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.

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.

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.

New paper: Temporal discrimination in older adults


New paper by graduate student Jared Roberts. Here he is with the paper pony!

Roberts J.M., Ly, M., Murray, E., Yassa, M.A. (2014) Temporal discrimination deficits as a function of lag interference in older adultsHippocampus DOI:10.1002/hipo.22303


A vital component of episodic memory is the ability to determine the temporal order of remembered events. Although it has been demonstrated that the hippocampus plays a crucial role in this ability, the details of its contributions are not yet fully understood. One proposed contribution of the hippocampus is the reduction of mnemonic interference through pattern separation. Prior studies have used behavioral paradigms designed to assess this function in the temporal domain by evaluating the ability to determine the order of remembered events as a function of proximity in time. Results from these paradigms in older adults (OA) have been mixed, possibly due to limitations in controlling elapsed time and narrow range of temporal lags. Here, we introduce a novel behavioral paradigm designed to overcome these limitations. We report that OAs are impaired relative to younger adults at moderate and high temporal lags but not at low lags (where performance approached floor). We evaluated OAs’ ability to benefit from primacy (enhanced order judgment on the first few items of any given sequence) and found two distinct subgroups: one group was on par with young adults [aged-unimpaired (AU)] and the other group was two standard deviations below the mean of young adults [aged-impaired (AI)]. Temporal discrimination performance in AU adults was consistent with a pattern separation deficit, while performance in AI adults was consistent with a generalized temporal processing deficit. We propose that the task introduced is a sensitive marker for episodic memory deficits with age, and may have diagnostic value for early detection of age-related pathology.

New paper: Pattern separation and emotional information


New paper by graduate student Stephanie Leal. Here she is holding the paper pony!

Leal, S.L., Tighe, S.K., Jones, C.K., Yassa, M.A. (2014) Pattern separation of emotional information in  hippocampal dentate and CA3.Hippocampus DOI:10.1002/hipo.22298.


Emotional arousal, mediated by the amygdala, is known to modulate episodic memories stored by the hippocampus, a region involved in pattern separation (the process by which similar representations are independently stored). While emotional modulation and pattern separation have been examined independently, this study attempts to link the two areas of research to propose an alternative account for how emotion modulates episodic memory. We used an emotional discrimination task designed to tax pattern separation of emotional information by concurrently varying emotional valence and similarity of stimuli. To examine emotional modulation of memory at the level of hippocampal subfields, we used high-resolution fMRI (1.5 mm isotropic) of the medial temporal lobe. Consistent with prior reports, we observed engagement of the hippocampal dentate gyrus (DG) and CA3 during accurate discrimination of highly similar items (behavioral correlate of pattern separation). Furthermore, we observed an emotional modulation of this signal (negative > neutral) specific to trials on which participants accurately discriminated similar emotional items. The amygdala was also modulated by emotion, regardless of the accuracy of discrimination. Additionally, we found aberrant amygdala-hippocampal network activity in a sample of adults with depressive symptoms. In this sample, amygdala activation was enhanced and DG/CA3 activation was diminished during emotional discrimination compared to those without depressive symptoms. Depressive symptom severity was also negatively correlated with DG/CA3 activity. This study suggests a novel mechanistic account for how emotional information is processed by hippocampal subfields as well as how this network may be altered in mood disorders.

News and Views: Ground Zero in Alzheimer’s Disease, Nature Neuroscience

Our News and Views piece covering the fantastic work by Khan and colleagues in Nature Neuroscience is out in the current issue.

Abstract: New findings in preclinical Alzheimer’s disease patients and mouse models of the disease suggest that it is the lateral, rather than the medial, entorhinal cortex that is most susceptible to tau pathology early in Alzheimer’s disease. Aberrations begin here and spread to other cortical sites. Read the full News and Views here | Original paper


New paper: Post-study caffeine administration enhances memory consolidation in humans – Nature Neuroscience

Our latest work has just been published in Nature Neuroscience. Advance online publication here. Congratulations to Daniel Borota, Liz Murray, Allen Chang, Gizem Keceli, Maria Ly, Joe Watabe and John Toscano for their hard work and collaborative spirit that made this work possible. Read more here.

CTT buzz: Frontiers rankings and Scientific American!

Our article on Competitive Trace Theory has apparently been a hit and is gaining traction at least with the online community. Here are some of the recent statistics reported by Altmetric. We’re in the top 5% of all articles ever tracked by Altmetric!

The article has also received some attention from Tweeters and bloggers. Of particular note, Emilie Reas (graduate student at UCSD) has written a very nice piece for Scientific American Mind Matters that highlights the core features of our model.

New paper: Spatial discrimination in older adults

A new paper from our lab just went in press!

Reagh, Z.M., Roberts, J.M., Ly, M., DiProspero, N., Murray, E., Yassa, M.A. (2013) Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment. Hippocampus DOI: 10.1002/hipo.22224

Congratulations to first author Zach Reagh!


It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5 × 7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline.