Multiple Neuroimaging Modalities Research Articles

Beta-informativeness-diffusion multilayer graph embedding for brain network analysis.

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.

A Thorough Review of Deep Learning in Autism Spectrum Disorder Detection: From Data to Diagnosis

Background: Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition with significant heterogeneity in its clinical presentation. Timely and precise identification of ASD is crucial for effective intervention and assistance. Recent advances in deep learning techniques have shown promise in enhancing the accuracy of ASD detection. Objective: This comprehensive review aims to provide an overview of various deep learning methods employed in detecting ASD, utilizing diverse neuroimaging modalities. We analyze a range of studies that use resting-state functional Magnetic Resonance Imaging (rsfMRI), structural MRI (sMRI), task-based fMRI (tfMRI), and electroencephalography (EEG). This paper aims to assess the effectiveness of these techniques based on criteria such as accuracy, sensitivity, specificity, and computational efficiency. Methods: We systematically review studies investigating ASD detection using deep learning across different neuroimaging modalities. These studies utilize various preprocessing tools, atlases, feature extraction techniques, and classification algorithms. The performance metrics of interest include accuracy, sensitivity, specificity, precision, F1-score, recall, and area under the curve (AUC). Results: The review covers a wide range of studies, each with its own dataset and methodology. Notable findings include a study employing rsfMRI data from ABIDE that achieved an accuracy of 80% using LeNet. Another study using rsfMRI data from ABIDE-II achieved an impressive accuracy of 95.4% with the ASGCN deep learning model. Studies utilizing different modalities, such as EEG and sMRI, also reported high accuracies ranging from 74% to 95%. Conclusion: Deep learning-based approaches for ASD detection have demonstrated significant potential across multiple neuroimaging modalities. These methods offer a more objective and data-driven approach to diagnosis, potentially reducing the subjectivity associated with clinical evaluations. However, challenges remain, including the need for larger and more diverse datasets, model interpretability, and clinical validation. The field of deep learning in ASD diagnosis continues to evolve, holding promise for early and accurate identification of individuals with ASD, which is crucial for timely intervention and support.

Autism Spectrum Disorder Detection by Hybrid Convolutional Recurrent Neural Networks from Structural and Resting State Functional MRI Images.

This study aims to increase the accuracy of autism spectrum disorder (ASD) diagnosis based on cognitive and behavioral phenotypes through multiple neuroimaging modalities. We apply machine learning (ML) algorithms to classify ASD patients and healthy control (HC) participants using structural magnetic resonance imaging (s-MRI) together with resting state functional MRI (rs-f-MRI and f-MRI) data from the large multisite data repository ABIDE (autism brain imaging data exchange) and identify important brain connectivity features. The 2D f-MRI images were converted into 3D s-MRI images, and datasets were preprocessed using the Montreal Neurological Institute (MNI) atlas. The data were then denoised to remove any confounding factors. We show, by using three fusion strategies such as early fusion, late fusion, and cross fusion, that, in this implementation, hybrid convolutional recurrent neural networks achieve better performance in comparison to either convolutional neural networks (CNNs) or recurrent neural networks (RNNs). The proposed model classifies subjects as autistic or not according to how functional and anatomical connectivity metrics provide an overall diagnosis based on the autism diagnostic observation schedule (ADOS) standard. Our hybrid network achieved an accuracy of 96% by fusing s-MRI and f-MRI together, which outperforms the methods used in previous studies.

Searching for biomarkers in the fluidity of mental ill-health.

Searching for biomarkers in the fluidity of mental ill-health.

Neurobiological Clusters Are Associated With Trajectories of Overall Psychopathology in Youth

BackgroundIntegrating multiple neuroimaging modalities to identify clusters of individuals and then associating these clusters with psychopathology is a promising approach for understanding neurobiological mechanisms that underlie psychopathology and the extent to which these features are associated with clinical symptoms. MethodsWe leveraged neuroimaging data from T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance images from the Adolescent Brain Cognitive Development (ABCD) Study (N = 8035) and used similarity network fusion and spectral clustering to identify subgroups of participants. We examined neuroimaging measures as a function of clustering profiles using 1, 2, or 3 imaging modalities (i.e., data combinations), calculated the stability of the clustering assignment in each respective data combination, and compared the consistency of clusters across different data combinations. We then compared the extent to which clusters were associated with overall psychopathology at the baseline assessment and at 2 yearly follow-up visits. ResultsEach data combination resulted in optimal clusters ranging from 2 to 4 subgroups for each data combination. Clusters were stable across subsampling of the ABCD Study cohort. Widespread structural measures (surface area, fractional anisotropy, and mean diffusivity) were important features contributing to clustering across different data combinations. Five of the seven data combinations were associated with overall psychopathology, both at baseline and over time (d = 0.08–0.41). Generally, lower global cortical volume and surface area, widespread reduced fractional anisotropy, and increased radial diffusivity were associated with increased overall psychopathology. ConclusionsProfiles constructed from neuroimaging data combinations are associated with concurrent and future psychopathology trajectories.

Neuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers.

Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological changes in AD patients occur up to 10-20 years before the emergence of clinical symptoms. Specific diagnosis and appropriate intervention strategies are crucial during the phase of mild cognitive impairment (MCI) and AD. The detection of biomarkers has emerged as a promising tool for tracking the efficacy of potential therapies, making an early disease diagnosis, and prejudging treatment prognosis. Specifically, multiple neuroimaging modalities, including magnetic resonance imaging (MRI), positron emission tomography, optical imaging, and single photon emission-computed tomography, have provided a few potential biomarkers for clinical application. The MRI modalities described in this review include structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy, and arterial spin labelling. These techniques allow the detection of presymptomatic diagnostic biomarkers in the brains of cognitively normal elderly people and might also be used to monitor AD disease progression after the onset of clinical symptoms. This review highlights potential biomarkers, merits, and demerits of different neuroimaging modalities and their clinical value in MCI and AD patients. Further studies are necessary to explore more biomarkers and overcome the limitations of multiple neuroimaging modalities for inclusion in diagnostic criteria forAD.

Ultra-high field neuroimaging in psychosis: A narrative review.

Schizophrenia and related psychoses are complex neuropsychiatric diseases representing dysconnectivity across multiple scales, through the micro (cellular), meso (brain network), manifest (behavioral), and social (interpersonal) levels. In vivo human neuroimaging, particularly at ultra-high field (UHF), offers unprecedented opportunity to examine multiscale dysconnectivity in psychosis. In this review, we provide an overview of the literature to date on UHF in psychosis, focusing on microscale findings from magnetic resonance spectroscopy (MRS), mesoscale studies on structural and functional magnetic resonance imaging (fMRI), and multiscale studies assessing multiple neuroimaging modalities and relating UHF findings to behavior. We highlight key insights and considerations from multiscale and longitudinal studies and provide recommendations for future research on UHF neuroimaging in psychosis.

The glymphatic system: implications for drugs for central nervous system diseases.

In the past decade, evidence for a fluid clearance pathway in the central nervous system known as the glymphatic system has grown. According to the glymphatic system concept, cerebrospinal fluid flows directionally through the brain and non-selectively clears the interstitium of metabolic waste. Importantly, the glymphatic system may be modulated by particular drugs such as anaesthetics, as well as by non-pharmacological factors such as sleep, and its dysfunction has been implicated in central nervous system disorders such as Alzheimer disease. Although the glymphatic system is best described in rodents, reports using multiple neuroimaging modalities indicate that a similar transport system exists in the human brain. Here, we overview the evidence for the glymphatic system and its role in disease and discuss opportunities to harness the glymphatic system therapeutically; for example, by improving the effectiveness of intrathecally delivered drugs.

Multimodal fusion analysis of functional, cerebrovascular and structural neuroimaging in healthy aging subjects.

Brain aging is a complex process that requires a multimodal approach. Neuroimaging can provide insights into brain morphology, functional organization, and vascular dynamics. However, most neuroimaging studies of aging have focused on each imaging modality separately, limiting the understanding of interrelations between processes identified by different modalities and their relevance to cognitive decline in aging. Here, we used a data-driven multimodal approach, linked independent component analysis (ICA), to jointly analyze magnetic resonance imaging (MRI) of grey matter volume, cerebrovascular, and functional network topographies in relation to measures of fluid intelligence. Neuroimaging and cognitive data from the Cambridge Centre for Ageing and Neuroscience study were used, with healthy participants aged 18-88 years (main dataset n=215 and secondary dataset n=433). Using linked ICA, functional network activities were characterized in independent components but not captured in the same component as structural and cerebrovascular patterns. Split-sample (n=108/107) and out-of-sample (n=433) validation analyses using linked ICA were also performed. Global grey matter volume with regional cerebrovascular changes and the right frontoparietal network activity were correlated with age-related and individual differences in fluid intelligence. This study presents the insights from linked ICA to bring together measurements from multiple imaging modalities, with independent and additive information. We propose that integrating multiple neuroimaging modalities allows better characterization of brain pattern variability and changes associated with healthy aging.

