Stress, cognition and the nervous system

Stress, as defined by Selye, is the non-specific response of an organism to any demand made upon it. The response varies in intensity, depending on age, experience and genetic makeup. These demands, or stressors, can be physical, social or psychological. This concept has been challenged by others and the importance of perception and cognition in the stress response is argued strongly here. The role or cognition in reacting to external stressors is reviewed in the light of the three brain model and the differing functions of the right and left hemisphere. Techniques such as drugs and cognitive restructuring for altering perception and cognition are discussed. Cognitive restructuring is an important technique used in psychotherapy to enable patients to achieve more appropriate emotional responses and consequent behaviours.     

Physical Exercise Enhances Cognitive Flexibility as Well as Astrocytic and Synaptic Markers in the Medial Prefrontal Cortex

Physical exercise enhances a wide range of cognitive functions in humans. Running-induced cognitive enhancement has also been demonstrated in rodents but with a strong emphasis on tasks that require the hippocampus. Additionally, studies designed to identify mechanisms that underlie cognitive enhancement with physical exercise have focused on running-induced changes in neurons with little attention paid to such changes in astrocytes. To further our understanding of how the brain changes with physical exercise, we investigated whether running alters performance on cognitive tasks that require the prefrontal cortex and whether any such changes are associated with astrocytic, as well as neuronal, plasticity. We found that running enhances performance on cognitive tasks known to rely on the prefrontal cortex. By contrast, we found no such improvement on a cognitive task known to rely on the perirhinal cortex. Moreover, we found that running enhances synaptic, dendritic and astrocytic measures in several brain regions involved in cognition but that changes in the latter measures were more specific to brain regions associated with cognitive improvements. These findings suggest that physical exercise induces widespread plasticity in both neuronal and nonneuronal elements and that both types of changes may be involved in running-induced cognitive enhancement.     

An anatomofunctional brain database

This study proposes a closer look at the neuropsychological method defined as the study of the neural bases of the behavioural and cognitive functions using an organisation-representation model for current data and knowledge of the brain, and the application of an anatomofunctional database. A Centre of Cognitive Anatomy (CAC) was set up for the collection and processing of neuronatomical, neuropsychological, and psycho-behavioural data for patients presenting sequels of focal brain damage. Such a system would allow concurrent treatment of anatomical and functional data. We would expect the results from such a model to produce stable 'anatomofunctional laws' that would be independent of all inter-individual variations in the functioning of the brain and could be checked against the entire database of information. A direct application would be the improvement of cognitive and/or behavioural rehabilitation of patients with brain damage.     

The Associations of Objectively Measured Physical Activity and Sedentary Time with Cognitive Functions in School-Aged Children

Low levels of physical activity among children have raised concerns over the effects of a physically inactive lifestyle, not only on physical health but also on cognitive prerequisites of learning. This study examined how objectively measured and self-reported physical activity and sedentary behavior are associated with cognitive functions in school-aged children. The study population consisted of 224 children from five schools in the Jyväskylä school district in Finland (mean age 12.2 years; 56% girls), who participated in the study in the spring of 2011. Physical activity and sedentary time were measured objectively for seven consecutive days using the ActiGraph GT1M/GT3X accelerometer. Self-reported moderate to vigorous physical activity (MVPA) and screen time were evaluated with the questions used in the “WHO Health Behavior in School-aged Children” study. Cognitive functions including visual memory, executive functions and attention were evaluated with a computerized Cambridge Neuropsychological Test Automated Battery by using five different tests. Structural equation modeling was applied to examine how objectively measured and self-reported MVPA and sedentary behavior were associated with cognitive functions. High levels of objectively measured MVPA were associated with good performance in the reaction time test. High levels of objectively measured sedentary time were associated with good performance in the sustained attention test. Objectively measured MVPA and sedentary time were not associated with other measures of cognitive functions. High amount of self-reported computer/video game play was associated with weaker performance in working memory test, whereas high amount of computer use was associated with weaker performance in test measuring shifting and flexibility of attention. Self-reported physical activity and total screen time were not associated with any measures of cognitive functions. The results of the present study propose that physical activity may benefit attentional processes. However, excessive video game play and computer use may have unfavorable influence on cognitive functions.     

