Many but not all cognitive abilities decline during ageing. Some even improve due to lifelong experience. The critical capacities of attention and executive functions have been widely posited to decline. However, these capacities are composed of multiple components, so multifaceted ageing outcomes might be expected. Indeed, prior findings suggest that whereas certain attention/executive functions clearly decline, others do not, with hints that some might even improve. We tested ageing effects on the alerting, orienting and executive (inhibitory) networks posited by Posner and Petersen’s influential theory of attention, in a cross-sectional study of a large sample (N = 702) of participants aged 58–98. Linear and nonlinear analyses revealed that whereas the efficiency of the alerting network decreased with age, orienting and executive inhibitory efficiency increased, at least until the mid-to-late 70s. Sensitivity analyses indicated that the patterns were robust. The results suggest variability in age-related changes across attention/executive functions, with some declining while others improve.
Decision-making and representations of arousal are intimately linked. Behavioral investigations have classically shown that either too little or too much bodily arousal is detrimental to decision-making, indicating that there is an inverted “U” relationship between bodily arousal and performance. How these processes interact at the level of single neurons as well as the neural circuits involved are unclear. Here we recorded neural activity from orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex (dACC) of macaque monkeys while they made reward-guided decisions. Heart rate (HR) was also recorded and used as a proxy for bodily arousal. Recordings were made both before and after subjects received excitotoxic lesions of the bilateral amygdala. In intact monkeys, higher HR facilitated reaction times (RTs). Concurrently, a set of neurons in OFC and dACC selectively encoded trial-by-trial variations in HR independent of reward value. After amygdala lesions, HR increased, and the relationship between HR and RTs was altered. Concurrent with this change, there was an increase in the proportion of dACC neurons encoding HR. Applying a population-coding analysis, we show that after bilateral amygdala lesions, the balance of encoding in dACC is skewed away from signaling either reward value or choice direction toward HR coding around the time that choices are made. Taken together, the present results provide insight into how bodily arousal and decision-making are signaled in frontal cortex.
Background and Objectives: Observational research has shown that a substantial proportion of all dementia cases worldwide is attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the LIfestyle for BRAin health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population. Methods: Cross-sectional data was used from the observational population-based cohort of The Maastricht Study.. The weighted compound score of LIBRA (including twelve dementia risk and protective factors, e.g. hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, grey matter, CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in three domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SD below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modelling were used, adjusted for age, sex, education, intracranial volume and type-2 diabetes. Results: Participants (n=4,164; mean age 59y; 49.7% men) with higher LIBRA scores (mean=1.19, range=-2.7 to +9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β=0.051, p=.002), and lower scores on information processing speed (β=-0.067, p=.001) and executive function and attention (β=-0.065, p=.004). Only in men, associations between LIBRA and volumes of grey matter (β=-0.093, p
The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.
Background The high prevalence of office stress and its detrimental health consequences are of concern to individuals, employers and society at large. Laboratory studies investigating office stress have mostly relied on data from participants that were tested individually on abstract tasks. In this study, we examined the effect of psychosocial office stress and work interruptions on the psychobiological stress response in a realistic but controlled group office environment. We also explored the role of cognitive stress appraisal as an underlying mechanism mediating the relationship between work stressors and the stress response. Methods and Materials Ninety participants (44 female; mean age 23.11 ± 3.80) were randomly assigned to either a control condition or one of two experimental conditions in which they were exposed to psychosocial stress with or without prior work interruptions in a realistic multi-participant laboratory setting. To induce psychosocial stress, we adapted the Trier Social Stress Test for Groups to an office environment. Throughout the experiment, we continuously monitored heart rate and heart rate variability. Participants repeatedly reported on their current mood, calmness, wakefulness and perceived stress and gave saliva samples to assess changes in salivary cortisol and salivary alpha-amylase. Additionally, cognitive appraisal of the psychosocial stress test was evaluated. Results Our analyses revealed significant group differences for most outcomes during or immediately after the stress test (i.e., mood, calmness, perceived stress, salivary cortisol, heart rate, heart rate variability) and during recovery (i.e., salivary cortisol and heart rate). Interestingly, the condition that experienced work interruptions showed a higher increase of cortisol levels but appraised the stress test as less threatening than individuals that experienced only psychosocial stress. Exploratory mediation analyses revealed a blunted response in subjective measures of stress, which was partially explained by the differences in threat appraisal. Discussion The results showed that experimentally induced work stress led to significant responses of subjective measures of stress, the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. However, there appears to be a discrepancy between the psychological and biological responses to preceding work interruptions. Appraising psychosocial stress as less threatening but still as challenging could be an adaptive way of coping and reflect a state of engagement and eustress.
