Modulation of cognitive and motor functions by temporal interference stimulation: a systematic review and...

Temporal interference stimulation (TIS) is a non-invasive brain stimulation technique proposed to focally modulate both cortical and subcortical brain regions. A growing number of human studies have examined its effects on cognitive and motor performance, but inconsistent findings across heterogeneous protocols leave its overall behavioral efficacy uncertain. We conducted the first meta-analysis of TIS in humans, quantifying both its behavioral efficacy and the variability of responses across studies. Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, and Embase for human in vivo studies applying TIS under both active and control conditions (sham or Δf = 0 Hz) and assessing behavioral outcomes in cognitive and/or motor domains. A total of 15 studies, comprising 19 outcomes and 509 participants, were included. These studies targeted both subcortical and cortical regions using envelope frequencies ranging from 5 to 130 Hz. We quantified mean stimulation effects using the standardized mean difference (Hedges' g) and response variability using the log coefficient of variation ratio (lnCVR), pooled with random-effects models. Active TIS improved behavioral performance relative to the control condition [g = 0.30, 95% CI (0.16, 0.44), p < 0.001], with no detectable between-study heterogeneity (I ² = 0.0%) and consistent benefits across motor and cognitive domains. Across all outcomes, response variability was lower under active TIS than under the control condition, although this difference did not reach statistical significance [lnCVR = -0.11, 95% CI (-0.25, 0.02), p = 0.093]. Subgroup analyses showed significantly lower variability for motor outcomes [lnCVR = -0.26, 95% CI (-0.48, -0.04), p = 0.019] but not for cognitive outcomes [lnCVR = -0.03, 95% CI (-0.20, 0.14), p = 0.764]. Behavioral efficacy and response variability were uncorrelated across outcomes. These findings provide the first quantitative evidence that TIS improves behavioral performance across cognitive and motor domains and may reduce behavioral response variability. This combination suggests a potential benefit of TIS for producing reliable behavioral modulation, an important requirement for its further development in experimental and therapeutic neuromodulation.