ArticleLiterature Review

Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: Review and meta-analysis

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Abstract

Poor memory ability and small hippocampal volume measurements in magnetic resonance images co-occur in neurological patients. Numerous studies have examined the relationship between memory performance and hippocampal volumes in participants without neurological or psychiatric disorders, with widely varying results. Three hypotheses about volume-memory relationships in the normal human brain are discussed: "bigger is always better", a neuropsychological view that volume decreases due to normal aging are accompanied by memory decline, and a developmental perspective that regressive events in development may result in negative correlations between hippocampal volume and memory ability. Meta-analysis of results from 33 studies led to little support for the bigger-is-better hypothesis. A negative relationship between hippocampal volume and memory (smaller is better) was significant for studies with children, adolescents, and young adults. For studies with older adults, the most striking observation was extreme variability: the evidence for a positive relationship between hippocampal size and episodic memory ability in older adults was surprisingly weak. Some of the variability in results from older adults was associated with statistical methods of normalizing for age and head size, which are discussed.

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... Using the subscales from the Montreal Cognitive Assessment, a screening tool for mild cognitive impairment, greater hippocampal volume also was significantly related to better delayed recall but was not related to attention or visual-spatial executive functioning (O'Shea et al., 2016). Note, however, that the aforementioned studies rely on specialized samples, and an association between hippocampal volume and cognitive functioning in healthy, younger samples is not always found (scene imagination, autobiographical memory, future thinking, and navigation in Clark et al., 2020;navigation ability in Weisberg et al., 2019; see also a meta-analysis on hippocampal volume and memory ability by Van Petten, 2004). ...
... The MIDUS study is a longitudinal national study of adults in the United States that began in 1994. Each wave of MIDUS consists of several subprojects; the second wave (MIDUS II;2004-2009) was the first to include a neuroscience project. Due to the original sample aging, a refresher sample was recruited in 2011 (MIDUS Refresher) to again include representation across the adult age-span. ...
... When examining the cognitive subtest of delayed recall, a significant negative bivariate correlation was found, but adding in additional covariates nullified the relationship. Although at first glance this negative correlation is surprising, a meta-analysis of 33 studies found a negative correlation between hippocampal volume and memory ability in younger adults, and noted the variability in the direction of this relationship among studies of older adults (Van Petten, 2004). More research is needed to better understand the nature of the relationship between hippocampal volume and memory ability as people get older. ...
Article
Greater engagement in a range of daily activities is associated with better cognitive functioning (Lee et al., Lee et al., 2020). The hippocampus, a subcortical brain structure implicated in learning, memory, spatial navigation and other aspects of cognitive functioning, may be structurally sensitive to exposure to and engagement with novel experiences and environments. The present study tested whether greater activity diversity, defined as the range of common daily activities engaged in and the proportion of time spent in each, is associated with larger hippocampal volume. Greater diversity of activities, as measured using daily diaries across an 8-day period, was related to greater hippocampal volume averaged across the left and right hemispheres, even when adjusting for estimated intracranial volume, total activity time, sociodemographic factors, and self-reported physical health. These findings are broadly consistent with nonhuman animal studies, demonstrating a link between enriched environments and structural changes to the hippocampus. Future longitudinal and experimental work can elucidate causal and directional relationships between diversity of daily activities and hippocampal volume.
... Some studies have found that, in children, WM ability is associated with social functioning 20 , and one study specifically observed WM deficits were related to poorer social functioningin children with ADHD 21 . The hippocampus is a key structure in WM and other executive functions, however the relationship between hippocampal volume and performance on tasks of executive function in children is not well defined [22][23][24] . In adult and aging populations, larger hippocampal volumes are associated with better performance on tasks of executive functioning, including WM [22][23][24] . ...
... The hippocampus is a key structure in WM and other executive functions, however the relationship between hippocampal volume and performance on tasks of executive function in children is not well defined [22][23][24] . In adult and aging populations, larger hippocampal volumes are associated with better performance on tasks of executive functioning, including WM [22][23][24] . However, this same relationship is not consistently observed in children, with some evidence suggesting that children with larger hippocampal volumes perform worse on tasks of memory 23 . ...
... In adult and aging populations, larger hippocampal volumes are associated with better performance on tasks of executive functioning, including WM [22][23][24] . However, this same relationship is not consistently observed in children, with some evidence suggesting that children with larger hippocampal volumes perform worse on tasks of memory 23 . The relationship between hippocampal volume and WM ability in the ADHD population remains largely unexplored. ...
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The symptoms of hyperactivity-impulsivity and inattention displayed by children with ADHD put them at risk of experiencing peer victimization. Hippocampal maturation, may reduce a child’s vulnerability to the experience of peer victimization, as it has been associated with decreased ADHD symptomatology. Working memory is an important executive function in the formation and maintenance of social relationships, which is often impaired in ADHD. We aimed to evaluate the relationship between problem behaviours, peer victimization, hippocampal morphology, and working memory in children with and without ADHD. 218 typically-developing participants (50.5% male) and 232 participants diagnosed with ADHD (77.6% male) were recruited. The ADHD group was subdivided into inattentive (ADHD-I) or combined (ADHD-C) types. The Child Behavior Checklist measured problem behaviours and peer victimization. Children underwent Magnetic Resonance Imaging (MRI). Hippocampal subfield volumes were obtained using FreeSurfer. The Wechsler Intelligence Scale for Children-fifth edition measured working memory (WM). The ADHD-C group displayed significantly higher levels of problem behaviours and peer victimization (all, p < 0.001), compared to the other groups. Left Cornu Ammonis 3 (CA3) volume was a positive predictor of peer victimization (all, p < 0.013). Left CA3 volume was a positive predictor of WM and left Cornu Ammonis 4 (CA4) volume negatively predicted WM (all, p < 0.025). A cluster analysis revealed that children displaying symptoms of hyperactivity-impulsivity are the most at risk for peer victimization. Interventions focusing on minimizing peer victimization may aid in mitigating adverse downstream effects, and assist in promoting brain health and cognitive function.
... In addition to its involvement in regulating the stress response, the hippocampus is also a key structure in executive functioning 23 . In adult and aging populations, larger hippocampal volumes are associated with better performance on tasks of executive functioning, including working memory (WM) 23,24,25 . However, this same relationship is not consistently observed in children, with some evidence suggesting that children with larger hippocampal volumes perform worse on tasks of memory 24 . ...
... In adult and aging populations, larger hippocampal volumes are associated with better performance on tasks of executive functioning, including working memory (WM) 23,24,25 . However, this same relationship is not consistently observed in children, with some evidence suggesting that children with larger hippocampal volumes perform worse on tasks of memory 24 . Children with ADHD exhibit de cits in WM, however the relationship between hippocampal volume and WM ability in the ADHD population remains largely unexplored 26 . ...
... CA3 and CA4 are both key hippocampal sub elds that are involved in WM 41 . Larger volumes predict better cognitive function in adult samples 24,25,31 . Yet, ndings in children and adolescents provide inconsistent results to support this view. ...
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Background Children with ADHD are at risk of experiencing peer victimization, which is associated with delayed brain development and cognitive difficulties. We aimed to evaluate the relationship between problem behaviours, peer victimization, hippocampal morphology, and working memory in children with and without ADHD. Methods 218 typically developing participants (50.5% male) and 232 participants diagnosed with ADHD (77.6% male) were recruited. The ADHD group was subdivided into inattentive (ADHD-I) or combined (ADHD-C) type. The Child Behaviour Checklist measured problem behaviours and peer victimization. Hippocampal subfield volumes were obtained using Magnetic Resonance Imaging and the Wechsler Intelligence Scale for Children-fifth edition measured working memory (WM). Results The ADHD-C group displayed significantly higher rates of problem behaviours and peer victimization (all, p < 0.001). Left Cornu Ammonis 3 (CA3) volume was a positive predictor of levels of peer victimization (all, p < 0.013). Left CA3 volume was a positive predictor of WM and left Cornu Ammonis 4 (CA4) volume was a negative predictor (all, p < 0.025). A cluster analysis revealed that children displaying symptoms of hyperactivity-impulsivity are the most at risk for peer victimization. Conclusions Interventions focusing on minimizing peer victimization may aid in mitigating adverse downstream effects, and aid in promoting brain health and cognitive function.
... In particular, it does not require an independent database of normal control subjects. A disadvantage of the proportion method is that it often does not remove the association of ROIV with TIV, whereas the residual method does [5,7,[9][10][11]. ...
... The impact of the TIV adjustment method on regional brain volumetry has been studied before. However, previous studies entirely focused on group level analyses to characterize disease-specific effects [10,12,13], or the impact of age and gender on brain volumetric measures [4,8,[14][15][16][17][18][19], or associations between brain volumetric measures and cognitive performance [11]. The aim of the present study was to evaluate the impact of the TIV adjustment method on z-scores used to support the interpretation of regional brain volume estimates in single subject analyses of individual patients. ...
... The findings of the present study are in line with previous studies demonstrating that the proportion method often does not remove the association of ROIV estimates with TIV [5,7,[9][10][11]. The proportion method implicitly assumes that in healthy subjects, ROIV is proportional to the TIV, that is, ROIV = slope × TIV. ...
Article
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Purpose Total intracranial volume (TIV) is often a nuisance covariate in MRI-based brain volumetry. This study compared two TIV adjustment methods with respect to their impact on z-scores in single subject analyses of regional brain volume estimates. Methods Brain parenchyma, hippocampus, thalamus, and TIV were segmented in a normal database comprising 5059 T1w images. Regional volume estimates were adjusted for TIV using the residual method or the proportion method. Age was taken into account by regression with both methods. TIV- and age-adjusted regional volumes were transformed to z-scores and then compared between the two adjustment methods. Their impact on the detection of thalamus atrophy was tested in 127 patients with multiple sclerosis. Results The residual method removed the association with TIV in all regions. The proportion method resulted in a switch of the direction without relevant change of the strength of the association. The reduction of physiological between-subject variability was larger with the residual method than with the proportion method. The difference between z-scores obtained with the residual method versus the proportion method was strongly correlated with TIV. It was larger than one z-score point in 5% of the subjects. The area under the ROC curve of the TIV- and age-adjusted thalamus volume for identification of multiple sclerosis patients was larger with the residual method than with the proportion method (0.84 versus 0.79). Conclusion The residual method should be preferred for TIV and age adjustments of T1w-MRI-based brain volume estimates in single subject analyses.
... The hippocampus plays a major role in different aspects of learning and memory, including, but not limited to, working memory [1], declarative and procedural memory [2], and short-and long-term memory [3,4]. The size of the hippocampus is linked to higher levels of memory and learning [1,5]. Children and adults with larger hippocampal volumes show higher memory levels [5,6], mainly working memory. ...
... The size of the hippocampus is linked to higher levels of memory and learning [1,5]. Children and adults with larger hippocampal volumes show higher memory levels [5,6], mainly working memory. Working memory refers to a system for combining the storage and manipulation of information to perform complex cognitive activities [7,8]. ...
... Regarding our main effect, this is consistent with studies that have shown a centr role of hippocampal volume in memory [1]. A small hippocampal volume has been show to be linked to poor memory [1,5]. Individuals with large hippocampal volumes show higher memory levels than their peers with smaller hippocampal volumes [5,6]. ...
