Abstract Although most research on navigation in aging focuses on allocentric processing deficits, impaired strategy switching may also contribute to navigational decline. Using a specifically ...designed task involving navigating a town-like virtual environment, we assessed the ability of young and old participants to switch from following learned routes to finding novel shortcuts. We found large age differences in the length of routes taken during testing and in use of shortcuts, as, while nearly all young participants switched from the egocentric route-following strategy to the allocentric wayfinding strategy, none of the older participants stably switched. Although secondary tasks confirmed that older participants were impaired both at strategy switching and allocentric processing, the difficulty in using shortcuts was selectively related to impaired strategy switching. This may in turn relate to dysfunction of the prefrontal-noradrenergic network responsible for coordinating switching behavior. We conclude that the large age difference in performance at the shortcutting task demonstrates for the first time, how strategy switching deficits can have a severe impact on navigation in aging.
Abstract
Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological ...traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44-77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.
There is evidence for differential stability in personality trait differences, even over decades. The authors used data from a sample of the Scottish Mental Survey, 1947 to study personality ...stability from childhood to older age. The 6-Day Sample (N = 1,208) were rated on six personality characteristics by their teachers at around age 14. In 2012, the authors traced as many of these participants as possible and invited them to take part in a follow-up study. Those who agreed (N = 174) completed a questionnaire booklet at age 77 years, which included rating themselves and asking someone who knew them well to rate them on the same 6 characteristics on which they were rated in adolescence. Each set of 6 ratings was reduced to the same single underlying factor, denoted dependability, a trait comparable to conscientiousness. Participants' and others' older-age personality characteristic ratings were moderately correlated with each other, and with other measures of personality and wellbeing, but correlations suggested no significant stability of any of the 6 characteristics or their underlying factor, dependability, over the 63-year interval. However, a more complex model, controlling rater effects, indicated significant 63-year stability of 1 personality characteristic, Stability of Moods, and near-significant stability of another, Conscientiousness. Results suggest that lifelong differential stability of personality is generally quite low, but that some aspects of personality in older age may relate to personality in childhood.
Efficient spatial navigation requires not only accurate spatial knowledge but also the selection of appropriate strategies. Using a novel paradigm that allowed us to distinguish between beacon, ...associative cue, and place strategies, we investigated the effects of cognitive aging on the selection and adoption of navigation strategies in humans. Participants were required to rejoin a previously learned route encountered from an unfamiliar direction. Successful performance required the use of an allocentric place strategy, which was increasingly observed in young participants over six experimental sessions. In contrast, older participants, who were able to recall the route when approaching intersections from the same direction as during encoding, failed to use the correct place strategy when approaching intersections from novel directions. Instead, they continuously used a beacon strategy and showed no evidence of changing their behavior across the six sessions. Given that this bias was already apparent in the first experimental session, the inability to adopt the correct place strategy is not related to an inability to switch from a firmly established response strategy to an allocentric place strategy. Rather, and in line with previous research, age-related deficits in allocentric processing result in shifts in preferred navigation strategies and an overall bias for response strategies. The specific preference for a beacon strategy is discussed in the context of a possible dissociation between beacon-based and associative-cue-based response learning in the striatum, with the latter being more sensitive to age-related changes.
Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control ...studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.
Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain ...provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N = 354) underwent 3T structural MRI <6 months after diagnosis and 1-year follow-up, as part of the Scottish multicentre 'FutureMS' study. MRI data were processed using FreeSurfer to derive volumetrics, and FSL for VBM (grey matter (GM) only), to establish regional patterns of change in GM and normal-appearing white matter (NAWM) over time throughout the brain. Volumetric analyses showed a decrease over time (q<0.05) in bilateral cortical GM and NAWM, cerebellar GM, brainstem, amygdala, basal ganglia, hippocampus, accumbens, thalamus and ventral diencephalon. Additionally, NAWM and GM volume decreased respectively in the following cortical regions, frontal: 14 out of 26 regions and 16/26; temporal: 18/18 and 15/18; parietal: 14/14 and 11/14; occipital: 7/8 and 8/8. Left GM and NAWM asymmetry was observed in the frontal lobe. GM VBM analysis showed three major clusters of decrease over time: 1) temporal and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex; and four smaller clusters within the occipital lobe. Widespread GM and NAWM atrophy was observed in this large recently-diagnosed RRMS cohort, particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions; indicative of neurodegeneration across tissue types, and in accord with limited previous studies in early disease. Volumetric and VBM results emphasise different features of longitudinal lobar and loco-regional change, however identify consistent atrophy patterns across individuals. Atrophy measures targeted to specific brain regions may provide improved markers of neurodegeneration, and potential future imaging stratifiers and endpoints for clinical decision making and therapeutic trials.
To investigate chronic inflammation in relation to cognitive aging by comparison of an epigenetic and serum biomarker of C-reactive protein and their associations with neuroimaging and cognitive ...outcomes.
At baseline, participants (n = 521) were cognitively normal, around 73 years of age (mean 72.4, SD 0.716), and had inflammation, vascular risk (cardiovascular disease history, hypertension, diabetes, smoking, alcohol consumption, body mass index), and neuroimaging (structural and diffusion MRI) data available. Baseline inflammatory status was quantified by a traditional measure of peripheral inflammation-serum C-reactive protein (CRP)-and an epigenetic measure (DNA methylation DNAm signature of CRP). Linear models were used to examine the inflammation-brain health associations; mediation analyses were performed to interrogate the relationship between chronic inflammation, brain structure, and cognitive functioning.
We demonstrate that DNAm CRP shows significantly (on average 6.4-fold) stronger associations with brain health outcomes than serum CRP. DNAm CRP is associated with total brain volume (β = -0.197, 95% confidence interval CI -0.28 to -0.12,
= 8.42 × 10
), gray matter volume (β = -0.200, 95% CI -0.28 to -0.12,
= 1.66 × 10
), and white matter volume (β = -0.150, 95% CI -0.23 to -0.07,
= 0.001) and regional brain atrophy. We also find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial, and memory) cognitive functioning and that brain structure partially mediates this CRP-cognitive association (up to 29.7%), dependent on lifestyle and health factors.
These results support the hypothesis that chronic inflammation may contribute to neurodegenerative brain changes that underlie differences in cognitive ability in later life and highlight the potential of DNAm proxies for indexing chronic inflammatory status.
This study provides Class II evidence that a DNAm signature of CRP levels is more strongly associated with brain health outcomes than serum CRP levels.
Navigation abilities decline with age, partly due to deficits in numerous component processes. Impaired switching between these various processes (i.e., switching navigational strategies) is also ...likely to contribute to age-related navigational impairments. We tested young and old participants on a virtual plus maze task (VPM), expecting older participants to exhibit a specific strategy switching deficit, despite unimpaired learning of allocentric (place) and egocentric (response) strategies following reversals within each strategy. Our initial results suggested that older participants performed worse during place trial blocks but not response trial blocks, as well as in trial blocks following a strategy switch but not those following a reversal. However, we then separated trial blocks by both strategy and change type, revealing that these initial results were due to a more specific deficit in switching to the place strategy. Place reversals and switches to response, as well as response reversals, were unaffected. We argue that this specific "switch-to-place" deficit could account for apparent impairments in both navigational strategy switching and allocentric processing and contributes more generally to age-related decline in navigation.
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