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 performs 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:

  • Kirwan, C.B., Hartshorn, J.A., Stark, S.M., Goodrich-Hunsaker, N.J., Hopkins, R.O., & Stark, C.E.L (In Press). Pattern Separation Deficits following Damage to the Hippocampus. Neuropsychologia.
  • Toner, C.K., Pirogovsky, E., Kirwan, C.B., & Gilbert, P.E. (2009). Visual object pattern separation deficits in nondemented older adults. Learning and Memory. 16:338-342. 
  • Bakker, A., Kirwan, C.B., Miller, M.I., & Stark, C.E.L. (2008). Pattern Separation in the human hippocampal CA3 and dentate gyrus subfields. Science. 319(5870):1640-1642. 
  • Kirwan, C.B., & Stark, C.E.L. (2007). Overcoming interference: An fMRI investigation of pattern separation in the medial temporal lobe. ​Learning and Memory. 14(9):625-633. [Downloads:]
  • 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. 

Functional Distinctions within the Medial Temporal Lobe

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 proposed functional distinctions that exist within and between medial temporal lobe structures.

Relevant abstracts and publications:

  • Jeneson, A., Kirwan, C.B., & Squire, L.R. (2010). Recognition without awareness: An elusive phenomenon. Learning and Memory. 17:454:459.
  • Kirwan, C.B., Wixted, J.T., & Squire, L.R. (2010). A demonstration that the hippocampus supports both recollection and familiarity.Proceedings of the National Academy of Sciences. 107(1):344-348.
  • Jeneson, A., Kirwan, C.B., Hopkins, R.O., Wixted, J.T., & Squire, L.R. (2010). Recognition memory and the hippocampus: A test of the hippocampal contribution to recollection and familiarity. Learning and Memory. 17:852-859. 
  • Kirwan, C.B., Shrager, Y, & Squire, L.R. (2009). Medial temporal lobe activity can distinguish between old and new stimuli independently of overt behavioral choice. Proceedings of the National Academy of Sciences. 106(34): 14617- 14621. 
  • Kirwan, C.B., Wixted, J.T., & Squire, L.R., (2008). Activity in the medial temporal lobe predicts memory strength, whereas activity in the prefrontal cortex predicts recollection. Journal of Neuroscience. 28(42):10541-10548 
  • Shrager, Y., Kirwan, C.B., & Squire, L.R. (2008). Activity in both hippocampus and perirhinal cortex predicts the memory strength of subsequently remembered information. Neuron, 59(4):547-553. 
  • Shrager, Y., Kirwan, C.B., & Squire, L.R. (2008). The neural basis of the cognitive map: path integration does not require hippocampus or entorhinal cortex. Proceedings of the National Academy of Sciences. 105(33):12034-12038. 
  • Kirwan, C.B., Galvan, V.V., Bayley, P.B., & Squire, L.R. (2008). Detailed Recollection of Remote Autobiographical Memory After Damage to the Medial Temporal Lobe. Proceedings of the National Academy of Sciences. 105(7):2676-2680. 
  • Kirwan, C.B., & Stark, C.E.L. (2004). Medial temporal lobe activation during encoding and retrieval of novel face-name pairs. Hippocampus. 14(7):919-930.

High Resolution fMRI and Advanced Cross Participant Alignment

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 used several advanced alignment techniques (including ROI-LDDMM and ANTs), which result in much better cross-participant alignment. 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.