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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This work was supported by a grant from the Australian National Health and Medical Research Council awarded to J.B.M. and P.E.D. (GNT1129715). J.B.M. was supported by a National Health and Medical Research Council Investigator Award (GNT2010141), and by the Australian Research Council Centre of Excellence for Integrative Brain Function (Australian Research Council Centre of Excellence grant CE140100007). The authors thank D. Lloyd for assistance with the figures, K. Garner for helpful discussion, and A. Harris, W. Harrison, D. Rangelov, R. Rideaux and R. Tweedale for their comments on earlier drafts of the manuscript.
The authors declare no competing interests.
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- Cognitive states
Finite periods of information processing or mental activity which, in conjunction with their associated neural activity, regulate functions such as attention, learning, memory, thought and reasoning.
(EEG). A non-invasive imaging technique that uses electrodes placed on the scalp to record stimulus-evoked or endogenous electrical activity in the brain with millisecond precision.
- Functional MRI
(fMRI). A non-invasive imaging technique used to measure changes in metabolic activity in the brain associated with local and distributed fluctuations in the blood oxygen level-dependent signal.
- Stochastic resonance
A phenomenon in which the addition of noise to a nonlinear system can, under certain conditions, improve performance or output-signal quality.
The alignment or synchronization of brain activity in response to rhythmic sensory stimuli or brain stimulation, and which may play a role in regulating perceptual and cognitive states.
Wave-like patterns of periodic brain activity in the 0- to ~200-Hz range, often defined in terms of characteristic ‘frequency bands’ such as delta (0.5–3 Hz), theta (4–7 Hz), alpha (8–14 Hz), beta (15–30 Hz) and gamma (more than 30 Hz).
The capacity of the brain to alter its structure and function, often in response to experience, and which is expressed at different anatomical scales, from individual neurons and synapses to cortical maps and networks.
- TMS-evoked potentials
Evoked changes in electrical potential generated in response to a transcranial magnetic stimulation (TMS) pulse and recorded by electroencephalography, resulting in region-specific changes in neural activity generally lasting ~500 ms.
- Effective connectivity
Pattern of interactions between different elements of the nervous system in which the direction of functional communication is causally inferred.
A data analysis technique that uses a computer algorithm — a ‘classifier’ — to predict which class of stimulus or experimental condition was present in a given trial, based on multivariate features of brain activity for that trial.
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Bradley, C., Nydam, A.S., Dux, P.E. et al. State-dependent effects of neural stimulation on brain function and cognition. Nat Rev Neurosci 23, 459–475 (2022). https://doi.org/10.1038/s41583-022-00598-1