Nathan Giles and Dr. C. Brock Kirwan, Psychology

It is widely known that as we age, our cognitive functions start to decrease, especially when it comes to memory. Memory in the human brain has major processes in the medial temporal lobe, specifically the hippocampus. It is widely accepted that in older adults, the areas in the medial temporal lobe start to atrophy and this decrease in brain tissue volume is what leads to difficulty in memory (Van Petten, 2004). Further, as we age the rate of new neuron growth (termed neurogenesis) in the dentate gyrus region of the hippocampus slows down (Small, 2001). Neurogenesis in the dentate gyrus has been linked to pattern separation, which is the ability to form distinct memory representations for overlapping stimuli. However, in a preliminary study, Dr. Kirwan found that the volume of the dentate gyrus in the hippocampus in older adults has no correlation to their performance on a memory task with high pattern separation demands. Because of this, we wanted to better understand what processes are actually happening in the brain that causes memory deficiencies in older adults. Our hypothesis was that a decrease in memory is due to a breakdown of neuronal connectivity in the brain.

In previous studies, researchers have shown that older adults do poorly at pattern separation tasks (Burke, 2010). What appears to happen is that older adults are more likely to generalize their memory representations, possibly due to a bias toward a process called pattern completion. In pattern separation, individuals are able to successfully recall specific details of a previously viewed stimulus and they are able to discriminate between similar-looking stimuli. On the other hand, in pattern completion, a previously stored memory representation is reactivated from similar cues, allowing the individuals to clump these memories into one single representation. Thus, a reliance on pattern completion results in an inability to discriminate between similar and old cues.

Using these definitions, we were able to create an experiment that measured how well a subject is able to pattern separate. Our study consisted of two parts. The first part involved a memory task with high pattern separation demand. The second part involved an MRI scan that we then used to calculate connectivity of the medial temporal lobe region of the brain. Our study included older participants (age 65+) and, as a control, younger participants (age 20-30).

The purpose of the MRI scan was to measure volumes of the structures in the medial temporal lobe and to determine the connectivity of the neurons in that area. In order to determine hippocampal volumes we used a high resolution imaging technique. Then we used a technique called Diffusion Tensor Imaging (DTI). DTI measures the flow of water as the magnetic current changes directions. The theory behind this is that when neurons are all going in the same direction, the water will then only be able to go in one direction. The percentage of water that goes in the same direction is what is termed fractional anisotropy (FA). Having a large FA value is theorized to equate to a specific, intact neuronal tract. In contrast, a low FA means one of two things: the neuronal tract has degraded and lost its structural integrity, or the area which is being measured has many different tracts all running in different directions through that part of the brain.

We also used the MRI to measure the functional connectivity of memory structures by measuring functional MRI (fMRI) at rest. During this scan, the participants were required to remain awake, but let their mind wander. While they do this we measured the flow of their blood to the different parts of the brain and looked for correlations to other areas in the brain that also had an increase of blood flow at the same time.

From this study, we found that there were two main determinates for performance on a pattern separation task. The first is age and the second is the volume of the left CA3/dentate gyrus in the hippocampus. When it comes to age, we found that the older group was more likely to label similar stimuli as “old” and in contrast, we found that the younger group was more likely to label similar stimuli as “similar”. This was consistent in what we believed would happen. We had also believed that specific subfields within the hippocampus would have a correlation to performance on a pattern separation task. We found that the size of the left CA3/dentate gyrus seems to have a larger contribution to the pattern separation process than any of the other hippocampal subfields, medial temporal lobe structures or other neuroimaging correlates.

Previous studies have given evidence that activity in the CA3/dentate gyrus region of the hippocampus is biased towards pattern separation, and that other areas that deal with memory, such as the medial temporal lobe and other subfields of the hippocampus, are biased towards pattern completion. Though we did not measure the activity within these subfields, the results that we got are in line with these types of studies. In our study, we were able to demonstrate that the volumes of these structures, and not just activity alone, do have a significant role in the pattern separation processes.

Another noteworthy aspect of our results is that the volume of left CA3/dentate gyrus was not significantly different between older and younger groups on average. This gives us reason to believe that age is another predictor of performance. One possibility is that in addition to areas in the hippocampus that are used in pattern separation processes, this kind of behavioral task relies on other processes that are affected by the age of the participant.

In conclusion, our study used a variety of imaging methods in order to understand the changes associated with aging that are correlated with poor memory discrimination performance. Our results indicate that better performance in a pattern separation task is associated with a larger CA3/dentate gyrus in the left hippocampus.

Scholarly Sources

Burke, S. N., Wallace, J. L., Nematollahi, S., Uprety, A. R., & Barnes, C. A. (2010). Pattern Separation Deficits May Contribute to Age-Associated Recognition Impairments. Behavioral Neuroscience, 124(5), 559-573. doi: 10.1037/a0020893

Small, S. A. (2001). Age-related memory decline: current concepts and future directions. Archives of Neurology, 58(3), 360-364.

Van Petten, C. (2004). Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: review and meta-analysis. Neuropsychologia, 42(10), 1394-1413. doi: 10.1016/j.neuropsychologia.2004.04.006