Designed especially for neurobiologists, FluoRender is an interactive tool for multi-channel fluorescence microscopy data visualization and analysis.
Large scale visualization on the Powerwall.
BrainStimulator is a set of networks that are used in SCIRun to perform simulations of brain stimulation such as transcranial direct current stimulation (tDCS) and magnetic transcranial stimulation (TMS).
Developing software tools for science has always been a central vision of the SCI Institute.

SCI Publications


U. Ruede, K. Willcox, L. C. McInnes, H. De Sterck, G. Biros, H. Bungartz, J. Corones, E. Cramer, J. Crowley, O. Ghattas, M. Gunzburger, M. Hanke, R. Harrison, M. Heroux, J. Hesthaven, P. Jimack, C. Johnson, K. E. Jordan, D. E. Keyes, R. Krause, V. Kumar, S. Mayer, J. Meza, K. M. Mrken, J. T. Oden, L. Petzold, P. Raghavan, S. M. Shontz, A. Trefethen, P. Turner, V. Voevodin, B. Wohlmuth,, C. S. Woodward. “Research and Education in Computational Science and Engineering,” Subtitled “Report from a workshop sponsored by the Society for Industrial and Applied Mathematics (SIAM) and the European Exascale Software Initiative (EESI-2), August 4-6, 2014, Breckenridge, Colorado,” Vol. abs/1610.02608, 2018.


This report presents challenges, opportunities and directions for computational science and engineering (CSE) research and education for the next decade. Over the past two decades the field of CSE has penetrated both basic and applied research in academia, industry, and laboratories to advance discovery, optimize systems, support decision-makers, and educate the scientific and engineering workforce. Informed by centuries of theory and experiment, CSE performs computational experiments to answer questions that neither theory nor experiment alone is equipped to answer. CSE provides scientists and engineers with algorithmic inventions and software systems that transcend disciplines and scales. CSE brings the power of parallelism to bear on troves of data. Mathematics-based advanced computing has become a prevalent means of discovery and innovation in essentially all areas of science, engineering, technology, and society; and the CSE community is at the core of this transformation. However, a combination of disruptive developments—including the architectural complexity of extreme-scale computing, the data revolution and increased attention to data-driven discovery, and the specialization required to follow the applications to new frontiers—is redefining the scope and reach of the CSE endeavor. With these many current and expanding opportunities for the CSE field, there is a growing demand for CSE graduates and a need to expand CSE educational offerings. This need includes CSE programs at both the undergraduate and graduate levels, as well as continuing education and professional development programs, exploiting the synergy between computational science and data science. Yet, as institutions consider new and evolving educational programs, it is essential to consider the broader research challenges and opportunities that provide the context for CSE education and workforce development.

W.Thevathasan, B. Debu, T. Aziz, B. R. Bloem, C. Blahak, C. Butson, V. Czernecki, T. Foltynie, V. Fraix, D. Grabli, C. Joint, A. M. Lozano, M. S. Okun, J. Ostrem, N. Pavese, C. Schrader, C. H. Tai, J. K. Krauss, E. Moro. “Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review,” In Movement Disorders, Vol. 33, No. 1, pp. 10--20. 2018.
ISSN: 1531-8257
DOI: 10.1002/mds.27098


Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology.


M. Berzins, D. A. Bonnell, Jr. Cizewski, K. M. Heeger, A.J.G. Hey, C. J. Keane, B. A. Ramsey, K. A. Remington, J.L. Rempe. “Department of Energy, Advanced Scientific Computing Advisory Committee (ASCAC), Subcommittee on LDRD Review Final Report,” May, 2017.

M. Berzins. “Nonlinear Stability of the MPM Method,” In V International Conference on Particle-based Methods – Fundamentals and Applications. PARTICLES 2017, Edited by P. Wriggers, M. Bischoff, E. O˜nate, D.R.J. Owen, & T. Zohdi, 2017.