Modification of gibberellin biosynthesis in the grafted apple scion allows control of tree height independent of the rootstock

The availability of short stature apple scions that required minimal applications of chemical growth retardants and could be used with a range of rootstocks would be of considerable benefit to fruit growers. We have suppressed the expression of a gene encoding the gibberellin (GA) biosynthetic enzyme GA 20-oxidase to reduce the levels of bioactive GAs in a scion variety, resulting in significant reductions in stem height. Application of GA3 reversed the effect. The scion remained dwarfed after grafting on to normally invigorating rootstocks, whilst control plants of the same cultivar displayed the expected vigour when grafted on to these rootstocks. This approach could be applicable to any perennial crop variety, allowing dwarf trees to be obtained on any available rootstock or on their own roots without the need for chemical growth retardant application. In effect, seedlings that are well suited to local conditions (drought, salinity) could be employed as tree rootstocks, as could existing rootstocks valued for characters other than vigour control, such as pest and disease resistance.     

Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

Objective

The decrease in verbal fluency in patients with Parkinson’s disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking.

Methods

To explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism.

Results

We did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency.

Conclusions

These results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms.     

OUGHT WE TO ENHANCE OUR COGNITIVE CAPACITIES?1

Ought we to improve our cognitive capacities beyond the normal human range? It might be a good idea to level out differences between peoples cognitive capacities; and some people's reaching beyond normal capacities may have some good side‐effects on society at large (but also bad side‐effects, of course). But is there any direct gain to be made from having ones cognitive capacities enhanced? Would this as such make our lives go better? No, I argue; or at least there doesn't seem to be any evidence suggesting that it would. And it doesn't matter whether we consider the question from a narrow hedonistic perspective, from a more refined hedonistic perspective, from a desire‐satisfaction view, or from some reasonable objective list view of what makes a life go well. Only an extremely perfectionist – and implausible – view of what makes our lives go well could support any direct value in cognitive enhancement. Finally, our sense of identity gives us no good reasons to enhance even our capacity to remember. So, cognitive enhancement as such would not improve our lives.     

Gebruiksvriendelijkheid van computerondersteunde cognitieve training bij psychogeriatrische patiënten met lichte tot matige cognitieve functiestoornissen

Cognitive impairment associated with dementia is characterized by a continuous decline. Cognitive training is a method to train specific brain functions such as memory and attention to prevent or slow down cognitive decline. A small number of studies has shown that cognitive training on a computer has a positive effect on both cognition and mood in people with cognitive impairment. This pilot study tested if serious games could be integrated in a psychogeriatric rehabilitation center. Fourteen psychogeriatric patients participated twice weekly in cognitive training sessions on a computer. Both the participants and the facilitator reported positive interactions and outcomes. However, after five weeks only half of the sample still participated in the training. This was partly because of patient turn-over as well as incorporating this new task in the facilitators’ daily work. Fear of failure, physical limitations and rapidly decreasing cognitive function led to drop out according to the facilitator. The engagement of patients in the games and the role of the facilitator seemed essential for success, especially monitoring (and adjusting) the difficulty level of the program for every individual participant.     

Pyruvate accumulation may contribute to acceleration-induced impairment of physical and cognitive abilities: an experimental study

Background: Fatigue can be induced after acceleration exposure, however its mechanism is still unclear. The aim of the present study was to examine whether metabolites’ changes can decrease cognitive and physical function after acceleration. Methods: Graybiel scale and Fatigue Self-rating scale were used to assess the seasickness and fatigue degrees of 87 male seafarers respectively after sailing. To test the effect of pyruvate on cognitive and physical functions, five different doses of pyruvate were administrated into rats. Insulin can reduce the accumulation of pyruvate. To observe the insulin effect on pyruvate, cognitive and physical functions after acceleration, insulin administration or treatment of promoting insulin secretion was used. Physical and cognitive functions were assessed using open field test (OFT), morris water maze (MWM) and loaded swimming test (LST) in animals. Results: Physical and cognitive abilities were decreased obviously, and serum pyruvate increased mostly in human and rats after acceleration. Compared with vehicle group, physical and cognitive abilities were significantly decreased after pyruvate administration. Besides, we found a significant decline in adenosine triphosphate (ATP) concentration and pyruvate dehydrogenase (PDH) activity in the hippocampus, prefrontal cortex, liver, and muscle of rats treated with acceleration or pyruvate injection, while insulin administration or treatment of promoting insulin secretion markedly alleviated this decline and the impairment of physical and cognitive abilities, compared with the control group. Conclusion: Our results indicate that pyruvate has a negative effect on physical and cognitive abilities after acceleration. Insulin can inhibit pyruvate accumulation and cognitive and physical function after acceleration exposure.     

