Tractography can generate millions of complex curvilinear fibers (streamlines) in 3D that exhibit the geometry of white matter pathways in the brain. Common approaches to analyzing white matter connectivity are based on adjacency matrices that quantify connection strength but do not account for any topological information. A critical element in neurological and developmental disorders is the topological deterioration and irregularities in streamlines. In this paper, we propose a novel Reeb graph-based method "ReeBundle" that efficiently encodes the topology and geometry of white matter fibers. Given the trajectories of neuronal fiber pathways (neuroanatomical bundle), we re-bundle the streamlines by modeling their spatial evolution to capture geometrically significant events (akin to a fingerprint). ReeBundle parameters control the granularity of the model and handle the presence of improbable streamlines commonly produced by tractography. Further, we propose a new Reeb graph-based distance metric that quantifies topological differences for automated quality control and bundle comparison. We show the practical usage of our method using two datasets: (1) For International Society for Magnetic Resonance in Medicine (ISMRM) dataset, ReeBundle handles the morphology of the white matter tract configurations due to branching and local ambiguities in complicated bundle tracts like anterior and posterior commissures; (2) For the longitudinal repeated measures in the Cognitive Resilience and Sleep History (CRASH) dataset, repeated scans of a given subject acquired weeks apart lead to provably similar Reeb graphs that differ significantly from other subjects, thus highlighting ReeBundle's potential for clinical fingerprinting of brain regions.

Even highly trained behaviors demonstrate variability, which is correlated with performance on current and future tasks. An objective of motor learning that is general enough to explain these phenomena has not been precisely formulated. In this six-week longitudinal learning study, participants practiced a set of motor sequences each day, and neuroimaging data were collected on days 1, 14, 28, and 42 to capture the neural correlates of the learning process. In our analysis, we first modeled the underlying neural and behavioral dynamics during learning. Our results demonstrate that the densities of whole-brain response, task-active regional response, and behavioral performance evolve according to a Fokker-Planck equation during the acquisition of a motor skill. We show that this implies that the brain concurrently optimizes the entropy of a joint density over neural response and behavior (as measured by sampling over multiple trials and subjects) and the expected performance under this density; we call this formulation of learning minimum free energy learning (MFEL). This model provides an explanation as to how behavioral variability can be tuned while simultaneously improving performance during learning. We then develop a novel variant of inverse reinforcement learning to retrieve the cost function optimized by the brain during the learning process, as well as the parameter used to tune variability. We show that this population-level analysis can be used to derive a learning objective that each subject optimizes during his or her study. In this way, MFEL effectively acts as a unifying principle, allowing users to precisely formulate learning objectives and infer their structure.

Large bundles of myelinated axons, called white matter, anatomically connect disparate brain regions together and compose the structural core of the human connectome. We recently proposed a method of measuring the local integrity along the length of each white matter fascicle, termed the local connectome [1]. If communication efficiency is fundamentally constrained by the integrity along the entire length of a white matter bundle [2], then variability in the functional dynamics of brain networks should be associated with variability in the local connectome. We test this prediction using two statistical approaches that are capable of handling the high dimensionality of data. First, by performing statistical inference on distance-based correlations, we show that similarity in the local connectome between individuals is significantly correlated with similarity in their patterns of functional connectivity. Second, by employing variable selection using sparse canonical correlation analysis and cross-validation, we show that segments of the local connectome are predictive of certain patterns of functional brain dynamics. These results are consistent with the hypothesis that structural variability along axon bundles constrains communication between disparate brain regions.