The Material Point Method (MPM) has been very successful in providing solutions to many challenging problems involving large deformations. The nonlinear nature of MPM makes it necessary to use a full nonlinear stability analysis to determine a stable timestep. The stability analysis of Spigler and Vianello is adapted to MPM and used to derive a stable timestep bound for a model problem. This bound is contrasted against a traditional CFL bound.

A. Bhatele, J. Yeom, N. Jain, C. J. Kuhlman, Y. Livnat, K. R. Bisset, L. V. Kale, M. V. Marathe. “Massively Parallel Simulations of Spread of Infectious Diseases over Realistic Social Networks,” In 2017 17th IEEE/ACM International Symposium on Cluster, Cloud and Grid Computing (CCGRID), May, 2017.
DOI: 10.1109/ccgrid.2017.141


Controlling the spread of infectious diseases in large populations is an important societal challenge. Mathematically, the problem is best captured as a certain class of reaction-diffusion processes (referred to as contagion processes) over appropriate synthesized interaction networks. Agent-based models have been successfully used in the recent past to study such contagion processes. We describe EpiSimdemics, a highly scalable, parallel code written in Charm++ that uses agent-based modeling to simulate disease spreads over large, realistic, co-evolving interaction networks. We present a new parallel implementation of EpiSimdemics that achieves unprecedented strong and weak scaling on different architectures — Blue Waters, Cori and Mira. EpiSimdemics achieves five times greater speedup than the second fastest parallel code in this field. This unprecedented scaling is an important step to support the long term vision of real-time epidemic science. Finally, we demonstrate the capabilities of EpiSimdemics by simulating the spread of influenza over a realistic synthetic social contact network spanning the continental United States (∼280 million nodes and 5.8 billion social contacts).

J. Cates, L. Nevell, S. I. Prajapati, L. D. Nelon, J. Y. Chang, M. E. Randolph, B. Wood, C. Keller, R. T. Whitaker. “Shape analysis of the basioccipital bone in Pax7-deficient mice,” In Scientific Reports, Vol. 7, No. 1, Springer Nature, Dec, 2017.
DOI: 10.1038/s41598-017-18199-9


We compared the cranial base of newborn Pax7-deficient and wildtype mice using a computational shape modeling technology called particle-based modeling (PBM). We found systematic differences in the morphology of the basiooccipital bone, including a broadening of the basioccipital bone and an antero-inferior inflection of its posterior edge in the Pax7-deficient mice. We show that the Pax7 cell lineage contributes to the basioccipital bone and that the location of the Pax7 lineage correlates with the morphology most effected by Pax7 deficiency. Our results suggest that the Pax7-deficient mouse may be a suitable model for investigating the genetic control of the location and orientation of the foramen magnum, and changes in the breadth of the basioccipital.

M. Chen, G. Grinstein, C. R. Johnson, J. Kennedy, M. Tory. “Pathways for Theoretical Advances in Visualization,” In IEEE Computer Graphics and Applications, IEEE, pp. 103--112. July, 2017.


More than a decade ago, Chris Johnson proposed the "Theory of Visualization" as one of the top research problems in visualization. Since then, there have been several theory-focused events, including three workshops and three panels at IEEE Visualization (VIS) Conferences. Together, these events have produced a set of convincing arguments.

C. Gritton, J. Guilkey, J. Hooper, D. Bedrov, R. M. Kirby, M. Berzins. “Using the material point method to model chemical/mechanical coupling in the deformation of a silicon anode,” In Modelling and Simulation in Materials Science and Engineering, Vol. 25, No. 4, pp. 045005. 2017.


The lithiation and delithiation of a silicon battery anode is modeled using the material point method (MPM). The main challenges in modeling this process using the MPM is to simulate stress dependent diffusion coupled with concentration dependent stress within a material that undergoes large deformations. MPM is chosen as the numerical method of choice because of its ability to handle large deformations. A method for modeling diffusion within MPM is described. A stress dependent model for diffusivity and three different constitutive models that fully couple the equations for stress with the equations for diffusion are considered. Verifications tests for the accuracy of the numerical implementations of the models and validation tests with experimental results show the accuracy of the approach. The application of the fully coupled stress diffusion model implemented in MPM is applied to modeling the lithiation and delithiation of silicon nanopillars.

