Convergence of brain mapping tools: neuronavigated TMS parameters of BOLD fMRI responses in the motor hand area

Background: Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are frequently used as brain mapping tools to investigate the motor system. While fMRI allows non-invasive investigations of motor system properties for different kind of motor tasks, TMS provides insights into the electrophysiological properties of the motor cortex and its interactions with other motor areas. However, data on the relationship between both methods are scarce. In this study we investigated the electrophysiological properties of the motor hand area activated in a hand movement task using functional magnetic resonance imaging (fMRI) and neuronavigated transcranial magnetic stimulation (TMS).

Methods: We scanned 18 healthy subjects at 3 Tesla while performing a wrist abduction task with the right or left hand using fMRI. The voxel showing the highest task-related BOLD response in the left motor hand area (M1) was identified in each subject and subsequently stimulated using neuronavigated TMS (Eximia NBS, Nexstim Ltd.). We assessed the following electrophysiological parameters at the local BOLD maximum: resting and active motor thresholds (RMT, AMT), short intracortical inhibition (SICI) and ipsilateral silent period (ISP) of the left M1. We then performed correlation analyses between TMS parameters, BOLD response estimates and effective connectivity among key motor areas assessed with dynamic causal modelling (DCM).

Results: Analyses of the fMRI and electrophysiological data revealed an inverse correlation between the movement-related BOLD response in the left M1 and the AMT. Additionally there was a positive correlation between left M1 activation and the ISP, i.e. the stronger the task-related BOLD response in the left M1 the higher the transcallosal inhibition targeting the right M1. The SICI showed an inverse correlation with the left M1, i.e. the stronger the M1 activation in the left M1 the lower the intracortical inhibition. The DCM analysis showed that the hand movement specific neuronal coupling between left SMA and left M1 was inversely correlated with the AMT assessed for left M1 as well as the SICI. By contrast, ISP duration at the left hand upon stimulation of left M1 was positively correlated with the influence SMA exerted upon M1 activity for both intrinsic and task-specific coupling.

Discussion: Our study was designed to elucidate the relationship between the task-evoked BOLD signal increases in the motor system and TMS parameters assessed at the local BOLD maximum in M1. These interactions seem to be critically dependent upon the causal influence SMA exerted on ipsilateral M1 as indicated by the DCM analyses. Therefore, TMS parameters assessed for M1 do not only reflect the intrinsic properties at the stimulation site but also task-dependent and independent interactions with remote areas of the motor system. Such information is crucial to further our understanding of the pathophysiological changes in brain activity and therapeutic modulation thereof by means of electrophysiological interventions.