The human brain can be represented as a graph in which neural units such as cells or small volumes of tissue are heterogeneously connected to one another through structural or functional links. Brain graphs are parsimonious representations of neural systems that have begun to offer fundamental insights into healthy human cognition, as well as its alteration in disease. A critical open question in network neuroscience lies in how neural units cluster into densely interconnected groups that can provide the coordinated activity that is characteristic of perception, action, and adaptive behaviors. Tools that have proven particularly useful for addressing this question are community detection approaches, which can identify communities or modules: groups of neural units that are densely interconnected with other units in their own group but sparsely interconnected with units in other groups. In this paper, we describe a common community detection algorithm known as modularity maximization, and we detail its application to brain graphs constructed from neuroimaging data. We pay particular attention to important algorithmic considerations, especially in recent extensions of these techniques to graphs that evolve in time. After recounting a few fundamental insights that these techniques have provided into brain function, we highlight potential avenues of methodological advancements for future studies seeking to better characterize the patterns of coordinated activity in the brain that accompany human behavior. This tutorial provides a reader with an introduction to theoretical considerations pertinent to the generation of brain graphs, an understanding of modularity maximization for community detection, a resource of statistical measures that can be used to characterize community structure, and an appreciation of the usefulness of these approaches in uncovering behaviorally relevant network dynamics in neuroimaging data.

The relationship between brain structure and function has been probed using a variety of approaches, but how the underlying structural connectivity of the human brain drives behavior is far from understood. To investigate the effect of anatomical brain organization on human task performance, we use a data-driven computational modeling approach and explore the functional effects of naturally occurring structural differences in brain networks. We construct personalized brain network models by combining anatomical connectivity estimated from diffusion spectrum imaging of individual subjects with a nonlinear model of brain dynamics. By performing computational experiments in which we measure the excitability of the global brain network and spread of synchronization following a targeted computational stimulation, we quantify how individual variation in the underlying connectivity impacts both local and global brain dynamics. We further relate the computational results to individual variability in the subjects' performance of three language-demanding tasks both before and after transcranial magnetic stimulation to the left-inferior frontal gyrus. Our results show that task performance correlates with either local or global measures of functional activity, depending on the complexity of the task. By emphasizing differences in the underlying structural connectivity, our model serves as a powerful tool to assess individual differences in task performances, to dissociate the effect of targeted stimulation in tasks that differ in cognitive demand, and to pave the way for the development of personalized therapeutics.

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.

Recent advances in signal processing for the detection of Steady-State Visual Evoked Potentials (SSVEPs) have moved away from traditionally calibrationless methods, such as canonical correlation analysis, and towards algorithms that require substantial training data. In general, this has improved detection rates, but SSVEP-based brain-computer interfaces (BCIs) now suffer from the requirement of costly calibration sessions. Here, we address this issue by applying transfer learning techniques to SSVEP detection. Our novel Adaptive-C3A method incorporates an unsupervised adaptation algorithm that requires no calibration data. Our approach learns SSVEP templates for the target user and provides robust class separation in feature space leading to increased classification accuracy. Our method achieves significant improvements in performance over a standard CCA method as well as a transfer variant of the state-of-the art Combined-CCA method for calibrationless SSVEP detection.

The ability to modulate brain states using targeted stimulation is increasingly being employed to treat neurological disorders and to enhance human performance. Despite the growing interest in brain stimulation as a form of neuromodulation, much remains unknown about the network-level impact of these focal perturbations. To study the system wide impact of regional stimulation, we employ a data-driven computational model of nonlinear brain dynamics to systematically explore the effects of targeted stimulation. Validating predictions from network control theory, we uncover the relationship between regional controllability and the focal versus global impact of stimulation, and we relate these findings to differences in the underlying network architecture. Finally, by mapping brain regions to cognitive systems, we observe that the default mode system imparts large global change despite being highly constrained by structural connectivity. This work forms an important step towards the development of personalized stimulation protocols for medical treatment or performance enhancement.

Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.

Neurotechnologies based on electroencephalography (EEG) and other physiological measures to improve task performance in complex environments will require tools and analysis methods that can account for increased environmental noise and task complexity compared to traditional neuroscience laboratory experiments. We propose a bag-of-words (BoW) model to address the difficulties associated with realistic applications in complex environments. In this paper, our proof-of-concept results show that a BoW classifier can discriminate two task-relevant states (high versus low task-load) while an individual performs a simulated security patrol mission with complex, concurrent tasking. Classifier performance is largely consistent across six simulation missions for a given participant, but performance decreases when trying to predict between two individuals. Overall, these initial results suggest that this BoW approach holds promise for detecting task-relevant states in real-world settings.