APOE-ε4 selectively modulates posteromedial cortex activity during scene perception and short- term memory in young healthy adults OPEN

Apolipoprotein E (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), yet the mechanisms by which APOE-ε4 influences early-life brain function, and hence, in turn, risk for later-life AD, are poorly understood. Here, we report a novel, and selective, pattern of functional brain activity alteration in healthy young adult human APOE-ε4 carriers. Our findings suggest that APOE-ε4 may influence vulnerability to poorer later life cognitive health via its effect on posteromedial cortex (PMC), a hub region within a brain network involved in spatial processing, and necessary for episodic memory. In two neuroimaging tasks, APOE-ε4 carriers showed an inability to effectively modulate PMC during scene, but not face and object, working memory and perception. This striking pattern overlaps both functionally and topographically, with the earliest cognitive deficits seen in clinical AD, as well as reported alterations in the default network in amyloid-positive individuals at increased risk of AD. Some of the earliest and most consistent metabolic changes in Alzheimer's disease (AD) are evident in posteromedial cortex (PMC), which comprises posterior cingulate, precuneus and retrosplenial cortice

Children and adolescents with all forms of shoulder instability demonstrate differences in their movement and muscle activity patterns when compared to age- and sex-matched controls.

BACKGROUND: Shoulder instability is a complex impairment and identifying biomarkers which differentiate subgroups is challenging. There is limited fundamental movement and muscle activity data for identifying different mechanisms for shoulder instability in children and adolescents which may inform subgrouping and treatment allocation. HYPOTHESIS: Children and adolescents with shoulder instability (irrespective of etiology) have differences in their movement and muscle activity profiles compared to age- and sex-matched controls (two-tailed). METHODS: Young people between eight to 18 years were recruited into two groups of shoulder instability (SI) or and age- and sex-matched controls (CG). All forms of SI were included and young people with co-existing neurological pathologies or deficits were excluded. Participants attended a single session and carried out four unweighted and three weighted tasks in which their movements and muscle activity was measured using 3D-movement analysis and surface electromyography. Statistical parametric mapping was used to identify between group differences. RESULTS: Data was collected for 30 young people (15 SI (6M:9F) and 15 CG (8M:7F)). The mean (SD) age for all participants was 13.6 years (3.0). The SI group demonstrated consistently more protracted and elevated sternoclavicular joint positions during all movements. Normalized muscle activity in Latissimus dorsi was lower in the SI group and had the most statistically significant differences across all movements. Where differences were identified, the SI group also had increased normalized activity of their middle trapezius, posterior deltoid and biceps muscles whilst activity of their latissimus dorsi, triceps and anterior deltoid were decreased compared to the CG group. No statistically significant differences were found for pectoralis major across any movements. Weighted tasks produced fewer differences in muscle activity patterns compared to unweighted tasks. DISCUSSION: Young people with SI may adapt their movements to minimize glenohumeral joint instability. This was demonstrated by reduced variability in acromioclavicular and sternoclavicular joint angles, adoption of different movement strategies across the same joints and increased activity of the scapular stabilizing muscles, despite achieving similar arm positions to the CG. CONCLUSION: Young people with shoulder instability demonstrated consistent differences in their muscle activity and movement patterns. Consistently observed differences at the shoulder girdle included increased sternoclavicular protraction and elevation accompanied by increased normalized activity of the posterior scapula stabilizing muscles. Existing methods of measurement may be used to inform clinical decision making, however, further work is needed evaluate the prognostic and clinical utility of derived 3D and sEMG data for informing decision making within shoulder instability

APOE-ε4 selectively modulates posteromedial cortex activity during scene perception and short-term memory in young healthy adults

Apolipoprotein E (APOE) ε4 is a major genetic risk factor for Alzheimer’s disease (AD), yet the mechanisms by which APOE-ε4 influences early-life brain function, and hence, in turn, risk for later-life AD, are poorly understood. Here, we report a novel, and selective, pattern of functional brain activity alteration in healthy young adult human APOE-ε4 carriers. Our findings suggest that APOE-ε4 may influence vulnerability to poorer later life cognitive health via its effect on posteromedial cortex (PMC), a hub region within a brain network involved in spatial processing, and necessary for episodic memory. In two neuroimaging tasks, APOE-ε4 carriers showed an inability to effectively modulate PMC during scene, but not face and object, working memory and perception. This striking pattern overlaps both functionally and topographically, with the earliest cognitive deficits seen in clinical AD, as well as reported alterations in the default network in amyloid-positive individuals at increased risk of AD

Subiculum – BNST structural connectivity in humans and macaques

Invasive tract-tracing studies in rodents implicate a direct connection between the subiculum and bed nucleus of the stria terminalis (BNST) as a key component of neural pathways mediating hippocampal regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. A clear characterisation of the connections linking the subiculum and BNST in humans and non-human primates is lacking. To address this, we first delineated the projections from the subiculum to the BNST using anterograde tracers injected into macaque monkeys, revealing evidence for a monosynaptic subiculum-BNST projection involving the fornix. Second, we used in vivo diffusion MRI tractography in macaques and humans to demonstrate substantial subiculum complex connectivity to the BNST in both species. This connection was primarily carried by the fornix, with additional connectivity via the amygdala, consistent with rodent anatomy. Third, utilising the twin-based nature of our human sample, we found that microstructural properties of these tracts were moderately heritable (h2 ∼ 0.5). In a final analysis, we found no evidence of any significant association between subiculum complex-BNST tract microstructure and indices of perceived stress/dispositional negativity and alcohol use, derived from principal component analysis decomposition of self-report data. Our findings address a key translational gap in our knowledge of the neurocircuitry regulating stress

Uncovering a role for the dorsal hippocampal commissure in recognition memory

The dorsal hippocampal commissure (DHC) is a white matter tract that provides interhemispheric connections between temporal lobe brain regions. Despite the importance of these regions for learning and memory, there is scant evidence of a role for the DHC in successful memory performance. We used diffusion-weighted magnetic resonance imaging (DW-MRI) and white matter tractography to reconstruct the DHC in both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings demonstrate a close consistency between the known anatomy and tract reconstructions of the DHC. Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in nonhuman primates. Finally, we derived diffusion tensor MRI metrics from the DHC in a large sample of human subjects to investigate whether interindividual variation in DHC microstructure is predictive of memory performance. The mean diffusivity of the DHC correlated with performance in a standardized recognition memory task, an effect that was not reproduced in a comparison commissure tract—the anterior commissure. These findings highlight a potential role for the DHC in recognition memory, and our tract reconstruction approach has the potential to generate further novel insights into the role of this previously understudied white matter tract in both health and disease

Forgetfulness without memory: Reconstruction, Landscape and the Politics of Everyday in Post-Earthquake Gujarat, India

For many good reasons, after natural disasters it is common to work with ‘memory’ as part of a collective catharsis and a globalized humanitarian logic. Long‐term anthropological research on the aftermath of the 2001 earthquake in Gujarat, however, also demonstrates the significance of forgetting in local practice. Immediately after the disaster, people vowed to abandon the sites of their loss, leave the ruins as monuments, and rebuild anew on safer ground. In time, though, life returned to the ruins as the terrible proximity of death receded, as memories and new salience were shaped by acts of reconstruction. The article explores some of the political and social factors that make this form of forgetting possible – or even necessary. Evidence of earlier earthquakes in the same region indicates that such ‘forgetting’ has an established history. Together, ethnographic and archival materials combine to cast doubt over the emphasis on ‘remembering’ as the only ‘memory solution’ to suffering