Using rare genetic mutations to revisit structural brain asymmetry.

Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We designed a pattern-learning approach to dissect the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior data fusion highlights the consequences of genetically controlled brain lateralization on uniquely human cognitive capacities.

Large-scale network dynamics underlying the first few hundred milliseconds after stimulus presentation: An investigation of visual recognition memory using iEEG.

Recognition memory is the ability to recognize previously encountered objects. Even this relatively simple, yet extremely fast, ability requires the coordinated activity of large-scale brain networks. However, little is known about the sub-second dynamics of these networks. The majority of current studies into large-scale network dynamics is primarily based on imaging techniques suffering from either poor temporal or spatial resolution. We investigated the dynamics of large-scale functional brain networks underlying recognition memory at the millisecond scale. Specifically, we analyzed dynamic effective connectivity from intracranial electroencephalography while epileptic subjects (n = 18) performed a fast visual recognition memory task. Our data-driven investigation using Granger causality and the analysis of communities with the Louvain algorithm spotlighted a dynamic interplay of two large-scale networks associated with successful recognition. The first network involved the right visual ventral stream and bilateral frontal regions. It was characterized by early, predominantly bottom-up information flow peaking at 115 ms. It was followed by the involvement of another network with predominantly top-down connectivity peaking at 220 ms, mainly in the left anterior hemisphere. The transition between these two networks was associated with changes in network topology, evolving from a more segregated to a more integrated state. These results highlight that distinct large-scale brain networks involved in visual recognition memory unfold early and quickly, within the first 300 ms after stimulus onset. Our study extends the current understanding of the rapid network changes during rapid cognitive processes.

Bayesian modeling disentangles language versus executive control disruption in stroke.

Stroke is the leading cause of long-term disability worldwide. Incurred brain damage disrupts cognition, often with persisting deficits in language and executive capacities. Despite their clinical relevance, the commonalities, and differences of language versus executive control impairments remain under-specified. We tailored a Bayesian hierarchical modeling solution in a largest-of-its-kind cohort (1080 stroke patients) to deconvolve language and executive control in the brain substrates of stroke insults. Four cognitive factors distinguished left- and right-hemispheric contributions to ischemic tissue lesion. One factor delineated language and general cognitive performance and was mainly associated with damage to left-hemispheric brain regions in the frontal and temporal cortex. A factor for executive control summarized control and visual-constructional abilities. This factor was strongly related to right-hemispheric brain damage of posterior regions in the occipital cortex. The interplay of language and executive control was reflected in two factors: executive speech functions and verbal memory. Impairments on both were mainly linked to left-hemispheric lesions. These findings shed light onto the causal implications of hemispheric specialization for cognition; and make steps towards subgroup-specific treatment protocols after stroke.

The default network dominates neural responses to evolving movie stories.

Neuroscientific studies exploring real-world dynamic perception often overlook the influence of continuous changes in narrative content. In our research, we utilize machine learning tools for natural language processing to examine the relationship between movie narratives and neural responses. By analyzing over 50,000 brain images of participants watching Forrest Gump from the studyforrest dataset, we find distinct brain states that capture unique semantic aspects of the unfolding story. The default network, associated with semantic information integration, is the most engaged during movie watching. Furthermore, we identify two mechanisms that underlie how the default network liaises with the amygdala and hippocampus. Our findings demonstrate effective approaches to understanding neural processes in everyday situations and their relation to conscious awareness.

Using rare genetic mutations to revisit structural brain asymmetry.

Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence.

Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleiotropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts. It remains unknown, for example, how distinct CNVs escalate vulnerability for the same developmental and psychiatric disorders. Here we quantitatively dissect the associations between brain organization and behavioural differentiation across 8 key CNVs. In 534 CNV carriers, we explored CNV-specific brain morphology patterns. CNVs were characteristic of disparate morphological changes involving multiple large-scale networks. We extensively annotated these CNV-associated patterns with ~1,000 lifestyle indicators through the UK Biobank resource. The resulting phenotypic profiles largely overlap and have body-wide implications, including the cardiovascular, endocrine, skeletal and nervous systems. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

Multimodal-neuroimaging machine-learning analysis of motor disability in multiple sclerosis.

