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A multi-scale computational model of the effects of TMS on motor cortex.

ABSTRACT: The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different pyramidal cell types in motor cortex due to TMS. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to calculate activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons' complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also shows differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of cortical pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical pyramidal cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.

SUBMITTER: Seo H

PROVIDER: S-EPMC5373428 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The embodied cognition hypothesis suggests that motor and premotor areas are automatically and necessarily involved in understanding action language, as word conceptual representations are embodied. This transcranial magnetic stimulation (TMS) study explores the role of the left primary motor cortex in action-verb processing. TMS-induced motor-evoked potentials from right-hand muscles were recorded as a measure of M1 activity, while participants were asked either to judge explicitly whether a verb was action-related (semantic task) or to decide on the number of syllables in a verb (syllabic task). TMS was applied in three different experiments at 170, 350 and 500 ms post-stimulus during both tasks to identify when the enhancement of M1 activity occurred during word processing. The delays between stimulus onset and magnetic stimulation were consistent with electrophysiological studies, suggesting that word recognition can be differentiated into early (within 200 ms) and late (within 400 ms) lexical-semantic stages, and post-conceptual stages. Reaction times and accuracy were recorded to measure the extent to which the participants' linguistic performance was affected by the interference of TMS with M1 activity. No enhancement of M1 activity specific for action verbs was found at 170 and 350 ms post-stimulus, when lexical-semantic processes are presumed to occur (Experiments 1-2). When TMS was applied at 500 ms post-stimulus (Experiment 3), processing action verbs, compared with non-action verbs, increased the M1-activity in the semantic task and decreased it in the syllabic task. This effect was specific for hand-action verbs and was not observed for action-verbs related to other body parts. Neither accuracy nor RTs were affected by TMS. These findings suggest that the lexical-semantic processing of action verbs does not automatically activate the M1. This area seems to be rather involved in post-conceptual processing that follows the retrieval of motor representations, its activity being modulated (facilitated or inhibited), in a top-down manner, by the specific demand of the task.

Project description:Previous research suggests that meaning-laden gestures, even when produced in the absence of language (i.e., pantomimed gestures), influence lexical retrieval. Yet, little is known about the neural mechanisms that underlie this process. Based on embodied cognition theories, many studies have demonstrated motor cortex involvement in the representation of action verbs and in the understanding of actions. The present study aimed to investigate whether the motor system plays a critical role in the behavioral influence of pantomimed gestures on action naming. Continuous theta burst stimulation (cTBS) was applied over the hand area of the left primary motor cortex and to a control site (occipital cortex). An action-picture naming task followed cTBS. In the naming task, participants named action pictures that were preceded by videos of congruent pantomimed gestures, unrelated pantomimed gestures or a control video with no movement (as a neutral, non-gestural condition). In addition to behavioral measures of performance, cTBS-induced changes in corticospinal activity were assessed. We replicated previous finding that exposure to congruent pantomimed gestures facilitates word production, compared to unrelated or neutral primes. However, we found no evidence that the left primary motor area is crucially involved in the mechanism underlying behavioral facilitation effects of gesture on verb production. Although, at the group level, cTBS induced motor cortex suppression, at the individual level we found remarkable variability of cTBS effects on the motor cortex. We found cTBS induction of both inhibition of corticospinal activity (with slower behavioral of responses) and enhancement (with faster behavioral responses). Our findings cast doubt on assumptions that the motor cortex is causally involved in the impact of gestures on action-word processing. Our results also highlight the importance of careful consideration of interindividual variability for the interpretation of cTBS effects.

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A multi-scale computational model of the effects of TMS on motor cortex.

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