ABERDEEN PROVING GROUND, Md. — A big data approach to neuroscience promises to significantly improve our understanding of the relationship between brain activity and performance.

To date, there have been relatively few attempts to use a big-data approach within the emerging field of neurotechnology. In this field, the few attempts at meta-analysis (analysis across multiple studies) combine only the results from individual studies rather than the raw data. A new study is one of the first to combine data across a diverse set of experiments to identify patterns of brain activity that are common across tasks and people.

The Army in particular is interested in how the cognitive state of Soldiers can affect their performance during a mission. If you can understand the brain, you can predict and even enhance cognitive performance.

Researchers from the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory teamed with the University of Texas at San Antonio and Intheon Labs to develop a first-of-its-kind mega-analysis of brain imaging data–in this case electroencephalography, or EEG.

In the two-part paper, they aggregate the raw data from 17 individual studies, collected at six different locations, into a single analytical framework, with their findings published in a series of two papers in the journal NeuroImage. The individual studies included in this analysis encompass a diverse set of tasks such simulated driving and visual search.

“The vast majority of human neuroscientific studies use a very small number of participants employed in very specific tasks,” said Dr. Jonathan Touryan, an Army scientist and co-author of the paper. “This limits how well the results from any single study can be generalized to a broader population and a larger range of activities.”

Mega-analysis of EEG is extremely challenging due to the many types of hardware systems (properties and configuration of the electrodes), the diversity of tasks, how different datasets are annotated, and the intrinsic variability between individuals and within an individual over time, Touryan said.

These sources of variability make it difficult to find robust relationships between brain and behavior. Mega-analysis seeks to address this by aggregating large, heterogeneous datasets to identify universal features that link neural activity, cognitive state and task performance.

Next-generation neurotechnologies will require a thorough understanding of this relationship in order to mitigate deficits or augment performance of human operators. Ultimately, these neurotechnologies will enable autonomous systems to better understand the Soldier and facilitate communications within multi-domain operations, he said.

To combine the raw data from the collection of studies, the researchers developed Hierarchical Event Descriptors (HED tags) — a novel labeling ontology that captures the wide range of experimental events encountered in diverse datasets. This HED tag system was recently adopted into the Brain Imaging Data Structure international standard, one of the most common formats for organizing and analyzing brain data, Touryan said.

The research team also developed a fully automated processing pipeline to perform large-scale analysis of their high-dimensional time-series data–amounting to more than 1,000 recording sessions.

Much of this data was collected over the last 10 years through the U.S. Army’s Cognition and Neuroergonomics Collaborative Technology Alliance and is now available in an online repository for the scientific community (see Related Links below). The U.S. Army continues to use this data to develop human-autonomy adaptive systems for both the Next Generation Combat Vehicle and Soldier Lethality Cross-Functional Teams.

By U.S. Army CCDC Army Research Laboratory Public Affairs

RESEARCH TRIANGLE PARK, N.C. — New Army research provides a better understanding of the swelling that occurs in the brain during a stroke, which could contribute to new treatment strategies for stroke patients and have potential implications for traumatic brain injuries.

Cerebral edema, swelling that occurs in the brain, is a severe and potentially fatal complication for stroke victims. Research, funded in part by the Army Research Office and conducted at The University of Rochester Medical Center, shows for the first time that the glymphatic system — normally associated with the beneficial task of waste removal — goes awry during a stroke and floods the brain, promoting edema and drowning brain cells.

The research, conducted with mice, appears in the journal Science.

“These findings show that the glymphatic system plays a central role in driving the acute tissue swelling in the brain after a stroke”, said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center Center for Translational Neuromedicine and senior author of the article. “Understanding this dynamic — which is propelled by storms of electrical activity in the brain — point the way to potential new strategies that could improve stroke outcomes.”

The glymphatic system, first discovered by the Nedergaard lab in 2012, consists of a network that piggybacks on the brain’s blood circulation system and is comprised of layers of plumbing, with the inner blood vessel encased by a ‘tube’ that transports cerebrospinal fluid. The system pumps the fluid through brain tissue primarily during sleep, washing away toxic proteins and other waste.

Before the findings of the new study, scientists assumed that the source of brain swelling was exclusively the result of fluid from blood.

“Our hope is that this new finding will lead to novel interventions to reduce the severity of ischemic events, as well as other brain injuries to which Soldiers may be exposed,” said Matthew Munson, Ph.D., program manager, fluid dynamics, ARO, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory. “What’s equally exciting is that this new finding was not part of the original research proposal. That is the power of basic science research and working across disciplines. Scientists ‘follow their nose’ where the data and their hypotheses lead them — often to important unanticipated applications.”

AN ELECTRICAL WAVE, THEN THE FLOOD
Ischemic stroke, the most common form of stroke, occurs when a vessel in the brain is blocked. This blockage denies the nutrients and oxygen cells need to function, which results in their rapid depolarization. As the cells release energy and fire, they trigger neighboring cells, creating a domino effect that results in an electrical wave that expands outward from the site of the stroke, called spreading depolarization.

During the spreading depolarization, vast amounts of potassium and neurotransmitters released by neurons into the brain cause the smooth muscle cells that line the walls of blood vessels to seize up and contract, cutting off blood flow in a process known as spreading ischemia. Cerebrospinal Fluid then flows into the ensuing vacuum, inundating brain tissue and causing edema. The already vulnerable brain cells in the path of the flood essentially drown in fluid and the brain begins to swell. These depolarization waves can continue in the brain for days and even weeks after the stroke, compounding the damage.

“When you force every single cell, which is essentially a battery, to release its charge it represents the single largest disruption of brain function you can achieve — you basically discharge the entire brain surface in one fell swoop,” said Humberto Mestre, M.D., a Ph.D. student in the Nedergaard lab and lead author of the study. “The double hit of the spreading depolarization and the ischemia makes the blood vessels cramp, resulting in a level of constriction that is completely abnormal and creating conditions for CSF to rapidly flow into the brain.”

The study correlated the brain regions in mice vulnerable to the fluid propelled by the glymphatic system with edema found in the brains of humans who had sustained an ischemic stroke.

POINTING THE WAY TO NEW STROKE THERAPIES
The findings suggest potential new treatment strategies that, used in combination with existing therapies, focus on restoring blood flow to the brain quickly after a stroke. The study could also have implications for brain swelling observed in other conditions such as subarachnoid hemorrhage and traumatic brain injury.

Approaches that block specific receptors on nerve cells could inhibit or slow the cycle of spreading depolarization. Additionally, a water channel called aquaporin-4 on astrocytes — an important support cell in the brain — regulates the flow of the fluid. When the research team conducted the stroke experiments in mice genetically modified to lack aquaporin-4, the fluid flow into the brain slowed significantly.

Aquaporin-4 inhibitors currently under development as a potential treatment for cardiac arrest and other diseases could eventually be candidates to treat stroke.

In additional to the Army Research Office, the research was supported with funding from National Institute of Neurological Disorders and Stroke, the National Institute of Aging, Fondation Leducq Transatlantic Networks of Excellence Program, the Novo Nordisk and Lundbeck Foundations, and E.U. Horizon 2020.

By U.S. Army CCDC Army Research Laboratory Public Affairs