A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices.

Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer's disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.

Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment (VE). We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex (RSC)/parieto-occipital sulcus (POS) and anterior hippocampus did not change systematically as a function learning in older compared with younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain's navigation system, highlighting the critical role of the hippocampus.SIGNIFICANCE STATEMENT Key structures of the brain's navigation circuit are particularly vulnerable to the deleterious consequences of aging, and declines in spatial navigation are among the earliest indicators for a progression from healthy aging to neurodegenerative diseases. Our study is among the first to provide a mechanistic account about how physiological changes in the aging brain affect the formation of spatial knowledge. We show that neural activity in the aging hippocampus and medial parietal areas is decoupled from individual learning states across repeated episodes in a novel spatial environment. Importantly, we find that increased excitability of the anterior hippocampus might constitute a potential neural mechanism for cognitive mapping deficits in old age.

The potential of virtual reality for spatial navigation research across the adult lifespan.

Older adults often experience serious problems in spatial navigation, and alterations in underlying brain structures are among the first indicators for a progression to neurodegenerative diseases. Studies investigating the neural mechanisms of spatial navigation and its changes across the adult lifespan are increasingly using virtual reality (VR) paradigms. VR offers major benefits in terms of ecological validity, experimental control and options to track behavioral responses. However, navigation in the real world differs from navigation in VR in several aspects. In addition, the importance of body-based or visual cues for navigation varies between animal species. Incongruences between sensory and motor input in VR might consequently affect their performance to a different degree. After discussing the specifics of using VR in spatial navigation research across species, we outline several challenges when investigating age-related deficits in spatial navigation with the help of VR. In addition, we discuss ways to reduce their impact, together with the possibilities VR offers for improving navigational abilities in older adults.

Dance Training Shapes Action Perception and Its Neural Implementation within the Young and Older Adult Brain.

How we perceive others in action is shaped by our prior experience. Many factors influence brain responses when observing others in action, including training in a particular physical skill, such as sport or dance, and also general development and aging processes. Here, we investigate how learning a complex motor skill shapes neural and behavioural responses among a dance-naïve sample of 20 young and 19 older adults. Across four days, participants physically rehearsed one set of dance sequences, observed a second set, and a third set remained untrained. Functional MRI was obtained prior to and immediately following training. Participants' behavioural performance on motor and visual tasks improved across the training period, with younger adults showing steeper performance gains than older adults. At the brain level, both age groups demonstrated decreased sensorimotor cortical engagement after physical training, with younger adults showing more pronounced decreases in inferior parietal activity compared to older adults. Neural decoding results demonstrate that among both age groups, visual and motor regions contain experience-specific representations of new motor learning. By combining behavioural measures of performance with univariate and multivariate measures of brain activity, we can start to build a more complete picture of age-related changes in experience-dependent plasticity.

Embodiment in the aging mind.

Bodily awareness is a central component of human sensation, action, and cognition. The human body is subject to profound changes over the adult lifespan. We live in an aging society: the mean age of people living in industrialized countries is currently over 40 years, and further increases are expected. Nevertheless, there is a lack of comprehensive knowledge that links changes in embodiment that occur with age to neuronal mechanisms and associated sensorimotor and cognitive deficits in older adults. Here, we synthesize existing evidence and introduce the NFL Framework of Embodied Aging, which links basic neuronal (N) mechanisms of age-related sensorimotor decline to changes in functional (F) bodily impairments, including deficits in higher-level cognitive functions, and impairments in daily life (L). We argue that cognitive and daily life impairments associated with old age are often due to deficits in embodiment, which can partly be linked to neuronal degradation at the sensorimotor level. The framework may encourage the development of novel approaches to improve autonomous living for older adults.

Space, time, and numbers in the right posterior parietal cortex: Differences between response code associations and congruency effects.

