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Multimodal Behavioral Assessment After Experimental Brain Trauma

Live Date:2/3/2021

Duration:60 minutes

Traumatic brain injuries (TBIs) affect 2.8 million individuals in the United States each year. Moreover, 500,000 yearly emergency room visits are attributed to childhood-acquired brain trauma, while the elderly also constitute another high-risk population segment due to falls, with patients enduring long-lasting cognitive, physical, or behavioral effects. Impaired attention is central to the cognitive deficits associated with long-term sequelae for many TBI survivors. Considering that cognitive deficits are often assessed using multi-domain neuropsychological cognitive battery tests, Dr. Bondi's group employed, for the first time, multimodal approaches to determine higher-order attentional capabilities after experimental TBI in rats. Their studies aimed to investigate complex cognitive deficits in adolescent and adult male and female rats subjected to frontal or parietal lobe injuries. They found that sustained attention and behavioral flexibility employed using operant chambers (e.g., 3-choice serial reaction time test and attentional set-shifting test, respectively) are impaired after experimental TBI in males and females. To maintain a parallel with the clinic where patients are given multi-domain cognitive test batteries, they employed two prefrontal cortex-dependent attentional set-shifting tasks, the operant (oAST) and digging (dAST) paradigms, as analogs of the Wisconsin Card Sorting Test. Chronic treatment with antidepressants or cholinergic drugs attenuate injury-induced cognitive dysfunction. Goal-directed behavior was assessed in operant chambers using an instrumental learning test in adolescent animals following pediatric TBI (focal or repeated concussions), which also rendered behavioral disturbances. Higher-order attentional testing will advance the understanding of long-term cognitive impairments in survivors of brain trauma and may provide reliable avenues towards developing more suitable therapeutic approaches.

Key learning objectives:

  • Cognitive functioning can be assessed via multiple test modalities in rodents, similar to the clinical setting.
  • Multiple domains of complex, higher-order cognitive functioning (sustained attention, behavioral flexibility, goal-directed behavior) are mediated by the frontal lobe in rodents in a similar fashion to the human brain, with long-lasting alterations after brain trauma occurring regardless of sex.
  • Differences between multiple classes of pharmacotherapies employed to restore neurobehavioral and cognitive performance after traumatic brain injury, such as antidepressants and cholinergic drugs.

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Corina Bondi, PhD

Assistant Professor

University of Pittsburgh

Dr. Corina Bondi is a tenure-track Assistant Professor in the Departments of Physical Medicine and Rehabilitation and Neurobiology, as well as Associate Director of Executive Function and Neuropharmacology at the Safar Center for Resuscitation Research (SCRR) of the University of Pittsburgh. She is an Academic Editor for Medicine® and BioMed Research International, and an Associate Editor for BMC Neuroscience. She currently serves as Secretary/Treasurer for the National Neurotrauma Society and as scientific reviewer on study sections with the National Institutes of Health, Department of Defense, Department of Veterans Affairs, and New Jersey Commission on Brain Injury Research. Dr. Bondi has over 50 peer-reviewed publications. Her laboratory explores therapeutic strategies after experimental traumatic brain injury (TBI), such as pharmacotherapies and environmental enrichment, for complex cognitive processing deficits and distinct neurobehavioral and neurochemical alterations relevant to psychiatric disorders. Her team pursues a variety of behavioral, neurochemical, and molecular-based approaches encompassing the overlap of cognitive neuroscience, stress circuitry, and TBI neuropathology, with complex and sensitive tasks such as attentional set-shifting tests, operant tasks of sustained attention and goal-directed behavior, or assays of affect and anxiety being customarily employed in the laboratory. Underlying pathomechanisms are further characterized using a diverse array of techniques such as tissue processing via microscopy, Western blotting, immunostaining, and proteomics. Studying altered monoaminergic neurotransmission responsible for behavioral and mood impairments after brain trauma across the life span (from pediatric to aged rats) is paramount to finding more effective clinically-relevant therapeutic and rehabilitative targets.
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