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Campbell, K. L.

Publications and source records attributed to Campbell, K. L..

14 recordsLinked to original sources

Not all memory declines with age: Neural correlates of implicit associative memory in younger and older adults.

While explicit associative memory declines with age, implicit associative memory remains preserved. Few studies have examined the neural basis of implicit associative memory in aging, and it remains unclear whether the hippocampus is required as it is more often associated with explicit associative memory. While undergoing functional magnetic resonance imaging, young and old adults completed a speeded object categorization task in which they viewed pictured objects with superimposed words. Implicit memory was tested by presenting intact (original pairs) and rearranged pairs (items previously presented, but not together) from encoding while participants did the same categorization task. Associative priming was defined as faster reaction times (behavioural associative priming) and less activation for intact than rearranged pairs at retrieval (neural associative priming). Whole-brain analyses revealed neural associative priming in occipitotemporal and frontal regions that did not differ by age. A region of interest analysis (using subject-specific masks of medial temporal lobe regions) showed that only older adults had greater posterior hippocampal activation to intact than rearranged items at test, though activation in the hippocampus did not relate to behavioural associative priming. In contrast, greater behavioural associative priming was related to greater neural associative priming in the perirhinal cortex in both age groups. Together, these findings suggest that implicit associative priming remains intact with age, possibly because it relies on additional processes outside the hippocampus such as perirhinal-dependent unitization.

neuroscience↗

Sky islands of Southwest China. II: Unraveling hidden species diversity of talpid moles using phylogenomics and skull-based deep learning

The sky islands of Southwest China, characterized by dramatic topographical and climatic variations, are prominent hotspots of biodiversity and endemism. Organisms inhabiting middle-to-high elevation habitats in this region are geographically isolated within distinct mountain chains, which over geological time have been subjected to isolation-by-distance and isolation-by-environment. These processes have led to profound allopatric diversification and strong phylogeographic structuring, resulting in a plethora of genetically distinct cryptic species, as is becoming increasingly evident for many small mammal families. However, morphological conservatism can pose significant challenges in delineating these clades within species complexes. In this study, we leverage artificial intelligence technologies to unravel the hidden species diversity of moles (family Talpidae) in Southwest Chinas sky islands. We first employed ultraconserved elements (UCEs) to investigate the evolutionary history of talpid moles, conducted molecular species delimitation using mitochondrial and multi-locus genes, and utilized both traditional and geometric morphometrics to examine their morphological disparity. To address the challenges of morphology based cryptic species identification, we developed a deep learning Hierarchical Identification of Species NETwork (HIS-NET) to create an image-based model that analyzes four different views of the skull/mandible to distinguish genera and species hierarchically. HIS-NET not only achieved expert-level accuracy in species identification but also effectively distinguished between cryptic and known species, aiding in the identification of key morphological variation intervals. Our results support the recognition of allopatrically distributed taxa in Euroscaptor and Parascaptor as full species, thereby confirming that species diversity in this region remains underestimated. Beyond advancing our understanding of speciation in this unique and fragile ecosystem, our study serves as a proof-of-concept, demonstrating the power of deep learning in unraveling hidden biodiversity within this and other species complexes.

zoology↗

Temporal dedifferentiation of neural states with age during naturalistic viewing

Highlights- Age affects neural activity patterns related to event perception - With age, neural state duration increases in multiple brain regions - This effect is strongest in the visual cortex and ventromedial prefrontal cortex - The overlap between neural states and event boundaries does not decline with age - This suggest that coarse event perception is relatively preserved with age While life is experienced continuously, we tend to perceive it as a series of events. At a neural level, this event segmentation process has been linked to changes in neural states. An open question is whether these neural states differ with age. Participants (N = 577) from the CamCAN cohort viewed an 8-min movie during fMRI. A data-driven state segmentation method was used to identify neural state changes. To study the effects of age, participants were sorted into 34 age groups. We show that neural states become significantly longer with increasing age, particularly in visual and ventromedial prefrontal cortices. Perceived event boundaries overlapped with state changes in superior temporal and dorsomedial prefrontal regions, but there was no effect of age on this relationship. Our results suggest reduced temporal differentiation of successive neural states with increasing age. Nevertheless, preserved alignment between neural states and perceived events suggests that coarse event segmentation remains intact.

