Social housing protects against age-related working memory decline independently of physical enrichment in rats.
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ABSTRACT:
SUBMITTER: Templer VL
PROVIDER: S-EPMC6349534 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Project description:Engagement in cognitive activity in adulthood is one of the factors that enable successful cognitive aging, both in humans and rodents. However, some studies emphasize that the beneficial effect on cognition of such an activity may reflect carry over from one test situation to another, including memory for procedural aspects of the behavioral tasks, and thus question whether this effect can be limited to the trained cognitive domain or whether it can be transferred to an untrained ones. In the current study, we assessed whether adulthood intermittent working memory training has beneficial effect on long-term memory of aged rats using two very different test situations. To this aim, rats trained in a delayed non-matching to position task in operant box at 3 and 15 months of age were tested in a place learning task in water maze when they were 24 months. The two tasks differ with regard to the cognitive domain but also in their spatial ability requirement and the nature of the reinforcer used. During the memory tests, accuracy of the platform search indicated age-related impairment only in the aged-untrained group. Thus, intermittent training during adult life in a task involving working memory protects aged animals from the deleterious effects of aging on spatial reference memory. This result highlights the long-term beneficial effects of training on a working memory task on an untrained cognitive domain.
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Project description:Human studies suggest that healthy social relationships benefit cognition, yet little is known about the underlying neural mechanisms of this protective effect. In rodents, studies on acute isolation and environmental enrichment (EE) confirm the importance of social exposure. Despite the widely recognized importance of sociality, however, rodent models have yet to explore the independent contributions of social housing divorced of other forms of enrichment. This study dissociates the effects of social and physical enrichment on spatial learning and memory from adulthood to old age. Rats were placed in either single or group housing, provided with ample enrichment, and tested at three time points on several phases/versions of the Barnes maze (BM) (standard, retention probes, variable location, and reversal). We found that sustained social housing enhanced cognitive flexibility, as evidenced by superior acquisition of task set (standard BM), adaptability to a new task set (variable BM), and improved reversal learning (reversal BM). Long-term retention (BM retention probes) of spatial memory was unaffected by housing conditions. Recent studies from our lab, including this report, are the first to show that social housing confers cognitive benefits beyond those of physical enrichment. Importantly, our experimental design is ideal for exploring the neural underpinnings of this socially induced cognitive protection. Understanding how sociality influences cognition will be invaluable to translational models of aging, neuropsychiatric disease, and neurological injury.
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Project description:Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.
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Project description:Accounts of decision-making have long posited the operation of separate, competing valuation systems in the control of choice behavior. Recent theoretical and experimental advances suggest that this classic distinction between habitual and goal-directed (or more generally, automatic and controlled) choice may arise from two computational strategies for reinforcement learning, called model-free and model-based learning. Popular neurocomputational accounts of reward processing emphasize the involvement of the dopaminergic system in model-free learning and prefrontal, central executive-dependent control systems in model-based choice. Here we hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis stress response--believed to have detrimental effects on prefrontal cortex function--should selectively attenuate model-based contributions to behavior. To test this, we paired an acute stressor with a sequential decision-making task that affords distinguishing the relative contributions of the two learning strategies. We assessed baseline working-memory (WM) capacity and used salivary cortisol levels to measure HPA axis stress response. We found that stress response attenuates the contribution of model-based, but not model-free, contributions to behavior. Moreover, stress-induced behavioral changes were modulated by individual WM capacity, such that low-WM-capacity individuals were more susceptible to detrimental stress effects than high-WM-capacity individuals. These results enrich existing accounts of the interplay between acute stress, working memory, and prefrontal function and suggest that executive function may be protective against the deleterious effects of acute stress.
| S-EPMC3876216 | biostudies-literature
Project description:Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient's return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear, because abnormality is often absent in structural imaging findings. Previous studies have demonstrated that WM functional activity estimated from functional magnetic resonance imaging (fMRI) has a high sensitivity to postconcussion WM deficits and may be used to not only evaluate but guide treatment strategies, especially targeting brain areas involved in postconcussion cognitive decline. The purpose of the study was to determine whether machine learning-based models using fMRI biomarkers and demographic or neuropsychological measures at the baseline could effectively predict the 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically matched healthy controls enrolled between September 2015 and August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to their significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after a concussion. Approximately half of the patients experienced prolonged cognitive impairment at the 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy = 87.5%), 6 months (accuracy = 83.3%), and 1 year (accuracy = 83.3%) and performed worse at the 1-year follow-up compared to the baseline assessment (accuracy = 83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.
