Multiple Neuroimaging Modalities Research Articles

BCI Training Effects on Chronic Stroke Correlate with Functional Reorganization in Motor-Related Regions: A Concurrent EEG and fMRI Study

Brain–computer interface (BCI)-guided robot-assisted training strategy has been increasingly applied to stroke rehabilitation, while few studies have investigated the neuroplasticity change and functional reorganization after intervention from multimodality neuroimaging perspective. The present study aims to investigate the hemodynamic and electrophysical changes induced by BCI training using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) respectively, as well as the relationship between the neurological changes and motor function improvement. Fourteen chronic stroke subjects received 20 sessions of BCI-guided robot hand training. Simultaneous EEG and fMRI data were acquired before and immediately after the intervention. Seed-based functional connectivity for resting-state fMRI data and effective connectivity analysis for EEG were processed to reveal the neuroplasticity changes and interaction between different brain regions. Moreover, the relationship among motor function improvement, hemodynamic changes, and electrophysical changes derived from the two neuroimaging modalities was also investigated. This work suggested that (a) significant motor function improvement could be obtained after BCI training therapy, (b) training effect significantly correlated with functional connectivity change between ipsilesional M1 (iM1) and contralesional Brodmann area 6 (including premotor area (cPMA) and supplementary motor area (SMA)) derived from fMRI, (c) training effect significantly correlated with information flow change from cPMA to iM1 and strongly correlated with information flow change from SMA to iM1 derived from EEG, and (d) consistency of fMRI and EEG results illustrated by the correlation between functional connectivity change and information flow change. Our study showed changes in the brain after the BCI training therapy from chronic stroke survivors and provided a better understanding of neural mechanisms, especially the interaction among motor-related brain regions during stroke recovery. Besides, our finding demonstrated the feasibility and consistency of combining multiple neuroimaging modalities to investigate the neuroplasticity change.

Machine learning-based multimodal prediction of language outcomes in chronic aphasia.

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left‐hemisphere stroke were included in the study. Neuroimaging data included task‐based functional magnetic resonance imaging (fMRI), diffusion‐based fractional anisotropy (FA)‐values, cerebral blood flow (CBF), and lesion‐load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00–.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53–.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p‐value range: <.001–.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.

Changes in the anterior cingulate cortex in Crohn's disease: A neuroimaging perspective.

IntroductionEvidence suggests that Crohn's disease (CD) pathophysiology goes beyond the gastrointestinal tract and is also strongly associated with the brain. In particular, the anterior cingulate cortex (ACC), which plays an integral role in the first brain as part of the default mode network (DMN) and pain matrix, shows abnormalities using multiple neuroimaging modalities. This review summarizes nine related studies that investigated changes in the ACC using structural magnetic resonance imaging, resting‐state functional magnetic resonance imaging, and magnetic resonance spectroscopy.MethodsAn extensive PubMed literature search was conducted from 1980 to August 2020. In a review of the articles identified, particular attention was paid to analysis methods, technical protocol characteristics, and specific changes in the ACC.ResultsIn terms of morphology, a decrease in gray matter volume and cortical thickness was observed along with an increase in local gyrification index. In terms of function, functional connectivity (FC) within the DMN was increased. FC between the ACC and the amygdala was decreased. Higher amplitudes of low‐frequency fluctuation and graph theory results, including connectivity strength, clustering coefficient, and local efficiency, were detected. In terms of neurotransmitter changes, the concentrations of glutamate increased along with a decrease in gamma‐aminobutyric acid, providing a rational explanation for abdominal pain. These changes may be attributed to stress, pain, and negative emotions, as well as changes in gut microbiota.ConclusionsFor patients with CD, the ACC demonstrates structural, functional, and metabolic changes. In terms of clinical findings, the ACC plays an important role in the onset of depression/anxiety and abdominal pain. Therefore, successful modulation of this pathway may guide treatment.

Quantitative multimodal imaging in traumatic brain injuries producing impaired cognition.

