Training-Induced Improvement of Response Selection and Error Detection in Aging Assessed by Task Switching: Effects of Cognitive, Physical, and Relaxation Training

Cognitive control functions decline with increasing age. The present study examines if different types of group-based and trainer-guided training effectively enhance performance of older adults in a task switching task, and how this expected enhancement is reflected in changes of cognitive functions, as measured in electrophysiological brain activity (event-related potentials). One hundred forty-one healthy participants aged 65 years and older were randomly assigned to one of four groups: physical training (combined aerobic and strength training), cognitive training (paper–pencil and computer-aided), relaxation and wellness (social control group), and a control group that did not receive any intervention. Training sessions took place twice a week for 90 min for a period of 4 months. The results showed a greater improvement of performance for attendants of the cognitive training group compared to the other groups. This improvement was evident in a reduction of mixing costs in accuracy and intraindividual variability of speed, indexing improved maintenance of multiple task sets in working memory, and an enhanced coherence of neuronal processing. These findings were supported by event-related brain potentials which showed higher amplitudes in a number of potentials associated with response selection (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken together, our findings suggest neurocognitive plasticity of aging brains which can be stimulated by broad and multilayered cognitive training and assessed in detail by electrophysiological methods

Age-Related Differences in Working Memory Performance in A 2-Back Task

The present study aimed to elucidate the neuro-cognitive processes underlying age-related differences in working memory. Young and middle-aged participants performed a two-choice task with low and a 2-back task with high working memory load. The P300, an event-related potential reflecting controlled stimulus–response processing in working memory, and the underlying neuronal sources of expected age-related differences were analyzed using sLORETA. Response speed was generally slower for the middle-aged than the young group. Under low working memory load the middle-aged participants traded speed for accuracy. The middle-aged were less efficient in the 2-back task as they responded slower while the error rates did not differ for groups. An age-related decline of the P300 amplitude and characteristic topographical differences were especially evident in the 2-back task. A more detailed analysis of the P300 in non-target trials revealed that amplitudes in the young but not middle-aged group differentiate between correctly detected vs. missed targets in the following trial. For these trials, source analysis revealed higher activation for the young vs. middle-aged group in brain areas which support working memory processes. The relationship between P300 and overt performance was validated by significant correlations. To sum up, under high working memory load the young group showed an increased neuronal activity before a successful detected target, while the middle-aged group showed the same neuronal pattern regardless of whether a subsequent target will be detected or missed. This stable memory trace before detected targets was reflected by a specific activation enhancement in brain areas which orchestrate maintenance, update, storage, and retrieval of information in working memory

What Does the n-Back Task Measure as We Get Older? Relations Between Working-Memory Measures and Other Cognitive Functions Across the Lifespan

Working memory (WM) declines with increasing age. The WM capacity is often measured by means of the computerized version of the n-back task. Although the n-back task is widely used in aging research, little is known about its construct validity and specific cognitive functions involved in this task. Moreover, to date, no studies analyzed the construct validity as a function of age. To this end, we conducted a study in a sample of N = 533 individuals aged between 20 and 80 years. The sample was divided into three age groups: young (20–40), middle-aged (41–60), and old (61–80 years). A number of psychometric tests was selected that measure attention, memory, and executive control to elucidate the impact of these constructs on n-back performance. A series of correlation analyses was conducted to assess the relationship between n-back performance and specific cognitive functions in each age group separately. The results show a progressive increase in reaction times and a decrease in the proportion of detected targets from young to old subjects. Age-related impairments were also found in all psychometric tests except for the vocabulary choice test measuring crystallized intelligence. Most importantly, correlations yielded different age-related patterns of functions contributing to performance in the n-back task: whereas performance was most related to executive functions in young age, a combination of attentional and executive processes was associated with performance in middle-aged subjects. In contrast, in older age, mainly attentional, verbal memory, and updating and to a lesser extent executive processes seem to play a crucial role in the n-back task, suggesting a shift of processing strategies across the lifespan

Cognitive aging at work and in daily life—a narrative review on challenges due to age-related changes in central cognitive functions

Demographic change is leading to an increasing proportion of older employees in the labor market. At the same time, work activities are becoming more and more complex and require a high degree of flexibility, adaptability, and cognitive performance. Cognitive control mechanism, which is subject to age-related changes and is important in numerous everyday and work activities, plays a special role. Executive functions with its core functions updating, shifting, and inhibition comprises cognitive control mechanisms that serve to plan, coordinate, and achieve higher-level goals especially in inexperienced and conflicting actions. In this review, influences of age-related changes in cognitive control are demonstrated with reference to work and real-life activities, in which the selection of an information or response in the presence of competing but task-irrelevant stimuli or responses is particularly required. These activities comprise the understanding of spoken language under difficult listening conditions, dual-task walking, car driving in critical traffic situations, and coping with work interruptions. Mechanisms for compensating age-related limitations in cognitive control and their neurophysiological correlates are discussed with a focus on EEG measures. The examples illustrate how to access influences of age and cognitive control on and in everyday and work activities, focusing on its functional role for the work ability and well-being of older people

Unmasking selective path integration deficits inAlzheimer’s disease risk carriers

Alzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE4-carriers during a virtual navigation task. We report a selective impairment in APOE4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset

Perspectives in melanoma: meeting report from the Melanoma Bridge (December 5th-7th, 2019, Naples, Italy).

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including sequential or combination treatment are being tested. Approaches to overcome resistance and to potentiate the immune response are being developed. Increasing evidence emerges that tissue and blood-based biomarkers can predict the response to a therapy. The latest findings in melanoma research, including insights into the tumor microenvironment and new biomarkers, improved understanding of tumor immune response and resistance, novel approaches for combination strategies and the role of neoadjuvant and adjuvant therapy, were the focus of discussions at the Melanoma Bridge meeting (5-7 December, 2019, Naples, Italy), which are summarized in this report

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Up, down, near, far: an online vestibular contribution to distance judgement

Whether a visual stimulus seems near or far away depends partly on its vertical elevation. Contrasting theories suggest either that perception of distance could vary with elevation, because of memory of previous upwards efforts in climbing to overcome gravity, or because of fear of falling associated with the downwards direction. The vestibular system provides a fundamental signal for the downward direction of gravity, but the relation between this signal and depth perception remains unexplored. Here we report an experiment on vestibular contributions to depth perception, using Virtual Reality. We asked participants to judge the absolute distance of an object presented on a plane at different elevations during brief artificial vestibular inputs. Relative to distance estimates collected with the object at the level of horizon, participants tended to overestimate distances when the object was presented above the level of horizon and the head was tilted upward and underestimate them when the object was presented below the level of horizon. Interestingly, adding artificial vestibular inputs strengthened these distance biases, showing that online multisensory signals, and not only stored information, contribute to such distance illusions. Our results support the gravity theory of depth perception, and show that vestibular signals make an on-line contribution to the perception of effort, and thus of distance