Join Dr. Yassa and other researchers at the next Ask the Doc forum!

When: March 1, 2016, 5:30-7:30PM
What: UCI MIND’s Panel of Researchers Meet to Answer Your Questions!
Where: Alzheimer’s Orange County | 2515 McCabe Way, Irvine, CA 92614
Following a brief introduction to dementia research by Dr. Joshua Grill, Director of Education for the UC Irvine Institute for Memory Impairments and Neurological Disorders (UCI MIND), panelists will spend time answering your questions about:
– diagnosis and treatment
– research and developments
– risk reduction strategies
Panelists for this event include Dr. Michael Yassa, Dr. Mark Capstone and Dr. Szofia Bullion

Ask the Doc 3.1.16
Click here for more information.

Register for free online:
For questions regarding this event please contact Chelsea Cox, Education Coordinator at or 949.824.9896

New review in Trends in Neurosciences

Our TiNS review “Neurocognitive aging and the hippocampus across species” is now online. Here are some of the trends we discuss in the article:

  1. The role of neurogenesis in the dentate gyrus in the context of neurocognitive aging has been recently revisited, given data suggesting that neurogenesis continues into older adulthood.
  2. The lateral entorhinal and perirhinal cortices represent early sites of vulnerability in aging and age-related decline. Designing tasks and approaches to examine these extrahippocampal pathways is crucial
  3. Hyperexcitability in the hippocampal network is a key pathological state in the aging brain that confers risk for Alzheimer’s disease (AD), potentially linking AD and subclinical epilepsy.
  4. Epigenetic imaging (e.g., HDAC PET) is an emerging technology that will allow more detailed examinations of epigenetic changes related to memory decline in the aging human brain.

2014 Walk to end Alzheimer’s – Huntington Beach Sat Nov 1, 2014 @ 10AM

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New paper on recognition memory and the hippocampal long-axis gets the cover of the Journal of Neuroscience!

Our latest paper entitled ‘Dissociated signals in human dentate gyrus and CA3 predict different facets of recognition memory‘ was published today in The Journal of Neuroscience! On top of that, our study is featured in the cover art!


See the cover art caption/blurb here.

Enormous thanks to Joe Watabe and Maria Ly, authors on the paper who contributed to this work invaluably.


A wealth of evidence has implicated the hippocampus and surrounding medial temporal lobe cortices in support of recognition memory. However, the roles of the various subfields of the hippocampus are poorly understood. In this study, we concurrently varied stimulus familiarization and repetition to engage different facets of recognition memory. Using high-resolution fMRI (1.5 mm isotropic), we observed distinct familiarity and repetition-related recognition signal profiles in the dentate gyrus (DG)/CA3 subfield in human subjects. The DG/CA3 demonstrated robust response suppression with repetition and familiarity-related facilitation. Both of these discrete responses were predictive of different aspects of behavioral performance. Consistent with previous work, we observed novelty responses in CA1 consistent with “match/mismatch detection,” as well as mixed recognition signaling distributed across medial temporal lobe cortices. Additional analyses indicated that the repetition and familiarity-related signals in the DG/CA3 were strikingly dissociated along the hippocampal longitudinal axis and that activity in the posterior hippocampus was strongly correlated with the retrosplenial cortex. These data provide novel insight into the roles of hippocampal subfields in support of recognition memory and further provide evidence of a functional heterogeneity in the human DG/CA3, particularly along the longitudinal axis.

New paper: Object vs. spatial memory interference functionally differentiate lateral and medial entorhinal cortex in humans

New paper by Zach Reagh in Proceedings of the National Academy of Sciences. Congrats all around – this one was in the works for a good while!

Reagh, Z.M. & Yassa, M.A. (2014). Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans. PNAS doi: 10.1073/pnas.1411250111  

Significance Statement:

Episodic memories are complex records of experience, consisting of “what” happened as well as “where” and “when” it happened. Animal studies have demonstrated distinct brain networks supporting memory for information about what experience occurred and information about where the experience occurred. However, such dissociations have been elusive in humans. Using a memory interference task that pits object (i.e., what) vs. spatial (i.e., where) memories against each other and high-resolution fMRI, we report evidence for two parallel but interacting networks in the human hippocampus and its input regions, supporting prior work in animals. We propose a conceptual model of how object and spatial interference are reduced in the regions providing input to the hippocampus, allowing rich, distinct memories to be built.


Recent models of episodic memory propose a division of labor among medial temporal lobe cortices comprising the parahippocampal gyrus. Specifically, perirhinal and lateral entorhinal cortices are thought to comprise an object/item information pathway, whereas parahippocampal and medial entorhinal cortices are thought to comprise a spatial/contextual information pathway. Although several studies in human subjects have demonstrated a perirhinal/parahippocampal division, such a division among subregions of the human entorhinal cortex has been elusive. Other recent work has implicated pattern separation computations in the dentate gyrus and CA3 subregions of the hippocampus as a mechanism supporting the resolution of mnemonic interference. However, the nature of contributions of medial temporal lobe cortices to downstream hippocampal computations is largely unknown. We used high-resolution fMRI during a task selectively taxing mnemonic discrimination of object identity or spatial location, designed to differentially engage the two information pathways in the medial temporal lobes. Consistent with animal models, we demonstrate novel evidence for a domain-selective dissociation between lateral and medial entorhinal cortex in humans, and between perirhinal and parahippocampal cortex as a function of information content. Conversely, hippocampal dentate gyrus/CA3 demonstrated signals consistent with resolution of mnemonic interference across domains. These results provide insight into the information processing capacities and hierarchical interference resolution throughout the human medial temporal lobe.