Biological Mechanisms of Physical Activity in Preventing Cognitive Decline

In order to guarantee better conditions for competition, the nervous system has developed not only mechanisms controlling muscle effectors, but also retrograde systems that, starting from peripheral structures, may influence brain functions. Under such perspective, physical activity could play an important role in influencing cognitive brain functions including learning and memory. The results of epidemiological studies (cross-sectional, prospective and retrospective) support a positive relationship between cognition and physical activities. Recent meta-analysis confirmed a significant effect of exercise on cognitive functions. However, the biological mechanisms that underlie such beneficial effects are still to be completely elucidated. They include supramolecular mechanisms (e.g. neurogenesis, synaptogenesis, and angiogenesis) which, in turn, are controlled by molecular mechanisms, such as BDNF, IGF-1, hormone and second messengers.     

Can physical activity improve the mental health of older adults?

The world population is aging rapidly. Whilst this dramatic demographic change is a desirable and welcome phenomenon, particularly in view of people's increasing longevity, it's social, financial and health consequences can not be ignored. In addition to an increase of many age related physical illnesses, this demographic change will also lead to an increase of a number of mental health problems in older adults and in particular of dementia and depression. Therefore, any health promotion approach that could facilitate introduction of effective primary, secondary and even tertiary prevention strategies in old age psychiatry would be of significant importance. This paper explores physical activity as one of possible health promotion strategies and evaluates the existing evidence that supports its positive effect on cognitive impairment and depression in later life.     

Principal Networks

Graph representations of brain connectivity have attracted a lot of recent interest, but existing methods for dividing such graphs into connected subnetworks have a number of limitations in the context of neuroimaging. This is an important problem because most cognitive functions would be expected to involve some but not all brain regions. In this paper we outline a simple approach for decomposing graphs, which may be based on any measure of interregional association, into coherent “principal networks”. The technique is based on an eigendecomposition of the association matrix, and is closely related to principal components analysis. We demonstrate the technique using cortical thickness and diffusion tractography data, showing that the subnetworks which emerge are stable, meaningful and reproducible. Graph-theoretic measures of network cost and efficiency may be calculated separately for each principal network. Unlike some other approaches, all available connectivity information is taken into account, and vertices may appear in none or several of the subnetworks. Subject-by-subject “scores” for each principal network may also be obtained, under certain circumstances, and related to demographic or cognitive variables of interest.     

Physician attitudes towards pharmacological cognitive enhancement: safety concerns are paramount

The ethical dimensions of pharmacological cognitive enhancement have been widely discussed in academic circles and the popular media, but missing from the conversation have been the perspectives of physicians - key decision makers in the adoption of new technologies into medical practice. We queried primary care physicians in major urban centers in Canada and the United States with the aim of understanding their attitudes towards cognitive enhancement. Our primary hypothesis was that physicians would be more comfortable prescribing cognitive enhancers to older patients than to young adults. Physicians were presented with a hypothetical pharmaceutical cognitive enhancer that had been approved by the regulatory authorities for use in healthy adults, and was characterized as being safe, effective, and without significant adverse side effects. Respondents overwhelmingly reported increasing comfort with prescribing cognitive enhancers as the patient age increased from 25 to 65. When asked about their comfort with prescribing extant drugs that might be considered enhancements (sildenafil, modafinil, and methylphenidate) or our hypothetical cognitive enhancer to a normal, healthy 40 year old, physicians were more comfortable prescribing sildenafil than any of the other three agents. When queried as to the reasons they answered as they did, the most prominent concerns physicians expressed were issues of safety that were not offset by the benefit afforded the individual, even in the face of explicit safety claims. Moreover, many physicians indicated that they viewed safety claims with considerable skepticism. It has become routine for safety to be raised and summarily dismissed as an issue in the debate over pharmacological cognitive enhancement; the observation that physicians were so skeptical in the face of explicit safety claims suggests that such a conclusion may be premature. Thus, physician attitudes suggest that greater weight be placed upon the balance between safety and benefit in consideration of pharmacological cognitive enhancement.     