Article
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Aim: This study tested sex differences in the association between hippocampal volume and working memory of a national sample of 9-10-year-old children in the US. As the hippocampus is functionally lateralized (especially in task-related activities), we explored the results for the right and the left hippocampus. Methods: This is a cross-sectional study using the Adolescent Brain Cognitive Development (ABCD) Study data. This analysis included baseline ABCD data (n = 10,093) of children between ages 9 and 10 years. The predictor variable was right and left hippocampal volume measured by structural magnetic resonance imaging (sMRI). The primary outcome, list sorting working memory, was measured using the NIH toolbox measure. Sex was the moderator. Age, race, ethnicity, household income, parental education, and family structure were the covariates. Results: In the overall sample, larger right (b = 0.0013; p < 0.001) and left (b = 0.0013; p < 0.001) hippocampal volumes were associated with higher children's working memory. Sex had statistically significant interactions with the right (b = -0.0018; p = 0.001) and left (b = -0.0012; p = 0.022) hippocampal volumes on children's working memory. These interactions indicated stronger positive associations between right and left hippocampal volume and working memory for females compared to males. Conclusion: While right and left hippocampal volumes are determinants of children's list sorting working memory, these effects seem to be more salient for female than male children. Research is needed on the role of socialization, sex hormones, and brain functional connectivity as potential mechanisms that may explain the observed sex differences in the role of hippocampal volume as a correlate of working memory.
... It is reassuring to note that other studies have found either a negative or a nonlinear relationship between cognitive performance and HC subfield volume in cases where the opposite effect might be expected (Foster et al., 1999;Riggins et al., 2018;Schlichting, Guarino, Schapiro, Turk-Browne, & Preston, 2017;Van Petten, 2004). For example, Schlichting et al. (2017) tested children, adolescents, and adults using an associative inference test, whereby participants had to learn multiple pairs of novel objects, after which they were presented with an object and asked to select the object that it was paired with. ...
... I also found that the relationship between novelty preference on the VPC is sensitive to volume of the subiculum subfield of the HC, but with a negative relationship in young adults and a positive one in older adults, which could be explained by theoretical models of cortical pruning (Van Petten, 2004 One of the strongest genetic risk factors for sporadic AD is the presence of an epsilon-4 allele on the APOE gene (Bertram & Tanzi, 2008). The gene codes for a protein that binds to cholesterols and other lipids, and transports them around the body (Bu, 2009). ...
Thesis
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My thesis investigated whether performance on complex scene and object perceptual and memory tasks would be influenced by possession of different variants of the APOE gene. A particular focus was on the effect of the APOE-e4 allele on scene processing. APOE-e4 is known to increase risk for Alzheimer's disease (AD) in later life and is associated with structural and functional changes in the medial temporal lobe (MTL) and posteromedial cortex, regions known to be affected early in AD. Previous studies have shown sensitivity to spatial processing in AD, including difficulties in differentiating scene, but not object, stimuli (Lee et al., 2006), impairments remembering scenes over a delay (Bird et al., 2010), and deficits in navigation around spatial environments (Pengas et al., 2010). These findings suggest that difficulties with complex spatial processing may be a hallmark of AD, and that investigation of scene processing in individuals at greater risk of developing AD later in life may be of interest in understanding the genesis of these later life cognitive impairments. In Chapter 1, I provide an overview of relevant literature on the APOE gene and its relationship to AD, and discuss experiments which have demonstrated brain and behaviour differences between APOE-e4 carriers and non-carriers. I interpret these findings in the context of recent models of memory which focus on representational networks, and where distinctions between scene and object processing are a key feature (Bussey & Saksida, 2007; Graham, Barense, & Lee, 2010; Murray, Wise, & Graham, 2017). The subsequent chapters describe experiments which aimed to extend the research described in Chapter 1 by investigating scene perception and memory in carriers of different APOE alleles in early- and mid-adulthood. In Chapter 2, I describe findings from applying a novel conjunctive learning task, in which participants were required to discriminate between objects and scenes. In Chapter 3, I report results from applying a new visual paired-comparison task in the same group of participants. Chapter 4 extends the approach outlined in Chapter 3, using the visual paired-comparison task in middle- aged participants, again focusing on the comparison of performance in groups with different APOE genotypes. Finally, in Chapter 5, I assess how performance in the tasks used in Chapters 2-4 are related to the volumes of brain regions (in the MTL and extrastriate cortex). As these have been strongly linked to object and scene perception and memory, I was interested in whether volume would be associated with performance on my new tasks. The final chapter summarises the experimental findings from Chapters 2-5 and explains how these build upon our current body of knowledge about how the APOE gene affects cognition in both early- and mid-adulthood.
... Adequate nutrition is very important in physical and mental development of humans. Poor nutrition has been shown to lead to reduced productivity and increased susceptibility to disease as a consequence of reduced immunity, as well as impaired physical and mental development [1]. e nutritional status of individuals is greatly influenced by dietary intake as well as physical activity. ...
... e nutritional status of individuals is greatly influenced by dietary intake as well as physical activity. Young adults may be particularly affected by poor dietary choices due to spouts of physical growth and the development of higher cognitive functions, such as abstraction and criticality [1,2]. Previous studies have demonstrated that the stress of academic activities predisposes university students to adoption of unhealthy eating habits, such as meal skipping, snacking, and frequent fast-food consumption [3]. ...
Article
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Background: The stress of academic life may predispose young adults to poor dietary habits, which could potentially precipitate nutritional deficiencies, such as iron deficiency. This study evaluated factors predictive of optimal iron stores as well as changes in haematological parameters over the course of an academic year in a cohort of tertiary students. Materials and methods: The repeated-measure cohort study recruited 117 undergraduate students from September 2018 to May 2019. Venous blood samples were drawn for full blood count estimation, qualitative glucose-6-phosphate dehydrogenase (G6PD) status, haemoglobin variants, and blood group determination during the first 2 weeks of semester 1. However, anthropometric parameters as well as full blood counts were determined for each participant during the first week and last week of semesters 1 and 2. Additionally, semistructured questionnaires were used to capture sociodemographic data. Also, serum ferritin was estimated for each participant using enzyme-linked immunosorbent assay. Results: Overall, 23.1% and 15.5% of participants inherited G6PD defect (G6PDd) or haemoglobin variants, respectively. However, group O (68/117; 58.1%) was the predominant ABO blood group and an overwhelming 90.6% (106/117) inherited Rh D antigen. The prevalence of anaemia increased from 20% at the beginning of the first semester to 45.1% at the latter part of the second semester. G6PDd participants had significantly higher median serum ferritin than G6PD normal participants (p = 0.003). Also, a significantly higher proportion of females were iron depleted (25% vs. 2.3%) or iron deficient (14.3% vs. 9.3%) compared to males. Moreover, being male, G6PD deficient, or 21-25 years was associated with increased odds of participants having optimal serum ferritin levels. Conclusion: The progression of anaemia prevalence from mild to severe public health problem over the course of one academic year should urgently be addressed.
... Indeed, such a finding has previously been reported in young healthy adults in relation to meta-cognitive ability (Allen et al., 2017). Here, however, we found no relationships between hippocampal grey matter myelination or iron content and performance on scene imagination, autobiographical memory recall, future thinking or spatial navigation tasks, aligning with previous null results relating to hippocampal grey matter volume more generally Maguire et al., 2003;Van Petten, 2004;Weisberg et al., 2019). Non-significant results can, of course, be difficult to interpret, and an absence of evidence is not necessarily evidence of absence. ...
... In older participants, for example, associations between hippocampal grey matter volume and performance on autobiographical and navigation tasks have been identified (e.g. Hedden et al., 2014;Moffat et al., 2006), despite less reliable evidence for such relationships in healthy young adults Maguire et al., 2003;Van Petten, 2004;Weisberg et al., 2019). Changes in the extent of grey matter myelination and iron content have been documented with ageing (e.g. ...
Article
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Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals.
... Like most brain structures, apart from brainstem, hippocampal volume decreases with age [18][19][20][21]. It has been hypothesized that reduced episodic memory with older age is mediated by hippocampal volume loss [18,22], and that the hippocampal volume loss is partly a consequence of increased brain amyloidosis [23]. ...
... However, there remained also a direct effect from age to episodic memory that was not mediated by hippocampal volume. In a number of previous cross-sectional analyses [20,57], the correlation between hippocampal volume and episodic memory disappeared when correcting for age. Hence, other factors must contribute to the relation between age and episodic memory decline than medial temporal lobe volume. ...
Article
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Background We examined in cognitively intact older adults the relative weight of cognitive, genetic, structural and amyloid brain imaging variables for predicting cognitive change over a 4-year time course. Methods One hundred-eighty community-recruited cognitively intact older adults (mean age 68 years, range 52–80 years, 81 women) belonging to the Flemish Prevent Alzheimer’s Disease Cohort KU Leuven (F-PACK) longitudinal observational cohort underwent a baseline evaluation consisting of detailed cognitive assessment, structural MRI and ¹⁸ F-flutemetamol PET. At inclusion, subjects were stratified based on Apolipoprotein E ( APOE ) ε 4 and Brain-Derived Neurotrophic Factor ( BDNF ) val66met polymorphism according to a factorial design. At inclusion, 15% were amyloid-PET positive (Centiloid >23.4). All subjects underwent 2-yearly follow-up of cognitive performance for a 4-year time period. Baseline cognitive scores were analysed using factor analysis. The slope of cognitive change over time was modelled using latent growth curve analysis. Using correlation analysis, hierarchical regression and mediation analysis, we examined the effect of demographic (age, sex, education) and genetic variables, baseline cognition, MRI volumetric (both voxelwise and region-based) as well as amyloid imaging measures on the longitudinal slope of cognitive change. Results A base model of age and sex explained 18.5% of variance in episodic memory decline. This increased to 41.6% by adding baseline episodic memory scores. Adding amyloid load or volumetric measures explained only a negligible additional amount of variance (increase to 42.2%). A mediation analysis indicated that the effect of age on episodic memory scores was partly direct and partly mediated via hippocampal volume. Amyloid load did not play a significant role as mediator between age, hippocampal volume and episodic memory decline. Conclusion In cognitively intact older adults, the strongest baseline predictor of subsequent episodic memory decline was the baseline episodic memory score. When this score was included, only very limited explanatory power was added by brain volume or amyloid load measures. The data warn against classifications that are purely biomarker-based and highlight the value of baseline cognitive performance levels in predictive models.
... Instead, the study reported significant negative relationships between hippocampal volume and memory performance in children, adolescents, and young adults. 39 In studies of older adults, evidence for a positive relationship between hippocampal size and episodic memory ability was found to be weak. 39 The investigation of the slope of best-fit regression line revealed a nonlinear relationship between hippocampal volume and verbal memory in which a fixed-rate decrease in hippocampal volume predicted an accelerated decrease in verbal memory ( Figure 3). ...
... 39 In studies of older adults, evidence for a positive relationship between hippocampal size and episodic memory ability was found to be weak. 39 The investigation of the slope of best-fit regression line revealed a nonlinear relationship between hippocampal volume and verbal memory in which a fixed-rate decrease in hippocampal volume predicted an accelerated decrease in verbal memory ( Figure 3). The slopes for several subfields were increasing faster, compared to whole hippocampus, as average volumes dropped. ...
Article
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Introduction: Hippocampal subfield volumes are more closely associated with cognitive impairment than whole hippocampal volume in many diseases. Both memory and whole hippocampal volume decline after stroke. Understanding the subfields' temporal evolution could reveal valuable information about post-stroke memory. Methods: We sampled 120 participants (38 control, 82 stroke), with cognitive testing and 3T-MRI available at 3 months and 3 years, from the Cognition and Neocortical Volume after Stroke (CANVAS) study. Verbal memory was assessed using the Hopkins Verbal Learning Test-Revised. Subfields were delineated using FreeSurfer. We used partial Pearson's correlation to assess the associations between subfield volumes and verbal memory scores, adjusting for years of education, sex, and stroke side. Results: The left cornu ammonis areas 2/3 and hippocampal tail volumes were significantly associated with verbal memory 3-month post-stroke. At 3 years, the associations became stronger and involved more subfields. Discussion: Hippocampal subfield volumes may be a useful biomarker for post-stroke cognitive impairment.
