C. Brock Kirwan, PhD

Research

Pattern Separation in the Medial Temporal Lobe

Ever wonder why it's so hard to find your car in the parking lot at the end of the day? Or why we can remember commercial jingles from our childhood, but not what we had for dinner last Tuesday night? These are just a few examples of how our memory succeeds (and fails) to resolve the interference in every-day experience. Computational models of the function of brain structures such as the hippocampus and related medial temporal lobe cortical structures assert that our brains form distinct memories of our experiences through a process called pattern separation. In pattern separation, overlapping representations are made as dissimilar as possible in order to reduce retrieval errors. Thus, we're able to form memories for events that happen in the same context, but at different times, and these memories typically don't get in each other's way. When we need to retrieve one of these memories, the hippocampus perforems the retrieval through a process called pattern completion, whereby the full representation is retrieved when given a partial or degraded cue.

One aspect of my research focuses on testing the predictions of computational models using a number of modalities, including functional magnetic resonance imaging (fMRI) in healthy younger adults, neuropsychological studies with amnesic patients who have damage to these brain structures, and lesion studies with animal models.

Relevant Abstracts and Publications:

Bakker, A., Kirwan, C.B., & Stark, C.E.L. (2008). Pattern separation in the human hippocampal CA3 and dentate gyrus. Science. 319:(5870):1640-1642. [link]

Kirwan, C.B., & Stark, C.E.L. (2007).  Overcoming interference: an fMRI investigation of pattern separation processes in the medial temporal lobe. Learning and Memory 14:625-633. [pdf]

Kirwan, C.B., Stark, S., Goodrich-Hunsaker, N., Gordon, B., Hopkins, R., & Stark, C.E.L. (2007). Pattern separation processes in the human medial temporal lob e. Poster presentation at the Cognitive Neuroscience Society 14th Annul Meeting, New York, May 2007.

Kirwan, C.B., & Stark, C.E.L. (2006).  High-resolution fMRI investigation of pattern completion and pattern separation in the medial temporal lobe: Evidence of dissociation.  Society for Neuroscience Abstracts, vol. 32, Program No. 777.10.

Kirwan, C.B., Gilbert, P.E., & Kesner, R.P. (2005).  The role of the hippocampus in spatial location retrieval. Neurobiology of Learning and Memory 83(1):65-71. [pdf]

Kirwan, C.B., Gilbert, P.E., and Kesner, R.P.  (2001).  The role of the hippocampus in spatial pattern completion.  Society for Neuroscience Abstracts, vol. 27, Program No. 315.3.

Kirwan, C.B., Gilbert, P.E., & Kesner, R.P. The role of the hippocampus in spatial pattern completion.  Poster presentation at the Intermountain Chapter of the Society for Neuroscience Fall Meeting, Lehi, UT, Oct. 2001.

Based on the anatomical connections within and between the hippocampus and the adjacent medial temporal lobe cortical areas, many researchers have proposed functional distinctions between these structures. We know from patients with damage to these areas that they are all involved in forming long-term declarative memories, but lesions rarely precisely affect one brain structure.

Much of my research focuses on examining on the functional distinctions (if any) that exist within and between medial temporal lobe structures.

Relevant abstracts and publications:

Kirwan, C.B., Shrager, Y., & Squire, L.R. (2007). Medial temporal lobe activity varies with strength of subsequent recognition memory.  Society for Neuroscience Abstracts, vol. 33, Program No. 526.10.

Kirwan, C.B., & Stark, C.E.L.  (2004).  Medial temporal lobe activation during encoding and retrieval of novel face-name pairs. Hippocampus 14:919-930. [pdf]

Kirwan, C.B., & Stark, C.E.L.  Medial temporal lobe activation in a cued recall fMRI paradigm.  Poster presentation at the Cognitive Neuroscience Society 11th Annual Meeting, San Francisco, April 2004.

Kirwan, C.B., & Stark, C.E.L.  (2003).  Medial temporal lobe activation in encoding and retrieval of novel face-name pairs.  Society for Neuroscience Abstracts, vol. 29, Program No. 514.7.

Two challenges posed to those who wish to use fMRI to examine the function of small brain structures such as the hippocampus are 1) typical functional resolution of fMRI is almost as large as the structures themselves in some places and 2) spatial normalization algorithms used to align different participants brains to one another tend to do a poor job with sub-cortical structures. We have attemptetd to address the first issue by developing high-resolution scanning techniques. To address the second question, we have collaborated with the Center for Imaging Science at Johns Hopkins University to develop an advanced method for cross-participant alignment, dubbed ROI-LDDMM. This increase in the alignment between subjects leads to greater power to detect real effects in group fMRI analyses.

Relevant abstracts and publications:

Kirwan, C.B., Jones, C.K., Miller, M.I., & Stark, C.E.L.  (2007).  High-Resolution fMRI Investigation of the Medial Temporal Lobe. Human Brain Mapping 28(10):959-966. [pdf]

Kirwan, C.B., Flanery, M.A., Jones, C.K., Pekar, J., & Stark, C.E.L. (2005).  High-resolution fMRI investigation of the medial temporal lobe.  Society for Neuroscience Abstracts, vol. 31, Program No. 315.11.