Aging is associated with cognitive impairment, but there are large individual differences in these declines. One neural measure that is lower in older adults and predicts these individual differences is moment-to-moment brain signal variability. Testing the assumption that GABA should heighten neural variability, we examined whether reduced brain signal variability in older, poorer performing adults could be boosted by increasing GABA pharmacologically. Brain signal variability was estimated using fMRI in 20 young and 24 older healthy human adults during placebo and GABA agonist sessions. As expected, older adults exhibited lower signal variability at placebo, and, crucially, GABA agonism boosted older adults' variability to the levels of young adults. Furthermore, poorer performing older adults experienced a greater increase in variability on drug, suggesting that those with more to gain benefit the most from GABA system potentiation. GABA may thus serve as a core neurochemical target in future work on ag...

Older adults tend to display greater brain activation in the nondominant hemisphere during even basic sensorimotor responses. It is debated whether this hemispheric asymmetry reduction in older adults (HAROLD) reflects a compensatory mechanism. Across two independent fMRI experiments involving adult life span human samples ( N = 586 and N = 81, approximately half female) who performed right-hand finger responses, we distinguished between these hypotheses using behavioral and multivariate Bayes (MVB) decoding approaches. Standard univariate analyses replicated a HAROLD pattern in motor cortex, but in and out of scanner behavioral results both demonstrated evidence against a compensatory relationship in that reaction time measures of task performance in older adults did not relate to ipsilateral motor activity. Likewise, MVB showed that this increased ipsilateral activity in older adults did not carry additional information, and if anything, combining ipsilateral with contralateral activity patterns reduced ...

Untreated age-related hearing loss increases audiovisual integration and impacts resting state functional brain connectivity. Further, there is a relation between crossmodal plasticity and audiovisual integration strength in cochlear implant patients. However, it is currently unclear whether amplification of the auditory input by hearing aids influences audiovisual integration and resting state functional brain connectivity. We conducted a randomized controlled pilot study to investigate how the McGurk illusion, a common measure for audiovisual integration, and resting state functional brain connectivity of the auditory cortex are altered by six-month hearing aid use. Thirty-two older participants with slight-to-moderate, symmetric, age-related hearing loss were allocated to a treatment or waiting control group and measured one week before and six months after hearing aid fitting with functional magnetic resonance imaging. Our results showed a statistical trend for an increased McGurk illusion after six mo...

Simulation software for spiking neuronal network models matured in the past decades regarding performance and flexibility. But the entry barrier remains high for students and early career scientists in computational neuroscience since these simulators typically require programming skills and a complex installation. Here, we describe an installation-free Graphical User Interface (GUI) running in the web browser, which is distinct from the simulation engine running anywhere, on the student’s laptop or on a supercomputer. This architecture provides robustness against technological changes in the software stack and simplifies deployment for self-education and for teachers. Our new open source tool, NEST Desktop, comprises graphical elements for creating and configuring network models, running simulations, and visualizing and analyzing the results. NEST Desktop allows students to explore important concepts in computational neuroscience without the need to learn a simulator control language before. Our experienc...

The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) causes familial Parkinson’s disease (PD) and is also found in a subset of idiopathic cases. Prior studies in Drosophila and human induced pluripotent stem cell (iPSC)-derived dopamine neurons uncovered a pronounced effect of G2019S LRRK2 on mRNA translation. It was previously reported that G2019S LRRK2 promotes translation of mRNAs with complex 5′ untranslated region (UTR) secondary structure, resulting in increased expression of calcium channels and dysregulated calcium homeostasis in human dopamine neurons. Here, we show that dysregulated translation occurs in the brains of mammalian LRRK2 models in vivo . Through ribosome profiling studies of global translation, we observe that mRNAs with complex 5′UTR structure are also preferentially translated in the G2019S LRRK2-expressing mouse brain. Reporter assays suggest that this 5′UTR preference is independent of translation initiation factors. Conversely, translation of mRNAs with complex 5′UTR seco...

When presented with a periodic stimulus, humans spontaneously adjust their movements from reacting to predicting the timing of its arrival, but little is known about how this sensorimotor adaptation changes across development. To investigate this, we analyzed saccade behavior in 114 healthy humans (ages 6-24 years) performing the visual metronome task, who were instructed to move their eyes in time with a visual target that alternated between two known locations at a fixed rate, and we compared their behavior to performance in a random task, where target onsets were randomized across 5 interstimulus intervals (ISIs) and thus the timing of appearance was unknown. Saccades initiated before registration of the visual target, thus in anticipation of its appearance, were labeled predictive (saccade reaction time: SRT < 90 ms) and saccades that were made in reaction to its appearance were labeled reactive (SRT > 90 ms). Eye-tracking behavior including saccadic metrics (e.g., peak velocity; amplitude), pupil size...

Decisions about what to eat recruit the orbitofrontal cortex (OFC) and involve the evaluation of food-related attributes, such as taste and health. These attributes are utilized differently by healthy individuals and patients with disordered eating behavior, but it is unclear whether these attributes are decodable from activity in the OFC in both groups and whether neural representations of these attributes are differentially related to decisions about food. We used fMRI combined with behavioral tasks to investigate the representation of taste and health attributes in the human OFC and the role of these representations in food choices in healthy women and women with anorexia nervosa (AN). We found that subjective ratings of tastiness and healthiness could be decoded from patterns of activity in the OFC in both groups. However, health-related patterns of activity in the OFC were more related to the magnitude of choice preferences among patients with AN than healthy individuals. These findings suggest that m...

Shahnaz Rahman Lone, Sheetal Potdar, Archana Venkataraman, Nisha Sharma, Rutvij Kulkarni, et al. (see pages [9403–9418][1]) Sleep timing is influenced by many factors, including circadian rhythms, environmental conditions, and homeostatic sleep drive, which increases over time awake. The ability