... Studies indicate that synaptic plasticity impairment in specific areas of the CNS, particularly the hippocampus, has been linked to mood disorders that usually occur during adolescence or early adulthood, which have major cognitive and emotional symptoms [7,8]. Substantial evidence suggests that the hippocampus plays a crucial role in memory formation, and memory dysfunction has been linked to suicide attempts [9][10][11]. The hippocampus is also involved in other complex behaviors, such as regulating emotional responses, executive function, sensorimotor integration, and goal-directed activity, the alterations of which may be associated with suicide attempts [12]. ...
Article
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Suicidal behavior is a leading cause of death and often commences during adolescence/young adulthood (15~29 years old). The hippocampus, which consists of multiple functionally specialized subfields, may contribute to the pathophysiology of depression and suicidal behavior. We aimed to investigate the differences of hippocampal subfield volume between major depressive disorder (MDD) patients with and without suicide attempts and healthy controls in adolescents and young adults. A total of 40 MDD suicide attempters (MDD+SA), 27 MDD patients without suicide attempt (MDD-SA), and 37 healthy controls (HC) were recruited. High-resolution T1 MRI images were analyzed with the automated hippocampal substructure module in FreeSurfer 6.0. Volume differences among the groups were analyzed by a generalized linear model controlling for intracranial cavity volume (ICV). The relationship between hippocampal subfield volumes and clinical characteristics (HAM-D and SSI scores) was assessed using two-tailed partial correlation controlling for ICV in MDD+SA and MDD-SA. We found that MDD-SA had significantly smaller bilateral hippocampal fissure volume than HC and MDD+SA. No significant correlation was observed between hippocampal subfield volume and clinical characteristics (HAM-D and SSI scores) in MDD+SA and MDD-SA. Adolescent/young adult suicide attempters with MDD suicide attempters have larger bilateral hippocampal fissures than depressed patients without suicide attempts, independently from clinical characteristics. Within the heterogeneous syndrome of major depressive disorder that holds a risk for suicidality for subgroups, hippocampal morphology may help to explain or possibly predict such risk, yet longitudinal and functional studies are needed for understanding the biological mechanisms underlying.
... To elucidate the underlying neural basis of neuropsychological tests, previous studies have examined the brain regional structures and functions highly associated with behavioral performance (Bayram, Caldwell, & Banks, 2018;Genon, Reid, Langner, Amunts, & Eickhoff, 2018;Mortamais et al., 2017). However, the previous studies typically narrowed down the region of interest within a focal brain structure (e.g., hippocampus) or averaged out overall brain measures features into fewer predictors (Charroud et al., 2016;Duchek et al., 2013;Shaw, Schultz, Sperling, & Hedden, 2015;Van Petten, 2004). While pinpointing or averaging the candidate neural correlate makes the theoretical account succinct, it is hard to discern whether the focally identified brain correlates are an optimal and exclusively relevant unit in explaining individual differences of cognitive function. ...
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Neuropsychological test is an essential tool in assessing cognitive and functional changes associated with late-life neurocognitive disorders. Despite the utility of the neuropsychological test, the brain-wide neural basis of the test performance remains unclear. Using the predictive modeling approach, we aimed to identify the optimal combination of functional connectivities that predicts neuropsychological test scores of novel individuals. Resting-state functional connectivity and neuropsychological tests included in the OASIS-3 dataset (n = 428) were used to train the predictive models, and the identified models were iteratively applied to the holdout internal test set (n = 216) and external test set (KSHAP, n = 151). We found that the connectivity-based predicted score tracked the actual behavioral test scores (r = 0.08-0.44). The predictive models utilizing most of the connectivity features showed better accuracy than those composed of focal connectivity features, suggesting that its neural basis is largely distributed across multiple brain systems. The discriminant and clinical validity of the predictive models were further assessed. Our results suggest that late-life neuropsychological test performance can be formally characterized with distributed connectome-based predictive models, and further translational evidence is needed when developing theoretically valid and clinically incremental predictive models.
... The WM-apparent thickness effects in development were relatively widespread, and did not survive inclusion of mean cortical thickness as covariate, suggesting that the effects are global rather than local. Even though there may be a mechanistic relationship between structural brain maturation and aging and changes in WM performance, it is not realistic to expect an anatomical one-to-one correspondence as structure-function relationships in general, especially in healthy groups, tend not to be strong (Van Petten, 2004). Successful completion of a WM task will depend on a range of different processes in the brain, where some will be more specific to WM and some more generally involved in demanding cognitive tasks, i.e. attention and control functions. ...
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Working memory (WM) supports several higher-level cognitive abilities, yet we know less about factors associated with development and decline in WM compared to other cognitive processes. Here, we investigated lifespan changes in WM capacity and their structural brain correlates, using a longitudinal sample including 2358 magnetic resonance imaging (MRI) scans and WM scores from 1656 participants (4.4–86.4 years, mean follow-up interval 4.3 years). 8764 participants (9.0–10.9 years) with MRI, WM scores and genetic information from the Adolescent Brain Cognitive Development study were used for follow-up analyses. Results showed that both the information manipulation component and the storage component of WM improved during childhood and adolescence, but the age-decline could be fully explained by reductions in passive storage capacity alone. Greater WM function in development was related to apparent thinner cortex in both samples, also when general cognitive function was accounted for. The same WM-apparent thickness relationship was found for young adults. The WM-thickness relationships could not be explained by SNP-based co-heritability or by socioeconomic status. A larger sample with genetic information may be necessary to disentangle the true gene-environment effects. In conclusion, WM capacity changes greatly through life and has anatomically extended rather than function-specific structural cortical correlates.
... Having data on likely etiology would also provide useful information about impairment rates and neuroanatomical correlates in specific patient populations, which is a future direction. However, as demonstrated by a large body of literature, associations between memory performance and hippocampal volumes are not unique to one particular disease process and are demonstrated in cognitive normal individuals as well (Van Petten, 2004). ...
Article
Objective Story memory tasks are among the most commonly used memory tests; however, research suggests they may be less sensitive to memory decline and have a weaker association with hippocampal volumes than list learning tasks. To examine its utility, we compared story memory to other memory tests on impairment rates and association with hippocampal volumes. Method Archival records from 1617 older adults (M age = 74.41, range = 65–93) who completed the Wechsler Memory Scale – 4 th edition (WMS-IV) Logical Memory (LM), Hopkins Verbal Learning Test – Revised (HVLT-R), and Brief Visuospatial Memory Test – Revised (BVMT-R) as part of a clinical neuropsychological evaluation were reviewed. Scores >1.5 SD below age-adjusted means were considered impaired, and frequency distributions were used to examine impairment rates. A subset of participants ( n = 179) had magnetic resonance imaging (MRI) data that underwent image quality assessment. Partial correlations and linear regression analyses, accounting for age, education, and total intracranial volume (TIV), examined associations between memory raw scores and hippocampal volumes. Results For delayed recall, nearly half of the sample was impaired on HVLT-R (48.8%) and BVMT-R (46.1%), whereas a little more than a third was impaired on LM (35.7%). Better performance on all three measures was related to larger hippocampal volumes ( r ’s =. 26–.43, p’s < .001). Individually adding memory scores to regression models predicting hippocampal volumes improved the model fit for all measures. Conclusions Despite findings suggesting that story memory is less sensitive to memory dysfunction, it was not differentially associated with hippocampal volumes compared to other memory measures. Results support assessing memory using different formats and modalities in older adults.
... In support, a previous study reported a significant relationship between lower BFCN volumes and lower IQ in preterm-born subjects, but no corresponding association was found in term-born individuals [57]. On a similar note, while variance in hippocampal volumes has been linked with memory performance in several neurologic conditions [83,84], such associations appear to be lacking in healthy subjects [85]. Finally, the association seen in patients might be amplified by the involvement of other attentional structures that present with lower volumes in patients (i.e., ACC, insula) [76,77]. ...
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A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients’ attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)–based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients’ impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients’ attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN.
... We additionally found that volume of the right hippocampus positively predicted overnight change in discrimination performance, which supports the idea that domain-general memory consolidation processes are at least partially involved in the learning trajectory of non-native speech sounds. This is consistent with some findings in the memory consolidation literature, in which a larger hippocampus is related to better delayed or sometimes even immediate recall in patients with Alzheimer's disease (Köhler et al., 1998) or healthy young adults (Pohlack et al., 2014; but see Van Petten, 2004). Learning non-native speech sounds is an interesting problem of learning and memory because of the difficulty and large amount of individual variability seen in adult learners. ...
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Studies of non-native speech sound learning report considerable individual variability in learning new sounds and retaining them in memory. The current study tested whether individual variation in brain structure (measured using MRI) accounts for differences in learning or retention of non-native speech sounds. Fifty-seven participants were tested on identification and discrimination of difficult non-native speech sounds in the evening before training, after training, and tested again the next morning. Surface area and volume of the left superior temporal gyrus positively predicted discrimination learning, whereas surface area of the left transverse temporal gyrus negatively predicted overnight improvement of identification. Hippocampal volume as well as gyrification of bilateral transverse temporal gyri positively predicted overnight improvement of discrimination. Findings suggest that individual differences in non-native speech sound learning can be traced to differences in brain structure supporting perception, while differences in retention are linked to the structure of hippocampal regions important for memory consolidation.
... Memory decline is one of the most common age-related cognitive impairments reported by older adults (Buckner, 2004). For example, age-related memory decline has been commonly reported by studies investigating retrospective memory (Sliwinski et al., 2003), episodic memory (Van Petten, 2004) and spatial memory (Erickson et al., 2010). The rapid growth of the older population and corresponding societal burden necessitates the identification of preventive measures and interventions that can ameliorate age-related cognitive decline. ...
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Prospective memory (PM), which enables one to remember to carry out delayed intentions, is crucial for everyday functioning. PM commonly deteriorates upon cognitive decline in older adults, but several studies have shown that PM in older adults can be improved by training. The current study aimed to summarise this evidence by conducting a qualitative systematic analysis and quantitative meta-analysis of the effects of PM training in older adults, for which systematic searches were conducted across seven databases (Cochrane Library, Embase, PubMed, PsycInfo, Web of Science, CINAHL and Scopus). Forty-eight studies were included in the qualitative analysis, and 43% of the assessed PM training interventions showed positive gains in enhancing PM. However, the methodological quality varied across the studies, with 41% of the non-randomised control trials (non-RCTs) rated as having either serious or critical risk of bias. Therefore, only 29 RCTs were included in the subsequent quantitative meta-analysis. We found a significant and moderate immediate efficacy (Hedges’ g = 0.54) of PM training in enhancing PM performance in older adults, but no significant long-term efficacy (Hedges’ g = 0.21). Two subgroup analyses also revealed a robust training efficacy across the study population (i.e., healthy and clinical population) and the number of training sessions (i.e., single session and programme-based). Overall, this study provided positive evidence to support PM training in older adults. Further studies are warranted to explore the mechanisms by which PM training exerts its effects, and better-quality RCTs are needed to provide more robust evidence supporting our findings.
