Comparative Effects of Temporal Interference and High-Definition Transcranial Direct Current Stimulation on Spontaneous Neuronal Activity in the Primary Motor Cortex: A Randomized Crossover Study

<b>Background:</b> Modulating spontaneous neuronal activity is critical for understanding and potentially treating neurological disorders, yet the comparative effects of different non-invasive brain stimulation techniques remain underexplored. <b>Objective:</b> This study aimed to systematically compare the effects of temporal interference (TI) stimulation and high-definition transcranial direct current stimulation (HD-tDCS) on spontaneous neuronal activity in the primary motor cortex. <b>Methods:</b> In a randomized, crossover design, forty right-handed participants underwent two 20 min sessions of either TI or HD-tDCS. Resting-state fMRI data were collected at four stages: pre-stimulus baseline (S1), first half of stimulation (S2), second half of stimulation (S3), and post-stimulation (S4). We analyzed changes in regional homogeneity (ReHo), dynamic ReHo (dReHo), fractional amplitude of low-frequency fluctuations (fALFFs), and dynamic fALFFs (dfALFFs) to assess the impact on spontaneous neuronal activity. <b>Results:</b> The analysis revealed that TI had a more significant impact on ReHo, especially in the left superior temporal gyrus and postcentral gyrus, compared with HD-tDCS. Both stimulation methods exhibited their strongest effects during the second half of the stimulation period, but only TI maintained significant activity in the post-stimulation phase. Additionally, both TI and HD-tDCS enhanced fALFFs in real-time, with TI showing more pronounced effects in sensorimotor regions. <b>Conclusions:</b> These findings suggest that TI exerts a more potent and sustained influence on spontaneous neuronal activity than HD-tDCS. This enhanced understanding of their differential effects provides valuable insights for optimizing non-invasive brain stimulation protocols for therapeutic applications.