State dependent modulation of neuronal activity during magnetic stimulation

The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Israel, Transcranial magnetic stimulation (TMS) is used extensively in cognitive psychology studies and in clinical treatments of multiple neurological and psychiatric conditions. Despite its growing popularity, little is known about the effect it exerts on the underlying neurons of the central nervous system (CNS). Unraveling the mechanism of TMS effects requires a multi-level approach combining multidisciplinary studies on the biophysical, cellular neurophysiology, system neurophysiology and cognitive neuroscience levels. As part of such a combined effort we set out to investigate this question by combining magnetic stimulation using our novel magnetic mini-coil with simultaneous recordings of neuronal activity in the behaving primate. This mini-coil fits into a chronic recording chamber and provides focal activation of cortical areas while enabling simultaneous extracellular multi-electrode recordings in multiple brain structures. This allows, for the first time, to record in multiple areas of the CNS during magnetic stimulation. This configuration enabled us to study the temporal and spatial activation patterns of cortical neurons directly activated by the induced electrical field and of sub-cortical neurons activated synaptically by the cortical neurons. The study was performed in two states: normal and parkinsonian (MPTP treated). The study demonstrates that equivalent modulation of cortical activity in the two states leads to drastically different activation patterns of basal ganglia neurons. The large stereotypic indirect modulation of the sub-cortical targets occurring in the parkinsonian state was completely missing in the normal state. This modification of the descending cortical activity transmission led to changes in both the single neuron level and the neural network level. These results emphasize the need to customize both scientific and clinical stimulation protocols to the underlying brain state.