Life-history theory suggests that trade-offs exist between fitness components, with organisms balancing investment in reproduction against survival and future reproduction. This study examined the influence of stress on physiological trade-offs in the dominant rocky intertidal mussel Mytilus californianus on the central Oregon coast, USA. The intertidal zone is a highly heterogeneous thermal environment that could lead to intrapopulation variation in stress responses. Stress increases along a vertical gradient, with higher physical stress occurring in the higher intertidal zone, both due to reduced feeding time and longer exposure to aerial conditions. Reproduction and carotenoid content were compared in mussels from the low and high vertical edges of the mussel bed. High-edge mussels invested less relative energy in reproduction and also spawned all of their gametes in the early summer, whereas low-edge mussels continuously spawned small batches of gametes throughout the year. Highedge mussels accumulated high concentrations of carotenoid pigments into their gonadal tissues, potentially to protect gametes from damaging oxidative stress experienced during aerial exposure. A reciprocal transplant experiment revealed plastic responses in growth and reproduction to increased stress. In contrast, carotenoid content did not increase in response to stress, suggesting that carotenoids may not change rapidly or may not be easily lost or gained. Our results indicate that mussels exhibit physiological trade-offs and, under increased stress predicted from climate change scenarios, may allocate energy away from reproduction toward costly physiological defenses.

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimer's disease. We tested whether functional connectivity (FC) within the entorhinal–hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and amyloid-β (Aβ) pathology in a sample of 64 cognitively normal human older adults (mean age, 71.3 ± 6.4 years; 67% female). FC was measured between entorhinal–hippocampal circuit nodes with known anatomical connectivity, as well as within cortical memory networks. Aβ pathology was measured with18F-florbetapir-PET, and neurodegeneration was assessed with subregional volume from structural MRI. Participants performed both object and spatial versions of a mnemonic discrimination task outside of the scanner and were classified into low-performing and high-performing groups on each task using a median split. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC and DG/CA3 was related to Aβ pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. Aβ was further associated with dysfunction within hippocampal subfields, particularly with decreased FC between CA1 and subiculum as well as reduced volume in these regions. Our findings suggest that Aβ may indirectly lead to memory impairment through entorhinal–hippocampal circuit dysfunction and neurodegeneration and provide a mechanism for increased vulnerability of object mnemonic discrimination.SIGNIFICANCE STATEMENTMnemonic discrimination is a critical episodic memory process that is performed in the dentate gyrus (DG) and CA3 subfield of the hippocampus, relying on input from entorhinal cortex. Mnemonic discrimination is particularly vulnerable to decline in older adults; however, the mechanisms behind this vulnerability are still unknown. We demonstrate that object mnemonic discrimination impairment is related to hyperconnectivity between the anterolateral entorhinal cortex and DG/CA3. This hyperconnectivity was associated with amyloid-β pathology and neurodegeneration in entorhinal cortex, suggesting aberrantly increased network activity is a pathological process. Our findings provide a mechanistic explanation of the vulnerability of object compared to spatial mnemonic discrimination in older adults and has translational implications for choice of outcome measures in clinical trials for Alzheimer's disease.

BackgroundEpisodic memory is one of the first cognitive domains to decline in preclinical Alzheimer’s disease. We investigated whether graph metrics of functional networks, specifically modularity and local efficiency, are related to episodic memory and amyloid‐β (Aβ) positivity in cognitively normal older adults.MethodSixty‐five cognitively normal older adults (mean age 72.3 ± 6.2 years; 62% female) underwent high‐resolution resting state fMRI (1.8mm3, partial acquisition) to measure functional connectivity, 18F‐Florbetapir‐PET to measure Aβ pathology, and cognitive assessment. Resting state fMRI data was processed with CONN. ROIs (n=135) from the Brainnetome Atlas contained within rsfMRI coverage were used to generate ROI‐to‐ROI functional connectivity matrices. Graph measures of modularity (Q) and local efficiency were computed with the Brain Connectivity Toolbox using binary graphs at costs ranging from 5%‐50% of network sparsity (5% step size). Aβ status was determined using a >1.11 SUVR threshold of a composite region spanning the association cortex, resulting in 32% of the sample being classified as Aβ+. Episodic memory was measured using the immediate recall measure of the Rey Auditory Verbal Learning Test (RAVLT A5).ResultAβ+ participants had significantly increased modularity compared to Aβ‐ (Fig1A, p<0.05 for costs 25 and 50), but no differences in local efficiency (Fig1B). There was no significant effect of Aβ positivity on RAVLT A5 performance (t(63)=‐0.67, p = 0.51). However, there were significant interactions between Aβ status and RAVLT A5 with both modularity and local efficiency at most cost functions (Fig2). Better RAVLT A5 performance was associated with higher modularity (Fig2A; ex. cost 25: r = 0.54, p=0.01) and higher local efficiency (Fig2B; ex. cost 25: r = 0.63, p=0.002) within Aβ+ participants, but not Aβ‐ participants (ps>0.36).ConclusionOur findings suggest that increases in functional network modularity and local efficiency within Aβ+ cognitively normal older adults may act as a compensatory mechanism to maintain equivalent levels of episodic memory performance.

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimer’s disease. We tested if functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and Aβ pathology, measured with PET, in nondemented older adults. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC-DG/CA3 was related to Aβ pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. Aβ was further associated with decreased FC and volume within hippocampal subfields. Our findings suggest that Aβ may indirectly lead to memory impairment through entorhinal-hippocampal circuit dysfunction and neurodegeneration, and provide a mechanism for vulnerability of object mnemonic discrimination.