Even within the healthy range, small differences in blood sodium were associated with measurable changes in brain excitability, offering new insight into how subtle physiology may shape neural function in healthy adults.
Study: Plasma sodium levels are related to resting motor threshold in healthy humans. Image Credit: Darya Komarova / Shutterstock
In a recent study published in the journal Scientific Reports, researchers investigated the relationship between blood electrolyte levels and cortical excitability in healthy adults. The study compared plasma electrolyte values and resting motor threshold (RMT) data from 42 participants and found a significant correlation between plasma sodium levels and interindividual differences in RMT.
Specifically, lower sodium concentrations within the normal physiological range were associated with increased cortical excitability. These findings suggest that the precise ionic composition of human blood may be associated with stable neurobiological characteristics, although the data reflect associations rather than causal effects.
Electrolyte Homeostasis in Brain Function
Modern neurobiology research posits that mammalian, and by extension human, brains operate on a delicate balance of charged ions, particularly sodium, calcium, and potassium, that translocate in and out of cells to generate electrical impulses. This process, termed electrolyte homeostasis, is highly critical for life, evolutionarily conserved, and tightly regulated.
When this balance is severely disrupted, such as in cases of hyponatremia, the consequences are often physiologically catastrophic, including seizures and other neurological crises. Previous research has established healthy boundaries for electrolyte concentrations, which are believed to be sufficient to maintain cortical excitability, and these are commonly assessed using indirect neurophysiological measures.
Emerging Evidence From Normal-Range Variability
More recent research challenges this view, suggesting that even slight between-individual variability in ionic concentrations may influence learning, memory, and susceptibility to neurological conditions. Prior attempts to verify these effects have produced conflicting results, often due to small sample sizes, methodological limitations, and insufficiently controlled exploratory analyses.
Study Design and Participant Characteristics
The present study aimed to determine whether variation in electrolyte levels among healthy individuals is associated with differences in brain electrical activity. The analysis was a secondary, non-prespecified evaluation of baseline data from 42 healthy young adults aged 18 to 30 years, collected initially as part of a randomized trial investigating the cognitive effects of fampridine.
Electrolyte Measurement and TMS Assessment
Blood samples were collected to measure plasma concentrations of sodium, chloride, potassium, calcium, and phosphate. Cortical excitability was assessed using transcranial magnetic stimulation, a non-invasive technique that induces small electrical currents in the brain via a magnetic coil placed over the scalp.
Resting motor threshold was calculated by stimulating the motor cortex region controlling hand muscles and adjusting stimulation intensity until the minimum strength required to elicit a muscle response in at least half of the attempts was reached. Lower RMT values indicate greater corticospinal excitability, although RMT reflects both cortical and non-cortical factors.
Sodium-Specific Associations With Motor Threshold
Analyses revealed a statistically robust association between plasma sodium levels and cortical excitability. A significant positive correlation was observed between sodium concentration and RMT, indicating that lower sodium levels were associated with lower motor thresholds and therefore higher excitability.
All participants had sodium levels within the standard clinical reference range of 136 to 143 mmol/L. When other electrolytes were examined individually, no significant associations with RMT were observed for chloride, potassium, calcium, or phosphate.
Adjusting for age and sex did not materially alter these findings, supporting the robustness of the association while not implying causality.
Interpretation, Mechanisms, and Future Research
These findings provide preliminary evidence that slight differences in blood sodium concentration, even within the normal range, are associated with differences in resting motor threshold. The estimated change in sodium equilibrium potential across this range is on the order of one to two millivolts.
The authors hypothesize that lower extracellular sodium may subtly influence membrane electrophysiology by affecting sodium channel dynamics or tissue conductivity, thereby altering the effective magnetic field during stimulation.
Future studies incorporating experimental manipulation of sodium levels, individualized electric field modeling, and longitudinal designs are needed to determine whether sodium levels directly influence cortical excitability.
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