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Making TMS more selective and effective John Rothwell.

Transcranial magnetic stimulation (TMS) employs a time-varying magnetic field applied over the head to induce a pulse of electrical stimulation in the brain where it depolarises neural axons and initiates action potentials. Since TMS can induce a relatively focal stimulation of a cortical area, it has become a standard “interference” tool in cognitive neuroscience and its lasting neuromodulatory effects are increasingly exploited in therapeutic applications to treat neurological and psychiatric disease. While TMS has gained popularity over the last decades, recent research has raised questions about the reproducibility of the effects of TMS protocols both within and between individuals.

Several factors are known to contribute to this variability. Age, sex, physical fitness, genetics and brain anatomy contribute to inter-individual differences; time of day, circulating hormones, drug levels and brain state contribute to both intra- and inter-individual differences. Apart from time of day most of these factors cannot easily be controlled. However recent advances in two fields offer the opportunity to reduce variability due to differences in (1) brain anatomy, which result in activation of different subpopulations of cortical neurones in each individual, and (2) in brain state, i.e. the moment-to-moment change in the excitability and neural firing pattern expressed in the target area.

The first point is presently being addressed by using new TMS devices that allow more flexible control over stimulus pulse parameters to improve selectivity of stimulation and open the possibility of probing the function of subpopulations of neurones in a single cortical area. The second point can be addressed by using feedback control from EEG activity to time TMS stimulation to particular patterns of brain activity. I will give some examples of each of these approaches.