Small changes in blood sodium levels can affect the excitability of the human brain

Small changes in blood sodium levels can affect the excitability of the human brain

Even within healthy ranges, small differences in blood sodium were associated with measurable changes in brain excitability, providing new insights into how subtle physiology can influence neuronal function in healthy adults.

In a study recently published in the journalScientific reportsResearchers examined the relationship between blood electrolyte levels and cortical excitability in healthy adults. The study compared plasma electrolyte levels and resting motor threshold (RMT) data from 42 participants and found a significant correlation between plasma sodium levels and inter-individual differences in RMT.

In particular, lower sodium concentrations within the normal physiological range were associated with increased cortical excitability. These results suggest that the precise ionic composition of human blood may be associated with stable neurobiological properties, although the data reflect associations rather than causal effects.

Electrolyte homeostasis in brain function

Modern neurobiological research assumes that the brain of mammals, and therefore humans, relies on a delicate balance of charged ions, particularly sodium, calcium and potassium, that move in and out of cells to generate electrical impulses. This process, called electrolyte homeostasis, is extremely vital, evolutionarily conserved, and tightly regulated.

When this balance is severely disrupted, as in hyponatremia, the consequences are often physiologically catastrophic, including seizures and other neurological crises. Previous research has established healthy limits for electrolyte concentrations thought to be sufficient to maintain cortical excitability, and these are commonly assessed using indirect neurophysiological measurements.

New insights from normal range variability

Recent research challenges this view and suggests that even small fluctuations in ion concentrations between individuals can influence learning, memory and susceptibility to neurological diseases. Previous attempts to verify these effects have produced conflicting results, often due to small sample sizes, methodological limitations, and inadequately controlled exploratory analyses.

Study design and participant characteristics

The aim of the present study was to determine whether fluctuations in electrolyte levels in healthy individuals are associated with differences in brain electrical activity. The analysis was a secondary, unspecified evaluation of baseline data from 42 healthy young adults aged 18 to 30 years, originally collected as part of a randomized trial examining 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.

The resting motor threshold was calculated by stimulating the motor cortex region that controls the hand muscles and adjusting the stimulation intensity until the minimum force required to elicit a muscle response on at least half of the trials was reached. Lower RMT values ​​indicate greater corticospinal excitability, although RMT reflects both cortical and noncortical factors.

Sodium-specific associations with motor threshold

Analyzes revealed a statistically robust relationship between plasma sodium levels and cortical excitability. A significant positive correlation was observed between sodium concentration and RMT, suggesting 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 gender did not significantly change these results, supporting the robustness of the association but not implying a causal relationship.

Interpretation, mechanisms and future research

These results provide preliminary evidence that subtle 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 in this area is on the order of one to two millivolts.

The authors propose that lower extracellular sodium content may subtly influence membrane electrophysiology by affecting sodium channel dynamics or tissue conductance, thereby altering the effective magnetic field during stimulation.

Future studies that include experimental manipulation of sodium levels, individualized electric field modeling, and longitudinal designs are needed to determine whether sodium levels directly affect cortical excitability.

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