Cognitive impairments are a devastating long-term consequence following traumatic brain injury (TBI). This review provides an update on the quantitative mutimodal neuroimaging studies that attempt to elucidate the mechanism(s) underlying cognitive impairments and their recovery following TBI. Recent studies have linked individual specific behavioural impairments and their changes over time to physiological activity and structural changes using EEG, PET and MRI. Multimodal studies that combine measures of physiological activity with knowledge of neuroanatomical and connectivity damage have also illuminated the multifactorial function-structure relationships that underlie impairment and recovery following TBI. The combined use of multiple neuroimaging modalities, with focus on individual longitudinal studies, has the potential to accurately classify impairments, enhance sensitivity of prognoses, inform targets for interventions and precisely track spontaneous and intervention-driven recovery.

On the time-course of functional connectivity: theory of a dynamic progression of concussion effects.

The current literature presents a discordant view of mild traumatic brain injury and its effects on the human brain. This dissonance has often been attributed to heterogeneities in study populations, aetiology, acuteness, experimental paradigms and/or testing modalities. To investigate the progression of mild traumatic brain injury in the human brain, the present study employed data from 93 subjects (48 healthy controls) representing both acute and chronic stages of mild traumatic brain injury. The effects of concussion across different stages of injury were measured using two metrics of functional connectivity in segments of electroencephalography time-locked to an active oddball task. Coherence and weighted phase-lag index were calculated separately for individual frequency bands (delta, theta, alpha and beta) to measure the functional connectivity between six electrode clusters distributed from frontal to parietal regions across both hemispheres. Results show an increase in functional connectivity in the acute stage after mild traumatic brain injury, contrasted with significantly reduced functional connectivity in chronic stages of injury. This finding indicates a non-linear time-dependent effect of injury. To understand this pattern of changing functional connectivity in relation to prior evidence, we propose a new model of the time-course of the effects of mild traumatic brain injury on the brain that brings together research from multiple neuroimaging modalities and unifies the various lines of evidence that at first appear to be in conflict.

T163. STRUCTURAL AND CONNECTIVITY CHANGES IN THE CEREBELLUM CONTRIBUTE TO EXPERIENCING AUDITORY VERBAL HALLUCINATIONS

BackgroundAuditory verbal hallucinations (AVH) have been explained in the context of the forward model, giving the cerebellum a prominent role. However, research utilizing multiple neuroimaging modalities has rendered results on the specificity of cerebellar contribution to AVH unclear.MethodsTo examine the reliability and regional specificity of cerebellar changes in AVH, a systematic search of electronic databases through October 2019 was conducted to identify neuroimaging studies of the cerebellum in psychotic patients or nonclinical participants reporting AVH, focusing on structural MRI, diffusion tensor imaging, and resting state functional connectivity studies. Twenty-two studies were selected, including 892 participants with AVH (792 psychotic patients; 100 at-risk subjects) and 775 healthy controls. Activation likelihood estimate analysis (ALE) examined the reported coordinates for reduced volume, fractional anisotropy (FA) or connectivity (control participants > participants with AVH) and increased volume, FA or connectivity (participants with AVH > control participants). The consistency of cerebellar changes and their relationship with sociodemographic and clinical measures were meta-analyzed.ResultsThe ALE meta-analysis revealed changes in both anterior and posterior cerebellar lobes, with opposite patterns: whereas decreased volume or connectivity was identified in the right anterior cerebellum (lobule IV/V), increased volume or connectivity was identified in the bilateral posterior cerebellum (Crus I and II). A random-effects model with small sample corrections identified consistent changes in both volume and functional connectivity of the cerebellum in participants with AVH (g = .84; SE = .24, 95% CI [.33, 1.34]), which were enhanced in Crus I (g = 1.52, SE = .28, p = .006, 95% CI [.73, 2.31]) but not moderated by age, sex, medication, or illness duration.DiscussionThe ALE meta-analysis confirms cerebellar structural and connectivity changes in psychotic and nonclinical participants reporting AVH. These changes may contribute to AVH due to altered sensory feedback and consequently to erratic prediction as described by the forward model. The current findings also indicate that not all cerebellar regions are equally affected by AVH: the most pronounced changes were observed in Crus I. Specifically, altered communication between Crus I and neocortical network nodes, including the prefrontal cortex, may contribute to ineffective cognitive control in AVH, leading to external misattributions of auditory feedback and a reduced sense of control over events in the environment.

