The MTL Controversy

There has been a controversy on whether the medial temporal lobe (MTL) subregions are operated together and activated to a similar degree during recollection and familiarity. Proponents of the majority view suggested that the MTL subregions have separate functions during recollection and familiarity. The supporters of the minority view have suggested that the “temporal lobe sub-regions operate together during both context memory/recollection and item memory/familiarity” (Slotnick). In other words, when one of the MTL subregions is active, the magnitude of activity in the rest of the subregions should be similar. In class, we discussed eight studies that had mixed views.

For example, Davachi et al. (2002), Yonelinas et al. (2005), Diana (2017), and Schoemaker et al. (2017) are all proponents of the majority view. Davachi et al. (2002) argued that the subregions in the MTL mediate different, but complementary, learning mechanisms that enhance declarative memory. For example, while the hippocampus (Hp) and parahippocampus (Php) correlate with later source recollection during learning, they do not correlate with subsequent item recognition. The study stated that the encoding activation in the perirhinal cortex correlated with “whether the studied item would be subsequently recognized, but failed to predict whether item recognition would be accompanied by source recollection” (p. 2160). Yonelinas et al. (2005) suggested that recollection and familiarity rely on different networks of brain regions. While the left lateral prefrontal cortex was related to familiarity confidence, the anterior medial prefrontal cortex was related to recollection. Also, two functionally distinct lateral parietal regions were identified. The inferior region “was related to recollection and the superior region was related to familiarity confidence” (p. 3006). The study found no evidence for functionally distinct subregions within the MTL. 

Diana (2017) argued that the Php is involved in encoding and retrieval of context information, rather than only spatial information. For example, the results of the first GLM analysis that examined encoding trials revealed a significant activation “for the contrast of source correct greater than incorrect in left PHc, left [Hp], and right [Hp]” (p. 1811). The results of the second GLM analysis that examined retrieval trials revealed a greater activation for the contrast of source correct than source incorrect in the right Php region, right Hp, and left Hp (Table 3). Schoemaker et al. (2017) compared the recollection and familiarity performance of young and older adults. In older adults, familiarity was positively correlated with the rate of false alarms. While significant positive correlations were found between recollection and Hp volumes, no positive correlations were found with perirhinal cortex. They concluded that the decrease in recollection observed in older adults is likely associated with a reduction in Hp structure. 

Gold et al. (2006), Kirwan et al. (2008) , Dede et al. (2013), and Gold and Squire (2005) are proponents of the minority view. Gold et al. (2006) suggested that the Hp was similarly involved during recollection and familiarity. For example, two regions in the MTL predicted subsequent item memory success (Figure 4). Their activity correlation with “remembered words” was greater than their activity correlation with “forgotten words.” Furthermore, figure 6 shows that patients with damage limited to the Hp performed similarly to controls who saw 100 words only once. The study concluded that patients were similarly imapried at item memory and source memory. Kirwan et al. (2008) identified regions in both Hp and perirhinal cortex in which activity varied as a function of subsequent item memory strength. The study concluded that while activity in the MTL is predictive of subsequent memory strength, activity in the prefrontal cortex is predictive of subsequent recollection. For example, the activity in the right “perirhinal cortex and in the right and left Hp varied as a function of the subsequent strength of item memory” (p. 10544) (Figure 3). Also, the linear response was significant in all three areas: right Hp, right perirhinal cortex, and left Hp.

Dede et al. (2013) found that Hp damage impairs both component processes of recognition memory. For example, figure 1 showed that familiarity and recollection estimates from the DPSD and UVSD were lower for patients with Hp lesions than controls. In other words, the results from the two models demonstrated that decelerate memory was broadly impaired in the patients. Gold and Squire (2005) measured the volume of the Hp and Php gyrus bilaterally in five memory-impaired patients. While four of the five patients exhibited significant reduction in Hp volume, none of the patients exhibited significant reduction in the volume of other MTL structures (Figure 2). Gold and Squire (2005) argued that normalization by ICV led to different results and that, in general, Talairach normalization is useful for normalizing measurements of Hp volume but is less useful for other regions of the MTL.

Taking all these articles together, I cannot ignore the significant findings of the Yonelinas et al. (2005) and Davachi et al. (2002) and I am siding with the proponents of the majority view. I would propose a study on undergraduate students and use functional connectivity analysis to identify regions that are functionally connected to the hippocampus. Then, I would target these regions that are correlated with associative memory (Wang et al., 2014). I will provide the students with object-in-scene decision tasks. Students will choose “related” if the object belongs to the picture of the room or choose “not related” if the object does not belong to the room. I would compare their judgments before and after the application of rTMS to the selected regions. I predict to see both context and context memories to be intact following TMS . 


Davachi, L., Mitchell, J. P., & Wagner, A. D. (2003). Multiple routes to memory: Distinct medial temporal lobe processes build item and source memories. Proceedings of the National Academy of Sciences, 100(4), 2157–2162. doi: 10.1073/pnas.0337195100

Dede, A. J. O., Wixted, J. T., Hopkins, R. O., & Squire, L. R. (2013). Hippocampal damage impairs recognition memory broadly, affecting both parameters in two prominent models of memory. Proceedings of the National Academy of Sciences, 110(16), 6577–6582. doi: 10.1073/pnas.1304739110

Diana, R. A. (2016). Parahippocampal Cortex Processes the Nonspatial Context of an Event. Cerebral Cortex. doi: 10.1093/cercor/bhw014

Gold, J. J., Smith, C. N., Bayley, P. J., Shrager, Y., Brewer, J. B., Stark, C. E. L., … Squire, L. R. (2006). Item memory, source memory, and the medial temporal lobe: Concordant findings from fMRI and memory-impaired patients. Proceedings of the National Academy of Sciences, 103(24), 9351–9356. doi: 10.1073/pnas.0602716103

Gold, J. J., & Squire, L. R. (2005). Quantifying medial temporal lobe damage in memory-impaired patients. Hippocampus, 15(1), 79–85. doi: 10.1002/hipo.20032

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. doi: 10.1523/jneurosci.3456-08.2008

Schoemaker, D., Mascret, C., Collins, D. L., Yu, E., Gauthier, S., & Pruessner, J. C. (2017). Recollection and familiarity in aging individuals: Gaining insight into relationships with medial temporal lobe structural integrity. Hippocampus, 27(6), 692–701. doi: 10.1002/hipo.22725

Slotnick, S. (2013). Controversies in Cognitive Neuroscience. doi: 10.1007/978-1-137-27236-2

Wang, J. X., Rogers, L. M., Gross, E. Z., Ryals, A. J., Dokucu, M. E., Brandstatt, K. L., … Voss, J. L. (2014). Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science, 345(6200), 1054–1057. doi: 10.1126/science.1252900

Yonelinas, A. P., Otten, L. J., Shaw, K. N., & Rugg, M. D. (2005). Separating the Brain Regions Involved in Recollection and Familiarity in Recognition Memory. Journal of Neuroscience, 25(11), 3002–3008. doi: 10.1523/jneurosci.5295-04.2005

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