Water and brain function: effects of hydration status on neurostimulation with transcranial magnetic stimulation

Neurostimulation/neurorecording are tools to study, diagnose, and treat neurological/psychiatric conditions. Both techniques depend on volume conduction between scalp and excitable brain tissue. Here, we examine how neurostimulation with transcranial magnetic stimulation (TMS) is affected by hydration status, a physiological variable that can influence the volume of fluid spaces/cells, excitability, and cellular/global brain functioning. Normal healthy adult participants (32, 9 males) had common motor TMS measures taken in a repeated-measures design from dehydrated (12-h overnight fast/thirst) and rehydrated (identical dehydration protocol followed by rehydration with 1 L water in 1 h) testing days. The target region was left primary motor cortex hand area. Response at the target muscle was recorded with electromyography. Urinalysis confirmed hydration status. Motor hotspot shifted in half of participants. Motor threshold decreased in rehydration, indicating increased excitability. Even after redosing/relocalizing TMS to the new threshold/hotspot, rehydration still showed evidence of increased excitability: recruitment curve measures generally shifted upward and the glutamate-dependent paired-pulse protocol, short intracortical facilitation (SICF), was increased. Short intracortical inhibition (SICI), long intracortical inhibition (LICI), long intracortical facilitation (LICF), and cortical silent period (CSP) were relatively unaffected. The hydration perturbations were mild/subclinical based on the magnitude/speed and urinalysis. Motor TMS measures showed evidence of expected physiological changes of osmotic challenges. Rehydration showed signs of macroscopic and microscopic volume changes including decreased scalp-cortex distance (brain closer to stimulator) and astrocyte swelling-induced glutamate release. Hydration may be a source of variability affecting any techniques dependent on brain volumes/volume conduction. These concepts are important for researchers/clinicians using such techniques or dealing with the wide variety of disease processes involving water balance.