neuroscience↗

Parallel genetic excisions of the cardiac troponin I N-terminal extension in tachycardic mammals

Mammalian cardiac troponin I (cTnI) contains a highly conserved N-terminal extension harboring protein kinase A targets (Ser23/24) which are phosphorylated during {beta}-adrenergic stimulation to increase cardiomyocyte relaxation rate. Here, we show that the Ser23/24 encoding exon 3 of TNNI3 was pseudoexonized multiple times in shrews and moles to mimic Ser23/24 phosphorylation without adrenergic stimulation, facilitating the evolution of exceptionally high resting heart rates ([~]1000 beats min-1). We further reveal alternative exon 3 splicing in distantly related bat families and that both exon 3- and exon 3+ cTnI isoforms are incorporated into cardiac myofibrils. Finally, exon 3 of human TNNI3 is shown to exhibit a relatively low splice strength score, offering an evolutionarily informed strategy to excise this exon to improve diastolic function during heart failure.

evolutionary biology↗

Improved cognitive-motor processing speed and decreased functional connectivity after high intensity aerobic exercise in individuals with chronic stroke

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in healthy populations and may be effective in altering cognitive function post-stroke. We sought to determine if high intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 {+/-} 11 years; 4 females), or control (n = 11; 68 {+/-} 8 years; 2 females) groups. Both groups performed five-days of paretic upper limb motor training after either high intensity aerobic exercise (3 intervals of 3 minutes each, total exercise duration of 23-minutes) or watching a documentary (control). Resting-state fMRI, and TMT-A and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < .001), but there was no added benefit of exercise (p = .738). Regardless of group, the changes in task score (p = .025), and dwell time (p = .043) were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (p = .024), which is thought to reflect a reduction in the cognitive demand and increased automaticity. The exercise group experienced greater overall cognitive-motor improvements measured with the trail making test part A (TMT-A: task score: p = .012; dwell time: p = .024; movement time: p = .567). Aerobic exercise may improve cognitive-motor processing speed post-stroke. Significance statementAfter stroke, impaired motor performance is linked to an increased demand for cognitive resources. In our work we show that high intensity aerobic exercise paired with an implicit motor learning task improves cognitive-motor processing speed and reduces resting-state functional connectivity between the dorsolateral prefrontal cortex and the sensorimotor network in individuals living with chronic stroke. These data likely reflect a reduction in cognitive resource dependence during a cognitive-motor task after stroke and a shift towards cognitive-motor automaticity.

neuroscience↗

Thermoconforming rays of the star-nosed mole

The star-nosed mole (Condylura cristata) is well known for its unique star-like rostrum ( star) which is formed by 22 nasal appendages highly specialised for tactile sensation. As a northerly distributed insectivorous mammal occupying both aquatic and terrestrial habitats, this sensory appendage is regularly exposed to cold water and thermally conductive soil, leading us to ask whether the surface temperature, a proxy for blood flow to the star, conforms to the local ambient temperature to conserve body heat. Alternatively, given the high functioning and sensory nature of the star, we posited it was possible that the rays may be kept continually warm when foraging, with augmented peripheral blood flow serving the metabolic needs of this tactile sensory organ. To test these ideas, we remotely monitored the surface temperatures of the star and other uninsulated appendages in response to changes in local water or ground temperature in captive, wild-caught star-nosed moles. While the tail responded to increasing heat load through vasodilation, the surface temperature of the star consistently thermoconformed, varying passively in surface temperature, suggesting little evidence for thermoregulatory vasomotion. This thermoconforming response may have evolved as a compensatory response related to the high costs of heat dissipation to water or soil in this actively foraging insectivore. Summary Statement (for JEB Submission)The highly mechanosensitive nasal rays of the star-nosed mole conform closely with ambient temperature thereby minimizing heat loss without apparent changes in sensory performance.

