Alcohol impacts an fMRI marker of neural inhibition in humans and rodents

• The fMRI Hurst exponent has been proposed as a marker of neural inhibition. • Alcohol was used to test the validity of the Hurst exponent across species. • Acute alcohol significantly reduced the cortical Hurst exponent in rats and humans. • Hurst reductions correlated with spatial distribution of GABAA receptor expression. • Results provide direct evidence linking the Hurst exponent to neural inhibition. Inhibitory neuronal activity is a key regulator of brain function and is implicated in numerous developmental and psychiatric disorders. However, measuring inhibition in vivo remains a challenge. The Hurst exponent of the fMRI signal has been shown to correlate spatially with cellular measures of neural inhibition, but there have been few causal tests of the relationship between the Hurst exponent and neural inhibition. Here, we used alcohol, a drug with known impacts on inhibition, as a way to evaluate the validity of the Hurst exponent as a marker of neural inhibition across rats and humans. In rats, acute alcohol administration significantly reduced the cortical Hurst exponent, with the spatial distribution of effects closely aligned with GABA A receptor expression. In humans, alcohol exposure similarly decreased the cortical Hurst exponent, particularly in regions with high GABA A receptor expression, demonstrating cross-species consistency. These results provide convergent in vivo evidence that the Hurst exponent is sensitive to pharmacologically induced changes in inhibitory neuronal activity.