Within functional magnetic resonance imaging (fMRI), the use of the traditional general linear model (GLM) based analysis methods is often restricted to strictly controlled research setups requiring a parametric activation model. Instead, Inter-Subject Correlation (ISC) method is based on voxel-wise correlation between the time series of the subjects, which makes it completely non-parametric and thus suitable for naturalistic stimulus paradigms such as movie watching. In this study, we compared an ISC based analysis results with those of a GLM based in five distinct controlled research setups. We used International Consortium for Brain Mapping functional reference battery (FRB) fMRI data available from the Laboratory of Neuro Imaging image data archive. The selected data included measurements from 37 right-handed subjects, who all had performed the same five tasks from FRB. The GLM was expected to locate activations accurately in FRB data and thus provide good grounds for investigating relationship between ISC and stimulus induced fMRI activation. The statistical maps of ISC and GLM were compared with two measures. The first measure was the Pearson's correlation between the non-thresholded ISC test-statistics and absolute values of the GLM Z-statistics. The average correlation value over five tasks was 0.74. The second was the Dice index between the activation regions of the methods. The average Dice value over the tasks and three threshold levels was 0.73. The results of this study indicated how the data driven ISC analysis found the same foci as the model-based GLM analysis. The agreement of the results is highly interesting, because ISC is applicable in situations where GLM is not suitable, for example, when analyzing data from a naturalistic stimuli experiment.

In the inter-subject correlation (ISC) based analysis of the functional magnetic resonance imaging (fMRI) data, the extent of shared processing across subjects during the experiment is determined by calculating correlation coefficients between the fMRI time series of the subjects in the corresponding brain locations. This implies that ISC can be used to analyze fMRI data without explicitly modeling the stimulus and thus ISC is a potential method to analyze fMRI data acquired under complex naturalistic stimuli. Despite of the suitability of ISC based approach to analyze complex fMRI data, no generic software tools have been made available for this purpose, limiting a widespread use of ISC based analysis techniques among neuroimaging community. In this paper, we present a graphical user interface (GUI) based software package, ISC Toolbox, implemented in Matlab for computing various ISC based analyses. Many advanced computations such as comparison of ISCs between different stimuli, time window ISC, and inter-subject phase synchronization are supported by the toolbox. The analyses are coupled with re-sampling based statistical inference. The ISC based analyses are data and computation intensive and the ISC toolbox is equipped with mechanisms to execute the parallel computations in a cluster environment automatically and with an automatic detection of the cluster environment in use. Currently, SGE-based (Oracle Grid Engine, Son of a Grid Engine, or Open Grid Scheduler) and Slurm environments are supported. In this paper, we present a detailed account on the methods behind the ISC Toolbox, the implementation of the toolbox and demonstrate the possible use of the toolbox by summarizing selected example applications. We also report the computation time experiments both using a single desktop computer and two grid environments demonstrating that parallelization effectively reduces the computing time. The ISC Toolbox is available in https://code.google.com/p/isc-toolbox/

Humor is crucial in human social interactions. To study the underlying neural processes, three comedy clips were shown twice to 20 volunteers during functional magnetic resonance imaging (fMRI). Inter-subject similarities in humor ratings, obtained immediately after fMRI, explained inter-subject correlation of hemodynamic activity in right frontal pole and in a number of other brain regions. General linear model analysis also indicated activity in right frontal pole, as well as in additional cortical areas and subcortically in striatum, explained by humorousness. The association of the right frontal pole with experienced humorousness is a novel finding, which might be related to humor unfolding over longer time scales in the movie clips. Specifically, frontal pole has been shown to exhibit longer temporal receptive windows than, e.g., sensory areas, which might have enabled processing of humor in the clips based on holding information and reinterpreting that in light of new information several (even tens of) seconds later. As another novel finding, medial and lateral prefrontal areas, frontal pole, posterior-inferior temporal areas, posterior parietal areas, posterior cingulate, striatal structures and amygdala showed reduced activity upon re-viewing of the clips, suggesting involvement in processing of humor related to novelty of the comedic events.

This study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single-nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18-0.98, P = 0.044) and 1236T-2677T-3435T (rs1128503-rs2032582-rs1045642) haplotype (HR 0.44, 95% CI, 0.20-0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C-2677G-3435C (HR 2.55, 95% CI, 1.03-6.36, P = 0.044) and 1236T-2677G-3435C (HR 5.88, 95% CI, 2.35-14.72, P < 0.001) haplotypes with an increased risk for thromboembolic outcomes in rivaroxaban users. The ABCB1 c.2482-2236G>A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16-0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.Direct oral anticoagulants (DOACs) are increasingly used in the context of various clinical conditions and procedures, including atrial fibrillation (ischemic stroke prevention), deep vein thrombosis, and pulmonary embolism. DOACs have favorable pharmacodynamic and pharmacokinetic properties and do not require continuous therapeutic monitoring except in specific

Inter-subject correlation (ISC) is a widely used method for analyzing functional magnetic resonance imaging (fMRI) data acquired during naturalistic stimuli. A challenge in ISC analysis is to define the required sample size in the way that the results are reliable. We studied the effect of the sample size on the reliability of ISC analysis and additionally addressed the following question: How many subjects are needed for the ISC statistics to converge to the ISC statistics obtained using a large sample? The study was realized using a large block design data set of 130 subjects. We performed a split-half resampling based analysis repeatedly sampling two nonoverlapping subsets of 10–65 subjects and comparing the ISC maps between the independent subject sets. Our findings suggested that with 20 subjects, on average, the ISC statistics had converged close to a large sample ISC statistic with 130 subjects. However, the split-half reliability of unthresholded and thresholded ISC maps improved notably when the number of subjects was increased from 20 to 30 or more.