Age-related impairments and influence of visual feedback when learning to stand with unexpected sensorimotor delays.

Background: While standing upright, the brain must accurately accommodate for delays between sensory feedback and self-generated motor commands. Natural aging may limit adaptation to sensorimotor delays due to age-related decline in sensory acuity, neuromuscular capacity and cognitive function. This study examined balance learning in young and older adults as they stood with robot-induced sensorimotor delays. Methods: A cohort of community dwelling young (mean = 23.6 years, N = 20) and older adults (mean = 70.1 years, N = 20) participated in this balance learning study. Participants stood on a robotic balance simulator which was used to artificially impose a 250 ms delay into their control of standing. Young and older adults practiced to balance with the imposed delay either with or without visual feedback (i.e., eyes open or closed), resulting in four training groups. We assessed their balance behavior and performance (i.e., variability in postural sway and ability to maintain upright posture) before, during and after training. We further evaluated whether training benefits gained in one visual condition transferred to the untrained condition. Results: All participants, regardless of age or visual training condition, improved their balance performance through training to stand with the imposed delay. Compared to young adults, however, older adults had larger postural oscillations at all stages of the experiments, exhibited less relative learning to balance with the delay and had slower rates of balance improvement. Visual feedback was not required to learn to stand with the imposed delay, but it had a modest effect on the amount of time participants could remain upright. For all groups, balance improvements gained from training in one visual condition transferred to the untrained visual condition. Conclusion: Our study reveals that while advanced age partially impairs balance learning, the older nervous system maintains the ability to recalibrate motor control to stand with initially destabilizing sensorimotor delays under differing visual feedback conditions.

Activated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model.

The phosphoinositide-3-kinase (PI3K) family plays a major role in cell signaling and is predominant in leukocytes. Gain-of-function (GOF) mutations in the PIK3CD gene lead to the development of activated PI3Kδ syndrome (APDS), a rare primary immunodeficiency disorder. A subset of APDS patients also displays neurodevelopmental delay symptoms, suggesting a potential role of PIK3CD in cognitive and behavioural function. However, the extent and nature of the neurodevelopmental deficits has not been previously quantified. Here, we assessed the cognitive functions of two APDS patients, and investigated the causal role of the PIK3CD GOF mutation in neurological deficits using a murine model of this disease. We used p110δE1020K knock-in mice, harbouring the most common APDS mutation in patients. We found that APDS patients present with visuomotor deficits, exacerbated by autism spectrum disorder comorbidity, whereas p110δE1020K mice exhibited impairments in motor behaviour, learning and repetitive behaviour patterning. Our data indicate that PIK3CD GOF mutations increase the risk for neurodevelopmental deficits, supporting previous findings on the interplay between the nervous and the immune system. Further, our results validate the knock-in mouse model, and offer an objective assessment tool for patients that could be incorporated in diagnosis and in the evaluation of treatments.