Deep residual learning for neuroimaging: An application to predict progression to Alzheimer’s disease

BackgroundThe unparalleled performance of deep learning approaches in generic image processing has motivated its extension to neuroimaging data. These approaches learn abstract neuroanatomical and functional brain alterations that could enable exceptional performance in classification of brain disorders, predicting disease progression, and localizing brain abnormalities. New MethodThis work investigates the suitability of a modified form of deep residual neural networks (ResNet) for studying neuroimaging data in the specific application of predicting progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Prediction was conducted first by training the deep models using MCI individuals only, followed by a domain transfer learning version that additionally trained on AD and controls. We also demonstrate a network occlusion based method to localize abnormalities. ResultsThe implemented framework captured non-linear features that successfully predicted AD progression and also conformed to the spectrum of various clinical scores. In a repeated cross-validated setup, the learnt predictive models showed highly similar peak activations that corresponded to previous AD reports. Comparison with existing methodsThe implemented architecture achieved a significant performance improvement over the classical support vector machine and the stacked autoencoder frameworks (p < 0.005), numerically better than state-of-the-art performance using sMRI data alone (> 7% than the second-best performing method) and within 1% of the state-of-the-art performance considering learning using multiple neuroimaging modalities as well. ConclusionsThe explored frameworks reflected the high potential of deep learning architectures in learning subtle predictive features and utility in critical applications such as predicting and understanding disease progression.

A multimodal neuroimaging classifier for alcohol dependence

With progress in magnetic resonance imaging technology and a broader dissemination of state-of-the-art imaging facilities, the acquisition of multiple neuroimaging modalities is becoming increasingly feasible. One particular hope associated with multimodal neuroimaging is the development of reliable data-driven diagnostic classifiers for psychiatric disorders, yet previous studies have often failed to find a benefit of combining multiple modalities. As a psychiatric disorder with established neurobiological effects at several levels of description, alcohol dependence is particularly well-suited for multimodal classification. To this aim, we developed a multimodal classification scheme and applied it to a rich neuroimaging battery (structural, functional task-based and functional resting-state data) collected in a matched sample of alcohol-dependent patients (N = 119) and controls (N = 97). We found that our classification scheme yielded 79.3% diagnostic accuracy, which outperformed the strongest individual modality – grey-matter density – by 2.7%. We found that this moderate benefit of multimodal classification depended on a number of critical design choices: a procedure to select optimal modality-specific classifiers, a fine-grained ensemble prediction based on cross-modal weight matrices and continuous classifier decision values. We conclude that the combination of multiple neuroimaging modalities is able to moderately improve the accuracy of machine-learning-based diagnostic classification in alcohol dependence.

Diagnosis of mild cognitive impairment using multiple neuroimaging modalities in addition to the Mini-Mental State Examination.

This prospective study investigated the additional utility of combining multiple imaging modalities with the Mini-Mental State Examination (MMSE) in discriminating individuals with mild cognitive impairment (MCI) from cognitively normal individuals. A total of 103 individuals with amnestic MCI and normal cognitive function were recruited from outpatients; they underwent examination using the MMSE, magnetic resonance imaging, 18 F-fluorodeoxyglucose positron emission tomography and 11 C-Pittsburgh compound B positron emission tomography. Binary logistic regression with receiver operator characteristic analysis was used to assess the combination of the abovementioned single or multiple imaging modalities with the MMSE. Eight models were constructed, and their area under the curve values and misclassification rates in discriminating individuals with amnestic MCI from cognitively normal individuals were evaluated. The addition of each of the imaging modalities improved the discrimination accuracy over that of the MMSE alone; the accuracy obtained with the addition of 18 F-fluorodeoxyglucose positron emission tomography was the highest. The best model with the highest accuracy included a combination of all the imaging modalities in addition to the MMSE (area under the curve value 0.902). The combination of all the imaging modalities in addition to the MMSE could facilitate more accurate diagnosis of amnestic MCI. Of the individual imaging modalities, the highest accuracy resulted from the addition of 18 F-fluorodeoxyglucose positron emission tomography to the MMSE. Geriatr Gerontol Int 2019; 19: 1193-1197.