J. K. Holmen, A. Humphrey, D. Sutherland, M. Berzins. “Improving Uintah's Scalability Through the Use of Portable Kokkos-Based Data Parallel Tasks,” In Proceedings of the Practice and Experience in Advanced Research Computing 2017 on Sustainability, Success and Impact, PEARC17, No. 27, pp. 27:1--27:8. 2017.
ISBN: 978-1-4503-5272-7
DOI: 10.1145/3093338.3093388


The University of Utah's Carbon Capture Multidisciplinary Simulation Center (CCMSC) is using the Uintah Computational Framework to predict performance of a 1000 MWe ultra-supercritical clean coal boiler. The center aims to utilize the Intel Xeon Phi-based DOE systems, Theta and Aurora, through the Aurora Early Science Program by using the Kokkos C++ library to enable node-level performance portability. This paper describes infrastructure advancements and portability improvements made possible by our integration of Kokkos within Uintah. Scalability results are presented that compare serial and data parallel task execution models for a challenging radiative heat transfer calculation, central to the center's predictive boiler simulations. These results demonstrate both good strong-scaling characteristics to 256 Knights Landing (KNL) processors on the NSF Stampede system, and show the KNL-based calculation to compete with prior GPU-based results for the same calculation.

M. Kern, A. Lex, N. Gehlenborg, C. R. Johnson. “Interactive Visual Exploration And Refinement Of Cluster Assignments,” In BMC Bioinformatics, Cold Spring Harbor Laboratory, April, 2017.
DOI: 10.1101/123844


With ever-increasing amounts of data produced in biology research, scientists are in need of efficient data analysis methods. Cluster analysis, combined with visualization of the results, is one such method that can be used to make sense of large data volumes. At the same time, cluster analysis is known to be imperfect and depends on the choice of algorithms, parameters, and distance measures. Most clustering algorithms don't properly account for ambiguity in the source data, as records are often assigned to discrete clusters, even if an assignment is unclear. While there are metrics and visualization techniques that allow analysts to compare clusterings or to judge cluster quality, there is no comprehensive method that allows analysts to evaluate, compare, and refine cluster assignments based on the source data, derived scores, and contextual data.

In this paper, we introduce a method that explicitly visualizes the quality of cluster assignments, allows comparisons of clustering results and enables analysts to manually curate and refine cluster assignments. Our methods are applicable to matrix data clustered with partitional, hierarchical, and fuzzy clustering algorithms. Furthermore, we enable analysts to explore clustering results in context of other data, for example, to observe whether a clustering of genomic data results in a meaningful differentiation in phenotypes.

Our methods are integrated into Caleydo StratomeX, a popular, web-based, disease subtype analysis tool. We show in a usage scenario that our approach can reveal ambiguities in cluster assignments and produce improved clusterings that better differentiate genotypes and phenotypes.

T.A.J. Ouermi, A. Knoll, R.M. Kirby, M. Berzins. “OpenMP 4 Fortran Modernization of WSM6 for KNL,” In Proceedings of the Practice and Experience in Advanced Research Computing 2017 on Sustainability, Success and Impact, PEARC17, No. 12, ACM, pp. 12:1--12:8. 2017.
ISBN: 978-1-4503-5272-7
DOI: 10.1145/3093338.3093387


Parallel code portability in the petascale era requires modifying existing codes to support new architectures with large core counts and SIMD vector units. OpenMP is a well established and increasingly supported vehicle for portable parallelization. As architectures mature and compiler OpenMP implementations evolve, best practices for code modernization change as well. In this paper, we examine the impact of newer OpenMP features (in particular OMP SIMD) on the Intel Xeon Phi Knights Landing (KNL) architecture, applied in optimizing loops in the single moment 6-class microphysics module (WSM6) in the US Navy's NEPTUNE code. We find that with functioning OMP SIMD constructs, low thread invocation overhead on KNL and reduced penalty for unaligned access compared to previous architectures, one can leverage OpenMP 4 to achieve reasonable scalability with relatively minor reorganization of a production physics code.

