Release of cognitive and multimodal MRI data including real-world tasks and hippocampal subfield segmentations

We share data from N = 217 healthy adults (mean age 29 years, range 20-41; 109 females, 108 males) who underwent extensive cognitive assessment and neuroimaging to examine the neural basis of individual differences, with a particular focus on a brain structure called the hippocampus. Cognitive data were collected using a wide array of questionnaires, naturalistic tests that examined imagination, autobiographical memory recall and spatial navigation, traditional laboratory-based tests such as recalling word pairs, and comprehensive characterisation of the strategies used to perform the cognitive tests. 3 Tesla MRI data were also acquired and include multi-parameter mapping to examine tissue microstructure, diffusion-weighted MRI, T2-weighted high-resolution partial volume structural MRI scans (with the masks of hippocampal subfields manually segmented from these scans), whole brain resting state functional MRI scans and partial volume high resolution resting state functional MRI scans. This rich dataset will be of value to cognitive and clinical neuroscientists researching individual differences, real-world cognition, brain-behaviour associations, hippocampal subfields and more. All data are freely available on Dryad

Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults

Characterizing age- and risk-related hippocampal vulnerabilities may inform about the neural underpinnings of cognitive decline. We studied the impact of three risk-factors, Apolipoprotein (APOE)-ε4, a family history of dementia, and central obesity, on the CA1, CA2/3, dentate gyrus and subiculum of 158 cognitively healthy adults (38-71 years). Subfields were labelled with the Automatic Segmentation of Hippocampal Subfields and FreeSurfer (version 6) protocols. Volumetric and microstructural measurements from quantitative magnetization transfer and Neurite Orientation Density and Dispersion Imaging were extracted for each subfield and reduced to three principal components capturing apparent myelin/neurite packing, size/complexity, and metabolism. Aging was associated with an inverse U-shaped curve on myelin/neurite packing and affected all subfields. Obesity led to reductions in myelin/neurite packing and size/complexity regardless of APOE and family history of dementia status. However, amongst individuals with a healthy Waist-Hip-Ratio, APOE ε4 carriers showed lower size/complexity than non-carriers. Segmentation protocol type did not affect this risk pattern. These findings reveal interactive effects between APOE and central obesity on the hippocampal formation of cognitively healthy adults

Convergence of cortical types and functional motifs in the human mesiotemporal lobe

The mesiotemporal lobe (MTL) is implicated in many cognitive processes, is compromised in numerous brain disorders, and exhibits a gradual cytoarchitectural transition from six-layered parahippocampal isocortex to three-layered hippocampal allocortex. Leveraging an ultra-high-resolution histological reconstruction of a human brain, our study showed that the dominant axis of MTL cytoarchitectural differentiation follows the iso-to-allocortical transition and depth-specific variations in neuronal density. Projecting the histology-derived MTL model to in-vivo functional MRI, we furthermore determined how its cytoarchitecture underpins its intrinsic effective connectivity and association to large-scale networks. Here, the cytoarchitectural gradient was found to underpin intrinsic effective connectivity of the MTL, but patterns differed along the anterior-posterior axis. Moreover, while the iso-to-allocortical gradient parametrically represented the multiple-demand relative to task-negative networks, anterior-posterior gradients represented transmodal versus unimodal networks. Our findings establish that the combination of micro- and macrostructural features allow the MTL to represent dominant motifs of whole-brain functional organisation

High resolution fMRI of hippocampal subfields and medial temporal cortex during working memory

Computational models combined with electrophysiological studies have informed our understanding about the role of hippocampal subfields (dentate gyrus, DG; CA subfields, subiculum) and Medial Temporal Lobe (MTL) cortex (entorhinal, perirhinal, parahippocampal cortices) during working memory (WM) tasks. Only recently have functional neuroimaging studies begun to examine under which conditions the MTL are recruited for WM processing in humans, but subfield contributions have not been examined in the WM context. High-resolution fMRI is well suited to test hypotheses regarding the recruitment of MTL subregions and hippocampal subfields. This dissertation describes three experiments using high-resolution fMRI to examine the role of hippocampal subfields and MTL structures in humans during WM. Experiment 1 investigated MTL activity when participants performed a task that required encoding and maintaining overlapping and non-overlapping stimulus pairs during WM. During encoding, activity in CA3/DG and CA1 was greater for stimulus pairs with overlapping features. During delay, activity in CA1 and entorhinal cortex was greater for overlapping stimuli. These results indicate that CA3/DG and CA1 support disambiguating overlapping representations while CA1 and entorhinal cortex maintain these overlapping items. Experiment 2 investigated MTL activity when participants performed a WM task that required encoding and maintaining either low or high WM loads. The results show a load effect in entorhinal and perirhinal cortex during the delay period and suggest that these regions act as a buffer for WM by actively maintaining novel information in a capacity-dependent manner. Experiment 3 investigated MTL activity when participants performed a WM task that required maintaining similar and dissimilar items at different loads. Analysis of a load by similarity interaction effect revealed areas of activity localized to the CA1 subfield. CA1 showed greater activity for higher WM loads for dissimilar, but not similar stimuli. Our findings help identify hippocampal and MTL regions that contribute to disambiguation in a WM context and regions that are active in a capacity-dependent manner which may support long-term memory formation. These results help inform our understanding of the contributions of hippocampal subfields and MTL subregions during WM and help translate findings from animal work to the cognitive domain of WM in humans

Making Waves in the Brain: What Are Oscillations, and Why Modulating Them Makes Sense for Brain Injury.