Multimodal Data Fusion of Deep Learning and Dynamic Functional Connectivity Features to Predict Alzheimer's Disease Progression.

Early prediction of diseased brain conditions is critical for curing illness and preventing irreversible neuronal dysfunction and loss. Generically regarding the different neuroimaging modalities as filtered, complementary insights of brain's anatomical and functional organization, multimodal data fusion could be hypothesized to enhance the predictive power as compared to a unimodal prediction of disease progression. More recently, deep learning (DL) based methods on structural MRI (sMRI) data have outperformed classical machine learning approaches in several neuroimaging applications including diagnostic classification and prediction. Similarly, functional MRI (fMRI) features estimated using a dynamic (i.e. time-varying) functional connectivity (FC) approach have been found to be more discriminative and predictive of the clinical diagnosis than those based on the static FC approach. Motivated by this, we introduce a novel multimodal data fusion framework featuring deep residual learning of non-linear sMRI features and dynamic FC (dFC) based extraction of fMRI features to predict the subset of individuals with mild cognitive impairments who would progress to Alzheimer's disease within a time-period of three years from the baseline scanning sessions. Our cross-validated results from the developed multimodal (sMRI-fMRI) data fusion framework demonstrate a significant improvement in performance over the unimodal prediction analyses with the fMRI (p = 7.03 x 10-7) and sMRI (p = 6.72 x 10-4) modalities. As such, the findings in this work highlight the benefits of combining multiple neuroimaging data modalities via data fusion, corroborate the predictive value of the tested DL and dFC features and argue in favor of exploration of similar approaches to learn neuroanatomical and functional alterations in the neuroimaging data.

Multimodal imaging reveals a complex pattern of dysfunction in corticolimbic pathways in major depressive disorder.

Major depressive disorder (MDD) is highly prevalent and associated with considerable morbidity, yet its pathophysiology remains only partially understood. While numerous studies have investigated the neurobiological correlates of MDD, most have used only a single neuroimaging modality. In particular, diffusion tensor imaging (DTI) studies have failed to yield uniform results. In this context, examining key tracts and using information from multiple neuroimaging modalities may better characterize potential abnormalities in the MDD brain. This study analyzed data from 30 participants with MDD and 26 healthy participants who underwent DTI, magnetic resonance spectroscopy (MRS), resting-state functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Tracts connecting the subgenual anterior cingulate cortex (sgACC) and the left and right amygdala, as well as connections to the left and right hippocampus and thalamus, were examined as target areas. Reduced fractional anisotropy (FA) was observed in the studied tracts. Significant differences in the correlation between medial prefrontal glutamate concentrations and FA were also observed between MDD and healthy participants along tracts connecting the sgACC and right amygdala; healthy participants exhibited a strong correlation but MDD participants showed no such relationship. In the same tract, a correlation was observed between FA and subsequent antidepressant response to ketamine infusion in MDD participants. Exploratory models also suggested group differences in the relationship between DTI, fMRI, and MEG measures. This study is the first to combine MRS, DTI, fMRI, and MEG data to obtain multimodal indices of MDD and antidepressant response and may lay the foundation for similar future analyses.

Towards an optimised processing pipeline for diffusion magnetic resonance imaging data: Effects of artefact corrections on diffusion metrics and their age associations in UK Biobank.