... None of these models revealed significant interaction effects. The existing literature on this topic is widely variable, especially for elderly populations, as demonstrated by a metaanalysis that examined 33 studies (Van Petten, 2004). ...
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Objective: To examine the relationship between depression and cognition, genetic risk, and hippocampal differences in a sample of older adults with a history of traumatic brain injury (TBI). Method: Participants were 85 males and 35 females (91 Caucasian, 29 African-American) with a mean age of 65.04 (±8.27) years and a history of moderate, severe, or complicated mild TBI. Participants were an average of 9.33 (±7.27) years post injury (range: 0.78-45.63). Participants underwent genetic testing, a comprehensive neuropsychological battery, surveys, and a subset underwent MRI scanning. Results: Apolipoprotein E (APOE) e4 carrier status predicted clinically significant depressive symptomatology on the Geriatric Depression Scale (GDS) with an odds ratio of 3.63, 95% CI [1.33, 9.29]. GDS was not associated with scores on measures of executive function, list learning recall, or retention. Although GDS score was initially associated with poorer confrontation naming scores and story memory recall, these effect sizes were small, and this variance was better accounted for by age and cognitive reserve. Higher GDS scores were also associated with decreased hippocampal volume. Conclusions: APOE carrier status was predictive of depression in a sample of older adults with a history of TBI. Depressive symptoms were also associated with decreased hippocampal volume but did not predict cognitive deficits in the examined domains beyond the effects of cognitive reserve. Despite the relationship between GDS and biological risks for decline, depressive symptoms in this population showed no direct relationship with cognitive decline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
... Developmental differences in memory abilities are accompanied by age-dependent changes in the underlying brain structures and functions during maturation and senescence (Li et al., 2004;Ofen and Shing, 2013;Sander et al., 2020a;Shing et al., 2010;Van Petten, 2004). Specifically, functional differences during encoding may influence the specificity of mnemonic contents and may thus account for performance differences across the lifespan (Bowman et al., 2019;Fandakova et al., 2019;Morcom, 2015;Park et al., 2013;Sander et al., 2020b). ...
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The specificity with which past experiences can be remembered varies across the lifespan, possibly due to differences in how precisely information is encoded. Memory formation can be investigated through repetition effects, the common finding that neural activity is altered when stimuli are repeated. However, whether differences in this indirect measure of memory formation relate to lifespan differences in memory specificity has not yet been established. In the present study, we examined repetition effects in event-related potentials and their relation to recognition. During incidental encoding, children (aged 7–9 years), young adults (18–30 years), and older adults (65–76 years) viewed repeated object images from different categories. During subsequent recognition, we distinguished memory for the specific items versus the general categories. We identified repetition suppression in all age groups, and repetition enhancement for adults. Furthermore, individual item recognition performance comprising lure discrimination was positively associated with the magnitude of the neural repetition effects, which did not differ between groups, indicating common neural mechanisms of memory formation. Our findings demonstrate that neural repetition effects reflect the formation of highly specific memory representations and highlight their significance as a neural indicator of individual differences in episodic memory encoding across the lifespan.
... This reduction is often attributed to neuronal and dendritic loss but the exact mechanisms behind this phenomenon remain unclear [56]. Others have highlighted contradictory results when investigating agerelated changes in hippocampal subfield volumes, with some reporting no evidence of association and others reporting associations limited to specific subfields [56][57][58][59]. Until recently, inadequacies in imaging resolution and available techniques have prevented accurate segmentation of the subfields and have contributed to discrepancies between studies [60]. ...
Article
Age-related alteration in neural stem cell function is linked to neurodegenerative conditions and cognitive decline. In rodents, this can be reversed by exposure to a young systemic milieu and conversely, the old milieu can inhibit stem cell function in young rodents. In this study, we investigated the in vitro effect of the human systemic milieu on human hippocampal progenitor cells (HPCs) using human serum from early adulthood, mid-life and older age. We showed that neuroblast number following serum treatment is predictive of larger dentate gyrus, CA3, CA4 and whole hippocampus volumes and that allogeneic human serum from asymptomatic older individuals induced a two-fold increase in apoptotic cell death of HPCs compared with serum from young adults. General linear models revealed that variability in markers of proliferation and differentiation was partly attributable to use of antihypertensive medication and very mild cognitive decline among older subjects. Finally, using an endophenotype approach and whole-genome expression arrays, we showed upregulation of established and novel ageing molecular hallmarks in response to old serum. Serum from older subjects induced a wide range of cellular and molecular phenotypes, likely reflecting a lifetime of environmental exposures. Our findings support a role for the systemic enviroment in neural stem cell maintenance and are in line with others highlighting a distinction between neurobiological and chronological ageing. Finally, the herein described serum assay can be used by future studies to further analyse the effect of environmental exposures as well as to determine the role of the systemic environment in health and disease.
... Accordingly, we included ICV as a covariate for regression control to enable the removal of individual variability that can be explained by brain size (Narvacan et al., 2017;Sawiak et al., 2018;Herting et al., 2014). Researchers have also demonstrated that the size of the amygdala often scales with the GMV (Van Petten, 2004;Rice et al., 2014). We thus accounted for brain size by controlling for the GMV in the GAMMs. ...
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The developmental pattern of the amygdala throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. To investigate the impact of volume extraction methods on amygdala volume, we compared FreeSurfer, FSL and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, which we used as the’gold standard’, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurfer and volBrain) and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae, and volBrain produced smaller amygdalae while FSL demonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project. Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to these trajectories, the shapes of developmental curves were similar when using the volBrain derived volumes. FreeSurfer derived trajectories had more nonlinearities and appeared flatter. FSL derived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves curves between manual tracing and the automatic methods (except FSL). Our findings revealed steady growth of the human amygdala, mirroring its functional development across the school age. Methodological improvements are warranted for current automatic tools to achieve more accurate tracing of the amygdala at school age, calling for next generation tools.
... An early meta-analysis of 33 studies on the association between hippocampal volume and memory (Van Petten, 2004) favored a "smaller is better" rather than a "bigger is better" hypothesis in childhood, adolescence, and young adulthood. More recent studies that tested for associations between memory and hippocampal subfield volumes in children using high-resolution MRI (summarized in Table S1) paint a less straightforward picture. ...
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Cross-sectional findings suggest that volumes of specific hippocampal subfields increase in middle childhood and early adolescence. In contrast, a small number of available longitudinal studies reported decreased volumes in most subfields over this age range. Further, it remains unknown whether structural changes in development are associated with corresponding gains in children’s memory. Here we report cross-sectional age differences in children’s hippocampal subfield volumes together with longitudinal developmental trajectories and their relationships with memory performance. In two waves, 109 participants aged 6 to 10 years (wave 1: MAge=7.25, wave 2: MAge=9.27) underwent high-resolution magnetic resonance imaging to assess hippocampal subfield volumes (imaging data available at both waves for 65 participants) and completed tasks assessing hippocampus dependent memory processes. We found that cross-sectional age-associations and longitudinal developmental trends in hippocampal subfield volumes were discrepant, both by subfields and in direction. Further, volumetric changes were largely unrelated to changes in memory, with the exception that increase in subiculum volume was associated with gains in spatial memory. Longitudinal and cross-sectional patterns of brain-cognition couplings were also discrepant. We discuss potential sources of these discrepancies. This study underscores that children’s structural brain development and its relationship to cognition cannot be inferred from cross-sectional age comparisons.
... We additionally found that volume of the right hippocampus positively predicted overnight change in discrimination performance, which supports the idea that domain-general memory consolidation processes are at least partially involved in the learning trajectory of non-native speech sounds. This is consistent with some findings in the memory consolidation literature, in which a larger hippocampus is related to better delayed or sometimes even immediate recall in patients with Alzheimer's disease (Köhler et al., 1998) or healthy young adults (Pohlack et al., 2014; but see Van Petten, 2004). Learning non-native speech sounds is an interesting problem of learning and memory because of the difficulty and large amount of individual variability seen in adult learners. ...
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Listeners perceive speech sounds categorically. While group-level differences in categorical perception have been observed in children or individuals with reading disorders, recent findings suggest that typical adults vary in how categorically they perceive sounds. The current study investigated neural sources of individual variability in categorical perception of speech. Fifty-seven participants rated phonetic tokens on a visual analogue scale; categoricity and response consistency were measured and related to measures of brain structure from MRI. Increased surface area of the right middle frontal gyrus predicted more categorical perception of a fricative continuum. This finding supports the idea that frontal regions are sensitive to phonetic category-level information and extends it to make behavioral predictions at the individual level. Additionally, more gyrification in bilateral transverse temporal gyri predicted less consistent responses on the task, perhaps reflecting subtle variation in language ability across the population.
... For instance, in fMRI studies, the vmPFC has been shown to be related to subjects' judgements about the attractiveness of destination pictures and subsequent destination visit intentions (Al-Kwifi, 2015). The hippocampus is involved in memory encoding and retrieval (Van Petten, 2004). EEG studies suggest that ERP components are associated with attention (Bastiaansen et al., 2018), unconscious perception (Hsu & Chen, 2020), and experience-based preferences (Boksem & Smidts, 2015). ...
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This paper provides a critical review of studies using neurophysiological measures in tourism and hospitality. Among 145 articles covering 20 years of research, 16 studies applied either electroencephalography (EEG), functional magnetic resonance imaging (fMRI), or skin conductance (SC) measures in tourism and hospitality settings. Results show that, in general, (1) EEG studies investigated the relationships between EEG components and attention/emotion induced by destination advertisements; (2) fMRI studies examined the correlation between brain area activation and behavior (e.g., visit intention); and (3) SC studies focused on emotional responses to tourism stimuli. Neurophysiological techniques are theoretically and practically useful in tourism and hospitality: these tools uncover subjects’ objective, unbiased, and real-time responses to provide academic insight and guide industry practitioners’ decisions. Directions for future research are proposed along with solutions to address the current limitations of neuroscience measures in tourism and hospitality applications.
... Findings from functional magnetic resonance imaging (fMRI) studies of cognitively normal adults also suggest that select subfields (i.e., DG, CA3, CA1) may be more central to encoding and retrieval processes than other subfields (Carr et al., 2017;Hrybouski et al., 2019;Suthana et al., 2015). Based on these findings, it is possible that some studies have not found an association between whole hippocampal volume and memory performances in MCI (Clark et al., 2020;La et al., 2019;Van Petten, 2004), if hippocampal volume loss is driven by select subfields that have little consequence to the specific memory processes measured (Tamnes, Bos, van de Kamp, Peters, & Crone, 2018). Alternatively, the absence of hippocampal-memory associations may reflect different causes of MCI that are less detrimental to specific memory processes or hippocampal integrity more generally. ...
Article
Background Evidence suggests that select hippocampal subfields are implicated in the initial stages of Alzheimer’s disease (AD) and are selectively involved in objective memory. Less is known whether subfields are associated with informant-reported memory difficulties of individuals with a diagnosis of mild cognitive impairment (MCI). Method Data from 56 participants with a diagnosis of amnestic MCI were included in the present study. To test whether FreeSurfer derived hippocampal subfields (CA1–4, subiculum, presubiculum, and dentate gyrus) were associated with objective (learning and delayed recall) and informant-reports of memory difficulties, we used multiple linear regression analysis. Subfields were adjusted for total intracranial volume, and age, sex, and years of education were included as covariates in all models. Results Larger presubiculum, subiculum, and CA4/dentate gyrus volumes were associated with higher delayed recall scores, and larger subiculum and CA4/dentate gyrus volumes were associated with fewer informant-reports of memory difficulties. There were no statistically significant associations between subfields and learning scores. Discussion Findings from the present study support the idea that difficulties with memory-dependent everyday tasks in older adults with MCI may signal a neurodegenerative process while increasing understanding of subfields correlates of these memory-specific functional difficulties. Continued investigations into identifying patterns of subfield atrophy in AD may aid early identification of those at higher risk of dementia conversion while advancing precision medicine.
