Hippocampal subfield associations with memory depend on stimulus modality and retrieval mode

Etienne Aumont; Aurélie Bussy; Marc-André Bedard; Gleb Bezgin; Joseph Therriault; Melissa Savard; Jaime Fernandez Arias; Viviane Sziklas; Paolo Vitali; Nina Margherita Poltronetti; Vanessa Pallen; Emilie Thomas; Serge Gauthier; Eliane Kobayashi; Nesrine Rahmouni; Jenna Stevenson; Cecile Tissot; Mallar M Chakravarty; Pedro Rosa-Neto

doi:10.1093/braincomms/fcad309

Hippocampal subfield associations with memory depend on stimulus modality and retrieval mode

Brain Commun. 2023 Nov 9;5(6):fcad309. doi: 10.1093/braincomms/fcad309. eCollection 2023.

Authors

Etienne Aumont^{1

2

3}, Aurélie Bussy^{4

5}, Marc-André Bedard^{1

2

3

6}, Gleb Bezgin^{2

3

6}, Joseph Therriault^{2

3

6}, Melissa Savard^{2

3

6}, Jaime Fernandez Arias^{2

3

6}, Viviane Sziklas³, Paolo Vitali^{2

6}, Nina Margherita Poltronetti², Vanessa Pallen², Emilie Thomas², Serge Gauthier^{2

3

6}, Eliane Kobayashi^{3

6}, Nesrine Rahmouni^{2

3

6}, Jenna Stevenson^{2

3

6}, Cecile Tissot^{2

3

6}, Mallar M Chakravarty^{4

5

7}, Pedro Rosa-Neto^{1

2

3

6}

Affiliations

¹ NeuroQAM Research Centre, Université du Québec à Montréal (UQAM), Montreal H2X 3P2, Canada.
² McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC H4H 1R3, Canada.
³ Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
⁴ Cerebral Imaging Center, Douglas Research Center, Montreal, QC H4H 1R3, Canada.
⁵ Computational Brain Anatomy (CoBrALab) Laboratory, Montreal, QC H4H 1R2, Canada.
⁶ Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 1A1, Canada.
⁷ Department of Psychiatry, McGill University, Montreal, QC H3A 1A1, Canada.

Abstract

Hippocampal atrophy is a well-known feature of age-related memory decline, and hippocampal subfields may contribute differently to this decline. In this cross-sectional study, we investigated the associations between hippocampal subfield volumes and performance in free recall and recognition memory tasks in both verbal and visual modalities in older adults without dementia. We collected MRIs from 97 (41 males) right-handed participants aged over 60. We segmented the right and left hippocampi into (i) dentate gyrus and cornu ammonis 4 (DG/CA4); (ii) CA2 and CA3 (CA2/CA3); (iii) CA1; (iv) strata radiatum, lacunosum and moleculare; and (v) subiculum. Memory was assessed with verbal free recall and recognition tasks, as well as visual free recall and recognition tasks. Amyloid-β and hippocampal tau positivity were assessed using [¹⁸F]AZD4694 and [¹⁸F]MK6240 PET tracers, respectively. The verbal free recall and verbal recognition performances were positively associated with CA1 and strata radiatum, lacunosum and moleculare volumes. The verbal free recall and visual free recall were positively correlated with the right DG/CA4. The visual free recall, but not verbal free recall, was also associated with the right CA2/CA3. The visual recognition was not significantly associated with any subfield volume. Hippocampal tau positivity, but not amyloid-β positivity, was associated with reduced DG/CA4, CA2/CA3 and strata radiatum, lacunosum and moleculare volumes. Our results suggest that memory performances are linked to specific subfields. CA1 appears to contribute to the verbal modality, irrespective of the free recall or recognition mode of retrieval. In contrast, DG/CA4 seems to be involved in the free recall mode, irrespective of verbal or visual modalities. These results are concordant with the view that DG/CA4 plays a primary role in encoding a stimulus' distinctive attributes, and that CA2/CA3 could be instrumental in recollecting a visual memory from one of its fragments. Overall, we show that hippocampal subfield segmentation can be useful for detecting early volume changes and improve our understanding of the hippocampal subfields' roles in memory.

Keywords: Alzheimer’s disease; ageing; automatic segmentation; hippocampus; memory.