Increasing interest in the structural and functional organisation of the human brain encourages the acquisition of big data sets comprising multiple neuroimaging modalities, often accompanied by additional information obtained from health records, cognitive tests, biomarkers and genotypes. Diffusion weighted magnetic resonance imaging data enables a range of promising imaging phenotypes probing structural connections as well as macroanatomical and microstructural properties of the brain. The reliability and biological sensitivity and specificity of diffusion data depend on processing pipeline. A state‐of‐the‐art framework for data processing facilitates cross‐study harmonisation and reduces pipeline‐related variability. Using diffusion magnetic resonance imaging (MRI) data from 218 individuals in the UK Biobank, we evaluate the effects of different processing steps that have been suggested to reduce imaging artefacts and improve reliability of diffusion metrics. In lack of a ground truth, we compared diffusion metric sensitivity to age between pipelines. By comparing distributions and age sensitivity of the resulting diffusion metrics based on different approaches (diffusion tensor imaging, diffusion kurtosis imaging and white matter tract integrity), we evaluate a general pipeline comprising seven postprocessing blocks: noise correction; Gibbs ringing correction; evaluation of field distortions; susceptibility, eddy‐current and motion‐induced distortion corrections; bias field correction; spatial smoothing and final diffusion metric estimations. Based on this evaluation, we suggest an optimised processing pipeline for diffusion weighted MRI data.

Biophysically based method to deconvolve spatiotemporal neurovascular signals from fMRI data

BackgroundFunctional magnetic resonance imaging (fMRI) is commonly used to infer hemodynamic changes in the brain after increased neural activity, measuring the blood oxygen level-dependent (BOLD) signal. An important challenge in the analyses of fMRI data is to develop methods that can accurately deconvolve the BOLD signal to extract the driving neural activity and the underlying cerebrovascular effects. New methodA biophysically based method is developed, which combines an extensively verified physiological hemodynamic model with a Wiener filter, to deconvolve the BOLD signal. ResultsThe method is able to simultaneously obtain spatiotemporal images of underlying neurovascular signals, including neural activity, cerebral blood flow, cerebral blood volume, and deoxygenated hemoglobin concentration. The method is tested on simulated data and applied to various experimental data to demonstrate its stability, accuracy, and utility. Comparison with existing methodsThe resulting profiles of the deconvolved signals are consistent with measurements reported in the literature, obtained via multiple neuroimaging modalities. ConclusionsThe method provides new testable predictions of the spatiotemporal relations of the deconvolved signals for future studies. This demonstrates the ability of the method to quantify and analyze the neurovascular mechanisms that underlie fMRI, thereby expanding its potential uses.

Combinations of Multiple Neuroimaging Markers using Logistic Regression for Auxiliary Diagnosis of Alzheimer Disease and Mild Cognitive Impairment

Background: Multiple neuroimaging modalities have been developed providing various aspects of information on the human brain. Objective: Used together and properly, these complementary multimodal neuroimaging data integrate multisource information which can facilitate a diagnosis and improve the diagnostic accuracy. Methods: In this study, 3 types of brain imaging data (sMRI, FDG-PET, and florbetapir-PET) were fused in the hope to improve diagnostic accuracy, and multivariate methods (logistic regression) were applied to these trimodal neuroimaging indices. Then, the receiver-operating characteristic (ROC) method was used to analyze the outcomes of the logistic classifier, with either each index, multiples from each modality, or all indices from all 3 modalities, to investigate their differential abilities to identify the disease. Results: With increasing numbers of indices within each modality and across modalities, the accuracy of identifying Alzheimer disease (AD) increases to varying degrees. For example, the area under the ROC curve is above 0.98 when all the indices from the 3 imaging data types are combined. Conclusion: Using a combination of different indices, the results confirmed the initial hypothesis that different biomarkers were potentially complementary, and thus the conjoint analysis of multiple information from multiple sources would improve the capability to identify diseases such as AD and mild cognitive impairment.

Disrupted topology of the resting state structural connectome in middle-aged APOE ε4 carriers

