Deep brain structures like the basal ganglia, the thalamus or the hippocampus are core brain areas involved in the pathophysiology of neurological and mental disorders, such as stroke, dementia, Parkinsons, essential tremor, anxiety, addiction or traumatic brain injury (TBI), as well as critical for transdiagnostic symptoms such as memory deficits, apathy or fatigue, frequently prevalent in multiple neurological and mental disorders. These deep brain structures are critically important in the pathophysiology of, the adaptation to and the recovery from these disorders. This makes them promising targets for interventional strategies based on brain stimulation. Due to their location deep in the brain and the steep depth-focality trade-off curve of classical non-invasive brain stimulation methods, such as TMS or tDCS, they were so far only accessible by classical invasive deep brain stimulation techniques (DBS).

Transcranial temporal interference electrical stimulation (tTIS), a novel non-invasive deep brain stimulation technique, provides the exciting opportunity to target deep brain structures focally allowing to neuromodulate them and determine its impact on behavior and brain activity. Here, first in human applications of tTIS to deep brain structures such as the striatum or the hippocampus and their functional impact on brain activity and behavioral impact on cognitive functions in healthy subjects and traumatic brain injury (TBI) patients will be presented and discussed in the light of the actual literature. Furthermore, current challenges such as e.g., individualized application or mechanistic understanding of tTIS that will have to be addressed, and the potential and future prospective of this promising translational approach will be critically discussed.