reorganization provides subject-independent networks together with subject-specific loadings enabling a group-wide segmentation of the resulting networks at the large scale.

A time domain frequency-selective multivariate Granger causality approach.

The investigation of effective connectivity is one of the major topics in computational neuroscience to understand the interaction between spatially distributed neuronal units of the brain. Thus, a wide variety of methods has been developed during the last decades to investigate functional and effective connectivity in multivariate systems. Their spectrum ranges from model-based to model-free approaches with a clear separation into time and frequency range methods. We present in this simulation study a novel time domain approach based on Granger's principle of predictability, which allows frequency-selective considerations of directed interactions. It is based on a comparison of prediction errors of multivariate autoregressive models fitted to systematically modified time series. These modifications are based on signal decompositions, which enable a targeted cancellation of specific signal components with specific spectral properties. Depending on the embedded signal decomposition method, a frequency-selective or data-driven signal-adaptive Granger Causality Index may be derived.

Large-Scale Granger Causality Analysis on Resting-State Functional MRI.

We demonstrate an approach to measure the information flow between each pair of time series in resting-state functional MRI (fMRI) data of the human brain and subsequently recover its underlying network structure. By integrating dimensionality reduction into predictive time series modeling, large-scale Granger Causality (lsGC) analysis method can reveal directed information flow suggestive of causal influence at an individual voxel level, unlike other multivariate approaches. This method quantifies the influence each voxel time series has on every other voxel time series in a multivariate sense and hence contains information about the underlying dynamics of the whole system, which can be used to reveal functionally connected networks within the brain. To identify such networks, we perform non-metric network clustering, such as accomplished by the Louvain method. We demonstrate the effectiveness of our approach to recover the motor and visual cortex from resting state human brain fMRI data and compare it with the network recovered from a visuomotor stimulation experiment, where the similarity is measured by the Dice Coefficient (DC). The best DC obtained was 0.59 implying a strong agreement between the two networks. In addition, we thoroughly study the effect of dimensionality reduction in lsGC analysis on network recovery. We conclude that our approach is capable of detecting causal influence between time series in a multivariate sense, which can be used to segment functionally connected networks in the resting-state fMRI.

Are Structural Changes Induced by Lithium in the HIV Brain Accompanied by Changes in Functional Connectivity?

Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.

Advanced Insights into Functional Brain Connectivity by Combining Tensor Decomposition and Partial Directed Coherence.

Quantification of functional connectivity in physiological networks is frequently performed by means of time-variant partial directed coherence (tvPDC), based on time-variant multivariate autoregressive models. The principle advantage of tvPDC lies in the combination of directionality, time variance and frequency selectivity simultaneously, offering a more differentiated view into complex brain networks. Yet the advantages specific to tvPDC also cause a large number of results, leading to serious problems in interpretability. To counter this issue, we propose the decomposition of multi-dimensional tvPDC results into a sum of rank-1 outer products. This leads to a data condensation which enables an advanced interpretation of results. Furthermore it is thereby possible to uncover inherent interaction patterns of induced neuronal subsystems by limiting the decomposition to several relevant channels, while retaining the global influence determined by the preceding multivariate AR estimation and tvPDC calculation of the entire scalp. Finally a comparison between several subjects is considerably easier, as individual tvPDC results are summarized within a comprehensive model equipped with subject-specific loading coefficients. A proof-of-principle of the approach is provided by means of simulated data; EEG data of an experiment concerning visual evoked potentials are used to demonstrate the applicability to real data.