September 26, 2020

Translational Neuroscience Program students win training grants from National Institutes of Health

James Matchynski, left, Nolan O'Hara and Nicole Zabik.

Three students enrolled in the Wayne State University Translational Neuroscience Program housed within the School of Medicine’s Department of Psychiatry and Behavioral Neurosciences have won significant training grants from the National Institutes of Health to support their innovative doctoral research projects.

James Matchynski

James Matchynski is a student in the School of Medicine’s M.D./Ph.D. program, now in his fourth year of the Ph.D. portion. He received his F30 Ruth L. Kirschstein National Research Service Award, his first external training grant, from the National Institute of Mental Health for “Novel method to quantify conditioned fear-based neuronal activity in rat brain in vivo using high-resolution photoacoustic imaging.”

 

“We are trying to use a new brain imaging system to monitor detailed activation patterns in a rodent model of fear-learning to better our understanding of the process,” Matchynski said. “The goal of this information is to help us better understand what is happening in the brain of patients with post-traumatic stress disorder and what can be done to prevent and treat it.”

 

The topic, he said, is an early step toward explaining complex neurological disorders in a more individualized way, paving the way for more precise and effective treatment targets.

He is mentored by Associate Professor of Neurosurgery Alana Conti, Ph.D., and Assistant Professor of Psychiatry and Behavioral Neurosciences Shane Perrine, Ph.D.

 

“Jim is developing into an outstanding clinician-scientist, becoming skilled in balancing the use of technological advances in the study of psychiatric disease,” Dr. Conti said. “His curiosity and quest for knowledge have driven his research progress and that of our labs’, and we look forward to the benefits his work will provide to our understanding of the neural control of fear-learning.”

A hallmark of PTSD is impaired fear-learning.

 

The understanding of fear behavior is limited due to the inability to analyze the selective microcircuitry that underlies it, in a translationally-relevant manner. “This proposal seeks to implement a novel neuroimaging technique -- photoacoustic imaging -- which will allow, for the first time, highly-resolved direct imaging of microcircuit (neuronal ensemble) activation associated with fear learning throughout the medial prefrontal cortex, in vivo,” Matchynski said. “The identification and longitudinal analysis of these neuronal ensembles will provide novel information on the development of maladaptive fear-learning processes in those who suffer from PTSD, with the ultimate goal of targeted therapy development.”

 

Nolan O’Hara

Nolan O’Hara is a student in the School of Medicine’s M.D./Ph.D. program, now in his fourth year of the Ph.D. portion. He expects to defend his dissertation next year. He received the F30, his first external training grant, from the National Institute of Neurological Disorders and Stroke for “Characterization and Modeling of Epileptic Spasm Propagation Dynamics.” He will work with his doctoral advisor, Associate Professor of Neurology Justin Jeong, Ph.D., along with his advisory team members, Drs. Csaba Juhász, Eishi Asano and Noa Ofen.

“He is a talented student with open-mindedness and a young researcher with a unique combination of advanced medical imaging background, machine-learning techniques, brain-network modeling and computational neuroscience,” Dr. Jeong said. “My grant project, (“Novel DWI methods to minimize postoperative deficits in pediatric epilepsy surgery”) motivated him to understand clinical needs in pediatric epilepsy and learn innovative multi-modal imaging techniques such as diffusion MRI and intracranial EEG for better imaging of seizure activity and propagation in children with drug-resistant epilepsy, leading to the successful conceptualization of his F30 award that will investigate a novel multi-modal brain connectivity approach to characterize neural pathways and electrophysiological mechanisms involved in infantile spasms.”

No one has yet attempted the approach in infantile spasms, Dr. Jeong added.

“I am so grateful for the award and am excited to now do the work that I spent time articulating and proposing. I'm eager to learn answers to questions I currently have and learn what new questions will arise for me to answer next,” O’Hara said.

He is studying magnetic resonance imaging and neurosurgery data from children who experience a type of seizure called epileptic spasms. “Epileptic spasms can be difficult to interpret in part because their activity spreads so rapidly across the brain,” O’Hara said. “My work aims to better characterize this spread using individualized brain models constructed with various MRI techniques. I hope to improve our ability to localize the origin of a patient’s epileptic spasm activity, which would eventually help efforts to surgically target it.”

The scale of brain development during infancy and childhood, both in brain structure and in cognitive ability, is “so impressive,” he added.