T.A.J. Ouermi, A. Knoll, R.M. Kirby, M. Berzins. “Optimization Strategies for WRF Single-Moment 6-Class Microphysics Scheme (WSM6) on Intel Microarchitectures,” In Proceedings of the fifth international symposium on computing and networking (CANDAR 17). Awarded Best Paper , IEEE, 2017.


Optimizations in the petascale era require modifications of existing codes to take advantage of new architectures with large core counts and SIMD vector units. This paper examines high-level and low-level optimization strategies for numerical weather prediction (NWP) codes. These strategies employ thread-local structures of arrays (SOA) and an OpenMP directive such as OMP SIMD. These optimization approaches are applied to the Weather Research Forecasting single-moment 6-class microphysics schemes (WSM6) in the US Navy NEPTUNE system. The results of this study indicate that the high-level approach with SOA and low-level OMP SIMD improves thread and vector parallelism by increasing data and temporal locality. The modified version of WSM6 runs 70x faster than the original serial code. This improvement is about 23.3x faster than the performance achieved by Ouermi et al., and 14.9x faster than the performance achieved by Michalakes et al.

B. Peterson, A. Humphrey, J. Schmidt, M. Berzins. “Addressing Global Data Dependencies in Heterogeneous Asynchronous Runtime Systems on GPUs. Awarded Best Paper,” In Proceedings of the Third International Workshop on Extreme Scale Programming Models and Middleware - ESPM2'17, ACM, 2017.
DOI: 10.1145/3152041.3152082


Large-scale parallel applications with complex global data dependencies beyond those of reductions pose significant scalability challenges in an asynchronous runtime system. Internodal challenges include identifying the all-to-all communication of data dependencies among the nodes. Intranodal challenges include gathering together these data dependencies into usable data objects while avoiding data duplication. This paper addresses these challenges within the context of a large-scale, industrial coal boiler simulation using the Uintah asynchronous many-task runtime system on GPU architectures. We show significant reduction in time spent analyzing data dependencies through refinements in our dependency search algorithm. Multiple task graphs are used to eliminate subsequent analysis when task graphs change in predictable and repeatable ways. Using a combined data store and task scheduler redesign reduces data dependency duplication ensuring that problems fit within host and GPU memory. These modifications did not require any changes to application code or sweeping changes to the Uintah runtime system. We report results running on the DOE Titan system on 119K CPU cores and 7.5K GPUs simultaneously. Our solutions can be generalized to other task dependency problems with global dependencies among thousands of nodes which must be processed efficiently at large scale.

W. Usher, J. Amstutz, C. Brownlee, A. Knoll, I. Wald . “Progressive CPU Volume Rendering with Sample Accumulation,” In Eurographics Symposium on Parallel Graphics and Visualization, Edited by Alexandru Telea and Janine Bennett, The Eurographics Association, 2017.
ISBN: 978-3-03868-034-5
ISSN: 1727-348X
DOI: 10.2312/pgv.20171090


We present a new method for progressive volume rendering by accumulating object-space samples over successively rendered frames. Existing methods for progressive refinement either use image space methods or average pixels over frames, which can blur features or integrate incorrectly with respect to depth. Our approach stores samples along each ray, accumulates new samples each frame into a buffer, and progressively interleaves and integrates these samples. Though this process requires additional memory, it ensures interactivity and is well suited for CPU architectures with large memory and cache. This approach also extends well to distributed rendering in cluster environments. We implement this technique in Intel's open source OSPRay CPU ray tracing framework and demonstrate that it is particularly useful for rendering volumetric data with costly sampling functions.