A longitudinal multi-scanner multimodal human neuroimaging dataset

Human neuroimaging has led to an overwhelming amount of research into brain function in healthy and clinical populations. However, a better appreciation of the limitations of small sample studies has led to an increased number of multi-site, multi-scanner protocols to understand human brain function. As part of a multi-site project examining social cognition in schizophrenia, a group of “travelling human phantoms” had structural T1, diffusion, and resting-state functional MRIs obtained annually at each of three sites. Scan protocols were carefully harmonized across sites prior to the study. Due to scanner upgrades at each site (all sites acquired PRISMA MRIs during the study) and one participant being replaced, the end result was 30 MRI scans across 4 people, 6 MRIs, and 4 years. This dataset includes multiple neuroimaging modalities and repeated scans across six MRIs. It can be used to evaluate differences across scanners, consistency of pipeline outputs, or test multi-scanner harmonization approaches.

Association of Neuroimaging Data with Behavioral Variables: A Class of Multivariate Methods and Their Comparison Using Multi-Task FMRI Data.

It is becoming increasingly common to collect multiple related neuroimaging datasets either from different modalities or from different tasks and conditions. In addition, we have non-imaging data such as cognitive or behavioral variables, and it is through the association of these two sets of data—neuroimaging and non-neuroimaging—that we can understand and explain the evolution of neural and cognitive processes, and predict outcomes for intervention and treatment. Multiple methods for the joint analysis or fusion of multiple neuroimaging datasets or modalities exist; however, methods for the joint analysis of imaging and non-imaging data are still in their infancy. Current approaches for identifying brain networks related to cognitive assessments are still largely based on simple one-to-one correlation analyses and do not use the cross information available across multiple datasets. This work proposes two approaches based on independent vector analysis (IVA) to jointly analyze the imaging datasets and behavioral variables such that multivariate relationships across imaging data and behavioral features can be identified. The simulation results show that our proposed methods provide better accuracy in identifying associations across imaging and behavioral components than current approaches. With functional magnetic resonance imaging (fMRI) task data collected from 138 healthy controls and 109 patients with schizophrenia, results reveal that the central executive network (CEN) estimated in multiple datasets shows a strong correlation with the behavioral variable that measures working memory, a result that is not identified by traditional approaches. Most of the identified fMRI maps also show significant differences in activations across healthy controls and patients potentially providing a useful signature of mental disorders.

Multimodal classification of extremely preterm and term adolescents using the fusiform gyrus: A machine learning approach

ObjectiveExtremely preterm birth has been associated with atypical visual and neural processing of faces, as well as differences in gray matter structure in visual processing areas relative to full-term peers. In particular, the right fusiform gyrus, a core visual area involved in face processing, has been shown to have structural and functional differences between preterm and full-term individuals from childhood through early adulthood. The current study used multiple neuroimaging modalities to build a machine learning model based on the right fusiform gyrus to classify extremely preterm birth status. MethodExtremely preterm adolescents (n = 20) and full-term peers (n = 24) underwent structural and functional magnetic resonance imaging. Group differences in gray matter density, measured via voxel-based morphometry (VBM), and blood-oxygen level-dependent (BOLD) response to face stimuli were explored within the right fusiform. Using group difference clusters as seed regions, analyses investigating outgoing white matter streamlines, regional homogeneity, and functional connectivity during a face processing task and at rest were conducted. A data driven approach was utilized to determine the most discriminative combination of these features within a linear support vector machine classifier. ResultsGroup differences in two partially overlapping clusters emerged: one from the VBM analysis showing less density in the extremely preterm cohort and one from BOLD response to faces showing greater activation in the extremely preterm relative to full-term youth. A classifier fit to the data from the cluster identified in the BOLD analysis achieved an accuracy score of 88.64% when BOLD, gray matter density, regional homogeneity, and functional connectivity during the task and at rest were included. A classifier fit to the data from the cluster identified in the VBM analysis achieved an accuracy score of 95.45% when only BOLD, gray matter density, and regional homogeneity were included. ConclusionConsistent with previous findings, we observed neural differences in extremely preterm youth in an area that plays an important role in face processing. Multimodal analyses revealed differences in structure, function, and connectivity that, when taken together, accurately distinguish extremely preterm from full-term born youth. Our findings suggest a compensatory role of the fusiform where less dense gray matter is countered by increased local BOLD signal. Importantly, sub-threshold differences in many modalities within the same region were informative when distinguishing between extremely preterm and full-term youth.

