Mnemonic Similarity Task: A Tool for Assessing Hippocampal Integrity

Stark, Shauna M.; Kirwan, C. Brock

doi:10.1016/j.tics.2019.08.003

Cited by 198 publications

(360 citation statements)

References 152 publications

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“…Although animal studies suggest that DG is necessary for such spatial mnemonic discrimination (Hunsaker and Kesner, 2013; Bui et al, 2018), it remains unclear whether this is the case in humans. In contrast, we used a non-spatial memory discrimination task that is known to be DG-dependent in humans (Baker et al, 2016; Stark et al, 2019), allowing us to conclude that impairments in TLE patients are likely due to DG alterations.…”

Section: Discussionmentioning

confidence: 99%

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Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy

Madar

Pfammatter

Bordenave

et al. 2020

Preprint

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8Health 9 Acknowledgement: We thank Lin Lin who helped start behavioral tests in mice in the Jones lab 10 and Drs. C.E.L Stark and M.A. Yassa for allowing us to use software and materials they 11 developed.12 Abstract: 24 In temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the 25 hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help 26 discriminate between similar memories by performing pattern separation, but whether epilepsy 27 leads to a breakdown in this neural computation, and thus to mnemonic discrimination 28 impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by 29 behavioral deficits in mnemonic discrimination tasks, in both humans and mice. Using a recently 30 developed assay in brain slices of the same epileptic mice, we reveal a decreased ability of the 31 dentate gyrus to perform certain forms of pattern separation. This is due to a subset of granule 32 cells with abnormal bursting that can develop independently of early EEG abnormalities. 33Overall, our results linking physiology, computation and cognition in the same mice, advance 34 our understanding of episodic memory mechanisms and their dysfunction in epilepsy. 35 36 Keywords: 37 Patch-clamp, low-dose systemic kainate model, kainic acid, interictal spikes, novelty 38 recognition, firing rate, spiking patterns, similarity metrics, input-output, entorhinal cortex, 39 perforant path, EPSC, excitation/inhibition ratio, dentate gate, Hebb-Marr theory 40 41 Introduction: 42 Temporal lobe epilepsy (TLE) represents about 60% of all epilepsy cases, a third of 43 which are refractory to medication (Tellez-Zenteno and Hernandez-Ronquillo, 2012). TLE is 44DG neural pattern separation and 2) that such a failure causes mnemonic discrimination 87 impairments remain experimentally untested. 88Here we tested, in humans and mice, whether TLE is characterized by deficits in 89 mnemonic discrimination and then recorded, in brain slices from the same mice, the spiking 90 patterns of single GCs in response to parametrically varied afferent stimulation in order to gauge 91 neuronal pattern separation. 92 93 Materials and Methods: 94 Human Behavior. A mnemonic similarity task (Stark et al., 2019), also known as a 95 behavioral pattern separation (BPS) task (Stark et al., 2013), was administered to 15 patients in 96 the University of Wisconsin-Madison Epilepsy Monitoring Unit. Under an approved Institutional 97 Review Board protocol and after obtaining informed consent, the task was administered in 98 conjunction with a standard neuropsychiatric evaluation and during electroencephalographic 99 (EEG) recording, both of which are part of standard practice for diagnosing the patients' seizures. 100 Patients were 18-65 years old, male and female. Only patients with a preliminary diagnosis of 101 TLE were included in our analysis. As controls, 20 subjects without epilepsy, recruited to match 102 the patients' age and sex distributions (family members of ...

