Novelty exploration can enhance hippocampal plasticity in animals through dopaminergic neuromodulation arising in the substantia nigra/ventral tegmental area (SN/VTA). This enhancement can outlast ...the exploration phase by several minutes. Currently, little is known about dopaminergic novelty processing and its relationship to hippocampal function in humans. In two functional magnetic resonance imaging (fMRI) studies, SN/VTA activations in humans were indeed driven by stimulus novelty rather than other forms of stimulus salience such as rareness, negative emotional valence, or targetness of familiar stimuli, whereas hippocampal responses were less selective. SN/VTA novelty responses were scaled according to absolute rather than relative novelty in a given context, unlike adaptive SN/VTA responses recently reported for reward outcome in animal studies. Finally, novelty enhanced learning and perirhinal/parahippocampal processing of familiar items presented in the same context. Thus, the human SN/VTA can code absolute stimulus novelty and might contribute to enhancing learning in the context of novelty.
The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that ...connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC.
Scene and object information reach the entorhinal-hippocampal circuitry in partly segregated cortical processing streams. Converging evidence suggests that such information-specific streams organize ...the cortical - entorhinal interaction and the circuitry's inner communication along the transversal axis of hippocampal subiculum and CA1. Here, we leveraged ultra-high field functional imaging and advance Maass et al., 2015 who report two functional routes segregating the entorhinal cortex (EC) and the subiculum. We identify entorhinal subregions based on preferential functional connectivity with perirhinal Area 35 and 36, parahippocampal and retrosplenial cortical sources (referred to as EC
, EC
, EC
, EC
, respectively). Our data show specific scene processing in the functionally connected EC
and distal subiculum. Another route, that functionally connects the EC
and a newly identified EC
with the subiculum/CA1 border, however, shows no selectivity between object and scene conditions. Our results are consistent with transversal information-specific pathways in the human entorhinal-hippocampal circuitry, with anatomically organized convergence of cortical processing streams and a unique route for scene information. Our study thus further characterizes the functional organization of this circuitry and its information-specific role in memory function.
•Magnetic resonance imaging studies of the human locus coeruleus (LC) are reviewed.•The methodology and outcomes for 69 structural and functional studies are reported.•Recommendations to optimize the ...reliability and validity of future studies are made.
The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson’s disease, Alzheimer’s disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and this paper systematically reviews the methodology and outcomes of sixty-nine structural and functional MRI studies of the LC in humans. Structural MRI studies consistently showed lower LC signal intensity and volume in clinical groups compared to healthy controls. Within functional studies, the LC was activated by a variety of tasks/stimuli and had functional connectivity to a range of brain regions. However, reported functional LC location coordinates were widely distributed compared to previously published neuroanatomical locations. Methodological and demographic factors potentially contributing to these differences are discussed, together with recommendations to optimize the reliability and validity of future LC imaging studies.
Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced ...structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.
•Exercise-related changes in BDNF, IGF, VEGF and PDGF were measured in older adults•Changes in hippocampal perfusion, volume (via 7T MRI) and memory were assessed•Fitness-related vascular hippocampal plasticity was not linked to growth factors•Changes in IGF-I, hippocampal volume and memory were linked independent of exercise•Potential reasons for negative findings and methodological shortcomings are discussed
Most current models of recognition memory fail to separately model item and person heterogeneity which makes it difficult to assess ability at the latent construct level and prevents the ...administration of adaptive tests. Here we propose to employ a General Condorcet Model for Recognition (GCMR) in order to estimate ability, response bias and item difficulty in dichotomous recognition memory tasks. Using a Bayesian modeling framework and MCMC inference, we perform 3 separate validation studies comparing GCMR to the Rasch model from IRT and the 2-High-Threshold (2HT) recognition model. First, two simulations demonstrate that recovery of GCMR ability estimates with varying sparsity and test difficulty is more robust and that estimates improve from the two other models under common test scenarios. Then, using a real dataset, face validity is confirmed by replicating previous findings of general and domain-specific age effects (Güsten et al. in Cortex 137:138-148, https://doi.org/10.1016/j.cortex.2020.12.017 , 2021). Using cross-validation we show better out-of-sample prediction for the GCMR as compared to Rasch and 2HT model. In addition, we present a hierarchical extension of the model that is able to estimate age- and domain-specific effects directly, without recurring to a two-stage procedure. Finally, an adaptive test using the GCMR is simulated, showing that the test length necessary to obtain reliable ability estimates can be significantly reduced compared to a non-adaptive procedure. The GCMR allows to model trial-by-trial performance and to increase the efficiency and reliability of recognition memory assessments.
Studies in humans and animals show that dopaminergic neuromodulation originating from the substantia nigra/ventral tegmental area (SN/VTA) of the midbrain enhances hippocampal synaptic plasticity for ...novel events and has a motivationally energizing effect on actions through striatal mechanisms. In this review, we discuss how these mechanisms of dopaminergic neuromodulation connect to the behavioural and functional consequences that age-related structural degeneration of the SN/VTA exerts on declarative memory. We propose a framework called ‘NOvelty-related Motivation of Anticipation and exploration by Dopamine’ (NOMAD) which captures existing links between novelty, dopamine, long-term memory, plasticity, energization and their relation to aging. We propose that maximizing the use of this mechanism by maintaining mobility and exploration of novel environments could be a potential mechanism to slow age-related decline of memory.
•We present a geometry-based method for the analysis of local hippocampal thickness.•An intrinsic hippocampal coordinate system permits comparisons across individuals.•The algorithm requires no ...manual intervention and produces various shape features.•We conduct extensive empirical validation in a range of application scenarios.•Our algorithm demonstrates sensitivity and added value for clinical analyses.
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The hippocampus is one of the most studied neuroanatomical structures due to its involvement in attention, learning, and memory as well as its atrophy in ageing, neurological, and psychiatric diseases. Hippocampal shape changes, however, are complex and cannot be fully characterized by a single summary metric such as hippocampal volume as determined from MR images. In this work, we propose an automated, geometry-based approach for the unfolding, point-wise correspondence, and local analysis of hippocampal shape features such as thickness and curvature. Starting from an automated segmentation of hippocampal subfields, we create a 3D tetrahedral mesh model as well as a 3D intrinsic coordinate system of the hippocampal body. From this coordinate system, we derive local curvature and thickness estimates as well as a 2D sheet for hippocampal unfolding. We evaluate the performance of our algorithm with a series of experiments to quantify neurodegenerative changes in Mild Cognitive Impairment and Alzheimer’s disease dementia. We find that hippocampal thickness estimates detect known differences between clinical groups and can determine the location of these effects on the hippocampal sheet. Further, thickness estimates improve classification of clinical groups and cognitively unimpaired controls when added as an additional predictor. Comparable results are obtained with different datasets and segmentation algorithms. Taken together, we replicate canonical findings on hippocampal volume/shape changes in dementia, extend them by gaining insight into their spatial localization on the hippocampal sheet, and provide additional, complementary information beyond traditional measures. We provide a new set of sensitive processing and analysis tools for the analysis of hippocampal geometry that allows comparisons across studies without relying on image registration or requiring manual intervention.
The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and ...Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer–weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18–88 years). Study participants were part of the Cambridge Centre for Ageing and Neuroscience—an open-access, population-based data set. We found a quadratic relationship between LC CR and age, the peak occurring around 60 years, with no differences between males and females. Subregional analyses revealed that age-related decline in LC CR was confined to the rostral portion of the LC. Older adults showed greater variance in overall LC CR than younger adults, and the functional and clinical implications of these observed age-related differences require further investigation. Visualization of the LC in this study may inform how future scanning parameters can be optimized, and provides insight into how LC integrity changes across the life span.
•A quadratic relationship between locus coeruleus signal intensity and age was found.•No differences between males and females were observed.•Older adults had higher variance than younger adults.•The functional and clinical implications of these changes require further research.
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