C. Brock Kirwan
Memory is an essential cognitive ability. It allows us to use past events to guide future actions. Research in my laboratory focuses on determining the mechanics of how the brain remembers what it does. We are interested in determining what will be remembered and what will be forgotten. Specifically, my research focuses on one aspect of memory encoding that allows us to form distinct memory representations for stimuli and events that are very similar. For example, the location where you parked your car this morning is probably very similar to the location where you parked your car many times before. In spite of this similarity, the brain is able to lay down a new, unique representation that allows us to find the right parking spot at the end of the day. The process whereby the brain (and specifically, the hippocampus) does this is called pattern separation.
In order to study the brain responses involved in pattern separation, we use a number of sophisticated methods including neuropsychological testing with memory-impaired patients, electroencephalography (EEG), and functional MRI (fMRI). Students in my laboratory help to design, administer, and analyze experiments using each of these research tools. This MEG allowed me to involve students in every stage of the research process in order to give them a richer experience that will help them in their future academic and professional endeavors. A large part of the research experience is effectively communicating experimental findings with colleagues. This is often done through scientific conferences. Accordingly, this MEG allowed me to fund undergraduate student research in my laboratory and to fund undergraduate student travel to present research findings at the 2011 meeting of the Society for Neuroscience. I have enumerated the projects supported by this MEG along with the associated journal articles and conference presentations below.
Results and Findings
Determining if age-related changes in neurogenesis affect pattern separation ability in healthy older adults.
We have shown previously that healthy older adults are impaired in distinguishing old stimuli from similar stimuli. In this project, we examined the relationship between brain structures and memory performance in a group of healthy older adults (ages 55-85). We predicted that lower brain structure volumes (specifically the dentate gyrus of the hippocampus) would be related to lower performance in a difficult memory task. We have completed data collection for this project and have begun preliminary data analysis of this large and complex dataset. Briefly, our preliminary analyses do not support our hypothesis. I.e., dentate gyrus volume is not related to performance on the memory task. However, overall white matter volume is negatively correlated with performance, indicating that communication between brain regions may be what is essential to performing well on this task. We have additional measures from MRI scanning of functional and structural connectivity, which we are now investigating for relationships with task performance.
The preliminary results from this study were presented by Quentin Smith (who was an undergraduate research assistant) at the 2011 Society for Neuroscience conference in Washington, DC. Other student co-authors included Andrew Hartshorn, Stefania Ashby, Jesse James, and Sarah Motley.
Smith, Q., Hartshorn, J.A., Ashby, S.A., James, J.R., Motley, S.E., & Kirwan, C.B. (2011). Hippocampal Volume and Pattern Separation Performance. Society for Neuroscience Abstracts, Vol 37. Program No. 288.13.
Determining if pattern separation is disproportionately affected following damage to the hippocampus
It is well known that damage to the MTL causes memory impairments. Damage that is selective to the hippocampus causes milder impairments than damage that includes the adjacent MTL cortex. Computational models of MTL function propose that damage limited to the hippocampus should disproportionately impair pattern separation processes while leaving other memory processes more or less intact. In this Specific Aim, we tested this prediction by testing a group of patients who have damage limited to the hippocampus and a group of matched controls on a pattern separation task. This work was done in collaboration with Dr. Ramona Hopkins of the BYU Psychology Department and Neuroscience Center.
We found that, consistent with our hypotheses, patients with damage limited to the hippocampus were differentially impaired at pattern separation. This is an important confirmation of the predictions of computational and mathematical models of how the brain functions. The results from this study were recently published in the journal Neuropsychologia, with Andrew Hartshorn as a student co-author.
Kirwan, C.B., Hartshorn, J.A., Stark, S.M., Goodrich-Hunsaker, N.J., Hopkins, R.O. & Stark, C.E.L. (2012). Pattern Separation Deficits following Damage to the Hippocampus. Neuropsychologia. 50:2408-2414. doi: http://dx.doi.org/10.1016/j.neuropsychologia.2012.06.011
Examining the brain response to parametric changes in pattern separation demands
In this Specific Aim, we used functional MRI (fMRI) to investigate the neural response as participants performed a continuous recognition memory task with a series of every-day objects. Participants were shown a series of objects and were required to determine if each object was new, a repeat of a previously seen object, or a related lure. The related lures were images of the same objects as previously seen, but the objects were rotated from the original orientation by 15°, 25°, 35°, or 55°. Participants were randomly assigned to either perform an explicit recognition memory task (as described above) or were shown the same stimulus series but were not required to make an overt memory decision about the stimuli (the implicit memory condition). We know from previous research that the brain treats old and new stimuli differently and that there is a larger fMRI signal for new stimuli compared to repeated stimuli. Our question was what the response would be for stimuli that are similar to, but parametrically varied from previously seen stimuli. We found that there was a linear response to rotated stimuli in visual processing regions, as expected, but that the response in memory regions was non-linear and that the exact pattern of responding differed according to the task demands.