SoCal Alzheimer’s Research Conference coming soon – 9/12/14

The time is almost here. The 25th annual Southern California Alzheimer’s Disease Research Conference is on 9/12/2014. All information about it is here. You can still register for the program!

Of particular note is Howard Federoff who is joining us from Georgetown to discuss the use of new blood lipid biomarkers for early/preclinical diagnosis and Ken Kosik who will discuss the Colombian cohort of familial inherited autosomal dominant AD and what we can learn from them. For my talk in the afternoon, I will be discussing the use of neuroimaging biomarkers as a research tool in Alzheimer’s disease, in particular as tools for early detection, tracking, and clinical trial enrichment.

If you’re interested in hearing us talk about this work and discuss the conference in more detail, KUCI did an hour-long interview with us (Andrea Tenner, Howard Federoff, and I) on the air on August 26th. Here is a link to the podcast.


Hosted by the UCI Institute for Memory Impairments and Neurological Disorders (UCI MIND) and the Alzheimer’s Association, Orange County Chapter, this conference convenes nationally and internationally recognized experts to address the progress our nation is making in the fight against Alzheimer’s disease. The 25th Annual Research Conference’s theme is “The Future of Alzheimer’s Research”, and will focus on exciting new developments that will take us into the next generation of Alzheimer’s research. 



Stimulus repetition paper gets the cover of Learning & Memory!

Our recent paper demonstrating that stimulus repetition alters memory performance was featured on the August issue of Learning & Memory! Here’s the cover art and caption:


Many theories of memory assume that repetition globally enhances memory representations. However, Reagh and Yassa (LearnMem 21: 342–346) demonstrate that although repetition may enhance general recognition, it can have detrimental effects on memory for details. The writing on the chalkboard, representing repeated memory experiences, schematizes this phenomenon. Central elements of the memory remain throughout repetitions, though contextual details are incrementally lost.

Press release on our Stimulus Repetition Paper in Learning & Memory!

Our recent paper in Learning & Memory, which tests a key prediction of our Competitive Trace Theory, was covered in a UC Irvine press release today!

Here’s the write-up:

UC Irvine neurobiologists Zachariah Reagh and Michael Yassa have found that while repetition enhances the factual content of memories, it can reduce the amount of detail stored with those memories. This means that with repeated recall, nuanced aspects may fade away.

In the study, which appears this month in Learning & Memory, student participants were asked to look at pictures either once or three times. They were then tested on their memories of those images. The researchers found that multiple views increased factual recall but actually hindered subjects’ ability to reject similar “imposter” pictures. This suggests that the details of those memories may have been shaken loose by repetition.

This discovery supports Reagh’s and Yassa’s Competitive Trace Theory – published last year in Frontiers in Behavioral Neuroscience – which posits that the details of a memory become more subjective the more they’re recalled and can compete with bits of other similar memories. The scientists hypothesize that this may even lead to false memories, akin to a brain version of the telephone game.

Yassa, an assistant professor of neurobiology & behavior, said that these findings do not discredit the practice of repetitive learning. However, he noted, pure repetition alone has limitations. For a more enriching and lasting learning experience through which nuance and detail are readily recalled, other memory techniques should be used to complement repetition.

We’ve also gotten some buzz in other venues. See our media page for complete updates.

Buzz About the Temporal Discrimination Paper!

Our recent paper in Hippocampus on temporal discrimination in young and older adults recently got a great write up on Dr. Ryan Hunsaker’s blog, Why Haven’t They Done That Yet?

From the post:

Roberts and colleagues developed a task to test temporal pattern separation (as well as primacy and recency) in a cohort of young and aged adults. They were not only able to identify a clear pattern separation deficit in the temporal domain (which makes me very happy as I have been harping on their group to do so for quite a long time), but they also were able to identify successful and unsuccessful cognitive aging as well.

To me, the more important part of their work was that they developed a behavioral task that appears to be a rather sensitive marker for episodic memory deficits that emerge with age (at least the “when” component of episodic memory), and appears also to have a potential diagnostic value for early detection of age-related pathology. The authors obviously need to run a much larger cohort to see what individual differences exist in this task similar to their work with the behavioral pattern separation tasks (mnemonic discrimination tasks as now renamed), but it appears they are off to a great start.

Thanks for the buzz, Ryan! And a hearty congrats to Jared Roberts for the solid paper!

New paper: Stimulus repetition and memory interference.

zach_paper_ponyNew paper by Zach Reagh in Learning and Memory. Here he is with the paper pony!

Reagh, Z.M. & Yassa, M.A. (2014). Repetition strengthens target recognition but impairs similar lure discrimination: evidence for trace competition. Learning & Memory DOI doi/10.1101/lm.034546.114.


Most theories of memory assume that representations are strengthened with repetition. We recently proposed Competitive Trace Theory, building on the hippocampus’ powerful capacity to orthogonalize inputs into distinct outputs. We hypothesized that repetition elicits a similar but nonidentical memory trace, and that contextual details of traces may compete for representation over time. We designed a task in which objects were incidentally encoded either one or three times. Supporting our theory, repetition improved target recognition, but impaired rejection of similar lures. This suggests that, in contrast to past beliefs, repetition may reduce the fidelity of memory representations.