“Childhood epilepsies, and in particular epileptic spasms, represent a common threat to this development but there are many unanswered questions about how seizure activity arises or spreads through the brain,” O’Hara said. “If we understand the bigger picture of how and where this activity spreads, then we may be better equipped to therapeutically target it. My hope is that by studying epileptic spasms now, I will help generate tools that allow me to be a better clinician in the future -- one who can work to preserve patient brain development as well as the unique insights patients can offer from their developing perspective.”

Nicole Zabik

Nicole Zabik received the F31 Ruth L. Kirschstein National Research Service Award from the National Institute of Mental Health. She will use it for her project, “Neural and Behavioral Mechanisms of Avoidance Behavior and its Impact on Fear Extinction in Adults with PTSD.” She works as a graduate research assistant in the Translational Neuropsychopharmacology Lab, led by mentor Associate Professor of Pharmacy Practice Christine Rabinek, Ph.D.

Zabik’s first training grant will run through 2023.

“It definitely feels surreal. I received the grant after only the first submission, which is not common. However, I am also extremely proud of myself because I worked very efficiently over the four months of writing it and coordinated multiple faculty members for the project, something I had never done before,” she said.

“Avoiding trauma reminders is a cyclical issue in post-traumatic stress disorder. It prevents people from recovering from a significant trauma and engaging in effective therapy modalities,” Zabik said. “This project’s goal is to understand what is going on in the brain and the body during trauma reminders. Ultimately, this will help us understand what prevents people from having long-lasting benefits from therapy.”

Although similar work has been conducted in healthy adults, it has never been applied to trauma-exposed adults, including individuals who suffer significantly from avoidance tendencies.

Avoidance is one of four symptoms of PTSD.

A large majority of translational/clinical research focuses on one symptom category, but PTSD is a complex disorder. “There are literally more than 1,000 ways to be diagnosed,” Zabik said. “This project is interesting to me because it steps outside of the typical focus of translational PTSD research and aims to identify the impact of another symptom on brain and behavior.”

Avoidance is also prevalent in anxiety, obsessive-compulsive disorder and substance use disorder. “Therefore, whatever we learn from the project's data has the capacity to help other individuals with mental health disorders. These findings will be useful for more than just those with PTSD,” she added. “Putting this grant together has truly made me appreciate the complexity of it, and also how important it is for researchers and clinicians to have communication. The brain is really cool, and humans in general are very complex. Trying to devise a paradigm for people to engage with to pinpoint this behavior/symptom was the biggest game of logic/chess

Three students enrolled in the Wayne State University Translational Neuroscience Program housed within the School of Medicine’s Department of Psychiatry and Behavioral Neurosciences have won significant training grants from the National Institutes of Health to support their innovative doctoral research projects.

James Matchynski

James Matchynski is a student in the School of Medicine’s M.D./Ph.D. program, now in his fourth year of the Ph.D. portion. He received his F30 Ruth L. Kirschstein National Research Service Award, his first external training grant, from the National Institute of Mental Health for “Novel method to quantify conditioned fear-based neuronal activity in rat brain in vivo using high-resolution photoacoustic imaging.”

 

“We are trying to use a new brain imaging system to monitor detailed activation patterns in a rodent model of fear-learning to better our understanding of the process,” Matchynski said. “The goal of this information is to help us better understand what is happening in the brain of patients with post-traumatic stress disorder and what can be done to prevent and treat it.”

 

The topic, he said, is an early step toward explaining complex neurological disorders in a more individualized way, paving the way for more precise and effective treatment targets.

He is mentored by Associate Professor of Neurosurgery Alana Conti, Ph.D., and Assistant Professor of Psychiatry and Behavioral Neurosciences Shane Perrine, Ph.D.

 

“Jim is developing into an outstanding clinician-scientist, becoming skilled in balancing the use of technological advances in the study of psychiatric disease,” Dr. Conti said. “His curiosity and quest for knowledge have driven his research progress and that of our labs’, and we look forward to the benefits his work will provide to our understanding of the neural control of fear-learning.”

A hallmark of PTSD is impaired fear-learning.

 

The understanding of fear behavior is limited due to the inability to analyze the selective microcircuitry that underlies it, in a translationally-relevant manner. “This proposal seeks to implement a novel neuroimaging technique -- photoacoustic imaging -- which will allow, for the first time, highly-resolved direct imaging of microcircuit (neuronal ensemble) activation associated with fear learning throughout the medial prefrontal cortex, in vivo,” Matchynski said. “The identification and longitudinal analysis of these neuronal ensembles will provide novel information on the development of maladaptive fear-learning processes in those who suffer from PTSD, with the ultimate goal of targeted therapy development.”

