Transcranial Electric Stimulation for Precision Medicine: A Spatiomechanistic Framework

Abstract

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.

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

“…Biomarker development incorporating multimodal measures, rather than a single modality, and taking advantage of both the high spatial resolution of fMRI and high temporal resolution of EEG is likely to provide a more complete picture of both the cognitive functions and the underlying mechanisms dysregulated in SUD. Identification of biomarkers for both risk and protective factors and targets for treatment will likely uncover a proximal, brain-based measure of dependence essential for individualized medicine and curbing the significant societal impact of SUDs (Yavari et al, 2017).…”

The Effects of Transcranial Electrical Stimulation on Human Motor Functions: A Comprehensive Review of Functional Neuroimaging Studies

“…The modulation effects of tES on cognitive and motor functions could be understood from different mechanistic levels ( Yavari et al, 2017 ). On the neurochemical level, neurotransmitters associated with cognitive functions [glutamatergic ( N -methyl- D -aspartate) ( Liebetanz et al, 2002 ; Nitsche et al, 2003 , 2004a,b ) and γ-aminobutyric acid–ergic receptors ( Nitsche et al, 2004c )] relate to tES long-term effects; on the neuroelectrical level, cortical neuronal excitability increased/decreased under anodal/cathodal tDCS ( Nitsche and Paulus, 2000 , 2001 ); on the brain oscillatory level, tES modifies brain waves and their synchronizations ( Keeser et al, 2011b ; Jacobson et al, 2012 ; Herrmann et al, 2013 ).…”

Analyzing the advantages of subcutaneous over transcutaneous electrical stimulation for activating brainwaves

“…Electrical stimulation is an efficacious therapeutic modality for neurological disorders, such as stroke, depression, and schizophrenia [1][2][3][4][5] . In this system, an electrical stimulus is delivered either invasively, e.g., deep brain stimulation (DBS), or non-invasively, e.g., transcranial magnetic stimulation (TMS), or by transcranial electrical stimulation (TES).…”