Improving Neurological Health in Aging Via Neuroplasticity-Based Computerized Exercise: Protocol for a Randomized Controlled Trial.

BACKGROUND: Our current understanding of how computerized brain training drives cognitive and functional benefits remains incomplete. This paper describes the protocol for Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE), a randomized controlled trial in healthy older adults designed to evaluate whether brain training improves cholinergic signaling. OBJECTIVE: INHANCE evaluates whether 2 computerized training programs alter acetylcholine binding using the vesicular acetylcholine transporter ligand [18F] fluoroethoxybenzovesamicol ([18F] FEOBV) and positron emission tomography (PET). METHODS: In this phase IIb, prospective, double-blind, parallel-arm, active-controlled randomized trial, a minimum of 92 community-dwelling healthy adults aged 65 years and older are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control program of computer games designed for entertainment (eg, Solitaire). Both programs consist of 30-minute sessions, 7 times per week for 10 weeks (35 total hours), completed remotely at home using either loaned or personal devices. The primary outcome is the change in FEOBV binding in the anterior cingulate cortex, assessed at baseline and posttest. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine are evaluated before, immediately after, and 3 months following the intervention to assess the maintenance of observed effects. RESULTS: The trial was funded in September 2019. The study received approval from the Western Institutional Review Board in October 2020 with Research Ethics Board of McGill University Health Centre and Health Canada approvals in June 2021. The trial is currently ongoing. The first participant was enrolled in July 2021, enrollment closed when 93 participants were randomized in December 2023, and the trial will conclude in June 2024. The study team will be unblinded to conduct analyses after the final participant exits the study. We expect to publish the results in the fourth quarter of 2024. CONCLUSIONS: There remains a critical need to identify effective and scalable nonpharmaceutical interventions to enhance cognition in older adults. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT04149457; https://clinicaltrials.gov/ct2/show/NCT04149457. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59705.

Eye movement function captured via an electronic tablet informs on cognition and disease severity in Parkinson's disease.

Studying the oculomotor system provides a unique window to assess brain health and function in various clinical populations. Although the use of detailed oculomotor parameters in clinical research has been limited due to the scalability of the required equipment, the development of novel tablet-based technologies has created opportunities for fast, easy, cost-effective, and reliable eye tracking. Oculomotor measures captured via a mobile tablet-based technology have previously been shown to reliably discriminate between Parkinson's Disease (PD) patients and healthy controls. Here we further investigate the use of oculomotor measures from tablet-based eye-tracking to inform on various cognitive abilities and disease severity in PD patients. When combined using partial least square regression, the extracted oculomotor parameters can explain up to 71% of the variance in cognitive test scores (e.g. Trail Making Test). Moreover, using a receiver operating characteristics (ROC) analysis we show that eye-tracking parameters can be used in a support vector classifier to discriminate between individuals with mild PD from those with moderate PD (based on UPDRS cut-off scores) with an accuracy of 90%. Taken together, our findings highlight the potential usefulness of mobile tablet-based technology to rapidly scale eye-tracking use and usefulness in both research and clinical settings by informing on disease stage and cognitive outcomes.

Cross-species conservation in the regulation of parvalbumin by perineuronal nets.

Parvalbumin (PV) neurons play an integral role in regulating neural dynamics and plasticity. Therefore, understanding the factors that regulate PV expression is important for revealing modulators of brain function. While the contribution of PV neurons to neural processes has been studied in mammals, relatively little is known about PV function in non-mammalian species, and discerning similarities in the regulation of PV across species can provide insight into evolutionary conservation in the role of PV neurons. Here we investigated factors that affect the abundance of PV in PV neurons in sensory and motor circuits of songbirds and rodents. In particular, we examined the degree to which perineuronal nets (PNNs), extracellular matrices that preferentially surround PV neurons, modulate PV abundance as well as how the relationship between PV and PNN expression differs across brain areas and species and changes over development. We generally found that cortical PV neurons that are surrounded by PNNs (PV+PNN neurons) are more enriched with PV than PV neurons without PNNs (PV-PNN neurons) across both rodents and songbirds. Interestingly, the relationship between PV and PNN expression in the vocal portion of the basal ganglia of songbirds (Area X) differed from that in other areas, with PV+PNN neurons having lower PV expression compared to PV-PNN neurons. These relationships remained consistent across development in vocal motor circuits of the songbird brain. Finally, we discovered a causal contribution of PNNs to PV expression in songbirds because degradation of PNNs led to a diminution of PV expression in PV neurons. These findings reveal a conserved relationship between PV and PNN expression in sensory and motor cortices and across songbirds and rodents and suggest that PV neurons could modulate plasticity and neural dynamics in similar ways across songbirds and rodents.