Medical Student Research Fellowship for Summer 2007

Mentor: Carlos Marquez de la Plata, PhD, Assistant Professor
Department: Psychiatry
Room number: F2.318
Mail Code: 9036
Phone number: 214-648-6329; Fax number: 214-648-3143
E-mail: Carlos.MarquezdelaPlata@UTSouthwestern.edu
Project titles: Evaluation of Diffuse Axonal Injury in Patients with Traumatic Brain Injury Using Functional Connectivity MRI.
Purpose: Examine the correlation of fcMRI BOLD signal to long term functional and neurocognitive outcomes post-TBI.
Human subjects IRB approved project numbers (where applicable): IRB # 012005-073
Animal subjects IRB approved project number (where applicable): Not applicable
Project Type: Patient-oriented research
Brief Description of Project:
TBI is a major problem, as the incidence in the United States is estimated between 92 and 250 per 100,000 population annually and approximately 50,000 individuals each year are left with long-term physical and psychological limitations that limit their independence and ability to work. DAI is a common subtype of TBI occurring in most MVC in which deceleration and rotational forces cause sheering of the brain's white matter. Cranial tomography is insensitive to white matter lesions resulting from DAI, but more novel neuroimaging modalities such as diffusion tensor imaging has shown sensitivity toward white matter injury. However, it is uncertain whether acute neuroimaging measures of white matter injury can be predictive of latter functional or neurocognitive outcome, as the investigations that involve acute neuroimaging studied mild cases of TBI and do not measure functional or neurocognitive outcomes. Our research group will study patients with moderate to severe DAI subtype of TBI and determine whether neuroimaging parameters can be used as biomarkers for long term functional and neurocognitive outcome.
Functional connectivity MRI is a technique that determines the functional relatedness of selected brain regions. It is based on determining brain regions that demonstrate temporally correlated blood oxygenation level-dependent (BOLD) signal. This technique has been used to show differential patterns of functional hippocampal connectivity during resting state between patients with Alzheimer's disease and healthy volunteers, as controls showed diffuse cortical and subcortical connectivity and patients demonstrated reduced connectivity including absence of connectivity with the frontal lobes. While patients in the aforementioned study were documented to have poorer performance on tasks of memory ability than controls, it is not known whether the extent of reduced connectivity observed in patients correlates with neurocognitive functions. This technique has never been applied to patients with traumatic brain injury, and based on our preliminary work over the last year1,2 we hypothesize that the degeneration that occurs in selected white matter regions after DAI may lead to cortical changes (i.e., Wallerian degeneration) and ultimately impact the efficiency in which the brain functions months after injury.

Student Role on project:
Ms. Garces will be primarily involved in analyzing the fcMRI chronic scans that were obtained from TBI patients. Last summer, she analyzed the hippocampal regions of the chronic TBI patients then enrolled in the study and presented the work at a national conference. This summer, she will expand the analysis to include the cingulate cortex and the dorsal lateral prefrontal cortex, both of which are associated with cognition, mood, emotions, learning and memory (i.e., domains commonly impacted by TBI). Ms. Garces will achieve this by using the Linux based program AFNI (which she is already trained on) to view the fcMRI scans and analyze the BOLD signal correlations after drawing the aforementioned regions of interest (ROI's). These data will then be compared to neurocognitive outcomes assessed using a focused neuropsychological outcome battery 6 months post injury. Ms. Garces will be trained to perform these evaluations under Dr. Marquez de la Plata's supervision.
Ms. Garces will also attend daily morning rounds with the neurosurgical service at Parkland Memorial Hospital, to help identify patients who meet eligibility criteria for the study, obtain informed consent from patients or family members, and collect intake information. Afternoons will be spent analyzing fcMRI data using the Linux based AFNI program previously mentioned and be trained on neuropsychological examinations for those patients. Additionally, Ms. Garces will be given greater writing responsibilities than she was given last summer, as the ultimate goal of this research placement is for her to write and submit a manuscript for publication by August 8, 2008.
Previous Research Activities or Publications with Medical Students:
Dr. Marquez de la Plata has mentored four students over the last two years (including Ms. Garces), and these relationships have led to abstracts presented at national meetings, and 1 publication.

References

1. Garces, J, Marquez de la Plata, C, Pidikiti, R, Youn, T.S., Ding, K., Moore, C., Harper, C., Madden, C.J., Devous, M., Diaz-Arrastia, R. Resting State Functional MRI in Traumatic Brain Injury Reveals Deficits in Connectivity of Hippocampal Circuits. Abstract presented at the annual meeting of the American Academy of Neurology, Chicago, Illinois, April 14, 2008.
2. Youn, T.S., Marquez de la Plata, C., Wang, J.Y., George, A.T., Jeon, T.J., Ding, K., Moore, C., Harper, C., Mumphrey, M., King R.D., Madden, C.J., Diaz-Arrastia, R. Diffusion tensor tractography of perforant pathway and hippocampal atrophy in diffuse traumatic axonal brain injury. Abstract presented at the UTSW Student Research Forum, Dallas, Texas, January 22, 2008.