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Computational anatomical atlases have shown to be of immense value in neuroimaging as they provide age appropriate reference spaces alongside ancillary anatomical information for automated analysis such as subcortical structural definitions, cortical parcellations or white fiber tract regions. Standard workflows in neuroimaging necessitate such atlases to be appropriately selected for the subject population of interest. This is especially of importance in early postnatal brain development, where rapid changes in brain shape and appearance render neuroimaging workflows sensitive to the appropriate atlas choice. We present here a set of novel computation atlases for structural MRI and Diffusion Tensor Imaging as crucial resource for the analysis of MRI data from non-human primate rhesus monkey (Macaca mulatta) data in early postnatal brain development. Forty socially-housed infant macaques were scanned longitudinally at ages 2 weeks, 3, 6, and 12 months in order to create cross-sectional structural and DTI atlases via unbiased atlas building at each of these ages. Probabilistic spatial prior definitions for the major tissue classes were trained on each atlas with expert manual segmentations. In this article we present the development and use of these atlases with publicly available tools, as well as the atlases themselves, which are publicly disseminated to the scientific community.

Several neural decoding algorithms have successfully converted brain signals into commands to control a computer cursor and prosthetic devices. A majority of decoding methods, such as population vector algorithms (PVA), optimal linear estimators (OLE), and neural networks (NN), are effective in predicting movement kinematics, including movement direction, speed and trajectory but usually require a large number of neurons to achieve desirable performance. This study proposed a novel decoding algorithm even with signals obtained from a smaller numbers of neurons. We adopted sliced inverse regression (SIR) to predict forelimb movement from single-unit activities recorded in the rat primary motor (M1) cortex in a water-reward lever-pressing task. SIR performed weighted principal component analysis (PCA) to achieve effective dimension reduction for nonlinear regression. To demonstrate the decoding performance, SIR was compared to PVA, OLE, and NN. Furthermore, PCA and sequential feature selection (SFS) which are popular feature selection techniques were implemented for comparison of feature selection effectiveness. Among SIR, PVA, OLE, PCA, SFS, and NN decoding methods, the trajectories predicted by SIR (with a root mean square error, RMSE, of 8.47 ± 1.32 mm) was closer to the actual trajectories compared with those predicted by PVA (30.41 ± 11.73 mm), OLE (20.17 ± 6.43 mm), PCA (19.13 ± 0.75 mm), SFS (22.75 ± 2.01 mm), and NN (16.75 ± 2.02 mm). The superiority of SIR was most obvious when the sample size of neurons was small. We concluded that SIR sorted the input data to obtain the effective transform matrices for movement prediction, making it a robust decoding method for conditions with sparse neuronal information.

Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS.

Quantification of dynamic causal interactions among brain regions constitutes an important component of conducting research and developing applications in experimental and translational neuroscience. Furthermore, cortical networks with dynamic causal connectivity in brain-computer interface (BCI) applications offer a more comprehensive view of brain states implicated in behavior than do individual brain regions. However, models of cortical network dynamics are difficult to generalize across subjects because current electroencephalography (EEG) signal analysis techniques are limited in their ability to reliably localize sources across subjects. We propose an algorithmic and computational framework for identifying cortical networks across subjects in which dynamic causal connectivity is modeled among user-selected cortical regions of interest (ROIs). We demonstrate the strength of the proposed framework using a “reach/saccade to spatial target” cognitive task performed by 10 right-handed individuals. Modeling of causal cortical interactions was accomplished through measurement of cortical activity using (EEG), application of independent component clustering to identify cortical ROIs as network nodes, estimation of cortical current density using cortically constrained low resolution electromagnetic brain tomography (cLORETA), multivariate autoregressive (MVAR) modeling of representative cortical activity signals from each ROI, and quantification of the dynamic causal interaction among the identified ROIs using the Short-time direct Directed Transfer function (SdDTF). The resulting cortical network and the computed causal dynamics among its nodes exhibited physiologically plausible behavior, consistent with past results reported in the literature. This physiological plausibility of the results strengthens the framework's applicability in reliably capturing complex brain functionality, which is required by applications, such as diagnostics and BCI.

Recent advances in multi-atlas based algorithms address many of the previous limitations in model-based and probabilistic segmentation methods. However, at the label fusion stage, a majority of algorithms focus primarily on optimizing weight-maps associated with the atlas library based on a theoretical objective function that approximates the segmentation error. In contrast, we propose a novel method—Autocorrecting Walks over Localized Markov Random Fields (AWoL-MRF)—that aims at mimicking the sequential process of manual segmentation, which is the gold-standard for virtually all the segmentation methods. AWoL-MRF begins with a set of candidate labels generated by a multi-atlas segmentation pipeline as an initial label distribution and refines low confidence regions based on a localized Markov random field (L-MRF) model using a novel sequential inference process (walks). We show that AWoL-MRF produces state-of-the-art results with superior accuracy and robustness with a small atlas library compared to existing methods. We validate the proposed approach by performing hippocampal segmentations on three independent datasets: (1) Alzheimer's Disease Neuroimaging Database (ADNI); (2) First Episode Psychosis patient cohort; and (3) A cohort of preterm neonates scanned early in life and at term-equivalent age. We assess the improvement in the performance qualitatively as well as quantitatively by comparing AWoL-MRF with majority vote, STAPLE, and Joint Label Fusion methods. AWoL-MRF reaches a maximum accuracy of 0.881 (dataset 1), 0.897 (dataset 2), and 0.807 (dataset 3) based on Dice similarity coefficient metric, offering significant performance improvements with a smaller atlas library (< 10) over compared methods. We also evaluate the diagnostic utility of AWoL-MRF by analyzing the volume differences per disease category in the ADNI1: Complete Screening dataset. We have made the source code for AWoL-MRF public at: https://github.com/CobraLab/AWoL-MRF.

We describe a low-cost system designed to document bodily movement and neural activity and deliver rewards to monkeys behaving freely in their home cage. An important application is to studying brain-machine interface (BMI) systems during free behavior, since brain signals associated with natural movement can differ significantly from those associated with more commonly used constrained conditions. Our approach allows for short-latency (<500 ms) reward delivery and behavior monitoring using low-cost off-the-shelf components. This system interfaces existing untethered recording equipment with a custom hub that controls a cage-mounted feeder. The behavior monitoring system uses a depth camera to provide real-time, easy-to-analyze, gross movement data streams. In a proof-of-concept experiment we demonstrate robust learning of neural activity using the system over 14 behavioral sessions.

One major problem in neuroscience is the comparison of functional brain networks of different populations, e.g., distinguishing the networks of controls and patients. Traditional algorithms are based on search for isomorphism between networks, assuming that they are deterministic. However, biological networks present randomness that cannot be well modeled by those algorithms. For instance, functional brain networks of distinct subjects of the same population can be different due to individual characteristics. Moreover, networks of subjects from different populations can be generated through the same stochastic process. Thus, a better hypothesis is that networks are generated by random processes. In this case, subjects from the same group are samples from the same random process, whereas subjects from different groups are generated by distinct processes. Using this idea, we developed a statistical test called ANOGVA to test whether two or more populations of graphs are generated by the same random graph model. Our simulations' results demonstrate that we can precisely control the rate of false positives and that the test is powerful to discriminate random graphs generated by different models and parameters. The method also showed to be robust for unbalanced data. As an example, we applied ANOGVA to an fMRI dataset composed of controls and patients diagnosed with autism or Asperger. ANOGVA identified the cerebellar functional sub-network as statistically different between controls and autism (p < 0.001).