White coat hyperglycaemia: disparity between diabetes clinic and home blood glucose concentrations.

OBJECTIVES--To identify patients with discrepantly high clinic blood glucose concentrations compared with self reported values and to assess whether such patients have errors in self monitoring technique. To determine whether, in patients with good technique, the discrepancy is a transient phenomenon related to clinic attendance. DESIGN--Prospective study of diabetes clinic patients recruited over six months. SETTING--Outpatient diabetes clinic of a teaching hospital. SUBJECTS--34 consecutive patients with non-insulin dependent diabetes who had had at least two consecutive clinic blood glucose concentrations more than 5 mmol/l higher than the mean self reported concentration. MAIN OUTCOME MEASURES--Assessment of monitoring technique; presence of cognitive or physical impairment; serum fructosamine concentration; home and clinic blood glucose concentrations. RESULTS--15 of 34 patients had errors in monitoring technique, 12 of whom had cognitive or physical impairment. In the remaining 19, the mean (SD) blood glucose concentrations of capillary and venous samples taken at home (10.2 (0.6) and 12.2 (1.1) mmol/l respectively) were significantly lower than in those taken at the clinic (16.8 (1.6) mmol/l, p < 0.0002). The fructosamine concentration was significantly higher in patients with monitoring errors than those without (2.4 (0.4) v 1.8 (0.4) mmol/l, p < 0.0001). CONCLUSIONS--"White coat" hyperglycaemia was detected in about half the patients but errors in technique accounted for the rest of the discrepancies. Patients'' ability should be assessed before teaching self monitoring and the technique checked regularly.     

Complementary remedy of aged-related learning and memory deficits via exogenous choline acetyltransferase

The present study aimed to examine whether the aged mice with naturally occurring cognitive deficits in learning and memory would benefit from supplementation of choline acetyltransferase (ChAT), the biosynthetic enzyme for neurotransmitter acetylcholine. Delivered by protein transduction domain (PTD), ChAT could pass through the blood-brain barrier, enter the neurons, interact with heat shock protein 70kDa, and retain enzyme activity. In behavior tests, PTD-ChAT given to the aged and memory-deficient mice almost completely reversed the behavioral changes, such as impairment of memory retention in the step-through test (an index of long-term memory) and prolonged swimming time in water maze test (an index of spatial recognition memory). The results suggest a novel and potential therapeutic use of PTD-ChAT in the age-related cognitive deficits.     

Comparison of total parathyroidectomy without autotransplantation and without thymectomy versus total parathyroidectomy with autotransplantation and with thymectomy for secondary hyperparathyroidism: TOPAR PILOT-Trial

Introduction

The clinical significance of a treatment effect demonstrated in a randomized trial is typically assessed by reference to differences in event rates at the group level. An alternative is to make individualized predictions for each patient based on a prediction model. This approach is growing in popularity, particularly for cancer. Despite its intuitive advantages, it remains plausible that some prediction models may do more harm than good. Here we present a novel method for determining whether predictions from a model should be used to apply the results of a randomized trial to individual patients, as opposed to using group level results.

Methods

We propose applying the prediction model to a data set from a randomized trial and examining the results of patients for whom the treatment arm recommended by a prediction model is congruent with allocation. These results are compared with the strategy of treating all patients through use of a net benefit function that incorporates both the number of patients treated and the outcome. We examined models developed using data sets regarding adjuvant chemotherapy for colorectal cancer and Dutasteride for benign prostatic hypertrophy.

Results

For adjuvant chemotherapy, we found that patients who would opt for chemotherapy even for small risk reductions, and, conversely, those who would require a very large risk reduction, would on average be harmed by using a prediction model; those with intermediate preferences would on average benefit by allowing such information to help their decision making. Use of prediction could, at worst, lead to the equivalent of an additional death or recurrence per 143 patients; at best it could lead to the equivalent of a reduction in the number of treatments of 25% without an increase in event rates. In the Dutasteride case, where the average benefit of treatment is more modest, there is a small benefit of prediction modelling, equivalent to a reduction of one event for every 100 patients given an individualized prediction.