The apolipoprotein E (APOE) ε4 allele is the best characterized genetic risk factor for Alzheimer's disease to date. Older APOE ε4 carriers (aged 60+years) are known to have disrupted structural and functional connectivity, but less is known about APOE-associated network integrity in middle age. The goal of this study was to characterize APOE-related differences in network topology in middle age, as disentangling the early effects of healthy versus pathological aging may aid early detection of Alzheimer's disease and inform treatments. We performed resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) in healthy, cognitively normal, middle-aged adults (age 40-60; N = 76, 38 APOE ε4 carriers). Graph theoretical analysis was used to calculate local and global efficiency of 1) a whole brain rs-fMRI network; 2) a whole brain DTI network; and 3) the resting state structural connectome (rsSC), an integrated functional-structural network derived using functional-by-structural hierarchical (FSH) mapping. Our results indicated no APOE ε4-associated differences in network topology of the rs-fMRI or DTI networks alone. However, ε4 carriers had significantly lower global and local efficiency of the integrated rsSC compared to non-carriers. Furthermore, ε4 carriers were less resilient to targeted node failure of the rsSC, which mimics the neuropathological process of Alzheimer's disease. Collectively, these findings suggest that integrating multiple neuroimaging modalities and employing graph theoretical analysis may reveal network-level vulnerabilities that may serve as biomarkers of age-related cognitive decline in middle age, decades before the onset of overt cognitive impairment.

Multi-View Multi-Graph Embedding for Brain Network Clustering Analysis

Network analysis of human brain connectivity is critically important for understanding brain function and disease states. Embedding a brain network as a whole graph instance into a meaningful low-dimensional representation can be used to investigate disease mechanisms and inform therapeutic interventions. Moreover, by exploiting information from multiple neuroimaging modalities or views, we are able to obtain an embedding that is more useful than the embedding learned from an individual view. Therefore, multi-view multi-graph embedding becomes a crucial task. Currently only a few studies have been devoted to this topic, and most of them focus on vector-based strategy which will cause structural information contained in the original graphs lost. As a novel attempt to tackle this problem, we propose Multi-view Multi-graph Embedding M2E by stacking multi-graphs into multiple partially-symmetric tensors and using tensor techniques to simultaneously leverage the dependencies and correlations among multi-view and multi-graph brain networks. Extensive experiments on real HIV and bipolar disorder brain network datasets demonstrate the superior performance of M2E on clustering brain networks by leveraging the multi-view multi-graph interactions.

Enhanced estimations of post-stroke aphasia severity using stacked multimodal predictions.

The severity of post-stroke aphasia and the potential for recovery are highly variable and difficult to predict. Evidence suggests that optimal estimation of aphasia severity requires the integration of multiple neuroimaging modalities and the adoption of new methods that can detect multivariate brain-behavior relationships. We created and tested a multimodal framework that relies on three information sources (lesion maps, structural connectivity, and functional connectivity) to create an array of unimodal predictions which are then fed into a final model that creates "stacked multimodal predictions" (STAMP). Crossvalidated predictions of four aphasia scores (picture naming, sentence repetition, sentence comprehension, and overall aphasia severity) were obtained from 53 left hemispheric chronic stroke patients (age: 57.1 ± 12.3 yrs, post-stroke interval: 20 months, 25 female). Results showed accurate predictions for all four aphasia scores (correlation true vs. predicted: r = 0.79-0.88). The accuracy was slightly smaller but yet significant (r = 0.66) in a full split crossvalidation with each patient considered as new. Critically, multimodal predictions produced more accurate results that any single modality alone. Topological maps of the brain regions involved in the prediction were recovered and compared with traditional voxel-based lesion-to-symptom maps, revealing high spatial congruency. These results suggest that neuroimaging modalities carry complementary information potentially useful for the prediction of aphasia scores. More broadly, this study shows that the translation of neuroimaging findings into clinically useful tools calls for a shift in perspective from unimodal to multimodal neuroimaging, from univariate to multivariate methods, from linear to nonlinear models, and, conceptually, from inferential to predictive brain mapping. Hum Brain Mapp 38:5603-5615, 2017. © 2017 Wiley Periodicals, Inc.

Fusing multiple neuroimaging modalities to assess group differences in perception-action coupling.

