Research reportRoles of hippocampal subfields in verbal and visual episodic memory
Introduction
The association between the hippocampus and episodic memory is well established [1], [2], [3], [4]; however, within the hippocampus, the roles of task-specific structures are still emerging, and only a few studies have investigated the association between hippocampal subfields and psychometric tests of memory in healthy older adults.
Hippocampal (HC) subfields include the cornu ammonis (CA1, CA2-3), CA4-dente gyrus (DG), the presubiculum and the subiculum. Previous research suggests that CA2, CA3, and DG are input structures, responsible for encoding, while the CA1 and subiculum are output structures, responsible for retrieval [5], [6], [7], [8], [9]. fMRI studies have further suggested specialized function for each subfield in hippocampal formation. Zeineh et al. [8] used a face-name associated task to study mnemonic processing in 10 healthy young adults; results showed that the CA2, CA3 and DG were involved in encoding whereas the subiculum showed more activation during recall, thus suggesting a double dissociation of activation patterns and tasks. In a similar experiment, Nauer et al. [9] assessed 34 healthy young adults on their working memory abilities for visuospatial information using complex visual outdoor scenes in delayed match-to-sample (DMS) tasks; results in this study showed that the hippocampal subfields CA1, CA3, DG and subiculum remained activated well into the delayed period, suggesting an ongoing mechanism of long-term information processing. Nauer et al. [9] refer to this as “ongoing encoding”, in which the immediate and delayed tasks are explained as one continuous process of activity reflecting ongoing encoding of stimuli.
Structural MRI studies have also shown these associations in case-control studies [10], [11], [12]. Muller et al. [12] explored verbal episodic memory using the California Verbal Learning Test II (CVLT-II) in individuals with temporal lobe deficits and healthy controls; they found that immediate verbal recall was associated with larger CA3 and DG volumes, while delayed verbal recall was associated with larger CA1 volumes. They also found similar results in another study using the same test on cognitively impaired older adults [11]. Research has also shown that CA1 volume declines with increasing age [13], and that compared to age-matched controls, Alzheimer’s disease (AD) subjects show more atrophy in the CA1 and subiculum [14], [15]. CA1 has also been associated with delayed verbal recall in AD [10], further suggesting CA1′s role in retrieval that is associated with AD [15]. These findings have been extended to younger healthy adults in a study [16] that applied structural MRI to the study of hippocampal formation in younger adults; results showed that CA1, CA2/CA3 and DG played significant roles in verbal and visual memory retrieval.
In this manuscript, we assess the relationships of HC subfield volume with standardized neuropsychological tests of visual and verbal memory. Identifying neurocognitive measures that tap onto hippocampal subfields may provide a more efficient method of targeting individuals at risk of AD. Psychometric tests that are associated with specific hippocampal subfields may suggest atrophy and consequently ensure a more proactive approach of referring at-risk individuals for imaging procedures and early diagnosis. Thus, the aim of our study was to explore the role of hippocampal subfields in delayed verbal and delayed visual recall in a sample of community-dwelling older adults without dementia. We hypothesized that CA1 and subiculum would be associated with performance on tests of visual and verbal memory recall.
Section snippets
Sample
This cross-sectional study was conducted on a subset of 133 older adults from the Einstein Aging Study (EAS). The EAS study design and methods have been described previously [17]. Briefly, the EAS is an ongoing community-based volunteer sample of individuals over the age of 70 living in the Bronx, New York. Participants are systematically recruited from Medicare and from voter registration lists from Bronx County, New York City Board of Elections. Participants with visual and/or auditory
Demographic and sample characteristics
The mean age of the sample was 78.9 years, 39.8% were male, and 60% were Caucasian. Average total number of years in education was 14.4 years. Global cognitive function, as measured by the Mini Mental State Examination was on average 26.5 (SD = 1.7). The mean scores on the Complex Figure Delayed Recall conditions were 11.6 (SD = 3.8). The mean score on the delayed recall from the FCSRT was 11.0 (SD = 3.7). Sample characteristics, visual and verbal episodic memory, and MRI-derived volumes of
Discussion
In this cross-sectional study we found strong associations between total hippocampal volume and the performance on tests of visual and verbal episodic memory. Within the hippocampal structure, CA1 and subiculum were strongly associated with both visual and verbal episodic memory as represented by Complex Figure Delayed Recall and FCSRT Delayed Recall. Specifically, smaller CA1 and smaller subiculum were associated with poorer performance on both these tests.