Conclusion

The size of the benefit associated with appropriate clinical implementation of a good prediction model is sufficient to warrant development of further models. However, care is advised in the implementation of prediction modelling, especially for patients who would opt for treatment even if it was of relatively little benefit.     

Evolution favors protein mutational robustness in sufficiently large populations

Background  

An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties.     

EEG power spectral density in locked-in and completely locked-in state patients: a longitudinal study

Persons with their eye closed and without any means of communication is said to be in a completely locked-in state (CLIS) while when they could still open their eyes actively or passively and have some means of communication are said to be in locked-in state (LIS). Two patients in CLIS without any means of communication, and one patient in the transition from LIS to CLIS with means of communication, who have Amyotrophic Lateral Sclerosis were followed at a regular interval for more than 1 year. During each visit, resting-state EEG was recorded before the brain–computer interface (BCI) based communication sessions. The resting-state EEG of the patients was analyzed to elucidate the evolution of their EEG spectrum over time with the disease’s progression to provide future BCI-research with the relevant information to classify changes in EEG evolution. Comparison of power spectral density (PSD) of these patients revealed a significant difference in the PSD’s of patients in CLIS without any means of communication and the patient in the transition from LIS to CLIS with means of communication. The EEG of patients without any means of communication is devoid of alpha, beta, and higher frequencies than the patient in transition who still had means of communication. The results show that the change in the EEG frequency spectrum may serve as an indicator of the communication ability of such patients.Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09639-w) contains supplementary material, which is available to authorized users.     

Do altered energy metabolism or spontaneous locomotion ‘mediate’ decelerated senescence?

That one or multiple measures of metabolic rate may be robustly associated with, or possibly even causative of, the progression of aging‐resultant phenotypes such as lifespan is a long‐standing, well‐known mechanistic hypothesis. To broach this hypothesis, we assessed metabolic function and spontaneous locomotion in two genetic and one dietary mouse models for retarded aging, and subjected the data to mediation analyses to determine whether any metabolic or locomotor trait could be identified as a mediator of the effect of any of the interventions on senescence. We do not test the hypothesis of causality (which would require some experiments), but instead test whether the correlation structure of certain variables is consistent with one possible pathway model in which a proposed mediating variable has a causal role. Results for metabolic measures, including oxygen consumption and respiratory quotient, failed to support this hypothesis; similar negative results were obtained for three behavioral motion metrics. Therefore, our mediation analyses did not find support that any of these correlates of decelerated senescence was a substantial mediator of the effect of either of these genetic alterations (with or without caloric restriction) on longevity. Further studies are needed to relate the examined phenotypic characteristics to mechanisms of aging and control of longevity.     

The Understanding and Interpretation of Innovative Technology-Enabled Multidimensional Physical Activity Feedback in Patients at Risk of Future Chronic Disease

BackgroundInnovative physical activity monitoring technology can be used to depict rich visual feedback that encompasses the various aspects of physical activity known to be important for health. However, it is unknown whether patients who are at risk of chronic disease would understand such sophisticated personalised feedback or whether they would find it useful and motivating. The purpose of the present study was to determine whether technology-enabled multidimensional physical activity graphics and visualisations are comprehensible and usable for patients at risk of chronic disease.MethodWe developed several iterations of graphics depicting minute-by-minute activity patterns and integrated physical activity health targets. Subsequently, patients at moderate/high risk of chronic disease (n=29) and healthcare practitioners (n=15) from South West England underwent full 7-days activity monitoring followed by individual semi-structured interviews in which they were asked to comment on their own personalised visual feedback Framework analysis was used to gauge their interpretation and of personalised feedback, graphics and visualisations.ResultsWe identified two main components focussing on (a) the interpretation of feedback designs and data and (b) the impact of personalised visual physical activity feedback on facilitation of health behaviour change. Participants demonstrated a clear ability to understand the sophisticated personal information plus an enhanced physical activity knowledge. They reported that receiving multidimensional feedback was motivating and could be usefully applied to facilitate their efforts in becoming more physically active.ConclusionMultidimensional physical activity feedback can be made comprehensible, informative and motivational by using appropriate graphics and visualisations. There is an opportunity to exploit the full potential created by technological innovation and provide sophisticated personalised physical activity feedback as an adjunct to support behaviour change.