Decoding Brain Activity Features to Recognize Distorted Objects.

Brain decoding is able to make human interact with an external machine or robot for assisting patient's rehabilitation. Brain generic object recognition ability can be decoded through multiple neuroimaging modalities like functional magnetic resonance imaging (fMRI). On the other hand, external machine may wrongly recognize objects due to distorted noisy or blurring images caused by many factors, and therefore deteriorate performance of brain-machine interaction. In order to create better machine, generalization capability of human brain is transferred to classifier for enhancing classification accuracy of distorted images. Since homology existing between human and machine vision has been demonstrated, through decoding neural activity features of fMRI signals into feature units of convolutional neural network layers, an enhanced object recognition method is proposed to integrate brain activity into classifier for increasing classification accuracy. Experimental results show that the proposed method is able to enhance generalization capability of distorted object recognition.

Fusing multimodal neuroimaging data with a variational autoencoder.

Neuroimaging studies often collect multimodal data. These modalities contain both shared and mutually exclusive information about the brain. This work aims to find a scalable and interpretable method to fuse the information of multiple neuroimaging modalities into a lower-dimensional latent space using a variational autoencoder (VAE). To assess whether the encoder-decoder pair retains meaningful information, this work evaluates the representations using a schizophrenia classification task. The linear classifier, trained on the representations obtained through dimensionality reduction, achieves an area under the curve of the receiver operating characteristic (ROC-AUC) of 0.8609. Thus, training on a multimodal dataset with functional brain networks and a structural magnetic resonance imaging (sMRI) scan, leads to dimensionality reduction that retains meaningful information. The proposed dimensionality reduction outperforms both early and late fusion principal component analysis on the classification task.Clinical relevance - This work examines the interplay between neuroimaging modalities and their relation to mental disorders. This allows for more complex and rigorous analysis of multimodal neuroimaging data throughout clinical settings.

Brain multimodal co-alterations related to delay discounting: a multimodal MRI fusion analysis in persons with and without cocaine use disorder

BackgroundDelay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD).MethodsAdults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function.ResultsThe sample was 58% male and 78% African–American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly.ConclusionsOur findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.

Neural Correlates of Motor Recovery after Robot-Assisted Training in Chronic Stroke: A Multimodal Neuroimaging Study.

Stroke is a leading cause of motor disability worldwide, and robot-assisted therapies have been increasingly applied to facilitate the recovery process. However, the underlying mechanism and induced neuroplasticity change remain partially understood, and few studies have investigated this from a multimodality neuroimaging perspective. The current study adopted BCI-guided robot hand therapy as the training intervention and combined multiple neuroimaging modalities to comprehensively understand the potential association between motor function alteration and various neural correlates. We adopted EEG-informed fMRI technique to understand the functional regions sensitive to training intervention. Additionally, correlation analysis among training effects, nonlinear property change quantified by fractal dimension (FD), and integrity of M1-M1 (M1: primary motor cortex) anatomical connection were performed. EEG-informed fMRI analysis indicated that for iM1 (iM1: ipsilesional M1) regressors, regions with significantly increased partial correlation were mainly located in contralesional parietal, prefrontal, and sensorimotor areas and regions with significantly decreased partial correlation were mainly observed in the ipsilesional supramarginal gyrus and superior temporal gyrus. Pearson's correlations revealed that the interhemispheric asymmetry change significantly correlated with the training effect as well as the integrity of M1-M1 anatomical connection. In summary, our study suggested that multiple functional brain regions not limited to motor areas were involved during the recovery process from multimodality perspective. The correlation analyses suggested the essential role of interhemispheric interaction in motor rehabilitation. Besides, the underlying structural substrate of the bilateral M1-M1 connection might relate to the interhemispheric change. This study might give some insights in understanding the neuroplasticity induced by the integrated BCI-guided robot hand training intervention and further facilitate the design of therapies for chronic stroke patients.

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.