The results of this experiment were presented at the Society for Neuroscience conference and were recently published in the Journal of Neuroscience with Sarah Motley, who was a Neuroscience MS student, as first author.
Motley, S.E.*, & Kirwan, C.B. (2011). A whole-brain fMRI investigation of pattern separation and pattern completion. Society for Neuroscience Abstracts, Vol 37, Program No. 288.12.
Motley, S.E* & Kirwan, C.B. (2012). A Parametric Investigation of Pattern Separation Processes in the Medial Temporal Lobe. Journal of Neuroscience. 32(28):13076-13084. doi: http://dx.doi.org/ 10.1523/JNEUROSCI.5920-11.2012
Examining the relationship between mood and memory in infants
One factor that repeatedly has been shown to influence memory in adults and children is emotion. While much is known regarding the influence emotion has on memory, surprisingly little is known about the effects of emotion on memory in human infants. The purpose of this study was to examine the behavioral effects of communicated affect on human infants’ visual recognition memory. In this experiment 5-month-old human infants participated in two conditions. In one condition infants viewed a dynamic face-voice pairing of a female actress conveying an angry expression and in the other condition infants viewed the same actress conveying a neutral affective expression. In both conditions infants accrued 90s of cumulative looking to the facevoice pairing infants. Following exposure to the angry/neutral face-voice pairing, infants were then exposed to a novel geometric pattern paired with the angry or neutral vocal expression until infants accrued 30s of looking. Following familiarization to the face-voice pairing and familiarization to the geometric pattern and voice pairing infants were given a 5-minute retention interval. Following the retention interval infants received six 5s visual paired comparison test trials. On each test trial infants viewed the geometric pattern of familiarization and a novel but similar geometric pattern. The dependent variable was infants’ looking behavior toward the novel geometric pattern. Results revealed that infants in the negative affective condition look proportionately longer to the novel geometric pattern (M = .59, SD = .15) than the familiar geometric pattern, p
These results were presented at the 2011 Society for Neuroscience conference by undergraduate researcher Megan Oliver. The data are currently being prepared for submission for publication.
Oliver, M., Carter, Z., Rutschke, S., Worsham, W., Romney, T., Nielson, K., Stroshine, S., Cobell, J., Flom, R., & Kirwan, C.B. (2011). The effect of emotion on recognition memory in human infants. Society for Neuroscience Abstracts, Vol 37, Program No. 287.03.
Using the neural correlates of recognition memory to examine the relationship between concreteness and recollection
Recognition memory is thought to depend on two processes: Recollection and familiarity. These processes have been theorized to be associated with separate neural mechanisms and distinct ERP components. It has been shown that stimulus features seem to differentially affect the contributions of these processes to recognition memory decisions. For example, highly concrete words tend to lead to greater contributions of recollection, while this is not he case for more abstract words. In this experiment, we explored the effects of word concreteness on both recollection and familiarity using both behavioral and ERP measures.
The results from this experiment were presented at the 2011 Society for Neuroscience conference by undergraduate students Marshall Rodel and Brett Wilson (pictured). The data are currently being prepared for submission for publication.
Roedel, M., Wilson, J.B., & Kirwan, C.B. (2011). The Relationship between Stimulus Features and Memory Quality. Society for Neuroscience Abstracts, Vol 37, Program No. 603.07.
Evaluation of Academic Objectives and Mentoring Environment
The MEG funds have greatly assisted me in my efforts in involving undergraduates in scientific research. A large part of the research process is disseminating research findings through conferences and scientific publications. The funding from the Fulton Chair allowed me to accompany five students (four undergraduates and one masters student) to the Annual Meeting of the Society for Neuroscience in Washington, DC in November 2011. This is the premier conference for the neuroscience community and is attended by about 30,000 researchers in a variety of sub-disciplines each year. Each of these students who attended the conference with me had a poster presentation in which they presented their own research to the neuroscience community. In addition to the poster presentation, each of these projects has either been published in the last year or is well on the way to being submitted for publication to a scientific journal with the students as co-authors on the paper.