In the last few decades, non-invasive neuroimaging has revealed macro-scale brain dynamics that underlie perception, cognition and action. Advances in non-invasive neuroimaging target two capabilities; 1) increased spatial and temporal resolution of measured neural activity, and 2) innovative methodologies to extract brain-behavior relationships from evolving neuroimaging technology. We target the second. Our novel methodology integrated three neuroimaging methodologies and elucidated expertise-dependent differences in functional (fused EEG-fMRI) and structural (dMRI) brain networks for a perception-action coupling task. A set of baseball players and controls performed a Go/No-Go task designed to mimic the situation of hitting a baseball. In the functional analysis, our novel fusion methodology identifies 50ms windows with predictive EEG neural correlates of expertise and fuses these temporal windows with fMRI activity in a whole-brain 2mm voxel analysis, revealing time-localized correlations of expertise at a spatial scale of millimeters. The spatiotemporal cascade of brain activity reflecting expertise differences begins as early as 200ms after the pitch starts and lasting up to 700ms afterwards. Network differences are spatially localized to include motor and visual processing areas, providing evidence for differences in perception-action coupling between the groups. Furthermore, an analysis of structural connectivity revealed that the players have significantly more connections between cerebellar and left frontal/motor regions, and many of the functional activation differences between the groups are located within structurally defined network modules that differentiate expertise. In short, our novel method illustrates how multimodal neuroimaging can provide specific macro-scale insights into the functional and structural correlates of expertise development.

The Indirect Effect of Age Group on Switch Costs via Gray Matter Volume and Task-Related Brain Activity.

Healthy aging simultaneously affects brain structure, brain function, and cognition. These effects are often investigated in isolation ignoring any relationships between them. It is plausible that age related declines in cognitive performance are the result of age-related structural and functional changes. This straightforward idea is tested in within a conceptual research model of cognitive aging. The current study tested whether age-related declines in task-performance were explained by age-related differences in brain structure and brain function using a task-switching paradigm in 175 participants. Sixty-three young and 112 old participants underwent MRI scanning of brain structure and brain activation. The experimental task was an executive context dual task with switch costs in response time as the behavioral measure. A serial mediation model was applied voxel-wise throughout the brain testing all pathways between age group, gray matter volume, brain activation and increased switch costs, worsening performance. There were widespread age group differences in gray matter volume and brain activation. Switch costs also significantly differed by age group. There were brain regions demonstrating significant indirect effects of age group on switch costs via the pathway through gray matter volume and brain activation. These were in the bilateral precuneus, bilateral parietal cortex, the left precentral gyrus, cerebellum, fusiform, and occipital cortices. There were also significant indirect effects via the brain activation pathway after controlling for gray matter volume. These effects were in the cerebellum, occipital cortex, left precentral gyrus, bilateral supramarginal, bilateral parietal, precuneus, middle cingulate extending to medial superior frontal gyri and the left middle frontal gyri. There were no significant effects through the gray matter volume alone pathway. These results demonstrate that a large proportion of the age group effect on switch costs can be attributed to individual differences in gray matter volume and brain activation. Therefore, age-related neural effects underlying cognitive control are a complex interaction between brain structure and function. Furthermore, the analyses demonstrate the feasibility of utilizing multiple neuroimaging modalities within a conceptual research model of cognitive aging.

Predicting the laterality of temporal lobe epilepsy from PET, MRI, and DTI: A multimodal study.

Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on information obtained from multiple neuroimaging modalities. The relationship between modalities and their combined power in predicting the seizure focus is currently unknown. We investigated asymmetries from three different modalities, PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and RTLE). Stepwise logistic regression models were built from each modality separately and from all three combined, while bootstrapped methods and split-sample validation verified the robustness of predictions. Among all multimodal asymmetries, three PET asymmetries formed the best predictive model (100% success in full sample, >95% success in split-sample validation). The combinations of PET with other modalities did not perform better than PET alone. Probabilistic classifications were obtained for new clinical cases, which showed correct lateralization for 7/7 new TLE patients (100%) and for 4/5 operated patients with discordant or non-informative PET reports (80%). Metabolism showed closer relationship with white matter in LTLE and closer relationship with gray matter in RTLE. Our data suggest that metabolism is a powerful modality that can predict seizure laterality with high accuracy, and offers high value for automated predictive models. The side of epileptogenic focus can affect the relationship of metabolism with brain structure. The data and tools necessary to obtain classifications for new TLE patients are made publicly available.