zoology↗

Lifespan differences in visual short-term memory load-modulated functional connectivity

Working memory is critical to higher-order executive processes and declines throughout the adult lifespan. However, our understanding of the neural mechanisms underlying this decline is limited. Recent work suggests that functional connectivity between frontal control and posterior visual regions may be critical, but examinations of age differences therein have been limited to a small set of brain regions and extreme group designs (i.e., comparing young and older adults). In this study, we build on previous research by using a lifespan cohort and a whole-brain approach to investigate working memory load-modulated functional connectivity in relation to age and performance. The article reports on analysis of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. Participants from a population-based lifespan cohort (N=111, age 23-86) performed a visual short-term memory task during functional magnetic resonance imaging. Visual short-term memory was measured with a delayed recall task for visual motion with three different loads. Whole-brain load-modulated connectivity was estimated using psychophysiological interactions in a hundred regions of interest, sorted into seven networks (Schaefer et al., 2018, Yeo et al., 2011). Results showed that load-modulated functional connectivity was strongest within the dorsal attention network followed by the visual network during encoding and maintenance. With increasing age, load-modulated functional connectivity strength decreased throughout the cortex. Within the dorsal attention network, increased load-modulated connectivity strength was related to better task performance in an age-invariant way. Our results demonstrate the widespread negative impact of age on the modulation of functional connectivity by working memory load. Older adults might already be close to ceiling in terms of their resources at the lowest load and therefore less able to further increase connectivity with increasing task demands. HighlightsO_LIWe examine visual short-term memory load-related functional connectivity C_LIO_LIAnd how age and performance affect modulation of connectivity by memory load C_LIO_LIModulation of connectivity is strongest in dorsal attention and visual networks C_LIO_LILoad-modulated connectivity strength decreases with increasing age C_LIO_LILoad-modulated connectivity in the dorsal attention network relates to performance C_LI

neuroscience↗

Evolution of an extreme hemoglobin phenotype contributed to the sub-Arctic specialization of extinct Steller's sea cows

The extinct Stellers sea cow (Hydrodamalis gigas; {dagger}1768) was a whale-sized marine mammal that manifested profound morphological specializations to exploit the harsh coastal climate of the North Pacific. Yet despite first-hand accounts of their biology, little is known regarding the physiological adjustments underlying their evolution to this environment. Here, the adult-expressed hemoglobin (Hb; 2{beta}/{delta}2) of this sirenian is shown to harbor a fixed amino acid replacement at an otherwise invariant position ({beta}/{delta}82Lys[->]Asn) that alters multiple aspects of Hb function. First, our functional characterization of recombinant sirenian Hb proteins demonstrate that the Hb-O2 affinity of this sub-Arctic species was less affected by temperature than those of living (sub)tropical sea cows. This phenotype presumably safeguarded O2 delivery to cool peripheral tissues and largely arises from a reduced intrinsic temperature sensitivity of the H. gigas protein. Additional experiments on H. gigas {beta}/{delta}82Asn[->]Lys mutant Hb further reveal this exchange renders Stellers sea cow Hb unresponsive to the potent intraerythrocytic allosteric effector 2,3-diphosphoglycerate, a radical modification that is the first documented example of this phenotype among mammals. Notably, {beta}/{delta}82Lys[->]Asn moreover underlies the secondary evolution of a reduced blood-O2 affinity phenotype that would have promoted heightened tissue and maternal/fetal O2 delivery. This conclusion is bolstered by analyses of two Stellers sea cow prenatal Hb proteins (Hb Gower I; {zeta}2{varepsilon}2 and HbF; 2{gamma}2) that suggest an exclusive embryonic stage expression pattern, and reveal uncommon replacements in H. gigas HbF ({gamma}38Thr[->]Ile and {gamma}101Glu[->]Asp) that increased Hb-O2 affinity relative to dugong HbF. Finally, the {beta}/{delta}82Lys[->]Asn replacement of the adult/fetal protein is shown to increase protein solubility, which may have elevated red blood cell Hb content within both the adult and fetal circulations and contributed to meeting the elevated metabolic (thermoregulatory) requirements and fetal growth rates associated with this species cold adaptation.