The mental representations of space, time, and number magnitude are inherently linked. The right posterior parietal cortex (PPC) has been suggested to contain a general magnitude system that underlies the overlap between various perceptual dimensions. However, comparative studies including spatial, temporal, and numerical dimensions are missing. In a unified paradigm, we compared the impact of right PPC inhibition on associations with spatial response codes (i.e., Simon, SNARC, and STARC effects) and on congruency effects between space, time, and numbers. Prolonged cortical inhibition was induced by continuous theta-burst stimulation (cTBS), a protocol for transcranial magnetic stimulation (TMS), at the right intraparietal sulcus (IPS). Our results show that congruency effects, but not response code associations, are affected by right PPC inhibition, indicating different neuronal mechanisms underlying these effects. Furthermore, the results demonstrate that interactions between space and time perception are reflected in congruency effects, but not in an association between time and spatial response codes. Taken together, these results implicate that the congruency between purely perceptual dimensions is processed in PPC areas along the IPS, while the congruency between percepts and behavioral responses is independent of this region.

The timing and precision of action prediction in the aging brain.

Successful social interactions depend on the ability to anticipate other people's actions. Current conceptualizations of brain function propose that causes of sensory input are inferred through their integration with internal predictions generated in the observer's motor system during action observation. Less is known concerning how action prediction changes with age. Previously we showed that internal action representations are less specific in older compared with younger adults at behavioral and neural levels. Here, we characterize how neural activity varies while healthy older adults aged 56-71 years predict the time-course of an unfolding action as well as the relation to task performance. By using fMRI, brain activity was measured while participants observed partly occluded actions and judged the temporal coherence of the action continuation that was manipulated. We found that neural activity in frontoparietal and occipitotemporal regions increased the more an action continuation was shifted backwards in time. Action continuations that were shifted towards the future preferentially engaged early visual cortices. Increasing age was associated with neural activity that extended from posterior to anterior regions in frontal and superior temporal cortices. Lower sensitivity in action prediction resulted in activity increases in the caudate. These results imply that the neural implementation of predicting actions undergoes similar changes as the neural process of executing actions in older adults. The comparison between internal predictions and sensory input seems to become less precise with age leading to difficulties in anticipating observed actions accurately, possibly due to less specific internal action models.

Action prediction in younger versus older adults: neural correlates of motor familiarity.

Generating predictions during action observation is essential for efficient navigation through our social environment. With age, the sensitivity in action prediction declines. In younger adults, the action observation network (AON), consisting of premotor, parietal and occipitotemporal cortices, has been implicated in transforming executed and observed actions into a common code. Much less is known about age-related changes in the neural representation of observed actions. Using fMRI, the present study measured brain activity in younger and older adults during the prediction of temporarily occluded actions (figure skating elements and simple movement exercises). All participants were highly familiar with the movement exercises whereas only some participants were experienced figure skaters. With respect to the AON, the results confirm that this network was preferentially engaged for the more familiar movement exercises. Compared to younger adults, older adults recruited visual regions to perform the task and, additionally, the hippocampus and caudate when the observed actions were familiar to them. Thus, instead of effectively exploiting the sensorimotor matching properties of the AON, older adults seemed to rely predominantly on the visual dynamics of the observed actions to perform the task. Our data further suggest that the caudate played an important role during the prediction of the less familiar figure skating elements in better-performing groups. Together, these findings show that action prediction engages a distributed network in the brain, which is modulated by the content of the observed actions and the age and experience of the observer.

Representing others' actions: the role of expertise in the aging mind.

A large body of evidence suggests that action execution and action observation share a common representational domain. To date, little is known about age-related changes in these action representations that are assumed to support various abilities such as the prediction of observed actions. The purpose of the present study was to investigate (a) how age affects the ability to predict the time course of observed actions; and (b) whether and to what extent sensorimotor expertise attenuates age-related declines in prediction performance. In a first experiment, older adults predicted the time course of familiar everyday actions less precisely than younger adults. In a second experiment, younger and older figure skating experts as well as age-matched novices were asked to predict the time course of figure skating elements and simple movement exercises. Both young age and sensorimotor expertise had a positive influence on prediction performance of figure skating elements. The expertise-related benefit did not show a transfer to movement exercises. Together, the results suggest a specific decline of action representations in the aging mind. However, extensive sensorimotor experience seems to enable experts to represent actions from their domain of expertise more precisely even in older age.