The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19.
View Article and Find Full Text PDFIn a changing environment, animals must process spatial signals in a flexible manner. The rat hippocampal formation projects directly upon the retrosplenial cortex, with most inputs arising from the dorsal subiculum and terminating in the granular retrosplenial cortex (area 29). The present study examined whether these same projections are required for spatial working memory and what happens when available spatial cues are altered.
View Article and Find Full Text PDFPrior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g.
View Article and Find Full Text PDFNeuropsychologia
December 2023
To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage.
View Article and Find Full Text PDFThe connectivity and interplay between the prefrontal cortex and hippocampus underpin various key cognitive processes, with changes in these interactions being implicated in both neurodevelopmental and neurodegenerative conditions. Understanding the precise cellular connections through which this circuit is organised is, therefore, vital for understanding these same processes. Overturning earlier findings, a recent study described a novel excitatory projection from anterior cingulate area to dorsal hippocampus.
View Article and Find Full Text PDFThe dense fiber pathways that connect the insular cortex with frontal cortices are thought to provide these frontal areas with interoceptive information, crucial for their involvement in executive functions. Using anterograde neuroanatomical tracing, we mapped the detailed organization of the projections from the rat insular cortex to its targets in orbitofrontal (OFC) and medial prefrontal (mPFC) cortex. In OFC, main insular projections distribute to lateral and medial parts, avoiding ventral parts.
View Article and Find Full Text PDFAs the functional properties of a cortical area partly reflect its thalamic inputs, the present study compared collateral projections arising from various rostral thalamic nuclei that terminate across prefrontal (including anterior cingulate) and retrosplenial areas in the rat brain. Two retrograde tracers, fast blue and cholera toxin B, were injected in pairs to different combinations of cortical areas. The research focused on the individual anterior thalamic nuclei, including the interanteromedial nucleus, nucleus reuniens and the laterodorsal nucleus.
View Article and Find Full Text PDFNeurosci Biobehav Rev
September 2022
After more than 80 years, Papez serial circuit remains a hugely influential concept, initially for emotion, but in more recent decades, for memory. Here, we show how this circuit is anatomically and mechanistically naïve as well as outdated. We argue that a new conceptualisation is necessitated by recent anatomical and functional findings that emphasize the more equal, working partnerships between the anterior thalamic nuclei and the hippocampal formation, along with their neocortical interactions in supporting, episodic memory.
View Article and Find Full Text PDFPrecise developmental control of jaw length is critical for survival, but underlying molecular mechanisms remain poorly understood. The jaw skeleton arises from neural crest mesenchyme (NCM), and we previously demonstrated that these progenitor cells express more bone-resorbing enzymes including () when they generate shorter jaws in quail embryos versus longer jaws in duck. Moreover, if we inhibit bone resorption or we can increase jaw length.
View Article and Find Full Text PDFNat Rev Neurosci
August 2022
Standard models of episodic memory focus on hippocampal-parahippocampal interactions, with the neocortex supplying sensory information and providing a final repository of mnemonic representations. However, recent advances have shown that other regions make distinct and equally critical contributions to memory. In particular, there is growing evidence that the anterior thalamic nuclei have a number of key cognitive functions that support episodic memory.
View Article and Find Full Text PDFInvasive tract-tracing studies in rodents implicate a direct connection between the subiculum and bed nucleus of the stria terminalis (BNST) as a key component of neural pathways mediating hippocampal regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. A clear characterisation of the connections linking the subiculum and BNST in humans and non-human primates is lacking. To address this, we first delineated the projections from the subiculum to the BNST using anterograde tracers injected into macaque monkeys, revealing evidence for a monosynaptic subiculum-BNST projection involving the fornix.
View Article and Find Full Text PDFCharacterizing 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.
View Article and Find Full Text PDFNeurobiol Learn Mem
November 2021
Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the brain and mediates between these, although it is not yet known how. It has two distinct subregions, granular (gRSC) and dysgranular (dRSC). The present study investigated how these subregions differ with respect to their electrophysiology and thalamic connectivity, as a step towards understanding their functions.
View Article and Find Full Text PDFRetrosplenial cortex contains two principal subdivisions, area 29 (granular) and area 30 (dysgranular). Their respective anatomical connections in the rat brain reveal that area 29 is the primary recipient of hippocampal and parahippocampal spatial and contextual information while area 30 is the primary interactor with current visual information. Lesion studies and measures of neuronal activity in rodents indicate that retrosplenial cortex helps to integrate space from different perspectives, e.
View Article and Find Full Text PDFBoth nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI.
View Article and Find Full Text PDFJust as hippocampal lesions are principally responsible for "temporal lobe" amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, "diencephalic" amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei.
View Article and Find Full Text PDFAims: Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model.
View Article and Find Full Text PDFIn a changing environment, organisms need to decide when to select items that resemble previously rewarded stimuli and when it is best to switch to other stimulus types. Here, we used chemogenetic techniques to provide causal evidence that activity in the rodent anterior cingulate cortex and its efferents to the anterior thalamic nuclei modulate the ability to attend to reliable predictors of important outcomes. Rats completed an attentional set-shifting paradigm that first measures the ability to master serial discriminations involving a constant stimulus dimension that reliably predicts reinforcement (intradimensional-shift), followed by the ability to shift attention to a previously irrelevant class of stimuli when reinforcement contingencies change (extradimensional-shift).
View Article and Find Full Text PDFAPOE-ε4 is a main genetic risk factor for developing late onset Alzheimer's disease (LOAD) and is thought to interact adversely with other risk factors on the brain. However, evidence regarding the impact of APOE-ε4 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterising APOE-ε4-related changes in the hippocampus, but LOAD pathology is known to spread through the whole of the Papez circuit including the limbic thalamus.
View Article and Find Full Text PDFNeurosci Biobehav Rev
December 2020
Two thalamic sites are of especial significance for understanding hippocampal - diencephalic interactions: the anterior thalamic nuclei and nucleus reuniens. Both nuclei have dense, direct interconnections with the hippocampal formation, and both are directly connected with many of the same cortical and subcortical areas. These two thalamic sites also contain neurons responsive to spatial stimuli while lesions within these two same areas can disrupt spatial learning tasks that are hippocampal dependent.
View Article and Find Full Text PDFDespite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle.
View Article and Find Full Text PDFBrain Neurosci Adv
June 2020
Rodents will spontaneously learn the location of an individual object, an ability captured by the object-in-place test. This review considers the network of structures supporting this behavioural test, as well as some potential confounds that may affect interpretation. A hierarchical approach is adopted, as we first consider those brain regions necessary for two simpler, 'precursor' tests (object recognition and object location).
View Article and Find Full Text PDFThe hippocampus is essential for normal memory but does not act in isolation. The anterior thalamic nuclei may represent one vital partner. Using DREADDs, the behavioral consequences of transiently disrupting anterior thalamic function were examined, followed by inactivation of the dorsal subiculum.
View Article and Find Full Text PDFThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has caused the coronavirus disease 2019 (COVID-19) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. The aim of this paper is to set out the shorter- and longer-term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. The research priorities were informed by an expert panel convened by the British Psychological Society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of 539 psychological scientists conducted early in May 2020.
View Article and Find Full Text PDFThe fornix is a key tract of the hippocampal formation, whose status is presumed to contribute to age-related cognitive decline. The precommissural and postcommissural fornix subdivisions form respective basal forebrain/frontal and diencephalic networks that may differentially affect aging and cognition. We employed multi-parametric magnetic resonance imaging (MRI) including neurite orientation density and dispersion imaging, quantitative magnetization transfer (qMT), and T-relaxometry MRI to investigate the microstructural properties of these fornix subdivisions and their relationship with aging and cognition in 149 asymptomatic participants (38-71 years).
View Article and Find Full Text PDF