evolutionary biology↗

Bacterioplankton taxa compete for iron along the early spring-summer transition in the Arctic Ocean

Microbial assemblages under sea ice of Dease Strait, Canadian Arctic, were sequenced for metagenomes and metatranscriptomes of the small size fraction (0.2 to 3 {micro}m). The community from early March was typical for this season, with Alpha- and Gammaproteobacteria as the dominant taxa, followed by Thaumarchaeota and Bacteroidetes. Towards summer, Bacteroidetes and particularly the genus Polaribacter, became increasingly dominant, followed by the Gammaproteobacteria. Analysis of genes responsible for microbial acquisition of iron showed an abundance of ABC transporters for divalent cations and ferrous iron. The most abundant transporters, however, were the outer membrane TonB dependent transporters of iron-siderophore complexes. The abundance of iron acquisition genes suggested this element was essential for the microbial assemblage. Interestingly, Gammaproteobacteria were responsible for most of the siderophore synthesis genes. On the contrary, Bacteroidetes did not synthesize siderophores but accounted for most of the transporters, suggesting a role as cheaters in the competition for siderophores as public goods. Likely, this cheating ability of the Bacteroidetes contributed to their dominance in summer.

ecology↗

Dive performance and aquatic thermoregulation of the world's smallest mammalian diver, the American water shrew (Sorex palustris)

Allometry predicts that the 12-17 g American water shrew (Sorex palustris)--the worlds smallest mammalian diver--will have the highest diving metabolic rate coupled with the lowest total body oxygen storage capacity, skeletal muscle buffering capacity, and glycolytic potential of any endothermic diver. Consistent with expectations, and potentially owing to their low thermal inertia, water shrews had a significantly higher diving metabolic rate in 10{degrees}C (8.77 mL O2 g-1 hr-1) compared to 30{degrees}C water (6.57 mL O2 g-1 hr-1). Unlike larger-bodied divers, muscle myoglobin contributed minimally (7.7-12.4%) to total onboard O2 stores of juvenile and adult water shrews, respectively, but was offset by high blood O2 carrying capacities (26.4-26.9 vol. %). Diving was predominantly aerobic, as only 1.2-2.3% of dives in 10 and 30{degrees}C water, respectively, exceeded the calculated aerobic dive limits at these temperatures (10.8-14.4 sec). The mean voluntary dive time of water shrews during 20-min trials in 3-30{degrees}C water was 5.0{+/-}0.1 sec (N=25, n=1628), with a mean maximum dive time of 10.1{+/-}0.4 sec. However, the average dive duration (6.9{+/-}0.2 sec, n=257) of radio-telemetered shrews exclusively foraging in a simulated riparian environment (3{degrees}C water) for 12- to 28-hr suggest that mean (but not maximum) dive times of water shrews in the wild may be longer. Mean dive duration, duration of the longest dive, and total time in water all decreased significantly as water temperature declined, suggesting that shrews employed behavioral thermoregulation to defend against immersion hypothermia. Additionally, free-diving shrews in the 24-hr trials consistently elevated core body temperature by [~]1{degrees}C immediately prior to initiating aquatic foraging bouts, and ended these bouts when body temperature was still at or above normal resting levels ([~]37.8{degrees}C). We suggest this observed pre-dive hyperthermia aids to heighten the impressive somatosensory physiology, and hence foraging efficiency, of this diminutive predator while submerged.

zoology↗

Multiple bouts of high-intensity interval exercise reverse age-related functional connectivity disruptions without affecting motor learning in older adults

Exercise has emerged as an intervention that may mitigate age-related resting state functional connectivity and sensorimotor declines. Here, 42 healthy older adults rested or completed 3 sets of high-intensity interval exercise for a total of 23 minutes, then immediately practiced an implicit motor task with their non-dominant hand across five separate sessions. Participants completed resting stage functional MRI before the first and after the fifth day of practice; they also returned 24-hours and 35-days later to complete short- and long-term retention. Independent component analysis of resting state functional MRI revealed increased connectivity in the frontoparietal, the dorsal attentional, and cerebellar networks and group. seed-based analysis showed strengthened connectivity between the limbic system and right cerebellum, and between the right cerebellum and bilateral middle temporal gyri in the exercise group. There was no motor learning advantage for the exercise group. Our data suggest that exercise paired with an implicit motor learning task in older adults can augment resting state functional connectivity without enhancing behaviour beyond that stimulated by skilled motor practice. Impact statementFive separate bouts of exercise paired with skilled motor practice strengthens resting state networks in brain regions that are susceptible to declines in older adults without affecting motor acquisition or learning.

neuroscience↗

Myoglobin primary structure reveals multiple convergent transitions to semi-aquatic life in the world smallest mammalian divers

Identifying the phylogenomic underpinnings of specialized phenotypes that fueled transitions into new adaptive zones is central to evolutionary biology but is often confounded by a fragmentary fossil record, morphological convergence, and unresolved phylogenetic relationships. The speciose mammalian order Eulipotyphla (e.g., moles, shrews, hedgehogs, solenodons) combines an unusual diversity of semi-aquatic, semi-fossorial, and fossorial forms that arose from terrestrial forbearers, yet the ecomorphological pathways leading to these lifestyles have been disputed for a century and more, calling for novel approaches. Here we resolve previously intractable eulipotyphlan intra-family relationships and establish the net surface charge of the oxygen-storing muscle protein myoglobin-readily determined from its primary structure-as a molecular signature to trace ancient lifestyle transitions based on protein sequence alone. Our analyses confidently resolve fossorial habits having evolved twice in talpid moles and reveal five independent origins of a semi-aquatic lifestyle in the order housing the worlds smallest endothermic divers.

evolutionary biology↗

Physical activity predicts population-level age-related differences in frontal white matter

Physical activity has positive effects on brain health and cognitive function throughout the lifespan. Thus far, few studies have examined the effects of physical activity on white matter (WM) microstructure and psychomotor speed within the same, population-based sample (critical if conclusions are to extend to the wider population). Here, using diffusion tensor imaging and a simple reaction time task within a relatively large population-derived sample (N = 399; 18-87 years) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN), we demonstrate that physical activity mediates the effect of age on white matter integrity, measured with fractional anisotropy. Higher self-reported daily physical activity was associated with greater preservation of WM in several frontal tracts, including the genu of corpus callosum, uncinate fasciculus, external capsule and anterior limb of the internal capsule. We also show that the age-related slowing is mediated by WM integrity in the genu. Our findings contribute to a growing body of work suggesting that a physically active lifestyle may protect against age-related structural disconnection and slowing.

neuroscience↗

Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades

Mitochondrial uncoupling protein 1 (UCP1) is essential for non-shivering thermogenesis in brown adipose tissue and is widely accepted to have played a key thermoregulatory role in small-bodied and neonatal placental mammals that enabled the exploitation of cold environments. Here we map ucp1 sequences from 133 mammals onto a species tree constructed from a [~]51-kb sequence alignment and show that inactivating mutations have occurred in at least eight of the 18 traditional placental orders, thereby challenging the physiological importance of UCP1 across Placentalia. Selection and timetree analyses further reveal that ucp1 inactivations temporally correspond with strong secondary reductions in metabolic intensity in xenarthrans and pangolins, or in six other lineages coincided with a [~]30 million year episode of global cooling in the Paleogene that promoted sharp increases in body mass and cladogenesis evident in the fossil record. Our findings also demonstrate that members of various lineages (e.g., cetaceans, horses, woolly mammoths, Stellers sea cows) evolved extreme cold hardiness in the absence of UCP1-mediated thermogenesis. Finally, we identify ucp1 inactivation as a historical contingency that is linked to the current low species diversity of clades lacking functional UCP1, thus providing the first evidence for species selection related to the presence or absence of a single gene product.

evolutionary biology↗