W. Usher, P. Klacansky, F. Federer, P. T. Bremer, A. Knoll, J. Yarch, A. Angelucci, V. Pascucci. “A Virtual Reality Visualization Tool for Neuron Tracing,” In IEEE Transactions on Visualization and Computer Graphics, IEEE, 2017.
ISSN: 1077-2626
DOI: 10.1109/TVCG.2017.2744079


Tracing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists.

Y. Wan, C. Hansen. “Uncertainty Footprint: Visualization of Nonuniform Behavior of Iterative Algorithms Applied to 4D Cell Tracking,” In Computer Graphics Forum, Wiley, 2017.


Research on microscopy data from developing biological samples usually requires tracking individual cells over time. When cells are three-dimensionally and densely packed in a time-dependent scan of volumes, tracking results can become unreliable and uncertain. Not only are cell segmentation results often inaccurate to start with, but it also lacks a simple method to evaluate the tracking outcome. Previous cell tracking methods have been validated against benchmark data from real scans or artificial data, whose ground truth results are established by manual work or simulation. However, the wide variety of real-world data makes an exhaustive validation impossible. Established cell tracking tools often fail on new data, whose issues are also difficult to diagnose with only manual examinations. Therefore, data-independent tracking evaluation methods are desired for an explosion of microscopy data with increasing scale and resolution. In this paper, we propose the uncertainty footprint, an uncertainty quantification and visualization technique that examines nonuniformity at local convergence for an iterative evaluation process on a spatial domain supported by partially overlapping bases. We demonstrate that the patterns revealed by the uncertainty footprint indicate data processing quality in two algorithms from a typical cell tracking workflow – cell identification and association. A detailed analysis of the patterns further allows us to diagnose issues and design methods for improvements. A 4D cell tracking workflow equipped with the uncertainty footprint is capable of self diagnosis and correction for a higher accuracy than previous methods whose evaluation is limited by manual examinations.

Y. Wan, H. Otsuna, H. A. Holman, B. Bagley, M. Ito, A. K. Lewis, M. Colasanto, G. Kardon, K. Ito, C. Hansen. “FluoRender: joint freehand segmentation and visualization for many-channel fluorescence data analysis,” In BMC Bioinformatics, Vol. 18, No. 1, Springer Nature, May, 2017.
DOI: 10.1186/s12859-017-1694-9


Image segmentation and registration techniques have enabled biologists to place large amounts of volume data from fluorescence microscopy, morphed three-dimensionally, onto a common spatial frame. Existing tools built on volume visualization pipelines for single channel or red-green-blue (RGB) channels have become inadequate for the new challenges of fluorescence microscopy. For a three-dimensional atlas of the insect nervous system, hundreds of volume channels are rendered simultaneously, whereas fluorescence intensity values from each channel need to be preserved for versatile adjustment and analysis. Although several existing tools have incorporated support of multichannel data using various strategies, the lack of a flexible design has made true many-channel visualization and analysis unavailable. The most common practice for many-channel volume data presentation is still converting and rendering pseudosurfaces, which are inaccurate for both qualitative and quantitative evaluations.

Here, we present an alternative design strategy that accommodates the visualization and analysis of about 100 volume channels, each of which can be interactively adjusted, selected, and segmented using freehand tools. Our multichannel visualization includes a multilevel streaming pipeline plus a triple-buffer compositing technique. Our method also preserves original fluorescence intensity values on graphics hardware, a crucial feature that allows graphics-processing-unit (GPU)-based processing for interactive data analysis, such as freehand segmentation. We have implemented the design strategies as a thorough restructuring of our original tool, FluoRender.

The redesign of FluoRender not only maintains the existing multichannel capabilities for a greatly extended number of volume channels, but also enables new analysis functions for many-channel data from emerging biomedical-imaging techniques.


K. Aras B. Burton, D. Swenson, R.S. MacLeod. “Spatial organization of acute myocardial ischemia,” In Journal of Electrocardiology, Vol. 49, No. 3, Elsevier, pp. 323–336. May, 2016.