 

Nolan O’Hara

Nolan O’Hara is a student in the School of Medicine’s M.D./Ph.D. program, now in his fourth year of the Ph.D. portion. He expects to defend his dissertation next year. He received the F30, his first external training grant, from the National Institute of Neurological Disorders and Stroke for “Characterization and Modeling of Epileptic Spasm Propagation Dynamics.” He will work with his doctoral advisor, Associate Professor of Neurology Justin Jeong, Ph.D., along with his advisory team members, Drs. Csaba Juhász, Eishi Asano and Noa Ofen.

“He is a talented student with open-mindedness and a young researcher with a unique combination of advanced medical imaging background, machine-learning techniques, brain-network modeling and computational neuroscience,” Dr. Jeong said. “My grant project, (“Novel DWI methods to minimize postoperative deficits in pediatric epilepsy surgery”) motivated him to understand clinical needs in pediatric epilepsy and learn innovative multi-modal imaging techniques such as diffusion MRI and intracranial EEG for better imaging of seizure activity and propagation in children with drug-resistant epilepsy, leading to the successful conceptualization of his F30 award that will investigate a novel multi-modal brain connectivity approach to characterize neural pathways and electrophysiological mechanisms involved in infantile spasms.”

No one has yet attempted the approach in infantile spasms, Dr. Jeong added.

“I am so grateful for the award and am excited to now do the work that I spent time articulating and proposing. I'm eager to learn answers to questions I currently have and learn what new questions will arise for me to answer next,” O’Hara said.

He is studying magnetic resonance imaging and neurosurgery data from children who experience a type of seizure called epileptic spasms. “Epileptic spasms can be difficult to interpret in part because their activity spreads so rapidly across the brain,” O’Hara said. “My work aims to better characterize this spread using individualized brain models constructed with various MRI techniques. I hope to improve our ability to localize the origin of a patient’s epileptic spasm activity, which would eventually help efforts to surgically target it.”

The scale of brain development during infancy and childhood, both in brain structure and in cognitive ability, is “so impressive,” he added.

“Childhood epilepsies, and in particular epileptic spasms, represent a common threat to this development but there are many unanswered questions about how seizure activity arises or spreads through the brain,” O’Hara said. “If we understand the bigger picture of how and where this activity spreads, then we may be better equipped to therapeutically target it. My hope is that by studying epileptic spasms now, I will help generate tools that allow me to be a better clinician in the future -- one who can work to preserve patient brain development as well as the unique insights patients can offer from their developing perspective.”

Nicole Zabik

Nicole Zabik received the F31 Ruth L. Kirschstein National Research Service Award from the National Institute of Mental Health. She will use it for her project, “Neural and Behavioral Mechanisms of Avoidance Behavior and its Impact on Fear Extinction in Adults with PTSD.” She works as a graduate research assistant in the Translational Neuropsychopharmacology Lab, led by mentor Associate Professor of Pharmacy Practice Christine Rabinek, Ph.D.

Zabik’s first training grant will run through 2023.

“It definitely feels surreal. I received the grant after only the first submission, which is not common. However, I am also extremely proud of myself because I worked very efficiently over the four months of writing it and coordinated multiple faculty members for the project, something I had never done before,” she said.

“Avoiding trauma reminders is a cyclical issue in post-traumatic stress disorder. It prevents people from recovering from a significant trauma and engaging in effective therapy modalities,” Zabik said. “This project’s goal is to understand what is going on in the brain and the body during trauma reminders. Ultimately, this will help us understand what prevents people from having long-lasting benefits from therapy.”

Although similar work has been conducted in healthy adults, it has never been applied to trauma-exposed adults, including individuals who suffer significantly from avoidance tendencies.

Avoidance is one of four symptoms of PTSD.

A large majority of translational/clinical research focuses on one symptom category, but PTSD is a complex disorder. “There are literally more than 1,000 ways to be diagnosed,” Zabik said. “This project is interesting to me because it steps outside of the typical focus of translational PTSD research and aims to identify the impact of another symptom on brain and behavior.”

Avoidance is also prevalent in anxiety, obsessive-compulsive disorder and substance use disorder. “Therefore, whatever we learn from the project's data has the capacity to help other individuals with mental health disorders. These findings will be useful for more than just those with PTSD,” she added. “Putting this grant together has truly made me appreciate the complexity of it, and also how important it is for researchers and clinicians to have communication. The brain is really cool, and humans in general are very complex. Trying to devise a paradigm for people to engage with to pinpoint this behavior/symptom was the biggest game of logic/chess