... Accordingly, we included ICV as a co-variate for regression control to enable the removal of individual variability that can be explained by brain size (Narvacan et al., 2017;Sawiak 210 et al., 2018;Herting et al., 2014). Researchers have also demonstrated that the size of the amygdala often scales with the GMV (Van Petten, 2004;Rice et al., 2014). We thus accounted for brain size by controlling for the GMV in the GAMMs. ...
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Full-text available
The developmental patterns of the amygdala in children and adolescences have been inconsistent in previous studies. This discrepancy may be partly due to methodological differences in segmentation by tracing the human amygdala. To investigate the impact of tracing methods on amygdala volume, we compared FreeSurfer and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, as the 'Gold Standard', exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae while volBrain produced smaller amygdalae. This tracing bias was larger for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project (total 427 magnetic resonance imaging scans from 198 participants aged 6-17 years at baseline). Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Comparing these trajectories, the shapes of developmental trajectories were similar when using the volBrain derived volumes while FreeSurfer led to more nonlinear and flattened, but statistically non-significant, growth patterns. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves across the three methods. Our findings revealed steady growth of the human amygdala, mirroring the functional development across the school age. We argue that methodological improvements are warranted for current automatic tools to achieve more accurate tracing of the amygdala at school age.
... Given previous demonstrations of age-differential relationships between brain function and structure in younger and older adults ( Burzynska et al., 2012 ;Koen & Rugg, 2019 ;Rieckmann et al., 2018 ;Van Petten, 2004 ), we performed age-stratified analyses with 2 groups of younger ( < 65 years) and older (65 years and above), in addition to whole sample analyses. In addition, moderation analyses were conducted, investigating age as a moderator of the WMI -PI relationships. ...
Article
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Proactive interference (PI)occurs when old information interferes with newly acquired information and has been suggested as a major cause of forgetting in working memory. In this study, we investigate cross-sectional (N=267) and longitudinal (N=148) associations between PI and white-matter integrity (WMI) using diffusion-weighted imaging in an adult life-span sample (25-80 yrs; Mage=60.15; 138 female). Older age was related to higher PI and lower WMI. Cross-sectional analyses showed associations between PI and WMI spanning several white-matter tracts as well as globally, suggesting that the age-related decline in PI may be driven primarily by global changes in WMI. Furthermore, longitudinal changes in PI were shown to be negatively correlated with concurrent changes in WMI in the fornix. Mediation analyses showed that WMI mediated the relationship between age and PI only in older adults, indicating that WMI becomes increasingly connected to cognitive functioning with increasing age. This is the first demonstration of WMI decline contributing to the age-related decline in PI.
... Using higher resolution scans to examine hippocampal subfields, such as CA2,3/DG and subiculum, may be more appropriate to capture specific relationships to hippocampal-dependent processes, such as AM (Barry & Maguire, 2019;Palombo et al., 2018). It is also possible that more extreme conditions, such as expertise (Weisberg & Ekstrom, 2021) or pathology (Van Petten, 2004) are needed to detect associations. ...
Article
Recollection of personal past events differs across the lifespan. Older individuals recall fewer episodic details and convey more semantic information than young. Here we examine how gray matter volumes in temporal lobe regions integral to episodic and semantic memory (hippocampus and temporal poles, respectively) are related to age differences in autobiographical recollection. Gray matter volumes were obtained in healthy young (n = 158) and old (n = 105) adults. The temporal pole was demarcated and hippocampus segmented into anterior and posterior regions to test for volume differences between age groups. The Autobiographical Interview was administered to measure episodic and semantic autobiographical memory. Volume associations with episodic and semantic autobiographical memory were then assessed. Brain volumes were smaller for older adults in the posterior hippocampus. Autobiographical memory was less episodic and more semanticized for older versus younger adults. Older adults also showed positive associations between temporal pole volumes and episodic autobiographical recall; in the young, temporal pole volume was positively associated with performance on standard laboratory measures of semantic memory. Exploratory analyses revealed that age‐related episodic autobiographical memory associations with anterior hippocampal volumes depended on sex. These findings suggest that age differences in brain structures implicated in episodic and semantic memory may portend reorganization of neural circuits to support autobiographical memory in later life.
... Healthy aging involves cortical thinning across the brain, with relative sparing of the lateral temporal cortex and the entorhinal cortex, while the hippocampus declines at increasingly higher rates with aging [66,67]. There appears to be a complex relationship between memory and hippocampal volume that is age-and test-dependent [68]. In depressed samples, hippocampus is consistently found to be reduced compared to nondepressed controls [69]. ...
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Growing evidence supports the concept that bidirectional brain–gut microbiome interactions play an important mechanistic role in aging, as well as in various neuropsychiatric conditions including depression. Gray matter volume (GMV) deficits in limbic regions are widely observed in geriatric depression (GD). We therefore aimed to explore correlations between gut microbial measures and GMV within these regions in GD. Sixteen older adults (>60 years) with GD (37.5% female; mean age, 70.6 (SD = 5.7) years) were included in the study and underwent high-resolution T1-weighted structural MRI scanning and stool sample collection. GMV was extracted from bilateral regions of interest (ROI: hippocampus, amygdala, nucleus accumbens) and a control region (pericalcarine). Fecal microbiota composition and diversity were assessed by 16S ribosomal RNA gene sequencing. There were significant positive associations between alpha diversity measures and GMV in both hippocampus and nucleus accumbens. Additionally, significant positive associations were present between hippocampal GMV and the abundance of genera Family_XIII_AD3011_group, unclassified Ruminococcaceae, and Oscillibacter, as well as between amygdala GMV and the genera Lachnospiraceae_NK4A136_group and Oscillibacter. Gut microbiome may reflect brain health in geriatric depression. Future studies with larger samples and the experimental manipulation of gut microbiome may clarify the relationship between microbiome measures and neuroplasticity. Keywords: gray matter volume (GMV); gut–brain axis; geriatric depression (GD)
... The age of controlled subjects in the previous study (Bigler 537 et al., 1997) ranged from 16-year-old to 65-year-old. Such a wide age window may further 538 compound the relationship of the hippocampus and temporal horn considering the development 539 variation to the brain in normal aging (Van Petten, 2004). However, it should be clarified that the 540 exact source responsible for this disparity remains elusive. ...
Preprint
Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.
... The advent of finer-grained imaging techniques has allowed researchers to focus on the role of hippocampus and medial temporal lobe subfields in episodic and autobiographical AUTOBIOGRAPHICAL MEMORY 15 memory. While hippocampal ablation causes dense amnesia, there is no corresponding relationship between whole hippocampal volume or activation on (non-autobiographical) episodic memory performance in healthy adults (Poppenk & Moscovitch, 2011;Van Petten, 2004). Hippocampal subfields are implicated in the formation of distinct neural representations of similar events (pattern separation) and retrieving previously stored memory representations based on incomplete cues (pattern completion; Grande et al., 2019;Knierim & Neunuebel, 2016). ...
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Autobiographical memory—memory for our personal past—is a multifaceted mnemonic activity that evolves throughout the lifespan and interacts with numerous other cognitive functions. Retrieving personal past events engages processes of cue specification, search, and elaboration of details within the specified event. The retrieved content varies from specific episodes unique in time and place to more general representations of autobiographical facts (personal semantics). As expected given this complexity, autobiographical memory is mediated by distributed brain networks, with key regions in the medial temporal lobes and their connections to both anterior and posterior cortical regions supporting different levels of specificity in memory retrieval. These patterns only partially overlap with those evoked by laboratory-based episodic memory paradigms. While most empirical work on autobiographical memory focuses on the recall of particular past events, more recent research concerns individual differences in the way that people tend to remember their past. The formal study of autobiographical memory dates to the 19th century, but research in this field is burgeoning, particularly in relation to brain network connectivity. New paradigms that bridge the gap between traditional laboratory memory tasks and rich, naturalistic autobiographical memories will enhance the understanding of memory as it operates in everyday life.
... However, prior studies have also reported significant improvement in episodic memory with aging and demonstrated that it was related to lower gray matter volume in brain areas belonging to the DMN [37]. Analogously, negative associations between regional gray matter volume and episodic memory have been also consistently reported, especially in young participants [38,39]. Another previous report supplemented that these regions with less gray matter volume were not only associated with efficient episodic memory; they were also functionally interconnected and were part of the DMN [40]. ...
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Background Intervention against age-related neurodegenerative diseases may be difficult once extensive structural and functional deteriorations have already occurred in the brain.AimInvestigating 6-year longitudinal changes and implications of regional brain atrophy and functional connectivity in the triple-network model as biomarkers of preclinical cognitive impairment in healthy aging.Methods We acquired longitudinal cognitive scores and magnetic resonance imaging (MRI) data from 74 healthy old adults. Resting-state functional MRI (rs-fMRI) analysis was conducted using FSL6.0.1 to examine functional connectivity changes and regional brain morphometries were quantified using FreeSurfer5.3. Finally, we cross-validated and compared two support vector machine (SVM) regression models to predict future 6-year cognition score from the baseline regional brain atrophy and resting-state functional connectivity (rs-FC) measures.ResultsAfter a 6-year follow-up, our results (P < 0.05-corrected) indicated significant connectivity reduction within all the three brain networks, significant differences in regional brain volumes and cortical thickness. We also observed significant improvement in episodic memory and significant decline in executive functions. Finally, comparing the two models, we observed that regional brain atrophy predictors were more efficient in approximating future 6-year cognitive scores (R = 0.756, P < 0.0001) than rs-FC predictors (R = 0.6, P < 0.0001).Conclusion This study used longitudinal data to keep subject variability low and to increase the validity of the results. We demonstrated significant changes in structural and functional MRI over 6 years. Our findings present a potential neuroimaging-based biomarker to detect cognitive impairment and prevent risks of neurodegenerative diseases in healthy old adults.
... Certain regions, such as the hippocampus, are more susceptible to the noxious effects of time 2,3 . Relevantly, hippocampal attrition predicts cognitive decline and dementia 4,5 , although the relationship between hippocampal volume and cognitive performance in older healthy individuals remains to be fully elucidated 6 . Therefore, to prevent cognitive decline, it is crucial to identify populations at higher risk of grey matter reductions as well as strategies to prevent neurodegeneration. ...
Preprint
As individuals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippocampus, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippocampal volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippocampal volume in a sample of 23,776 cognitively normal older adults from the UK Biobank. We found that, in individuals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippocampal volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippocampal volumes in individuals older than 60. Hence this study might serve to identify populations at higher risk of hippocampal attrition and cognitive decline.
... Neurogenesis is an important contributor to hippocampal volume and structure [44,45]. Reduced hippocampal volume is associated with cognitive decline in neuronal disorders [46][47][48]. In addition, it is well known that cognitive decline in Alzheimer's disease and type 2 diabetes mellitus are correlated with a decrease in hippocampal volume [49,50]. ...
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Background Neuroinflammation is a key pathological component of neurodegenerative disease and is characterized by microglial activation and the secretion of proinflammatory mediators. We previously reported that a surge in prostaglandin D2 (PGD2) production and PGD2-induced microglial activation could provoke neuroinflammation. We also reported that a lipid sensor GPR120 (free fatty acid receptor 4), which is expressed in intestine, could be activated by polyunsaturated fatty acids (PUFA), thereby mediating secretion of glucagon-like peptide-1 (GLP-1). Dysfunction of GPR120 results in obesity in both mice and humans. Methods To reveal the relationship between PGD2-microglia-provoked neuroinflammation and intestinal PUFA/GPR120 signaling, we investigated neuroinflammation and neuronal function with gene and protein expression, histological, and behavioral analysis in GPR120 knockout (KO) mice. Results In the current study, we discovered notable neuroinflammation (increased PGD2 production and microglial activation) and neurodegeneration (declines in neurogenesis, hippocampal volume, and cognitive function) in GPR120 KO mice. We also found that Hematopoietic–prostaglandin D synthase (H-PGDS) was expressed in microglia, microglia were activated by PGD2, H-PGDS expression was upregulated in GPR120 KO hippocampus, and inhibition of PGD2 production attenuated this neuroinflammation. GPR120 KO mice exhibited reduced intestinal, plasma, and intracerebral GLP-1 contents. Peripheral administration of a GLP-1 analogue, liraglutide, reduced PGD2-microglia-provoked neuroinflammation and further neurodegeneration in GPR120 KO mice. Conclusions Our results suggest that neurological phenotypes in GPR120 KO mice are probably caused by dysfunction of intestinal GPR120. These observations raise the possibility that intestinal GLP-1 secretion, stimulated by intestinal GPR120, may remotely contributed to suppress PGD2-microglia-provoked neuroinflammation in the hippocampus.
... In a more detailed specification, structural equation modeling (SEM) was used to investigate associative memory and hippocampal volume before the language intervention as predictors of vocabulary learning success. Evidence of age-related reductions of hippocampal volume and associative memory performance suggests that these factors may be important limiting factors for second language learning in older adults (Naveh-Benjamin, 2000;Van Petten, 2004;Raz et al., 2004). Given the requirement in the vocabulary learning to encode, store and retrieve associations between foreign words and their native counterparts, associative memory ability was hypothesized to be an important predictor of vocabulary learning success. ...
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It has previously been demonstrated that short-term foreign language learning can lead to structural brain changes in younger adults. Experience-dependent brain plasticity is known to be possible also in older age, but the specific effect of foreign language learning on brain structure in language-and memory-relevant regions in the old brain remains unknown. In the present study, 160 older Swedish adults (65–75 years) were randomized to complete either an entry-level Italian course or a relaxation course, both with a total duration of 11 weeks. Structural MRI scans were conducted before and after the intervention in a subset of participants to test for differential change in gray matter in the two groups in the inferior frontal gyrus, the superior temporal gyrus, and the hippocampus, and in white matter microstructure in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), fronto-occipital fasciculus, and the hippocampal (HC) section of the cingulum. The study found no evidence for differential structural change following language training, independent of achieved vocabulary proficiency. However, hippocampal volume and associative memory ability before the intervention were found to be robust predictors of vocabulary proficiency at the end of the language course. The results suggest that having greater hippocampal volume and better associative memory ability benefits vocabulary learning in old age but that the very initial stage of foreign language learning does not trigger detectable changes in brain morphometry in old age.
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The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce, and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus, and is implicated in adult neurogenesis in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 301, 174 f) with a broad age range (20-55 years, mean 40.7) recruited in the context of the ReSource project. We related HCV to basal sBDNF and, in a subsample (n = 113, 65 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null-results provide a first reference point on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.
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Altern geht mit metabolischen, strukturellen und anatomischen Veränderungen auf Hirnebene einher. Sehr viele Hirnregionen sind in unterschiedlichem Ausmaß davon betroffen, insbesondere präfrontale und medio-temporale Regionen. Es besteht kein sicherer Nachweis für asymmetrische Neurodegeneration, aber für asymmetrische Netzwerktopologien. Systematische Studien zu Veränderungen der Netzwerkprozesse im Alter stehen noch aus. Änderungen des Hirnmetabolismus spezifisch für unterschiedliche Altersphasen sind evident. Der Bedeutung von Neuroinflammation bei Älteren wird ein großes Potenzial für die Beschreibung alterskorrelierter Veränderungen zugeschrieben. Die Bedeutung von Sexualhormonen für neuronale und kognitive Funktion im Alter ist für den Menschen noch nicht ausreichend aufgeklärt. Veränderungen von Neurotransmitterbalancen bei Älteren sind gezeigt worden. Es besteht konvergente Evidenz, dass die anatomischen und physiologischen Veränderungen im Alter mit Änderungen der kognitiven und emotionalen Verarbeitung einhergehen. Auf kognitiver Ebene ist eine deutliche Leistungsheterogenität sichtbar. Relative Leistungsstabilität ist insbesondere für Wortschatz, semantische und implizite Gedächtnisleistungen zu erwarten, relativer Leistungsabfall für episodische und Arbeitsgedächtnisleistung, selektive und geteilte Aufmerksamkeitsleistung sowie für Exekutivfunktionen. Ältere Personen haben ein erhöhtes Risiko postoperativ ein Delir und/oder eine kognitive Beeinträchtigung zu erleiden, was neben der Leistungsheterogenität bei der Organisation und Durchführung von neuropsychologischer Diagnostik spezifisch zu berücksichtigen ist. Trotz vieler Einzelbefunde bleibt das Gesamtbild noch lückenhaft. Kausale Erklärungen sind schwierig, da Ursachen für Veränderungen im Alter vielfältig sind und mit vielen biologischen und psychologischen Faktoren interagieren.
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MDMA (3,4-Methylenedioxymethamphetamine) is a common recreational drug of abuse which causes neurodegeneration. Nicotine and modafinil provide antioxidant and neuroprotective properties and may be beneficial in the management of MDMA-induced neurotoxicity. The purpose of this study was to characterize how acute and chronic administration of nicotine and/or modafinil exert protective effects against the MDMA-induced impaired cognitive performance, oxidative stress, and neuronal loss. Adult male rats were divided into three groups, namely control, MDMA and treatment (modafinil and/or nicotine). MDMA (10 mg/kg) was administered intraperitoneally during a three-week schedule (two times/day for two consecutive days/week). The treated-groups were classified based on the acute or chronic status of treatment. In the groups which underwent acute treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected just prior to the MDMA administration (acute nicotine (NA), acute modafinil (MA), and acute nicotine and modafinil (NMA)). In the rats which received chronic treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected every day during the three week-schedule administration of MDMA (chronic nicotine (NC), chronic modafinil (MC), and chronic nicotine and modafinil (NMC)). Learning and memory performance, as well as avoidance response, were assessed by Morris water maze and Shuttle box, respectively. Our findings indicate enhanced learning and memory and avoidance response in the NMC group. By TUNEL test and Cresyl Violet staining we evaluated neuronal loss and apoptosis in the hippocampal CA1 and found increased neuronal viability in the NMC group. On the other hand, chronic administration of modafinil and nicotine significantly down-regulated the caspase 3 and up-regulated both BDNF and TrkB levels in the MDMA-received rats. The serum levels of glutathione peroxidase (GPx) and total antioxidant capacity (TAC) were evaluated and we found that the alterations of serum levels of GPx and TAC were considerably prevented in the NMC group. The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA.
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Background Physical activity interventions have had varying results on modifying hippocampal volume. Methods The Retirement in Action (REACT) study conducted a randomised-controlled trial of a 12-month physical activity and behaviour maintenance intervention in older adults at risk of mobility impairments. The physical activity sessions were delivered twice weekly for the first twelve weeks, and then reduced to once weekly, to groups of 15 participants. Activities included cardiovascular, strength, balance and flexibility exercises. A sub-sample of participants in the physical activity (N = 54) and control arms (N = 48) underwent a 3T MRI brain scan and cognitive assessments at baseline, 6- and 12-months (mean age = 76.6 years, 6.8 SD). It was hypothesised that the intervention would lead to a reduced rate of decline in hippocampal volume. Group differences in changes in cognition were also examined. Results As hypothesised, we found a maintenance in left hippocampal volume in the intervention arm, in comparison with the control arm after 12 months (p=0.027). In a secondary analysis, this effect was attenuated after including age, sex and education level as covariates (p = 0.057). There was no significant between-group difference in the right hippocampus (p = 0.405). Contrary to our hypothesis, we did not find a beneficial effect of the intervention on cognitive outcomes. Conclusions Our findings suggest that a community-based physical activity intervention can significantly ward-off hippocampal atrophy in older adults. While the lack of effects on cognition may limit the interpretability of our results, our findings of hippocampal maintenance are promising given the potential clinical relevance of protecting the hippocampus from age-related decline.
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Objectives The underlying mechanism of the association between olfactory impairment and dementia may be explained by neurodegenerative changes detected on magnetic resonance imaging (MRI). The purpose of this systematic review is to describe neurodegenerative changes on MRI in patients with olfactory impairment and mild cognitive impairment (MCI) or dementia. Study design Systematic review. Methods A literature search encompassing PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Google Scholar for studies with MRI and olfactory testing among participants diagnosed with MCI or dementia was performed. Sample size, study design, cognitive impairment type, olfactory testing, and MRI findings were abstracted. Two investigators independently reviewed all articles. Results The search yielded 556 nonduplicate abstracts, from which 86 articles were reviewed and 24 were included. Seventeen (71%) of 24 studies reported hippocampal volume findings, with 14 studies reporting a relationship between hippocampal volume and olfactory performance. Two (50%) of four prospective studies reported the potential utility of baseline hippocampal volume as a marker of dementia conversion from MCI. Five (21%) of 24 studies reporting olfactory functional MRI (fMRI) findings highlighted the utility of olfactory fMRI to identify individuals in the early stages of cognitive decline. Conclusion Current evidence suggests hippocampal volume correlates with olfactory performance in individuals with cognitive impairment, and that olfactory fMRI may improve early detection of AD. However, the predictive utility of these imaging markers is limited in prospective studies. MRI may be a useful modality for selecting patients at high risk of future cognitive decline for enrollment in early treatment trials. Laryngoscope, 2021
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Background Aquaporin-4 (AQP4) water channel is involved in hippocampal plasticity and is the target of neuromyelitis optica spectrum disorders (NMOSD) autoimmunity. We measured volumes of hippocampal subfields and their association with cognitive performance in AQP4-seropositive NMOSD patients. Methods Global and regional hippocampal volumes were derived from 28 AQP4-seropositive NMOSD patients and 101 healthy controls (HC) from 3D-T1-weighted images. Normalized brain volumes were also calculated. A neuropsychological evaluation, including the Brief Repeatable Battery of Neuropsychological Tests, was performed in patients. Based on HC data, we estimated mean z-scores of volumes in the whole NMOSD group and compared them according to the status of global and domain-selective cognitive impairment. Results Global cognitive impairment was detected in 46.4% of NMOSD patients, with attentive (60.7%) and executive (21.4%) domains being the most affected. NMOSD patients had left hippocampal atrophy at global (p=0.012) and regional level (fimbria, Cornus Ammonis [CA] 3, molecular layer, dentate gyrus [DG] and subicular complex, p-values ranging between 0.033 and <0.001). On the right side the fimbria and hippocampal tail were atrophic (p=0.024 for both). Cognitively impaired patients showed atrophy in the left CA3 and CA4 (p=0.025-0.028), while patients presenting verbal and visual memory impairment had significant CA3 and DG atrophy. Those patients with attentive or executive impairment had preserved brain and hippocampal volumes. Conclusions NMOSD patients showed hippocampal atrophy associated with verbal and visual memory impairment. Such a damage did not explain attention and executive function alterations, which were the most common cognitive deficits in this population.
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Die fünf Systeme des menschlichen Langzeitgedächtnisses haben jeweils spezifische neurofunktionelle Grundlagen und sind unterschiedlich anfällig für anatomische und neurochemische Schädigungen des Gehirns. Die behavioralen und neurofunktionellen Charakteristika des episodisch-autobiographischen Gedächtnisses ermöglichen das Erinnern persönlicher Erlebnisse im Kontext der individuellen Lebensgeschichte eines Menschen. Das Kapitel fokussiert Prozesse des Lernens, der Gedächtnisbildung und die wichtigsten Gehirnstrukturen, die im Zusammenhang mit dem episodisch-autobiographischen Gedächtnis relevant sind. Das episodisch-autobiographische Gedächtnis basiert vorwiegend auf der Interaktion zwischen Gehirnregionen innerhalb eines komplexen fronto-temporalen neuronalen Netzwerks. Es erlaubt uns, eine Zeitreise in unsere persönliche Vergangenheit zu unternehmen und unsere Lebensgeschichte stets neu von einer aktuellen Situation aus zu rekonstruieren. Diese Form des Gedächtnisses hat daher auch eine besonders große Relevanz für die Entwicklung und Veränderung von Persönlichkeitsmerkmalen und Selbstkonzepten eines Individuums über die gesamte Lebensspanne hinweg. Kinder im Alter zwischen 3 und 4 Jahren können episodisch-autobiographische Erinnerungen abrufen. Sie zeigen jedoch eine stärkere Suggestibilität als ältere Kinder und Erwachsene und verwechseln nicht selten Orte, Menschen und Ereignisse. Die Kapazität des episodischen Gedächtnisses verstärkt sich deutlich bei Kindern bis zum Alter von 11 Jahren. Die Abrufgeschwindigkeit und -strategien entwickeln sich jedoch weiter bis in das frühe Erwachsenenalter. Im höheren Alter gesunder Menschen nimmt das episodisch-autobiographische Gedächtnis für rezente Ereignisse ab, bleibt jedoch in der Regel weitreichend unbeeinträchtigt für Kindheitserlebnisse. Es werden zudem Beeinträchtigungen episodischer Gedächtnisfunktionen bei Patienten mit Schädigungen bestimmter Strukturen des Gehirns diskutiert. Für eine erfolgreiche Behandlung beeinträchtigter Gedächtnisfunktionen bildet die neuronale Plastizität des Gehirns die ausschlaggebende Basis. Der Befund, dass Umweltbedingungen Konsequenzen für den Aufbau und die Funktion des Nervensystems haben, ist auch von zentraler Bedeutung für die Wirksamkeit therapeutischer Interventionen bei Personen mit Gedächtnisstörungen und anderen kognitiven Beeinträchtigungen infolge neurologischer oder psychiatrischer Erkrankungen. Dies ist auch insbesondere im Zusammenhang mit dem Auftreten von Posttraumatischen Belastungsstörungen und den damit typischerweise einhergehenden Gedächtnisdefiziten nach emotional belastenden Ereignissen von großer Bedeutung. Die neuronale Plastizität bildet insofern die Grundlage für die Wirksamkeit des Trainings von Gedächtnisleistungen. Wie jede andere Umwelterfahrung formt und re-modelliert das Gedächtnistraining funktionelle Systeme des Gehirns und ermöglicht durch die zielgerichtete Intervention eine Verbesserung von Gedächtnisleistungen. Sogar bei Patienten mit schwerwiegenden Gedächtnisdefiziten aufgrund neuroanatomischer Läsionen können andere intakte Gehirnstrukturen durch ein gezieltes Training viele Gedächtnisfunktionen übernehmen.
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Background and Aims: Age-related hearing loss (presbycusis) refers to symmetrical bilateral hearing loss, which results from aging and affects most people over 70, and its effects are more frequent at high frequencies, which are important in speech recognition. This progressive hearing loss is characterized by features such as changing the audiometric threshold and speech perception problems in noisy environments. Recent findings suggest that in addition to audibility of the signal, cognitive factors such as attention, working memory, and speed of processing also play a significant role in speech perception both in noise and silence. Although hearing aids enhance hearing, they cannot compensate for the defects that occur in the auditory temporal processing. Another solution is to use auditory training. Auditory-based training can partially restore age-related defects in temporal processing in the brain, and this plasticity in turn leads to improved cognitive and perceptual skills. Materials and Methods: In the current review article, some of the topics discussed about auditory processing and speech perception in the elderly, as well as the role of amplification and training in them, were selected in articles obtained from Scopus PubMed, Google scholar, and Science direct databases published between 1971-2019. Conclusion: With regard to the results of auditory training in increment of auditory perception in the elderly, a primary assessment of central auditory processing capabilities and auditory training program should be considered as a basic step for their management. Therefore, the role of audiologists become very important in the detection of central aspects of presbycusis and explaining the importance of auditory training program as a part of selecting and fitting hearing aids for the elderly.
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Background: Hippocampal volumetric data are widely used in research but are rarely examined in clinical populations in regard to aiding diagnosis or correlating with objective memory test scores. Objective: To replicate and expand on the few prior clinical examinations of the utility of hippocampal volumetric data. We evaluated MRI volumetric data to determine (a) the degree of hippocampal loss across diagnostic groups compared with a cognitively intact group, (b) if total or lateralized hippocampal volumes predict diagnostic group membership, and (c) how total and lateralized volumes correlate with memory tests. Method: We retrospectively examined hippocampal volumetric data and memory test scores for 294 individuals referred to a memory clinic. Results: Individuals with mild cognitive impairment or Alzheimer disease had smaller hippocampal volumes compared with cognitively intact individuals. The raw and normalized total and lateralized hippocampal volumes were essentially equal for predicting diagnostic group membership, and notably low hippocampal volumes evidenced greater specificity than sensitivity. All of the volumetric data correlated with the memory test scores, with the total and left hippocampal volumes accounting for the slightly more variance in the diagnostic groups. Conclusion: The diagnostic groups exhibited hippocampal volume loss, which can be a potential biomarker for neurodegenerative disease in clinical practice. However, solely using hippocampal volumetric data to predict diagnostic group membership or memory test failure was not supported. While extreme hippocampal volume loss was rare in the cognitively intact group, the sensitivity of these volumetric data suggests a need for supplementation by other tools when making a diagnosis.
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Memory is supported by a network of brain regions, with the hippocampus serving a critical role in this cognitive process. Previous meta‐analyses on the association between hippocampal structure and memory have largely focused on adults. Multiple studies have since suggested that hippocampal volume is related to memory performance in children and adolescents; however, the strength and direction of this relation varies across reports, and thus, remains unclear. To further understand this brain–behavior relation, we conducted a meta‐analysis to investigate the association between hippocampal volume (assessed as total volume) and memory during typical development. Across 25 studies and 61 memory outcomes with 1357 participants, results showed a small, but significant, positive association between total hippocampal volume and memory performance. Estimates of the variability across studies in the relation between total volume and memory were not explained by differences in memory task type (delayed vs. immediate; relational vs. nonrelational), participant age range, or the method of normalization of hippocampal volumes. Overall, findings suggest that larger total hippocampal volume relates to better memory performance in children and adolescents and that this relation is similar across the memory types and age ranges assessed. To facilitate enhanced generalization across studies in the future, we discuss considerations for the field moving forward.
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Although age-related differences in episodic memory function are well established, the differential reduction in fine-grain memory components and its underlying hippocampal mechanism remains unclear. Hence, the current study investigated, first, age-related differences in the recollection of the four components (who, when, where, and what) of verbal episodic memory and, second, these components’ associations with volumetric alterations in the hippocampal subfields. A total of 60 older and younger adults completed the Logical Memory test. The measurements of the volumes of the hippocampal subfields were obtained. The results revealed that older age was associated with poorer learning performance for when, where, and what components but not for who component; the reduced learning scores were differentially correlated with the age-related regional vulnerability of the dentate gyrus, CA1 subfield, and subiculum. The age-related vulnerability in the retention of the when component was associated with smaller subiculum, CA1, CA4, and dentate gyrus, but a reduction in the subiculum alone mediated the inverse relationship between age and the retention score for the when component. Our findings underscore the value of differentiating between memory components in evaluations of verbal contextual episodic memory which allows the analyst to examine aging-related associations between subtle cognitive changes and hippocampal substructures.
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Memories are thought to become more gist-like over time. Multiple related memories might form generalized memory representations, losing specific details but enhancing or retaining gist. The time course within which gist memory emerges, however, is the subject of less consensus. To address this question, we focused our design on four kinds of gist: inferential gist (relations extracted across non-contiguous events), statistical learning (regularities extracted from a series), summary gist (a theme abstracted from a temporally contiguous series of items), and category gist (characterization of a stimulus at a higher level in the semantic hierarchy). Seventy participants (31 men, 39 women) completed memory encoding tasks addressing these types of gist and corresponding retrieval tasks the same evening, the morning after, and one week later, as well as an MRI at a later time point. We found little evidence that gist slowly emerges over time or that gist traces are more resistant to forgetting than detail traces. Instead, we found that initial gist memory shortly after encoding was either retained over time or decayed. Inferential gist and statistical learning were retained over a week, whereas memory for category and summary gist decayed. We discuss several interpretations for differences between these two subtypes of gist. Individual differences in REM or slow-wave sleep and hippocampal volumes did not predict changes in memory for these four kinds of gist in a healthy young adult population.
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Aging is often accompanied by learning and memory problems, many of which resemble deficits associated with hippocampal damage. Studies of aging in nonhuman animals have demonstrated hippo-campus-related memory decline, and point to a possible locus for impairments associated with normal and pathological aging in humans. Two well-characterized hippocampus-dependent tasks in nonhuman animal literature are the Morris water task (MWT) and the transverse patterning discrimination task (TPDT). We employed the virtual MWT and the TPDT to assess hippocampus-dependent cogni-tion in humans. Magnetic resonance imaging and proton magnetic resonance spectroscopy were employed to measure hippocampal volume and neurochemistry respectively. Age-related deficits were observed in performance on both hippocampus-dependent tasks. This pattern of impairment was accompanied by decreased hippo-campal NAA/Cre ratios and volume, both of which imply neuronal loss and/or decrease in neuronal density. Collectively, our results suggest that hippocampus undergoes structural and biochemical changes with normal aging and that these changes may represent an important component of age-related deterioration in hippocampus-dependent cognition.
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To determine whether the medial temporal lobe is atrophic in subjects with mild cognitive impairment, and whether atrophy of this structure is a better predictor of dementia than memory dysfunction. Forty-five noninstitutionalized subjects aged 65–85 years were randomly selected from a population based study to obtain a sample with Alzheimer’s disease (AD; n = 7), and a clinically nondemented sample (n = 38). Twenty of the latter subjects displayed some cognitive impairment and fulfilled CAMDEX criteria for “minimal dementia.” Coronal T1-weighted magnetic resonance imaging was used to visualize the medial temporal lobe. The volume of the parahippocampal gyrus and hippocampus was measured, and medial temporal lobe atrophy was assessed qualitatively. The memory subscore from the CAMCOG was used as a measure of memory functioning. The follow-up period was 3 years. Nine subjects who were diagnosed as being minimally demented at baseline met the criteria for AD during follow-up. At baseline the volume of the parahippocampal gyrus of these subjects was smaller than that of the other subjects with minimal dementia. The memory score was the best predictor of clinical outcome. All medial temporal lobe measures increased the accuracy of prediction compared with only the memory score, by reducing the number of false-negative classifications of dementia. Severe medial temporal lobe atrophy is present even in some subjects with mild cognitive impairment and is an indicator of subsequent AD. The absence of medial temporal lobe atrophy, however, does not exclude the development of dementia. In the majority of subjects memory impairment was a better predictor of dementia than atrophy of the medial temporal lobe. The combination of the two increased predictive accuracy. Nondemented subjects with severe atrophy of the medial temporal lobe could be enrolled in drug trials aimed at slowing the progression of AD.
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Neuroimaging and lesion studies have demonstrated that hippocampal volume correlates with memory performance, but material-specific lateralization of this structure-function relationship has been inconsistent. This MRI study examined the relative contributions of left and right temporal lobe volumes to verbal and nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients. There was a significant relationship between extent of right hippocampal and right temporal gray matter tissue volume deficit and performance on the face recognition subtest of the Warrington Recognition Memory Test. The face recognition test correlated with right hemisphere volume but not to left, indicating a material-specific relationship between brain structure and function in this patient group. Right temporal horn volume did not account for a significant proportion of variance in face recognition memory. Although word recognition was not significantly correlated with either left or right hippocampal volume in the total group, there was a strong correlation between left hippocampal volume and word recognition memory in the female AD patients. Thus, face recognition shows a material specific relationship with select lateralized hippocampal and temporal cortical volumes in AD patients, regardless of gender, whereas the verbal recognition-left-hippocampal volume relationship may be mediated by gender.
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Studies examining age-related changes typically report findings as age-based generalizations that neglect the phenomenon of variability in gerontological research. This paper examines the degree of attention given in 185 studies to individual differences and the empirical patterns of variability reported in those studies that present measures of dispersion. Measures of dispersion were reported in 43% of the gerontological studies reviewed and in 24% of the developmental studies. Overall, a majority of all gerontological studies presenting data reported increases in variability with increasing age (65%). This pattern was more pronounced in longitudinal studies than in cross-sectional ones.
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Introduction Volume of Visual Cortex (Area 17) Neuronal Number in Visual Cortex Dendritic Development in Visual Cortex Synaptogenesis in Visual Cortex Frontal Cortex Discussion
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The development of most regions of the vertebrate nervous system includes a distinct phase of neuronal degeneration during which a substantial proportion of the neurons initially generated die. This degeneration primarily adjusts the magnitude of each neuronal population to the size or functional needs of its projection field, but in the process it seems also to eliminate many neurons whose axons have grown to either the wrong target or an inappropriate region within the target area. In addition, many connections that are initially formed are later eliminated without the death of the parent cell. In most cases such process elimination results in the removal of terminal axonal branches and hence serves as a mechanism to "fine-tune" neuronal wiring. However, there are now also several examples of the large-scale elimination of early-formed pathways as a result of the selective degeneration of long axon collaterals. Thus, far from being relatively minor aspects of neural development, these regressive phenomena are now recognized as playing a major role in determining the form of the mature nervous system.
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Adolescent development involves progressive changes in brain structure and cognitive function, but relatively few studies have documented the cognitive correlates of differences in structural brain volumes in this age group. We examined the relations among age, cognitive processing, and mesial temporal lobe volume in 37 children and adolescents. Participants completed a brief cognitive assessment battery and underwent volumetric structural magnetic resonance imaging. For the sample as a whole, amygdala volume correlated positively with age, and larger volumes of both the left and right amygdala were significantly associated with better performance on several cognitive tasks assessing academic skills and acquired knowledge in long-term memory. In contrast, hippocampal volumes did not correlate with adolescents' age and were less frequently correlated with cognitive performance. Amygdala volumes were most predictive of cognitive abilities in boys, whereas for girls, the volume of the hippocampus contributed more frequently to the prediction of cognitive abilities. These data suggest that mensurable differences in mesial temporal volumes during adolescence are reliably associated with long-term cognitive abilities, particularly academic skills and the acquisition of intellectual knowledge, and that these relationships may differ as a function of the sex of the child.
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Background Clues to the causes of schizophrenia can be derived from studying first-degree relatives because they are genetically related to an ill family member. Abnormalities observed in nonpsychotic relatives are indicators of possible genetic vulnerability to illness, independent of psychosis. We tested 4 hypotheses: (1) that hippocampal volume is smaller in nonpsychotic relatives than in controls, particularly in the left hemisphere; (2) that hippocampi will be smaller in multiplex relatives as compared with simplex relatives, and both will be smaller than in controls;(3) that hippocampal volumes and verbal declarative memory function will be positively correlated; and (4) that hippocampi will be smaller in patients with schizophrenia than in their nonpsychotic relatives or in controls. Methods Subjects were 45 nonpsychotic adult first-degree relatives from families with either 2 people ("multiplex," n = 17) or 1 person ("simplex," n = 28) diagnosed with schizophrenia, 18 schizophrenic relatives, and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3-dimensional magnetic resonance images of the brain were acquired on a 1.5-T magnet. Volumes of the total cerebrum and the hippocampus were measured. Results Compared with controls, relatives, particularly from multiplex families, had significantly smaller left hippocampi. Verbal memory and left hippocampal volumes were significantly and positively correlated. Within families, hippocampal volumes did not differ between schizophrenic patients and their nonpsychotic relatives. Conclusions Results support the hypothesis that the vulnerability to schizophrenia includes smaller left hippocampi and verbal memory deficits. Findings suggest that smaller left hippocampi and verbal memory deficits are an expression of early neurodevelopmental compromise, reflecting the degree of genetic liability to schizophrenia.
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We present evidence for continuous generation of neurons, oligodendrocytes, and astrocytes in the hippocampal dentate gyrus of adult macaque monkeys, using immunohistochemical double labeling for bromodeoxyuridine and cell-type-specific markers. We estimate that the relative rate of neurogenesis is approximately 10 times less than that reported in the adult rodent dentate gyrus. Nevertheless, the generation of these three cell types in a discreet brain region suggests that a multipotent neural stem cell may be retained in the adult primate hippocampus. This demonstration of adult neurogenesis in nonhuman Old World primates-with their phylogenetic proximity to humans, long life spans, and elaborate cognitive abilities-establishes the macaque as an unexcelled animal model to experimentally investigate issues of neurogenesis in humans and offers new insights into its significance in the adult brain.
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遠隔記憶障害を検出する場合,想起された内容の真実性,再学習の有無,興味や関心の個人差,時間的傾斜の検出の可否が問題となる。社会的なことがらを利用した遠隔記憶検査では興味や関心の個人差が,自伝的なことがらを利用した遠隔記憶検査では想起された内容の真実性が特に問題となる。また,比較的やさしい課題で健常群の天井効果を認める場合,または,比較的難しい課題で健忘群の床効果を認める場合には,時間的傾斜の有無に関して確実なことがいえなくなる。流暢性ベースの遠隔記憶検査は,単位時間内に知人の名前や体験した出来事をできるだけたくさん想起する課題であり,検査の構造上,天井効果が起こりえないために時間的傾斜の問題を考える場合には好都合である。また,内容の異なる遠隔記憶でも流暢性ベースで質問することにより,記憶以外の条件を等しくできる利点もある。コルサコフ症候群において,自伝的記憶流暢性検査の成績は,従来までの自伝的記憶検査の成績と有意な相関を認めており,遠隔記憶検査として有用性が高いと思われた。
Article
Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N-acetyl-moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age-related changes in brain MRS metabolites. Magn Reson Med 41:276–284, 1999. Published 1999 Wiley-Liss, Inc.
Article
(1) If the ratio of two absolute measurements on the same or different organs be taken it is convenient to term this ratio an index . If u = f 1 ( x , y ) and v = f 2 ( x , y ) be two functions of the three variables x, y, z , and these variables be selected at random so that there exists no correlation between x, y , y, z , or z, x , there will still be found to exist correlation between u and v . Thus a real danger arises when a statistical biologist attribntes the correlation between two functions like u and v to organic relationship. The particular case that is likely to occur is when u and v are indices with the same denominator for the correlation of indices seems at first sight a very plausible measure of organic correlation.
Article
The hypothesis that explicit memory impairment in Alzheimer's disease (AD) depends in part on hippocampal formation atrophy was tested in 47 persons with AD. Volumes of the hippocampal formation, parahippocampal gyrus, and temporal neocortex (excluding the hippocampal formation, amygdala, and parahippocampal gyrus) were estimated by reconstruction of magnetic resonance images. Tests of explicit memory, language, and constructional praxis were administered. Psychometric-volumetric associations were evaluated in regression analyses controlling for age, gender, education, and intracranial volume. Hippocampal formation volume was associated with a delayed-recall measure but not with immediate recall: temporal neocortical volume was correlated with performance on measures of language and constructional praxis. The results suggest that patterns of mnemonic and cognitive impairment in AD are due in part to differences in the distribution of pathology in the temporal lobe. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
[reviews] morphological features of aging and of Alzheimer's disease (AD) / particular attention is given to the relation of the pathological brain changes to the clinical features of aging and of AD, the interrelations of these changes to each other, and their relation to brain circuitry and brain organization brain weight, gyral atrophy, ventricular dilation / myelin / cortical width / neuronal cell loss / neuronal processes / glia / neurofibrillary tangle / neuritic (senile) plaque / vascular changes / granulovacuolar degeneration / Hirano body / Lewy body / lipofuscin, melanin (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
In this chapter, the developments that led to the establishment of an animal model of amnesia are summarized, and recent work with nonhuman primates is reviewed that addresses the specific role in memory of the hippocampal region itself (the hippocampus proper, the dentate gyrus, and the subicular complex). (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Considers the planning of experiments and analysis of experimental data, presenting some of the newer developments in statistical analysis, particularly with respect to small sample theory, as related to psychology, sociology, and education. Examples (with answers in an appendix) at the end of each chapter are designed to illustrate the kinds of analysis described in the text. 84 formulas are listed. Tables in the appendix contain random numbers, squares, square roots, and reciprocals, areas and ordinates of the normal curve, X2, t, r, z', and F. 148-item bibliography. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4–18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders. © 1996 Wiley-Liss, Inc.†
Article
Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.
Article
Positron emission tomography (PET) was used to investigate human episodic memory for spatial location and object identity. We measured regional cerebral bloodflow (rCBF) while subjects engaged in perceptual matching of the location or the identity of line drawings of objects. Perceptual matching also involved incidental encoding of the presented information. Subsequently, rCBF was measured when subjects retrieved the location or the identity of these objects from memory. Using the multivariate partial least squares image analysis, we identified three patterns of activity across the brain that allowed us to distinguish structures that are differentially involved in processing spatial location and object identity from structures that are differentially involved in encoding and retrieval but operate across both domains. Domain-specificity was evident by increased rCBF during the processing of spatial location in the right middle occipital gyrus, supramarginal gyrus, and superior temporal sulcus, and by increased rCBF during the processing of object identity in portions of bilateral lingual and fusiform gyri. There was a nearly complete overlap between domain-specific dorsal and ventral extrastriate cortex activations during perceptual matching and memory retrieval. Evidence of domain-specificity was also found in the prefrontal cortex and the left hippocampus, but the effect interacted with encoding and retrieval. Domain-general structures included bilateral superior temporal cortex regions, which were preferentially activated during encoding, and portions of bilateral middle and inferior frontal gyri, which were preferentially activated during retrieval. Together, our data suggest that encoding and retrieval in episodic memory depend on the interplay between domain-specific structures, most of which are involved in memory as well as perception, and domain-general structures, some of which operate more at encoding and others more at retrieval.