Myocardial ischemia is a pathological condition initiated by supply and demand imbalance of the blood to the heart. Previous studies suggest that ischemia originates in the subendocardium, i.e., that nontransmural ischemia is limited to the subendocardium. By contrast, we hypothesized that acute myocardial ischemia is not limited to the subendocardium and sought to document its spatial distribution in an animal preparation. The goal of these experiments was to investigate the spatial organization of ischemia and its relationship to the resulting shifts in ST segment potentials during short episodes of acute ischemia.

We conducted acute ischemia studies in open-chest canines (N = 19) and swines (N = 10), which entailed creating carefully controlled ischemia using demand, supply or complete occlusion ischemia protocols and recording intramyocardial and epicardial potentials. Elevation of the potentials at 40% of the ST segment between the J-point and the peak of the T-wave (ST40%) provided the metric for local ischemia. The threshold for ischemic ST segment elevations was defined as two standard deviations away from the baseline values.

The relative frequency of occurrence of acute ischemia was higher in the subendocardium (78% for canines and 94% for swines) and the mid-wall (87% for canines and 97% for swines) in comparison with the subepicardium (30% for canines and 22% for swines). In addition, acute ischemia was seen arising throughout the myocardium (distributed pattern) in 87% of the canine and 94% of the swine episodes. Alternately, acute ischemia was seen originating only in the subendocardium (subendocardial pattern) in 13% of the canine episodes and 6% of the swine episodes (p < 0.05).

Our findings suggest that the spatial distribution of acute ischemia is a complex phenomenon arising throughout the myocardial wall and is not limited to the subendocardium.

P.R. Atkins, S.Y. Elhabian, P. Agrawal, M.D. Harris, R.T. Whitaker, J.A. Weiss, C.L. Peters, A.E. Anderson. “Quantitative comparison of cortical bone thickness using correspondence-based shape modeling in patients with cam femoroacetabular impingement,” In Journal of Orthopaedic Research, Wiley-Blackwell, Nov, 2016.
DOI: 10.1002/jor.23468


The proximal femur is abnormally shaped in patients with cam-type femoroacetabular impingement (FAI). Impingement
may elicit bone remodeling at the proximal femur, causing increases in cortical bone thickness. We used correspondence-based shape modeling to quantify and compare cortical thickness between cam patients and controls for the location of the cam lesion and the proximal femur. Computed tomography images were segmented for 45 controls and 28 cam-type FAI patients. The segmentations were input to a correspondence-based shape model to identify the region of the cam lesion. Median cortical thickness data over the region of the cam lesion and the proximal femur were compared between mixed-gender and gender-specific groups. Median [interquartile range] thickness was significantly greater in FAI patients than controls in the cam lesion (1.47 [0.64] vs. 1.13 [0.22] mm, respectively; p < 0.001) and proximal femur (1.28 [0.30] vs. 0.97 [0.22] mm, respectively; p < 0.001). Maximum thickness in the region of the cam lesion was more anterior and less lateral (p < 0.001) in FAI patients. Male FAI patients had increased thickness compared to male controls in the cam lesion (1.47 [0.72] vs. 1.10 [0.19] mm, respectively; p < 0.001) and proximal femur (1.25 [0.29] vs. 0.94 [0.17] mm, respectively; p < 0.001). Thickness was not significantly different between male and female controls. Clinical significance: Studies of non-pathologic cadavers have provided guidelines regarding safe surgical resection depth for FAI patients. However, our results suggest impingement induces cortical thickening in cam patients, which may strengthen the proximal femur. Thus, these previously established guidelines may be too conservative.

J.L. Baker, J. Ryou, X.F. Wei, C.R. Butson, N.D. Schiff, K.P. Purpura. “Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates,” In Journal of Neurophysiology, Vol. 116, No. 5, American Physiological Society, pp. 2383--2404. Aug, 2016.
DOI: 10.1152/jn.01129.2015


The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients.