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This article originally appeared in the 2018 Engineering @ Northeastern magazine.

Faculty and researchers from the College of Engineering collaborate here at Northeastern and all over the world to tackle one of the most complex topics imaginable—the human brain.

Inherently multidisciplinary, research on the brain has relevance to nearly every scientific field—engineering, psychology, chemistry, medicine, pharmacology, neuroscience, and more. The brain can be studied from individual molecules at the nanoscale level, to its entirety as a complex organ that influences every aspect of our daily lives, including memory, physical function, mental well-being, and even overall health, leading to prolific, trans-disciplinary collaborations right here at Northeastern.

“If we just thought about the brain from a purely engineering point of view, the models and tools we create would not capture the critical aspects of how brains and minds actually work,” says Professor Dana Brooks of the Department of Electrical and Computer Engineering (ECE). “With a system as complex as the brain, we have to be actively working and struggling creatively and synergistically to solve problems together.”

 
Dana Brooks, professor of electrical and computer engineering

Dana Brooks: Brain-related modeling and signal processing research

Using computational modeling, Brooks and his collaborators are enabling other researchers in industry and medicine to make better use of brain stimulation technology to modulate neural activity, using electrodes on the scalp and, via surgical procedures, directly on the cortical surface, as well as magnetic coils held above the head.

Working with colleagues, Brooks builds individualized models of brain anatomies from MRI or CAT scan images, constructs computational models that respect internal structures inside the head, and then suggests the best way to transmit electrical currents to each part of the brain doctors want to stimulate for the desired outcome, while also optimizing patient safety.

The results encouraged Brooks’ collaborators at Electrical Geodesics Inc. (now part of Royal Philips) to develop hardware and software enabling their customers to use electroencephalography (EEG) electrodes for targeted brain stimulation. Brooks’ group is working closely with researchers at the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center and at the University of Washington in Seattle to better target their stimulation treatments.

“At the University of Washington,” says Brooks, “they use cortical surface electrode arrays to help treat children and adolescents with epilepsy when drugs aren’t enough to control their seizures. By using the electric stimulation to discover which areas of the brain are responsible for which sensory and motor functions, doctors hope to better patient outcomes when surgically removing the tissue causing the problem without effecting any other areas or functions.”

More broadly, Brooks and several College of Engineering collaborators are working closely with the Institute for Affective Science in Northeastern’s Department of Psychology, along with faculty in the computer science and physical therapy departments, in an ambitious research effort to integrate engineering, neuroscience, and psychology perspectives to address fundamental questions about how the brain creates the mind. The brain stimulation work plays a key role in this effort because it offers a unique means to directly but safely alter specific aspects of brain function and then observe the consequent mental affects.

 
Heather Clark, professor of bioengineering

Heather Clark: Nanosensors with diverse applications

Using nanosensors capable of measuring chemical activity in the brain in real time, Bioengineering Professor Heather Clark is working to help round out the toolbox that neuroscience researchers can access to answer their questions about memory, function, disease states, and more.

“For many researchers, it is a scramble to find a tool to answer specific questions about the brain, such as what chemical is being used or transmitted and when,” says Clark. “A further issue is that many of the existing tools can only be implemented after the fact. Our nanosensors are not only designed to answer specific questions, but they are also capable of collecting this crucial data as it happens.”

Clark’s nanosensor is a modular system that selectively binds to the molecule being measured and communicates when that process has occurred. By varying the elements of the sensor, it can be tuned to measure different molecules, or to be compatible with a variety of imaging instruments.

Clark has received funding from the National Institutes of Health (NIH) for her research, including a Research Project Grant (R01) and money from the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program.

Working with the Northeastern engineering students in her lab—undergraduate through post-doctorate—is one of the favorite parts of Clark’s job. While examining brain tissue samples in mice and rats, Clark and her team look not for trends, but for the precise analytical information the researchers they partner with need to measure to see how robust the tool they’ve created is.

The nanosensors that Clark creates have wide-reaching applications, such as measuring the level of specific neurotransmitters like acetylcholine in certain disease stages or during different emotional states. For her, working with the brain is a fascinating area that offers boundless opportunities for exploration.

“The chemical processes that happen in the brain lead to memories and thoughts that cannot be recreated in a beaker. Why? And what are the spatial or temporal things going on that we can’t see or experience yet? Finding answers to these questions is what excites me.”

 
Samuel Chung, assistant professor of bioengineering

Samuel Chung: Nerve regeneration

Samuel Chung, assistant professor in the Department of Bioengineering, is working on a model for central nervous system regeneration with a rather unusual animal: an invertebrate worm that’s 1mm in length.

Chung’s research started from his background in physics and optics, where he learned about surgical technology using a laser that emits very short pulses as the scalpel, which is highly effective in very precise surgeries on the human eye. Chung has adapted this technology to cut individual axons—short extensions of nerve cells—from each of his worm’s brain cells and then watch them regenerate after surgery.

Thanks to funding from the Morton Cure Paralysis Fund and Northeastern’s Department of Bioengineering Start-Up Fund, Chung’s lab is working to very quickly screen for genetic mutations that affect regeneration in the worm. Using these invertebrates is vastly faster than conducting the process with other animals—regeneration requires hours to days for worms, compared to weeks or even months for mammals.

Chung’s main goal is to be able to find the genes responsible for regenerating the worm’s central nervous system. Through collaboration with other scientists and engineers working with mammals, he eventually hopes to apply these genetic findings to human spinal injuries and neurodegenerative diseases like Amyotrophic Lateral Sclerosis, commonly referred to as ALS or Lou Gehrig’s disease.

“Scientists have known for 30 years that the human spinal cord can regenerate under the right conditions,” explains Chung. “We want to better understand these conditions and the genes responsible for them so we can help improve human quality of life in the future.”

 
Lee Makowski, professor and chair of bioengineering

Lee Makowski: Alzheimer’s disease studies

Lee Makowski, professor and chair of the Department of Bioengineering, is working to slow the march of Alzheimer’s disease.

Alzheimer’s is a slow-moving disease that can take years, even decades to reach its hallmark point of neural degradation, during which time the victim suffers from progressive memory loss and dementia. Because of the singular challenges of carrying out experiments on human brain tissue, scientists have found it exceedingly difficult to understand the processes behind the disease.

Neuronal degradation in Alzheimer’s is linked to the presence of amyloid fibrils composed of Abeta proteins and neurofibrillary tangles made of the protein called “tau.” However, there isn’t a clear correlation between the amount of these aggregates and the state of disease progression: People with advanced Alzheimer’s can have low levels of these proteins, just as those who have only begun to show symptoms can have relatively high levels.

Over the past four years, Makowski has been working with neuropathologists at Massachusetts General Hospital to analyze brain tissue samples collected from Alzheimer’s patients during autopsy using scanning x-ray microdiffraction. Makowski and his team then interpret the data to map the molecular structure of what they find, particularly in the case of the amyloid fibrils.

“We’re trying to understand how different strains of amyloid proteins might end up expressing different levels of toxicity,” explains Makowski. “By looking at different parts of the brain in subjects with different clinical presentations of Alzheimer’s, we hope to correlate the molecular differences we see in our data with what they see in the clinic.”

By using this data to understand the mechanism of disease progression, Makowski and his collaborators hope it could help researchers design a therapy to further slow Alzheimer’s, or even halt it in its tracks.

“I’m very upbeat about our chances for making progress,” says Makowski. “I feel that researchers and clinicians are beginning to connect the dots, and I think there’s real potential for future solutions.”

 
Sarah Ostadabbas (center), assistant professor of electrical and
computer engineering, with Yu Yin, MS student, and Adaeze
Adigwe, BS student, in the Augmented Cognition Lab

Sarah Ostadabbas: Computer vision and human-computer interaction

Sarah Ostadabbas, director of the Augmented Cognition Lab and assistant professor in the Department of Electrical and Computer Engineering, primarily researches digital prosthetics. These cognitive and neurological assistive devices can be used for rehabilitation, Parkinson’s patients, diabetics, and individuals on the autism spectrum.

The emerging field of digital prosthetics requires two important elements: real-time understanding of the cognitive/neurological state of the user, and real-time understanding of the state of the world around him/her. To help accomplish these technological hurdles—which Ostadabbas calls “pose of the user” and “pose of the world,” respectively—her lab uses deep learning, physics-based generative models, and subspace modeling/factorization to develop solutions.

In addition, Ostadabbas collaborates closely with members of the psychology, neuroscience, and rehabilitation departments on another key technological aspect of her research: augmented/virtual reality (AR/VR).

“Using AR and VR technology can help us produce digital prosthetics that impact a variety of human situations, including a VR system in which a patient’s low-functioning leg seems to mirror the actions of the functioning leg to jump-start movement, and using AR to draw short-range walking targets to prevent gait freezing in Parkinson’s patients,” says Ostadabbas. “These new technologies offer patients more freedom than the lower-tech assistive devices currently in use, such as using physical mirrors and objects to accomplish the same task.”

Collaborating with experts in other fields to solve difficult problems is an important element of Professor Ostadabbas’s worldview.

“We’ve entered the 21st century surrounded by massive amounts of data and some incredible technological tools, which can be used to ease human suffering and solve some of our most long-standing problems. The key to tackling these grand challenges in a humane way is a nuanced and cross-domain collaborative approach, and I look forward to working with colleagues around the world to address these issues.”