Understanding the factors that determine if a person can successfully learn a novel sensory skill is essential for understanding how the brain adapts to change, and for providing rehabilitative support for people with sensory loss. We report a training study investigating the effects of blindness and age on the learning of a complex auditory skill: click-based echolocation. Blind and sighted participants of various ages (21–79 yrs; median blind: 45 yrs; median sighted: 26 yrs) trained in 20 sessions over the course of 10 weeks in various practical and virtual navigation tasks. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life. We found that both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training. Somewhat surprisingly, sighted people performed better than those who were blind in some cases, although our analyses suggest that this might be better explained by the younger age (or superior binaural hearing) of the sighted group. Importantly, however, neither age nor blindness was a limiting factor in participants’ rate of learning (i.e. their difference in performance from the first to the final session) or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing. Overall, our results suggest that the ability to learn click-based echolocation is not strongly limited by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss.

We studied a new amyloid-beta precursor protein (App) knock-in mouse model of Alzheimer's disease (AppNL-G-F), containing the Swedish KM670/671NL mutation, the Iberian I716F mutation and the Artic E693G mutation, which generates elevated levels of amyloid beta (Aβ)40 and Aβ42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. AppNL-G-F knock-in mice exhibited subtle deficits in tasks assessing social olfaction, but not in social motivation tasks. In anxiety-assessing tasks, AppNL-G-F knock-in mice exhibited: (1) increased thigmotaxis in the open field (OF), yet; (2) reduced closed-arm, and increased open-arm, time in the elevated plus maze (EPM). Their ostensibly anxiogenic OF profile, yet ostensibly anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. ‘disinhibition’), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of AppNL-G-F knock-in mice. Thus, insoluble Aβ overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.

Echolocation is the ability to use sound-echoes to infer spatial information about the environment. People can echolocate for example by making mouth clicks. Previous research suggests that echolocation in blind people activates brain areas that process light in sighted people. Research has also shown that echolocation in blind people may replace vision for calibration of external space. In the current study we investigated if echolocation may also draw on ‘visual’ resources in the sighted brain. To this end, we paired a sensory interference paradigm with an echolocation task. We found that exposure to an uninformative visual stimulus (i.e. white light) while simultaneously echolocating significantly reduced participants’ ability to accurately judge object size. In contrast, a tactile stimulus (i.e. vibration on the skin) did not lead to a significant change in performance (neither in sighted, nor blind echo expert participants). Furthermore, we found that the same visual stimulus did not affect performance in auditory control tasks that required detection of changes in sound intensity, sound frequency or sound location. The results suggest that processing of visual and echo-acoustic information draw on common neural resources.

Echolocating bats adapt their emissions to succeed in noisy environments. In the present study we investigated if echolocating humans can detect a sound-reflecting surface in the presence of noise and if intensity of echolocation emissions (i.e. clicks) changes in a systematic pattern. We tested people who were blind and had experience in echolocation, as well as blind and sighted people who had no experience in echolocation prior to the study. We used an echo-detection paradigm where participants listened to binaural recordings of echolocation sounds (i.e. they did not make their own click emissions), and where intensity of emissions and echoes changed adaptively based on participant performance (intensity of echoes was yoked to intensity of emissions). We found that emission intensity had to systematically increase to compensate for weaker echoes relative to background noise. In fact, emission intensity increased so that spectral power of echoes exceeded spectral power of noise by 12 dB in 4-kHz and 5-kHz frequency bands. The effects were the same across all participant groups, suggesting that this effect occurs independently of long-time experience with echolocation. Our findings demonstrate for the first time that people can echolocate in the presence of noise and suggest that one potential strategy to deal with noise is to increase emission intensity to maintain signal-to-noise ratio of certain spectral components of the echoes.

We studied two new App knock-in mice models of Alzheimer's disease (App NL-F and App NL-G-F ), which generate elevated levels of Aβ 40 and Aβ 42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxietyrelated and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. App NL-G-F knock-in mice exhibited subtle deficits in tasks assessing social olfaction, but not in social motivation tasks.In anxiety-assessing tasks, App NL-G-F knock-in mice exhibited: 1) increased thigmotaxis in the Open Field (OF), yet; 2) reduced closed-arm, and increased openarm, time in the Elevated Plus Maze (EPM). Their ostensibly-anxiogenic OF profile, yet ostensibly-anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. 'disinhibition'), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations, and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of App NL-G-F knockin mice. Thus, insoluble Aβ overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.