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Advances in Rehabilitation Medicine

Traumatic Brain Injury: Understanding the Biological Underpinnings of Cognitive Impairment

Dr. Sudhin A. Shah

Sudhin A. Shah, PhD, a cognitive neuroscientist in the Department of Rehabilitation Medicine at NewYork-Presbyterian/Weill Cornell Medical Center, is advancing understanding of traumatic brain injury through research examining the biological basis of cognitive impairment to augment and improve cognitive recovery after TBI.

According to the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control, the prevalence of individuals with a TBI-related disability in the United States is estimated to be 5.3 million or 2 percent of the population. In children and young adults, it is the leading cause of death and disability. Because the brain is one of the few areas of the body where neurons do not regenerate after cell death, predicting the degree and rate of recovery has been notoriously very difficult.

“Chronic cognitive impairment is a devastating sequela following TBI. At present, we lack the ability to predict how cognitive impairment will evolve after injury, and lack the ability to effectively encourage it,” says Dr. Shah, who is an NIH-funded investigator with the Weill Cornell Medicine Department of Rehabilitation Medicine and the Feil Family Brain and Mind Research Institute.

“We are heavily focused on multimodal, longitudinal neuroimaging to understand the biological basis of cognitive impairments that are caused by traumatic brain injury.” — Dr. Sudhin A. Shah

Dr. Shah received her PhD in Systems Neuroscience at Cornell University and her MS in biomedical engineering at Columbia University. Her research career has focused on understanding the neurobiological changes that underlie cognition and its impairments following an acquired brain injury. By paying close attention to the recovery process of adults and children with TBI, Dr. Shah is working to track spontaneous and intervened recovery, inform therapeutic interventions to reduce impairment, and create prognostic models that predict how cognitive ability will change over time.

Studying Biomarkers of Cognitive Impairment to Predict Cognitive Outcomes

Dr. Shah and Amy Kuceyeski, PhD, Associate Professor of Mathematics in Radiology in the Department of Radiology at Weill Cornell Medicine and an Associate Professor of Mathematics in Neuroscience with the Weill Cornell Medicine Feil Family Brain and Mind Research Institute, are using multimodal imaging to study the effects of TBI on executive attention recovery in a cohort of 75 adults. Chronic executive attention deficits and cognitive dysfunction are commonplace in patients with TBI. The researchers are recruiting participants over a five-year period and are in their third year of the study. Criteria for patient enrollment include moderate to severe brain injury as a result of a fall, motor vehicle accident, pedestrian accident, a fight, or an assault. Study participants will be compared to age-matched healthy controls.

“TBI, by nature, is a heterogeneous condition. We are recruiting patients who did not have neurological impairments prior to the TBI to help us link the cognitive impairment and biological changes to the injury itself,” explains Dr. Shah.

Study participants are asked to complete an attention task while researchers use different imaging modalities to examine activity patterns and underlying structures in specific regions of the brain. Electroencephalography (EEG) is used to measure the electrical activity of the cortex, and diffusion magnetic resonance imaging (dMRI) is used to inform the researchers about structure and connections in the brain. The participants are evaluated at two time points:
1) during the subacute phase at three to six months, and 2) at one-year post-TBI, to bookend the steepest recovery post-TBI.

Dr. Shah and her colleagues hypothesize that individually measured EEG responses and anatomic injuries within the anterior forebrain mesocircuit will correlate with executive attention deficits and accurately predict cognitive outcomes. Their innovative approach measures the physiology and connectivity of brain structures specific to cognition and predicts outcomes using machine learning.

images of MRIs of patient with TBI

Caption: A) Anatomical magnetic resonance imaging of a patient with TBI; red circle indicates abnormal hyperintensity in the frontal and temporal regions B) Fractional anisotropy map of a patient with TBI; red circle indicates white matter microstructure abnormality C) Z-score versus healthy controls shows the frontal and temporal area with thicker, darker lines indicating increasingly disconnected regions of the brain. (Image courtesy of Keith Jamison, Amy Kuceyeski, PhD, and Sudhin A. Shah, PhD)

Advancing Research in Children with TBI

As Scientific Director of the Cognitive Recovery Research program at Blythedale Children’s Hospital, Dr. Shah is also conducting studies in children with TBI, a population that to date has been greatly understudied. Cognitive impairment is the primary, most persistent, and disabling sequela of pediatric acquired brain injury. Current methods to accurately diagnose, prognose, and therapeutically treat cognitive impairments following pediatric TBI are far from ideal.

Along with pediatric rehabilitation experts, Dr. Shah recently led the creation of a new Pediatric Brain Injury Consortium (PBIC) – eight inpatient rehabilitation hospitals in the U.S. collaborating to create the infrastructure for multicenter studies of outcomes, mechanism, and intervention. Together, they are working with the Trial Innovation Network, an initiative of the NIH National Center for Advancing Translational Sciences, to conduct randomized placebo-controlled trials involving children with TBI in rehabilitation settings to allow for careful measurement of clinical and cognitive outcomes paired with neuroimaging.

“Studies in children oftentimes lag behind similar populations in adults, which results in drugs being prescribed without the appropriate knowledge of safety, tolerability, and effective dosing,” says Dr. Shah. “In addition to rigorous, age-appropriate clinical studies, we can use quantitative neuroimaging to tie the clinically observed behavioral changes to measures of the brain, which is essential to derive mechanisms and track recovery — intervened or therapeutic.”

Working with colleagues in the PBIC, multicenter efforts to objectively assess cognitive impairments through direct measurement of cognitive processing is underway. Dr. Shah and her colleagues are developing a novel, clinically feasible, pediatric friendly, motor function independent, neuroimaging battery for the hierarchical assessment of cognitive function recovery. This, in turn, is expected to improve prognostic models and the ability to track recovery – intervened or spontaneous.

Ultimately, Dr. Shah plans to use her research findings to inform future work. “We are hoping to obtain funding for other novel imaging tools such as PET [positron emission tomography] studies to elucidate the circuit-level changes underlying executive attention impairment and its recovery,” says Dr. Shah. “A careful characterization of the biology as it relates to cognitive impairments is instrumental to future therapeutic interventions.”

Weill Cornell Medicine TBI Research Registry

A TBI research registry has recently been established at Weill Cornell Medicine identifying adult TBI research underway by Dr. Shah and her colleagues. If you have a patient who has suffered a TBI and would be interested in participating in TBI research, registration information is available at TBI Research Registry.

Reference Articles

Shah SA, Lowder R, Kuceyeski A. Quantitative multimodal imaging in traumatic brain injuries producing impaired cognition. Current Opinion in Neurology. 2020 Dec;33(6):691-698.

Watson WD, Suskauer SJ, Askin G, Nowak S, Baum KT, Gerber LM, Blackwell LS, Koterba CH, Hoskinson KR, Kurowski BG, McLaughlin M, Tlustos SJ, Zimmerman KO, Shah SA. Cognitive recovery during inpatient rehabilitation following pediatric traumatic brain injury: A pediatric brain injury consortium study. Journal of Head Trauma Rehabilitation. (In Press)

 

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Dr. Sudhin A. Shah

NewYork-Presbyterian

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