Digital-twin optimized transcranial temporal interference electrical stimulation alters rat brain activity patterns and metabolism including deep structures

Non-invasive deep-brain stimulation through transcranial alternating current stimulation (tACS) with temporal interference (TI) has shown promise for treating motor and neuropsychiatric disorders in rats. Researchers developed a preclinical TI tACS protocol using a digital twin of the rat head to optimize electrode placement and current levels for a specific deep brain target.

This model was tested in live rats to measure brain-wide neural responses, alterations in functional connectivity, and changes in neurotransmitter levels.

The optimized stimulation targeted the ventral thalamus, a key motor-related area. Stimulation-evoked functional MRI revealed that the activation of brain regions was bilateral, affecting both subcortical structures like the thalamus, hippocampus, amygdala, retrosplenial cortex, and anterior cingulate cortex. These activations indicated both direct and indirect influences of TI tACS on brain circuitries.

Changes in resting-state functional MRI connectivity were minimal, except for some overlap with stimulated fMRI patterns in the hippocampus' fimbria region. MR spectroscopy suggested a potential increase in the glutamate to GABA ratio within the thalamus. This study demonstrates that TI tACS is a viable and effective non-invasive DBS approach in rodents and highlights the utility of digital twin-based optimization combined with in vivo validation for personalized stimulation and future disease model studies.