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Project description:Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.
| S-EPMC4283640 | biostudies-literature
Project description:OBJECTIVES:To investigate associations between level and changes in social isolation and in memory in older men and women. METHODS:The sample included 6,123 women and 5,110 men aged 50+ from the English Longitudinal Study of Aging (ELSA). Extended latent change score models from six measurement occasions every 2 years from 2002 were used to investigate associations between social isolation and memory. Models were adjusted for age, socioeconomic position, and health. RESULTS:Social isolation increased and memory decreased over time. Among men an initially high level of social isolation was associated with a somewhat greater decrease in memory. Among women a greater increase in social isolation predicted a greater decrease in memory and a larger change in social isolation was associated with further larger changes in isolation, although when social isolation reached a higher level it subsequently decreased. CONCLUSIONS:Results suggest that the association between social isolation and memory decline arises because social isolation is associated with increased memory decline rather than poor memory leading to increases in social isolation. Men with high levels of social isolation and women with accumulated social isolation over time are especially affected as these patterns of isolation were associated with more profound memory decline.
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Project description:Previous studies have shown that a rate of temporal decline in visual working memory (vWM) highly depends on a number of memory items. When people retain the information of many (≥ 4) stimuli simultaneously, their memory representations are fragile and rapidly degrade within 2-3 s after an offset (called the "competition" among memory items). When a memory load is low (1 or 2 items), in contrast, the fidelity of vWM is preserved for a longer time because focused attention to the small number of items prevents the temporal degradation. In the present study, we explored neural correlates of this load-dependent decline of vWM in the human brain. Using electroencephalography and a classical change-detection task, we recorded neural measures of vWM that have been reported previously, such as the contralateral delay activity (CDA) and a suppression of alpha power (8-12 Hz). Results indicated that the load-dependent decline of vWM was more clearly reflected in the change in power and speed of alpha/beta rhythm than CDA, suggesting a close relationship of those signals to an attention-based preservation of WM fidelity.
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Project description:Social threat can have adverse effects on cognitive performance, but the brain mechanisms underlying its effects are poorly understood. We investigated the effects of social evaluative threat on working memory (WM), a core component of many important cognitive capabilities. Social threat impaired WM performance during an N-back task and produced widespread reductions in activation in lateral prefrontal cortex and intraparietal sulcus (IPS), among other regions. In addition, activity in frontal and parietal regions predicted WM performance, and mediation analyses identified regions in the bilateral IPS that mediated the performance-impairing effects of social threat. Social threat also decreased connectivity between the IPS and dorsolateral prefrontal cortex, while increasing connectivity between the IPS and the ventromedial prefrontal cortex, a region strongly implicated in the generation of autonomic and emotional responses. Finally, cortisol response to the stressor did not mediate WM impairment but was rather associated with protective effects. These results provide a basis for understanding interactions between social and cognitive processes at a neural systems level.
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Project description:Primates can store sensory stimulus parameters in working memory for subsequent manipulation, but until now, there has been no demonstration of this capacity in rodents. Here we report tactile working memory in rats. Each stimulus is a vibration, generated as a series of velocity values sampled from a normal distribution. To perform the task, the rat positions its whiskers to receive two such stimuli, "base" and "comparison," separated by a variable delay. It then judges which stimulus had greater velocity SD. In analogous experiments, humans compare two vibratory stimuli on the fingertip. We demonstrate that the ability of rats to hold base stimulus information (for up to 8 s) and their acuity in assessing stimulus differences overlap the performance demonstrated by humans. This experiment highlights the ability of rats to perceive the statistical structure of vibrations and reveals their previously unknown capacity to store sensory information in working memory.
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