MRI Markers of Feedback Timing during Learning in Individuals with TBI with and without Clinical Depression

Kessler Foundation, Inc., West Orange NJ

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Abstract

Project Summary/Abstract The overall objective of the proposed project is to investigate brain mechanisms during learning in individuals with traumatic brain injury (TBI) with and without clinical depression. Such knowledge can help guide rehabilita- tion strategies and reduce the burden of TBI. Feedback about the accuracy of one’s actions can improve learn- ing by informing individuals whether their action is correct or not. Individuals with depression have been shown to have learning deficits and altered brain activity during learning compared to healthy individuals when feed- back is presented immediately. Impaired learning through immediate feedback has also been observed in Par- kinson’s disease (PD) patients. However, PD patients are able to learn from feedback when it is presented af- ter a delay through engagement of separate neural mechanisms. We show that individuals with TBI exhibit def- icits in learning through immediate feedback that are likely exacerbated by depressive symptoms. Deficits in learning through immediate feedback can lead to perseveration of incorrect actions and decreased strategy use during rehabilitation. However, there is no evidence directly examining the neural mechanisms of learning in individuals with TBI with and without depression. The proposed research fills this gap. The identification of the neural mechanisms associated with learning in individuals with TBI with and without clinical depression will inform 1) scientific knowledge about the effect of depression on the injured brain, 2) TBI interventions about the effectiveness of feedback and its timing, and 3) the development of generalized interventions for other clinical populations that require rehabilitation and have high occurrence of depression. These objectives lie at the heart of the mission of the NINDS as they will broaden “fundamental knowledge about the brain and nervous system” associated with learning in TBI. The knowledge gained from fulfilling the above objectives will “reduce the burden” of learning deficits after TBI. To test our hypotheses, TBI participants will be recruited based on structured clinical interview. Qualified participants will perform an experiment where they study word pairs out- side of the functional magnetic resonance imaging (MRI) scanner. Then, in the MRI, participants will see word pairs in multiple-choice format, along with novel distractors, and select the correct paired-associate. After each choice, feedback will be experimentally manipulated to be presented either immediately or after a 25-minute delay. During the final phase outside of the MRI, participants complete a second diagnostic paired-associate multiple-choice assessment to evaluate the influence of immediate vs. delayed feedback on learning. We hy- pothesize that depressed individuals with TBI will show improvements in learning from delayed compared to immediate feedback. This learning dissociation will occur because learning through delayed feedback relies on neurocircuitry that is not negatively affected by TBI and depression. Non-depressed individuals without TBI and clinically depressed individuals without TBI will also be recruited to differentiate the influences of depres- sion from the impact of TBI on the brain.