Figure 1.

The relationship between excitation/inhibition (E/I) balance and efficiency of a given cortical region. (A) According to the current hypothesis, E/I balance within a brain area can be viewed as an inverted-U shape in which the optimal performance is achieved when excitation and inhibition interact efficiently, allowing for both plasticity and stability. The degree of baseline E/I might, however, differ per brain region and individual. If the optimal balance is achieved, homeostatic control of activity-dependent plasticity and synaptic efficiency are possible and can lead to meaningful behavioral output. Deviations from the ideal balance are associated with atypical behavior and the severity of the deficit may vary with the degree of imbalance. tDCS can be used to target and restore the individual abnormalities in E/I imbalance in different neurological conditions. Only a moderate level of activation, i.e., balanced E/I levels, can reach the optimal level of processing efficiency and allow for homeostatic plasticity. High levels of GABA can lead to cortical over-inhibition that will reduce network output, whereas hyperactive glutamatergic activity can lead to excessive output and eventually to excitotoxicity and cell death (Faden et al., 1989; Belousov, 2012). (B) An example of the distribution of E/I balance in the healthy population: the finding that most anodal tDCS studies report behavioral improvements suggests that the distribution may be skewed with the majority showing non-optimal E/I ratio. However, for some individuals with increased E/I ratios, anodal tDCS will shift the non-pathological imbalance even further towards over-activation and therefore reduce behavioral outcomes.