Within the hippocampus, the subiculum
Conclusion
In this study we explored associations between delayed visual and verbal recall measures using the RBANS Complex Figure subtest and the FCSRT Delayed Recall subtest and hippocampal sub-regions in healthy older adults. Our results showed CA1 and subiculum subfields as strongly associated with both verbal and visual episodic memory. Our results suggested that hippocampal atrophy, specifically, CA1 and subiculum may be markers of normative cognitive decline, and that the R-BANS Complex Figure and
Conflict of interest
AZ, EZ, MZ, ML and MK declare that there are no financial, personal, or other potential conflicts of interest. RBL serves on the editorial boards of Neurology and as senior advisor to Headache. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics; serves as consultant, advisory board member, or has received honoraria from: Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb,
Funding sources
This research was supported by the Einstein Aging Study (PO1 AG03949) from the National Institutes on Aging program; the National Institutes of Health CTSA (1UL1TR001073) from the National Center for Advancing Translational Sciences (NCATS), the Sylvia and Leonard Marx Foundation, and the Czap Foundation. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Statement of human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Acknowledgements
We thank the EAS research participants. We thank Charlotte Magnotta, Diane Sparracio and April Russo for assistance in participant recruitment; Betty Forro, Wendy Ramratan, and Mary Joan Sebastian for assistance in clinical and neuropsychological assessments; Michael Potenza for assistance in data management.
References (36)
Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: review and meta-analysis
Neuropsychologia
(2004)- et al.
The human hippocampus and spatial and episodic memory
Neuron
(2002) - et al.
Semantic memory and the human hippocampus
Neuron
(2003) Hippocampal region-specific contributions to memory performance in normal elderly
Brain Cogn.
(2010)Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease
Neuroimage
(2012)Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4 T
Neuroimage
(2011)Measurement of hippocampal subfields and age-related changes with high resolution MRI at 4T
Neurobiol. Aging
(2007)Hippocampal neurons in pre-clinical Alzheimer's disease
Neurobiol. Aging
(2004)Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease
Lancet
(1994)High field structural MRI reveals specific episodic memory correlates in the subfields of the hippocampus
Neuropsychologia
(2014)
Selective reminding for analysis of memory and learning
J. Verbal Learn. Verbal Behav.
Hippocampal subfields differentially correlate with chronic pain in older adults
Brain Res.
Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain
Neuron
A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume
Neuroimage
Roles for the subiculum in spatial information processing: memory, motivation and the temporal control of behaviour
Prog. Neuro Psychopharmacol. Biol. Psychiatry
High field structural MRI reveals specific episodic memory correlates in the subfields of the hippocampus
Neuropsychologia
Differential but complementary mnemonic functions of the hippocampus and subiculum
Neuron
Subregional hippocampal atrophy predicts Alzheimer’s dementia in the cognitively normal
Neurobiol. Aging
Cited by (69)
Hippocampal subfields volume changes and its correlation with memory functions in patients with mild cognitive impairment
2024, Aging and Health ResearchThe impact of pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities in young adults
2023, Environment InternationalMonocytosis in the acute phase of SARS-CoV-2 infection predicts the presence of anosognosia for cognitive deficits in the chronic phase
2022, Brain, Behavior, and Immunity - HealthCitation Excerpt :Furthermore, it has been shown that monocytes are involved in brain damage following viral infections such as picornavirus and SARS-CoV-2 (Howe et al., 2012; Boucas et al., 2022). In particular, monocytic reactions in response to these different viral infections appear to damage hippocampal regions (Boucas et al., 2022), known to be the neuroanatomical basis of cognitive capacities in verbal episodic memory (Zammit et al., 2017). Social lockdown measures may well have had repercussions for the immune system, and several empirical studies have indeed already highlighted the impact of lockdown on metabolism and immune processes (Filgueira et al., 2021).