Strong Evidence for Pattern Separation in Human Dentate Gyrus

Berron, David; Schütze, Hartmut; Maaß, Anne; Cárdenas-Blanco, Arturo; Kuijf, Hugo J.; Kumaran, Dharshan; Düzel, Emrah

doi:10.1523/jneurosci.0518-16.2016

Cited by 236 publications

(217 citation statements)

References 57 publications

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“…The current results lend validity to cross-species studies and less direct methods of investigating dentate gyrus contributions to pattern separation in humans, including computational models and high-resolution fMRI (Berron et al, 2016;Rosenbaum, Gilboa, & Moscovitch, 2014).…”

Section: Discussionsupporting

confidence: 60%

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

et al. 2016

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Episodic memory provides us with the ability to re-experience unique events in rich detail. For this to occur, we must be able to 1) behaviorally "pattern separate" or discriminate new from old experiences, and 2) "pattern complete" or reinstate memories from partial cues. I report a rare individual with a specific lesion to the dentate gyrus of his hippocampus who has difficulty distinguishing between studied targets and unstudied lures that are visually similar. In addition, he displays a heightened tendency to recognize studied scenes from degraded pictures. These results provide the first direct evidence in humans that discriminating new memories cannot wholly function without an intact dentate gyrus and that this mnemonic ability is dissociable from, but likely interacts with, completion processes in the CA3 subfield of the hippocampus.iii Acknowledgements

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Section: Discussionsupporting

confidence: 60%

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

et al. 2016

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“…Recent neuroimaging studies using multivariate classification approaches have also demonstrated that neural patterns are largely uncorrelated in the DG/CA3 subregion 56 . Recently, ultrahigh-resolution 7T fMRI was used to demonstrate that the DG, but not other hippocampal subfields or medial temporal cortices, exhibits distinct neural patterns for similar items, thus suggesting that the human DG is perhaps selectively engaged in pattern separation 57 . Interestingly, patient B.L., a 54-year-old man with selective bilateral ischemic lesions to the DG subregion of the hippocampus, was found to have impaired performance on a mnemonic discrimination task, which further suggests that the DG is required for pattern separation 58 .…”

Section: Hippocampal Pattern Separation and Episodic Memorymentioning

confidence: 99%

“…A smaller number of studies have met condition 3 35,52,123 , and we find that this condition is often overlooked in clinical samples where performance could be altered on a number of untested conditions. Condition 4 has often been met 20,31,35,36,51,57,114 , but perhaps not in the same studies that satisfy conditions 1-3. One reason that concurrently satisfying all four conditions may be difficult is that imposition of an explicit task will sometimes lead to a diminished ability to record subfield-specific evidence of pattern separation 33 .…”

Section: Figmentioning

confidence: 99%

Integrating new findings and examining clinical applications of pattern separation

2018

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Pattern separation, the ability to independently represent and store similar experiences, is a crucial facet of episodic memory. Growing evidence suggests that the hippocampus possesses unique circuitry that is computationally capable of resolving mnemonic interference by using pattern separation. In this Review, we discuss recent advances in the understanding of this process and evaluate the caveats and limitations of linking across animal and human studies. We summarize clinical and translational studies using methods that are sensitive to pattern separation impairments, an approach that stems from the fact that the hippocampus is a major site of disruption in many brain disorders. We critically evaluate the assumptions that guide fundamental and translational studies in this area. Finally, we suggest guidelines for future research and offer ways to overcome potential interpretational challenges to increase the utility of pattern separation as a construct that can further understanding of both memory processes and brain disease.

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“…Scenes require the integration of multiple visual features, which is impaired in patients with hippocampal damage [47]. Further, hippocampal activity has been shown for complex discrimination of scenes [48], with evidence for the orthogonalization of scenes in the dentate gyrus [49]. Thus, we investigated whether the MST-Scenes would be more sensitive to age-related decline, with a greater relationship to hippocampal volume than MST-Objects.…”

Section: Introductionmentioning

confidence: 99%

Age-related deficits in the mnemonic similarity task for objects and scenes

Stark

2017

Behavioural Brain Research

113

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A B S T R A C TUsing the Mnemonic Similarity Task (MST), we have demonstrated an age-related impairment in lure discrimination, or the ability to recognize an item as distinct from one that was similar, but not identical to one viewed earlier. A growing body of evidence links these behavioral changes to age-related alterations in the hippocampus. In this study, we sought to evaluate a novel version of this task, utilizing scenes that might emphasize the role of the hippocampus in contextual and spatial processing. In addition, we investigated whether, by utilizing two stimulus classes (scenes and objects), we could also interrogate the roles of the PRC and PHC in aging. Thus, we evaluated differential contributions to these tasks by relating performance on objects versus scenes to volumes of the hippocampus and surrounding medial temporal lobe structures. We found that while there was an age-related impairment on lure discrimination performance for both objects and scenes, relationships to brain volumes and other measure of memory performance were stronger when using objects. In particular, lure discrimination performance for objects showed a positive relationship with the volume of the hippocampus, specifically the combined dentate gyrus (DG) and CA3 subfields, and the subiculum. We conclude that though using scenes was effective in detecting age-related lure discrimination impairments, it does not provide as strong a brain-behavior relationship as using objects.

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Strong Evidence for Pattern Separation in Human Dentate Gyrus

Cited by 236 publications

References 57 publications

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

Integrating new findings and examining clinical applications of pattern separation

Age-related deficits in the mnemonic similarity task for objects and scenes

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