Homeostatic activity regulation as a mechanism underlying the effect of brain stimulation

Hyperexcitability of the neural network often occurs after brain injuries or degeneration and is a key pathophysiological feature in certain neurological diseases such as epilepsy, neuropathic pain, and tinnitus. Although the standard approach of pharmacological treatments is to directly suppress the hyperexcitability through reducing excitation or enhancing inhibition, different techniques for stimulating brain activity are often used to treat refractory neurological conditions. However, it is unclear why stimulating brain activity would be effective for controlling hyperexcitability. Recent studies suggest that the pathogenesis in these disorders exhibits a transition from an initial activity loss after acute injury or progressive neurodegeneration to subsequent development of hyperexcitability. This process mimics homeostatic activity regulation and may contribute to developing network hyperexcitability that underlies neurological symptoms. This hypothesis also predicts that stimulating brain activity should be effective in reducing hyperexcitability due to homeostatic activity regulation and in relieving symptoms. Here we review current evidence of homeostatic plasticity in the development of hyperexcitability in some neurological diseases and the effects of brain stimulation. The homeostatic plasticity hypothesis may provide new insights into the pathophysiology of neurological diseases and may guide the use of brain stimulation techniques for treating them.