• Twenty healthy subjects were studied before and after administration of 200 mg caffeine or placebo, delivered as chewing gum. • Short-latency afferent inhibition (SAI), using amplitude and threshold-tracking protocols, was measured before and after caffeine. • Caffeine significantly enhanced conventional amplitude short-latency afferent inhibition (SAI), but not threshold-tracking SAI. Transcranial Magnetic Stimulation (TMS) tests of Short-latency Afferent Inhibition (SAI) by conventional amplitude (A-SAI) and threshold-tracking (T-SAI) are important methods to investigate cortical excitability and, more specifically, sensory motor-integration. Since beverages containing caffeine are widely consumed, and caffeine has been reported to affect cortical excitability, it is of interest to explore if SAI is modulated by caffeine. Twenty healthy subjects (11 females, 9 males; mean age: 27 ± 5.5) were studied in a single fixed-dose randomized double-blind placebo-controlled cross-over trial of 200 mg caffeine or placebo administered as chewing gum. Changes in A-SAI and T-SAI at 12 interstimulus intervals between 18 ms and 30 ms were assessed by conventional fixed stimulus and threshold-tracking techniques. There was no effect of caffeine on SAI across the full range of ISIs with either of the methods. However, caffeine significantly enhanced peak A-SAI (ISIs 19–21 ms) when compared to placebo (p = 0.011), while no effect on peak T-SAI was found. Caffeine enhances SAI as evaluated with the conventional A-SAI protocol, but not with the threshold-tracking method. Caffeinés effect may result from its modulation of the cholinergic system, providing insights into both its physiological action and brain disorder pathophysiology.
Carrozzo et al. (2026) studied this question.