Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can ...increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age.
Cognitive control over conflicting information has been studied extensively using tasks such as the color-word Stroop, flanker, and spatial conflict task. Neuroimaging studies typically identify a ...fronto-parietal network engaged in conflict processing, but numerous additional regions are also reported. Ascribing putative functional roles to these regions is problematic because some may have less to do with conflict processing per se, but could be engaged in specific processes related to the chosen stimulus modality, stimulus feature, or type of conflict task. In addition, some studies contrast activation on incongruent and congruent trials, even though a neutral baseline is needed to separate the effect of inhibition from that of facilitation. In the first part of this article, we report a systematic review of 34 neuroimaging publications, which reveals that conflict-related activity is reliably reported in the anterior cingulate cortex and bilaterally in the lateral prefrontal cortex, the anterior insula, and the parietal lobe. In the second part, we further explore these candidate “conflict” regions through a novel functional magnetic resonance imaging experiment, in which the same group of subjects perform related visual and auditory Stroop tasks. By carefully controlling for the same task (Stroop), the same to-be-ignored stimulus dimension (word meaning), and by separating out inhibitory processes from those of facilitation, we attempt to minimize the potential differences between the two tasks. The results provide converging evidence that the regions identified by the systematic review are reliably engaged in conflict processing. Despite carefully matching the Stroop tasks, some regions of differential activity remained, particularly in the parietal cortex. We discuss some of the task-specific processes which might account for this finding.
Quantitative microscopy has proven a versatile and powerful phenotypic screening technique. Recently, image-based profiling has shown promise as a means for broadly characterizing molecules' effects ...on cells in several drug-discovery applications, including target-agnostic screening and predicting a compound's mechanism of action (MOA). Several profiling methods have been proposed, but little is known about their comparative performance, impeding the wider adoption and further development of image-based profiling. We compared these methods by applying them to a widely applicable assay of cultured cells and measuring the ability of each method to predict the MOA of a compendium of drugs. A very simple method that is based on population means performed as well as methods designed to take advantage of the measurements of individual cells. This is surprising because many treatments induced a heterogeneous phenotypic response across the cell population in each sample. Another simple method, which performs factor analysis on the cellular measurements before averaging them, provided substantial improvement and was able to predict MOA correctly for 94% of the treatments in our ground-truth set. To facilitate the ready application and future development of image-based phenotypic profiling methods, we provide our complete ground-truth and test data sets, as well as open-source implementations of the various methods in a common software framework.
Abstract
Studies using simple low-level stimuli show that multisensory stimuli lead to greater improvements in processing speed for older adults than young adults. However, there is insufficient ...evidence to explain how these benefits influence performance for more complex processes such as judgement and memory tasks. This study examined how presenting stimuli in multiple sensory modalities (audio–visual) instead of one (audio-only or visual-only) may help older adults to improve their memory and cognitive processing compared to young adults. Young and older adults completed lexical decision (real word vs. pseudoword judgement) and word recall tasks, either independently, or in combination (dual-task), with and without perceptual noise. Older adults were better able to remember words when encoding independently. In contrast, young adults were better able to remember words when encoding in combination with lexical decisions. Both young and older adults had better word recall in the audio–visual condition compared with the audio-only condition. The findings indicate significant age differences when dealing with multiple tasks during encoding. Crucially, there is no greater multisensory benefit for older adults compared to young adults in more complex processes, rather multisensory stimuli can be useful in enhancing cognitive performance for both young and older adults.
Age deficits in memory are widespread, this impacts individuals at a personal level, and investigating memory has been a key focus in cognitive ageing research. Age deficits occur in memory for an ...episode, where information from the environment is integrated through the senses into an episodic event via associative memory. Associating items in memory has been shown to be particularly difficult for older adults but can often be alleviated by providing support from the external environment. The current investigation explored the potential for increased sensory input (multimodal stimuli) to alleviate age deficits in associative memory. Here, we present compelling evidence, supported by Bayesian analysis, for a null age-by-modality interaction.
Across three pre-registered studies, young and older adults (n = 860) completed associative memory tasks either in single modalities or in multimodal formats. Study 1 used either visual text (unimodal) or video introductions (multimodal) to test memory for name-face associations. Studies 2 and 3 tested memory for paired associates. Study 2 used unimodal visual presentation or cross modal visual-auditory word pairs in a cued recall paradigm. Study 3 presented word pairs as visual only, auditory only or audiovisual and tested memory separately for items (individual words) or associations (word pairings).
Typical age deficits in associative memory emerged, but these were not alleviated by multimodal presentation.
The lack of multimodal support for associative memory indicates that perceptual manipulations are less effective than other forms of environmental support at alleviating age deficits in associative memory.
In Spring/Summer 2020, most individuals living in the United States experienced several months of social distancing and stay-at-home orders because of the coronavirus (COVID-19) pandemic. Clinicians, ...restaurant cooks, cashiers, transit operators, and other essential workers (EWs), however, continued to work outside the home during this time in order to keep others alive and maintain a functioning society. In the United States, EWs are often low-income persons of color who are more likely to face socioeconomic vulnerabilities, systemic racism, and health inequities. To assess the various impacts of COVID-19 on EWs, an online survey was distributed to a representative sample of individuals residing in six states during May/June 2020. The sample included 990 individuals who identified as EWs and 736 nonessential workers (NWs). We assessed differences between EW and NW respondents according to three categories related to health equity and social determinants of health: (1) demographics (e.g. race/ethnicity); (2) COVID-19 exposure risk pathways (e.g. ability to social distance); and (3) COVID-19 risk perceptions (e.g. perceived risk of contracting COVID-19). EWs were more likely to be Black or Hispanic than NWs and also had lower incomes and education levels on average. Unsurprisingly, EWs were substantially more likely to report working outside the home and less likely to report social distancing and wearing masks indoors as compared to NWs. EWs also perceived a slightly greater risk of contracting COVID-19. These findings, which we discuss in the context of persistent structural inequalities, systemic racism, and health inequities within the United States, highlight ways in which COVID-19 exacerbates existing socioeconomic vulnerabilities faced by EWs.
Auditory perceptual learning studies tend to focus on the nature of the target stimuli. However, features of the background noise can also have a significant impact on the amount of benefit that ...participants obtain from training. This study explores whether perceptual learning of speech in background babble noise generalizes to other, real-life environmental background noises (car and rain), and if the benefits are sustained over time.
Normal-hearing native English speakers were randomly assigned to a training (
= 12) or control group (
= 12). Both groups completed a pre- and post-test session in which they identified Bamford-Kowal-Bench (BKB) target words in babble, car, or rain noise. The training group completed speech-in-babble noise training on three consecutive days between the pre- and post-tests. A follow up session was conducted between 8 and 18 weeks after the post-test session (training group:
= 9; control group:
= 7).
Participants who received training had significantly higher post-test word identification accuracy than control participants for all three types of noise, although benefits were greatest for the babble noise condition and weaker for the car- and rain-noise conditions. Both training and control groups maintained their pre- to post-test improvement over a period of several weeks for speech in babble noise, but returned to pre-test accuracy for speech in car and rain noise.
The findings show that training benefits can show some generalization from speech-in-babble noise to speech in other types of environmental noise. Both groups sustained their learning over a period of several weeks for speech-in-babble noise. As the control group received equal exposure to all three noise types, the sustained learning with babble noise, but not other noises, implies that a structural feature of babble noise was conducive to the sustained improvement. These findings emphasize the importance of considering the background noise as well as the target stimuli in auditory perceptual learning studies.
About 70% of all breast cancers are estrogen receptor alpha positive (ER+) and are treated with antiestrogens. However, 50% of ER + tumors develop resistance to these drugs (endocrine resistance). In ...endocrine resistant cells, an adaptive pathway called the unfolded protein response (UPR) is elevated that allows cells to tolerate stress more efficiently than in sensitive cells. While the precise mechanism remains unclear, the UPR can trigger both pro-survival and pro-death outcomes that depend on the nature and magnitude of the stress. In this study, we identified MYC, an oncoprotein that is upregulated in endocrine resistant breast cancer, as a regulator of the UPR in glucose-deprived conditions.
ER+ human breast cancer cell lines (LCC1, LCC1, LY2 and LCC9) and rat mammary tumors were used to confirm upregulation of MYC in endocrine resistance. To evaluate functional relevance of proteins, siRNA-mediated inhibition or small molecule inhibitors were used. Cell density/number was evaluated with crystal violet assay; cell cycle and apoptosis were measured by flow cytometry. Relative quantification of glutamine metabolites were determined by mass spectrometry. Signaling molecules of the UPR, apoptosis or autophagy pathways were investigated by western blotting.
Increased MYC function in resistant cells correlated with increased dependency on glutamine and glucose for survival. Inhibition of MYC reduced cell growth and uptake of both glucose and glutamine in resistant cells. Interestingly, in glucose-deprived conditions, glutamine induced apoptosis and necrosis, arrested autophagy, and triggered the unfolded protein response (UPR) though GRP78-IRE1α with two possible outcomes: (i) inhibition of cell growth by JNK activation in most cells and, (ii) promotion of cell growth by spliced XBP1 in the minority of cells. These disparate effects are regulated, at different signaling junctions, by MYC more robustly in resistant cells.
Endocrine resistant cells overexpress MYC and are better adapted to withstand periods of glucose deprivation and can use glutamine in the short term to maintain adequate metabolism to support cell survival. Our findings reveal a unique role for MYC in regulating cell fate through the UPR, and suggest that targeting glutamine metabolism may be a novel strategy in endocrine resistant breast cancer.
We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of ...routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome.
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