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Section: Discussionmentioning

confidence: 99%

“…Participants were asked to classify each image of the Phase 2 set as “Old”, “Similar”, or “New”. BPS was evaluated with a discrimination index computed as the difference between p(“Similar”|Lure) and p(“Similar”|Novel), as in past research (Yassa et al, 2011; Stark et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy

Madar

Pfammatter

Bordenave

et al. 2020

Preprint

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“…Here, we projected task-based functional activations into this alternative space governed by connectivity gradients in both neocortical and hippocampal regions. An adapted version of the MST paradigm was used, as it allows for sensitive functional mapping and the calculation of behavioral pattern separation scores at the group and single subject levels (Stark, Yassa et al 2013, Stark, Kirwan et al 2019. Prior task-based fMRI analyses identified both hippocampal and isocortical activations during pattern separation (Bakker, Kirwan et al 2008, Berron, Schutze et al 2016, Pidgeon and Morcom 2016, Reagh, Murray et al 2017; notably, these studies generally carried out conventional region-of-interests analyses, either at the level of the entire hippocampus (Bakker, Kirwan et al 2008, Pidgeon andMorcom 2016) or hippocampal subfields (Bakker, Kirwan et al 2008, Reagh, Watabe et al 2014, or ran unconstrained voxel-wise analysis , Reagh, Murray et al 2017.…”

Section: Discussionmentioning

confidence: 99%

Human brain function during pattern separation follows hippocampal and neocortical connectivity gradients

Tavakol

Royer

et al. 2020

Preprint

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Episodic memory is our ability to remember past events accurately. Pattern separation, the process of of orthogonalizing similar aspects of external information into nonoverlapping representations, is one of its mechanisms. Converging evidence suggests a pivotal role of the hippocampus, in concert with neocortical areas, in this process. The current study aimed to identify principal dimensions of functional activation associated with pattern separation in hippocampal and neocortical areas, in both healthy individuals and patients with lesions to the hippocampus. Administering a pattern separation fMRI paradigm to a group of healthy adults, we detected task-related activation in bilateral hippocampal and distributed neocortical areas. Capitalizing on manifold learning techniques applied to parallel resting-state fMRI data, we could identify that hippocampal and neocortical activity patterns were efficiently captured by their principal gradients of intrinsic functional connectivity, which follows the hippocampal long axis and sensory-fugal cortical organization. Functional activation patterns and their alignment with these principal dimensions were altered in patients. Notably, inter-individual differences in the concordance between task-related activity and intrinsic functional gradients were correlated with pattern separation performance in both patients and controls. Our work outlines a parsimonious approach to capture the functional underpinnings of episodic memory processes at the systems level, and to decode functional reorganization in clinical populations.

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“…Much research using 'similar lure' stimuli (novel stimuli similar to items that have been studied) to identify memory classification errors exists 3,[6][7][8][9][10] . False alarms (FAs), or the incorrect rating of previously unseen items as 'old', in recognition memory tests are unsurprisingly most pronounced when presented items are similar lures, but also occur for completely new items 8,10 .…”

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confidence: 99%

Precise and imprecise memories may fool you: Continuous memory measures uncover different sources of errors in recognition memory

Richter¹

2020

Preprint

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Recognition memory can be faulty. Participants sometimes incorrectly judge unseen stimuli as seen before (false alarms, FAs), or seen stimuli as not seen (misses). However, the sources of these memory errors remain poorly understood. This study combines an identical(old)/similar/new recognition memory task with a memory precision task to explore sources of recognition memory errors. The results demonstrate that while FAs to similar but unseen items are associated with surprisingly high memory precision, incorrect classification of identical items as ‘similar’ is associated with a marked decline in memory precision. Lastly, incorrect ‘new’ ratings to both identical and similar items showed most severely decreased memory precision, over and above that seen for other memory misclassifications. These results suggest that misses are due to memory decay processes, while FAs stem from recollection-based interference between stimuli. The findings lay the groundwork to explore specific memory deficits in different populations.

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Mnemonic Similarity Task: A Tool for Assessing Hippocampal Integrity

Cited by 198 publications

References 152 publications

Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy

Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy

Human brain function during pattern separation follows hippocampal and neocortical connectivity gradients

Precise and imprecise memories may fool you: Continuous memory measures uncover different sources of errors in recognition memory

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