During music listening, humans routinely acquire the regularities of the acoustic sequences and use them to anticipate and interpret the ongoing melody. Specifically, in line with this predictive framework, it is thought that brain responses during such listening reflect a comparison between the bottom-up sensory responses and top-down prediction signals generated by an internal model that embodies the music exposure and expectations of the listener. To attain a clear view of these predictive responses, previous work has eliminated the sensory inputs by inserting “artificial” silences (or sound omissions) that leave behind only the corresponding predictions of the thwarted expectations. Here we demonstrate a new alternate approach in which we decode the predictive EEG responses to the silent intervals that are naturally interspersed within the music. We did this as participants (experiment 1: twenty participants, ten female; experiment 2: twenty-one participants, 6 female) both listened or imagined Bach piano melodies. Prediction signals were quantified and assessed via a computational model of the melodic structure of the music, and were shown to exhibit the same response characteristics when measured during listening or imagining. These include an inverted polarity for both silence and imagined responses relative to listening, as well as response magnitude modulations that precisely reflect the expectations of notes and silences in both listening and imagery conditions. These findings therefore provide a unifying view that links results from many previous paradigms, including omission reactions and the expectation modulation of sensory responses, all in the context of naturalistic music listening. SIGNIFICANCE STATEMENT: Music perception depends on our ability to learn and detect melodic structures. Our brain has been suggested to do so by actively predicting upcoming music notes, a process inducing instantaneous neural responses as the music confronts these expectations. Here we studied this prediction process using EEG recorded while participants listen to and imagine Bach melodies. Specifically, we examined neural signals during the ubiquitous musical pauses (or silent intervals) in a music stream, and analyzed them in contrast to the imagery responses. We find that imagined predictive responses are routinely co-opted during ongoing music listening. These conclusions are revealed by a new paradigm using listening and imagery of naturalistic melodies.
During aesthetically appealing visual experiences, visual content provides a basis for computation of affectively tinged representations of aesthetic value. How this happens in the brain is largely unexplored. Using engaging video clips of natural landscapes, we tested whether cortical regions that respond to perceptual aspects of an environment (e.g., spatial layout, object content and motion) were directly modulated by rated aesthetic appeal. Twenty-four participants watched a series of videos of natural landscapes while being scanned using functional magnetic resonance imaging (fMRI) and reported both continuous ratings of enjoyment (during the videos) and overall aesthetic judgments (after each video). Although landscape videos engaged a greater expanse of high-level visual cortex compared to that observed for images of landscapes, independently localized category-selective visual regions (e.g., scene-selective parahippocampal place area and motion-selective hMT+) were not significantly modulated by aesthetic appeal. Rather, a whole-brain analysis revealed modulations by aesthetic appeal in ventral (collateral sulcus) and lateral (middle occipital sulcus, posterior middle temporal gyrus) clusters that were adjacent to scene and motion selective regions. These findings suggest that aesthetic appeal per se is not represented in well-characterized feature- and category-selective regions of visual cortex. Rather, we propose that the observed activations reflect a local transformation from a feature-based visual representation to a representation of “elemental affect”, computed through information-processing mechanisms that detect deviations from an observer’s expectations. Furthermore, we found modulation by aesthetic appeal in subcortical reward structures but not in regions of the default-mode network (DMN) nor orbitofrontal cortex, and only weak evidence for associated changes in functional connectivity. In contrast to other visual aesthetic domains, aesthetically appealing interactions with natural landscapes may rely more heavily on comparisons between ongoing stimulation and well-formed representations of the natural world, and less on top-down processes for resolving ambiguities or assessing self-relevance.
INTRODUCTION Fundamental circuit features of the mouse visual system emerge before the onset of vision, allowing the mouse to perceive objects and detect visual motion immediately upon eye opening. How the mouse visual system achieves self-organization by the time of eye opening without structured external sensory input is not well understood. In the absence of sensory drive, the developing retina generates spontaneous activity in the form of propagating waves. Past work has shown that spontaneous retinal waves provide the correlated activity necessary to refine the development of gross topographic maps in downstream visual areas, such as retinotopy and eye-specific segregation, but it is unclear whether waves also convey information that instructs the development of higher-order visual response properties, such as direction selectivity, at eye opening. RATIONALE Spontaneous retinal waves exhibit stereotyped changing spatiotemporal patterns throughout development. To characterize the spatiotemporal properties of waves during development, we used one-photon wide-field calcium imaging of retinal axons projecting to the superior colliculus in awake neonatal mice. We identified a consistent propagation bias that occurred during a transient developmental window shortly before eye opening. Using quantitative analysis, we investigated whether the directionally biased retinal waves conveyed ethological information relevant to future visual inputs. To understand the origin of directional retinal waves, we used pharmacological, optogenetic, and genetic strategies to identify the retinal circuitry underlying the propagation bias. Finally, to evaluate the role of directional retinal waves in visual system development, we used pharmacological and genetic strategies to chronically manipulate wave directionality and used two-photon calcium imaging to measure responses to visual motion in the midbrain superior colliculus immediately after eye opening. RESULTS We found that spontaneous retinal waves in mice exhibit a distinct propagation bias in the temporal-to-nasal direction during a transient window of development (postnatal day 8 to day 11). The spatial geometry of directional wave flow aligns strongly with the optic flow pattern generated by forward self-motion, a dominant natural optic flow pattern after eye opening. We identified an intrinsic asymmetry in the retinal circuit that enforced the wave propagation bias involving the same circuit elements necessary for motion detection in the adult retina, specifically asymmetric inhibition from starburst amacrine cells through γ-aminobutyric acid type A (GABA A ) receptors. Finally, manipulation of directional retinal waves, through either the chronic delivery of gabazine to block GABAergic inhibition or the starburst amacrine cell–specific mutation of the FRMD7 gene, impaired the development of responses to visual motion in superior colliculus neurons downstream of the retina. CONCLUSION Our results show that spontaneous activity in the developing retina prior to vision onset is structured to convey essential information for the development of visual response properties before the onset of visual experience. Spontaneous retinal waves simulate future optic flow patterns produced by forward motion through space, due to an asymmetric retinal circuit that has an evolutionarily conserved link with motion detection circuitry in the mature retina. Furthermore, the ethologically relevant information relayed by directional retinal waves enhances the development of higher-order visual function in the downstream visual system prior to eye opening. These findings provide insight into the activity-dependent mechanisms that regulate the self-organization of brain circuits before sensory experience begins.
Accumulating evidence shows that Coronavirus Disease 19 (COVID-19) survivors may encounter prolonged mental issues, especially post-traumatic stress symptoms (PTSS). Despite manifesting a plethora of behavioral or mental issues in COVID-19 survivors, previous studies illustrated that static brain functional networks of these survivors remain intact. The insignificant results could be due to the conventional statistic network analysis was unable to reveal information that can vary considerably in different temporal scales. In contrast, time-varying characteristics of the dynamic functional networks may help reveal important brain abnormalities in COVID-19 survivors. To test this hypothesis, we assessed PTSS and collected functional magnetic resonance imaging (fMRI) with COVID-19 survivors discharged from hospitals and matched controls. Results showed that COVID-19 survivors self-reported a significantly higher PTSS than controls. Tapping into the moment-to-moment variations of the fMRI data, we captured the dynamic functional network connectivity (dFNC) states, and three discriminative reoccurring brain dFNC states were identified. First of all, COVID-19 survivors showed an increased occurrence of a dFNC state with heterogeneous patterns between sensorimotor and visual networks. More importantly, the occurrence rate of this state was significantly correlated with the severity of PTSS. Finally, COVID-19 survivors demonstrated decreased topological organizations in this dFNC state than controls, including the node strength, degree, and local efficiency of the supplementary motor area. To conclude, our findings revealed the altered temporal characteristics of functional networks and their associations with PTSS due to COVID- 19. The current results highlight the importance of evaluating dynamic functional network changes with COVID-19 survivors.
Compulsive drug use despite adverse consequences defines addiction. While mesolimbic dopamine signaling is sufficient to drive compulsion, psychostimulants such as cocaine also boost extracellular serotonin (5-HT) by inhibiting reuptake. We used SERT Met172 knockin (SertKI) mice carrying a transporter that no longer binds cocaine to abolish 5-HT transients during drug self-administration. SertKI mice showed an enhanced transition to compulsion. Conversely, pharmacologically elevating 5-HT reversed the inherently high rate of compulsion transition with optogenetic dopamine self-stimulation. The bidirectional effect on behavior is explained by presynaptic depression of orbitofrontal cortex–to–dorsal striatum synapses induced by 5-HT via 5-HT1B receptors. Consequently, in projection-specific 5-HT1B receptor knockout mice, the fraction of individuals compulsively self-administering cocaine was elevated. Prevention of compulsive cocaine taking Over time, about 20% of chronic cocaine users lose control and become addicted. There are indications that the differential efficacy of the brain serotonin (5-HT) system may be involved in the vulnerability to drug addiction. However, the relevant circuits and underlying cellular processes remain elusive. Li et al. discovered a synaptic mechanism in mice that underlies the modulatory role of 5-HT in reducing the likelihood of transition to compulsion and eventually addiction (see the Perspective by Miyazaki and Miyazaki). Cocaine binds to 5-HT transporters to block 5-HT reuptake. The elevated extracellular 5-HT activates 5-HT1B receptors and causes presynaptic depression of a projection from the orbitofrontal cortex to the dorsal striatum. These changes reduce the likelihood of inducing postsynaptic potentiation at these synapses, which ultimately drives compulsion. —PRS