Involvement of hippocampal subfields and anterior-posterior subregions in encoding and retrieval of item, spatial, and associative memories: Longitudinal versus transverse axis

The functional role of the hippocampal formation in episodic memory has been studied using functional magnetic resonance imaging (fMRI) for many years. The hippocampus can be segmented into three major anteroposterior sections, called head, body and tail, and into the Cornu Ammonis (CA), dentate gyrus (DG), and subiculum (Sub) subfields based on its transverse axis. However, the exact role of these subregions and subfields in memory processes is less understood. In the present study we combined ultra-high resolution structural Magnetic Resonance Imaging (MRI) at 4.7 T with an event-related high-resolution fMRI paradigm based on the ‘Designs’ subtest of the Wechsler Memory Scale to investigate how the hippocampal subfields and longitudinal subregions are involved in encoding and retrieval of item, spatial, and associative memories. Our results showed that during memory encoding, regardless of the type of memory being learned, all subregions and all subfields were active. During the retrieval phase, on the other hand, we observed an anterior to posterior gradient in hippocampal activity for all subfields and all types of memory. Our findings also confirmed presence of an anterior to posterior gradient in hippocampal activity during spatial learning. Comparing subfield activities to each other revealed that the DG was more active than the CA1-3 and Sub during both encoding and retrieval. Finally, our results showed that for every subfield, encoding vs. retrieval activity differences were larger in the hippocampal head than in the hippocampal body and tail. Furthermore, these encoding vs. retrieval activity differences were similar in all subfields, highlighting the importance of studying both the longitudinal and transverse axis specialization simultaneously. Current findings further elucidate the structure–function relationship between the human hippocampus and episodic memory

Amygdala subnuclei response and connectivity during emotional processing

The involvement of the human amygdala in emotion-related processing has been studied using functional magnetic resonance imaging (fMRI) for many years. However, despite the amygdala being comprised of several subnuclei, most studies investigated the role of the entire amygdala in processing of emotions. Here we combined a novel anatomical tracing protocol with event-related high-resolution fMRI acquisition to study the responsiveness of the amygdala subnuclei to negative emotional stimuli and to examine intra-amygdala functional connectivity. The greatest sensitivity to the negative emotional stimuli was observed in the centromedial amygdala, where the hemodynamic response amplitude elicited by the negative emotional stimuli was greater and peaked later than for neutral stimuli. Connectivity patterns converge with extant findings in animals, such that the centromedial amygdala was more connected with the nuclei of the basal amygdala than with the lateral amygdala. Current findings provide evidence of functional specialization within the human amygdala

Investigating the effects of healthy cognitive aging on brain functional connectivity using 4.7 T resting-state functional Magnetic Resonance Imaging

Functional changes in the aging human brain have been previously reported using functional magnetic resonance imaging (fMRI). Earlier resting-state fMRI studies revealed an age-associated weakening of intra-system functional connectivity (FC) and age-associated strengthening of inter-system FC. However, the majority of such FC studies did not investigate the relationship between age and network amplitude, without which correlation-based measures of FC can be challenging to interpret. Consequently, the main aim of this study was to investigate how three primary measures of resting-state fMRI signal—network amplitude, network topography, and inter-network FC—are affected by healthy cognitive aging. We acquired resting-state fMRI data on a 4.7 T scanner for 105 healthy participants representing the entire adult lifespan (18–85 years of age). To study age differences in network structure, we combined ICA-based network decomposition with sparse graphical models. Older adults displayed lower blood-oxygen-level-dependent (BOLD) signal amplitude in all functional systems, with sensorimotor networks showing the largest age differences. Our age comparisons of network topography and inter-network FC demonstrated a substantial amount of age invariance in the brain’s functional architecture. Despite architecture similarities, old adults displayed a loss of communication efficiency in our inter-network FC comparisons, driven primarily by the FC reduction in frontal and parietal association cortices. Together, our results provide a comprehensive overview of age effects on fMRI-based FC

Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance

This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation

Hippocampal Subfields Group progress update: Consensus protocol to segment subfields within the hippocampal body on high-resolution in vivo MRI

Hippocampal subfields are differentially sensitive in development, aging, and neurodegenerative disease. High-resolution imaging techniques have accelerated clinical research of hippocampal subfields; however, substantial differences in protocols impede comparisons in the literature across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically-valid, reliable, and freely available segmentation protocol for high-resolution T2-weighted 3T MRI (http://www.hippocampalsubfields.com). This progress update presents the consensus draft protocol for segmenting subfields within the hippocampal body. The segmentation protocol is based on a novel histological reference data set labeled by multiple expert neuroanatomists. Two naïve raters demonstrated feasibility on an MRI dataset including brains from children and adults, and all subfield volume measurements had good reliability. Twenty-six labs with reported 4 years or more experience segmenting hippocampal subfields in healthy lifespan and patient populations participated in an online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. Due to the complexity of the internal anatomy, two approaches for segmenting the boundary between cornu ammonis (CA) 3 and dentate gyrus subfields were presented, and the majority approved a geometric heuristic-based protocol over one that referenced the endfolial pathway anatomy: 58% geometric, 23% endfolial, and with 19% expressing no opinion. Labs rated each internal boundary definition for clarity and agreement with the protocol on a scale 1 (low) to 9 (high). All definitions were rated with high clarity (M = 8.42 – 8.65) and reached consensus agreement (binomial ps < 0.01). The geometric heuristic protocol includes labels for the internal boundaries between subiculum, each CA field, and dentate gyrus, which when combined with the external boundaries that previously reached consensus, labels subfield volumes throughout the hippocampal body. We are now conducting a formal reliability test of the hippocampal body protocol with a group of expert and novice raters who are naïve to the protocol. With confirmation of reliability, we will disseminate the validated harmonized segmentation protocol and resources for automated segmentation. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in disease