Motor disability is a dominant and restricting symptom in multiple sclerosis, yet its neuroimaging correlates are not fully understood. We apply statistical and machine learning techniques on multimodal neuroimaging data to discriminate between multiple sclerosis patients and healthy controls and to predict motor disability scores in the patients. We examine the data of sixty-four multiple sclerosis patients and sixty-five controls, who underwent the MRI examination and the evaluation of motor disability scales. The modalities used comprised regional fractional anisotropy, regional grey matter volumes, and functional connectivity. For analysis, we employ two approaches: high-dimensional support vector machines run on features selected by Fisher Score (aiming for maximal classification accuracy), and low-dimensional logistic regression on the principal components of data (aiming for increased interpretability). We apply analogous regression methods to predict symptom severity. While fractional anisotropy provides the classification accuracy of 96.1% and 89.9% with both approaches respectively, including other modalities did not bring further improvement. Concerning the prediction of motor impairment, the low-dimensional approach performed more reliably. The first grey matter volume component was significantly correlated (R = 0.28-0.46, p < 0.05) with most clinical scales. In summary, we identified the relationship between both white and grey matter changes and motor impairment in multiple sclerosis. Furthermore, we were able to achieve the highest classification accuracy based on quantitative MRI measures of tissue integrity between patients and controls yet reported, while also providing a low-dimensional classification approach with comparable results, paving the way to interpretable machine learning models of brain changes in multiple sclerosis.

Typicality of functional connectivity robustly captures motion artifacts in rs-fMRI across datasets, atlases, and preprocessing pipelines.

Functional connectivity analysis of resting-state fMRI data has recently become one of the most common approaches to characterizing individual brain function. It has been widely suggested that the functional connectivity matrix is a useful approximate representation of the brain's connectivity, potentially providing behaviorally or clinically relevant markers. However, functional connectivity estimates are known to be detrimentally affected by various artifacts, including those due to in-scanner head motion. Moreover, as individual functional connections generally covary only very weakly with head motion estimates, motion influence is difficult to quantify robustly, and prone to be neglected in practice. Although the use of individual estimates of head motion, or group-level correlation of motion and functional connectivity has been suggested, a sufficiently sensitive measure of individual functional connectivity quality has not yet been established. We propose a new intuitive summary index, Typicality of Functional Connectivity, to capture deviations from standard brain functional connectivity patterns. In a resting-state fMRI dataset of 245 healthy subjects, this measure was significantly correlated with individual head motion metrics. The results were further robustly reproduced across atlas granularity, preprocessing options, and other datasets, including 1,081 subjects from the Human Connectome Project. In principle, Typicality of Functional Connectivity should be sensitive also to other types of artifacts, processing errors, and possibly also brain pathology, allowing extensive use in data quality screening and quantification in functional connectivity studies as well as methodological investigations.

Breathing Analysis Using Thermal and Depth Imaging Camera Video Records.

The paper is devoted to the study of facial region temperature changes using a simple thermal imaging camera and to the comparison of their time evolution with the pectoral area motion recorded by the MS Kinect depth sensor. The goal of this research is to propose the use of video records as alternative diagnostics of breathing disorders allowing their analysis in the home environment as well. The methods proposed include (i) specific image processing algorithms for detecting facial parts with periodic temperature changes; (ii) computational intelligence tools for analysing the associated videosequences; and (iii) digital filters and spectral estimation tools for processing the depth matrices. Machine learning applied to thermal imaging camera calibration allowed the recognition of its digital information with an accuracy close to 100% for the classification of individual temperature values. The proposed detection of breathing features was used for monitoring of physical activities by the home exercise bike. The results include a decrease of breathing temperature and its frequency after a load, with mean values -0.16 °C/min and -0.72 bpm respectively, for the given set of experiments. The proposed methods verify that thermal and depth cameras can be used as additional tools for multimodal detection of breathing patterns.

Complex continuous wavelet coherence for EEG microstates detection in insight and calm meditation.

Complex continuous wavelet coherence (WTC) can be used for non-stationary signals, such as electroencephalograms. Areas of the WTC with a coherence higher than the calculated optimal threshold were obtained, and the sum of their areas was used as a criterion to differentiate between groups of experienced insight-focused meditators, calm-focused meditators and a control group. This method demonstrated the highest accuracy for the real WTC parts in the frontal region, while for the imaginary parts, the highest accuracy was shown for the frontal occipital pairs of electrodes. In the frontal area, in the broadband frequency, both types of experienced meditators demonstrated an enlargement of the increased coherence areas for the real WTC parts. For the imaginary parts unaffected by the volume conduction and global artefacts, the most significant increase occurred for the frontal occipital pair of electrodes.