Abstract

Invasive and non-invasive brain stimulation methods are widely used in neuroscience to establish causal relationships between distinct brain regions and the sensory, cognitive and motor functions they subserve. When combined with concurrent brain imaging, such stimulation methods can reveal patterns of neuronal activity responsible for regulating simple and complex behaviours at the level of local circuits and across widespread networks. Understanding how fluctuations in physiological states and task demands might influence the effects of brain stimulation on neural activity and behaviour is at the heart of how we use these tools to understand cognition. Here we review the concept of such 'state-dependent' changes in brain activity in response to neural stimulation, and consider examples from research on altered states of consciousness (for example, sleep and anaesthesia) and from task-based manipulations of selective attention and working memory. We relate relevant findings from non-invasive methods used in humans to those obtained from direct electrical and optogenetic stimulation of neuronal ensembles in animal models. Given the widespread use of brain stimulation as a research tool in the laboratory and as a means of augmenting or restoring brain function, consideration of the influence of changing physiological and cognitive states is crucial for increasing the reliability of these interventions.

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