Optimizing transcranial magnetic stimulation for spaceflight applications.

As space agencies aim to reach and build installations on Mars, the crews will face longer exposure to extreme environments that may compromise their health and performance. Transcranial magnetic stimulation (TMS) is a painless non-invasive brain stimulation technique that could support space exploration in multiple ways. However, changes in brain morphology previously observed after long-term space missions may impact the efficacy of this intervention. We investigated how to optimize TMS for spaceflight-associated brain changes. Magnetic resonance imaging T1-weighted scans were collected from 15 Roscosmos cosmonauts and 14 non-flyer participants before, after 6 months on the International Space Station, and at a 7-month follow-up. Using biophysical modeling, we show that TMS generates different modeled responses in specific brain regions after spaceflight in cosmonauts compared to the control group. Differences are related to spaceflight-induced structural brain changes, such as those impacting cerebrospinal fluid volume and distribution. We suggest solutions to individualize TMS to enhance its efficacy and precision for potential applications in long-duration space missions.

Targeting neural correlates of placebo effects.

Harnessing the placebo effects would prompt critical ramifications for research and clinical practice. Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and multifocal transcranial electric stimulation, could manipulate the placebo response by modulating the activity and excitability of its neural correlates. To identify potential stimulation targets, we conducted a meta-analysis to investigate placebo-associated regions in healthy volunteers, including studies with emotional components and painful stimuli. Using biophysical modeling, we identified NIBS solutions to manipulate placebo effects by targeting either a single key region or multiple connected areas. Moving to a network-oriented approach, we then ran a quantitative network mapping analysis on the functional connectivity profile of clusters emerging from the meta-analysis. As a result, we suggest a multielectrode optimized montage engaging the connectivity patterns of placebo-associated functional brain networks. These NIBS solutions hope to provide a starting point to actively control, modulate or enhance placebo effects in future clinical studies and cognitive enhancement studies.

The Sleep Side of Aging and Alzheimer's Disease.

As we age, sleep patterns undergo significant modifications in micro and macrostructure, worsening cognition and quality of life. These are associated with remarkable brain changes, like deterioration in synaptic plasticity, gray and white matter, and significant modifications in hormone levels. Sleep alterations are also a core component of mild cognitive impairment (MCI) and Alzheimer's Disease (AD). AD night time is characterized by a gradual decrease in slow-wave activity and a substantial reduction of REM sleep. Sleep abnormalities can accelerate AD pathophysiology, promoting the accumulation of amyloid-ß (Aß) and phosphorylated tau. Thus, interventions that target sleep disturbances in elderly people and MCI patients have been suggested as a possible strategy to prevent or decelerate conversion to dementia. Although cognitive-behavioral therapy and pharmacological medications are still first-line treatments, despite being scarcely effective, new interventions have been proposed, such as sensory stimulation and Noninvasive Brain Stimulation (NiBS). The present review outlines the current state of the art of the relationship between sleep modifications in healthy aging and the neurobiological mechanisms underlying age-related changes. Furthermore, we provide a critical analysis showing how sleep abnormalities influence the prognosis of AD pathology by intensifying Aß and tau protein accumulation. We discuss potential therapeutic strategies to target sleep disruptions and conclude that there is an urgent need for testing new therapeutic sleep interventions.

Noninvasive Brain Stimulation & Space Exploration: Opportunities and Challenges.

As NASA prepares for longer space missions aiming for the Moon and Mars, astronauts' health and performance are becoming a central concern due to the threats associated with galactic cosmic radiation, unnatural gravity fields, and life in extreme environments. In space, the human brain undergoes functional and structural changes related to fluid shift and changes in intracranial pressure. Behavioral abnormalities, such as cognitive deficits, sleep disruption, and visuomotor difficulties, as well as psychological effects, are also an issue. We discuss opportunities and challenges of noninvasive brain stimulation (NiBS) methods - including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) - to support space exploration in several ways. NiBS includes safe and portable techniques already applied in a wide range of cognitive and motor domains, as well as therapeutically. NiBS could be used to enhance in-flight performance, supporting astronauts during pre-flight Earth-based training, as well as to identify biomarkers of post-flight brain changes for optimization of rehabilitation/compensatory strategies. We review these NiBS techniques and their effects on brain physiology, psychology, and cognition.