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During recent years, non-invasive brain stimulation, including transcranial electrical stimulation (tES) in general, and transcranial direct current stimulation (tDCS) in particular, have created new hopes for treatment of neurological and psychiatric diseases. Despite promising primary results in some brain disorders, a more widespread application of tES is hindered by the unsolved question of determining optimum stimulation protocols to receive meaningful therapeutic effects. tES has a large parameter space including various montages and stimulation parameters. Moreover, inter- and intra-individual differences in responding to stimulation protocols have to be taken into account. These factors contribute to the complexity of selecting potentially effective protocols for each disorder, different clusters of each disorder, and even each single patient. Expanding knowledge in different dimensions of basic and clinical neuroscience could help researchers and clinicians to select potentially effective protocols based on tES modulatory mechanisms for future clinical studies. In this article, we propose a heuristic spatiomechanistic framework which contains nine levels to address tES effects on brain functions. Three levels refer to the spatial resolution (local, small-scale networks and large-scale networks) and three levels of tES modulatory effects based on its mechanisms of action (neurochemical, neuroelectrical and oscillatory modulations). At the group level, this framework could be helpful to enable an informed and systematic exploration of various possible protocols for targeting a brain disorder or its neuroscience-based clusters. Considering recent advances in exploration of neurodiversity at the individual level with different brain mapping technologies, the proposed framework might also be used in combination with personal data to design individualized protocols for tES in the context of precision medicine in the future.

During recent years, non-invasive brain stimulation, including transcranial electrical stimulation (tES) in general, and transcranial direct current stimulation (tDCS) in particular, have created new hopes for treatment of neurological and psychiatric diseases. Despite promising primary results in some brain disorders, a more widespread application of tES is hindered by the unsolved question of determining optimum stimulation protocols to receive meaningful therapeutic effects. tES has a large parameter space including various montages and stimulation parameters. Moreover, inter- and intra-individual differences in responding to stimulation protocols have to be taken into account. These factors contribute to the complexity of selecting potentially effective protocols for each disorder, different clusters of each disorder, and even each single patient. Expanding knowledge in different dimensions of basic and clinical neuroscience could help researchers and clinicians to select potentially effective protocols based on tES modulatory mechanisms for future clinical studies. In this article, we propose a heuristic spatiomechanistic framework which contains nine levels to address tES effects on brain functions. Three levels refer to the spatial resolution (local, small-scale networks and large-scale networks) and three levels of tES modulatory effects based on its mechanisms of action (neurochemical, neuroelectrical and oscillatory modulations). At the group level, this framework could be helpful to enable an informed and systematic exploration of various possible protocols for targeting a brain disorder or its neuroscience-based clusters. Considering recent advances in exploration of neurodiversity at the individual level with different brain mapping technologies, the proposed framework might also be used in combination with personal data to design individualized protocols for tES in the context of precision medicine in the future.