Traumatic brain injury (TBI) can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson's disease (PD) and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following TBI. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI

Spatial maps and oscillations in the healthy hippocampus of Octodon degus, a natural model of sporadic Alzheimer’s disease

The Octodon degus is a South American rodent that is receiving increased attention as a potential model of aging and sporadic late-onset Alzheimer’s disease (AD). Impairments in spatial memory tasks in Octodon degus have been reported in relation to either advanced AD-like disease or hippocampal lesion, opening the way to investigate how the function of hippocampal networks affects behavior across AD stages. However, no characterization of hippocampal electrophysiology exists in this species. Here we describe in young, healthy specimens the activity of neurons and local field potential rhythms during spatial navigation tasks with and without objects. Our findings show similarities between the Octodon degus and laboratory rodents. First, place cells with characteristics similar to those found in rats and mice exist in the CA1 subfield of the Octodon degus. Second, the introduction of objects elicits novelty-related exploration and an increase in activity of CA1 cells, with location specific and unspecific components. Third, oscillations of the local field potential are organized according to their spectral content into bands similar to those found in laboratory rodents. These results suggest a common framework of underlying mechanisms, opening the way to future studies of hippocampal dysfunction in this species associated to aging and disease.Fil: Mugnaini, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Polania, Diana. Universidad de Chile; ChileFil: Díaz, Yannina Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ezquer, Marcelo. Universidad del Desarrollo; ChileFil: Ezquer, Fernando. Universidad del Desarrollo; ChileFil: Deacon, Robert M. J.. Universidad de Chile; ChileFil: Cogram, Patricia. Universidad de Chile; Chile. University of California at Irvine; Estados UnidosFil: Kropff, Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

A Role for the Longitudinal Axis of the Hippocampus in Multiscale Representations of Large and Complex Spatial Environments and Mnemonic Hierarchies

The hippocampus is involved in spatial navigation and memory in rodents and humans. Anatomically, the hippocampus extends along a longitudinal axis that shows a combination of graded and specific interconnections with neocortical and subcortical brain areas. Functionally, place cells are found all along the longitudinal axis and exhibit gradients of properties including an increasing dorsal-to-ventral place field size. We propose a view of hippocampal function in which fine-dorsal to coarse-ventral overlapping representations collaborate to form a multi-level representation of spatial and episodic memory that is dominant during navigation in large and complex environments or when encoding complex memories. This view is supported by the fact that the effects of ventral hippocampal damage are generally only found in larger laboratory-scale environments, and by the finding that human virtual navigation studies associate ventral hippocampal involvement with increased environmental complexity. Other mechanisms such as the ability of place cells to exhibit multiple fields and their ability to scale their fields with changes in environment size may be utilized when forming large-scale cognitive maps. Coarse-grained ventral representations may overlap with and provide multi-modal global contexts to finer-grained intermediate and dorsal representations, a mechanism that may support mnemonic hierarchies of autobiographical memory in humans

Unravelling The Subfields Of The Hippocampal Head Using 7-Tesla Structural MRI

Probing the functions of human hippocampal subfields is a promising area of research in cognitive neuroscience. However, defining subfield borders in Magnetic Resonance Imaging (MRI) is challenging. Here, we present a user-guided, semi-automated protocol for segmenting hippocampal subfields on T2-weighted images obtained with 7-Tesla MRI. The protocol takes advantage of extant knowledge about regularities in hippocampal morphology and ontogeny that have not been systematically considered in prior related work. An image feature known as the hippocampal ‘dark band’ facilitates tracking of subfield continuities, allowing for unfolding and segmentation of convoluted hippocampal tissue. Initial results suggest that this protocol offers sufficient precision and flexibility to accommodate inter-individual differences in morphology and produces segmentations that have improved accuracy and detail compared to other prominent protocols, with similar inter-rater reliability. We anticipate that this protocol will allow for improved anatomical precision in future research on hippocampal subfields in health and neurological disease

Fitness is positively associated with hippocampal formation subfield volumes in schizophrenia: a multiparametric magnetic resonance imaging study

Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean [SD] age, 37.4 [11.8] years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies

Spatial encoding in primate hippocampus during free navigation.

The hippocampus comprises two neural signals-place cells and θ oscillations-that contribute to facets of spatial navigation. Although their complementary relationship has been well established in rodents, their respective contributions in the primate brain during free navigation remains unclear. Here, we recorded neural activity in the hippocampus of freely moving marmosets as they naturally explored a spatial environment to more explicitly investigate this issue. We report place cells in marmoset hippocampus during free navigation that exhibit remarkable parallels to analogous neurons in other mammalian species. Although θ oscillations were prevalent in the marmoset hippocampus, the patterns of activity were notably different than in other taxa. This local field potential oscillation occurred in short bouts (approximately .4 s)-rather than continuously-and was neither significantly modulated by locomotion nor consistently coupled to place-cell activity. These findings suggest that the relationship between place-cell activity and θ oscillations in primate hippocampus during free navigation differs substantially from rodents and paint an intriguing comparative picture regarding the neural basis of spatial navigation across mammals