Off-line Transcranial Magnetic Stimulation Research Articles

Dissociating the Role of the pre-SMA in Response Inhibition and Switching: A Combined Online and Offline TMS Approach

The pre-supplementary motor area (pre-SMA) is considered to be a key node in the cognitive control of actions that require rapid updating, inhibition, or switching, as well as working memory. It is now recognized that the pre-SMA is part of a “cognitive control” network involving the inferior frontal gyrus (IFG) and subcortical regions, such as the striatum and subthalamic nucleus. However, two important questions remain to be addressed. First, it is not clear if the main role of the pre-SMA in cognitive control lies in inhibition or switching of actions. From imaging evidence, the right pre-SMA is consistently recruited during inhibition and switching, but the extent to which it participates specifically in either of these processes is unknown. Secondly, the pre-SMA may perform inhibition and switching alone or as part of a larger brain network. The present study used online and offline transcranial magnetic stimulation (TMS) to dissociate the roles of pre-SMA in cognitive control, but also to investigate the potential contribution of connectivity between the pre-SMA and IFG. We applied continuous theta burst stimulation (cTBS) over the right IFG before participants performed a stop switching task while receiving single TMS pulses over the right pre-SMA. The results were compared to a sham cTBS session and pulses applied over the vertex region. Significant worsening of inhibition as well as response adaptation during inhibition was found when applying pulses over the pre-SMA. However, no such worsening was observed in switch trials. Additionally, after cTBS over the IFG, inhibition was also delayed, suggesting its critical necessity in stopping of actions. The results reveal a key contribution of the pre-SMA in inhibition and could suggest a dissociative role in the switching of actions. These findings indicate there is an essential union between IFG and pre-SMA during inhibition.

Controlling Human Striatal Cognitive Function via the Frontal Cortex

Cognitive flexibility is known to depend on the striatum. However, the striatum does not act in isolation to bias cognitive flexibility. In particular, cognitive flexibility also implicates the frontal cortex. Here we tested the hypothesis that the human frontal cortex controls cognitive flexibility by regulating striatal function via topographically specific frontostriatal connections. To this end, we exploited a repetitive transcranial magnetic stimulation (TMS) protocol over frontal cortex that is known to increase dopamine release in the striatum. This intervention was combined with functional magnetic resonance imaging to determine the functional and topographic specificity of its consequences at the whole brain level. Participants were scanned both before and after off-line TMS while performing a cognitive switching task that is known to depend on a specific striatal substructure, the putamen. Frontal stimulation perturbed task-specific functional signals in the putamen, while reducing fronto-striatal functional connectivity. There were no such effects of TMS over the medial parietal cortex. These data strengthen the hypothesis that cognitive flexibility involves topographic frontal control of striatal function.

Compensatory Plasticity in the Action Observation Network: Virtual Lesions of STS Enhance Anticipatory Simulation of Seen Actions

Observation of snapshots depicting ongoing motor acts increases corticospinal motor excitability. Such motor facilitation indexes the anticipatory simulation of observed (implied) actions and likely reflects computations occurring in the parietofrontal nodes of a cortical network subserving action perception (action observation network, AON). However, direct evidence for the active role of AON in simulating the future of seen actions is lacking. Using a perturb-and-measure transcranial magnetic stimulation (TMS) approach, we show that off-line TMS disruption of regions within (inferior frontal cortex, IFC) and upstream (superior temporal sulcus, STS) the parietofrontal AON transiently abolishes and enhances the motor facilitation to observed implied actions, respectively. Our findings highlight the critical role of IFC in anticipatory motor simulation. More importantly, they show that disruption of STS calls into play compensatory motor simulation activity, fundamental for counteracting the noisy visual processing induced by TMS. Thus, short-term plastic changes in the AON allow motor simulation to deal with any gap or ambiguity of ever-changing perceptual worlds. These findings support the active, compensatory, and predictive role of frontoparietal nodes of the AON in the perception and anticipatory simulation of implied actions.

Decoding emotional prosody: Resolving differences in functional neuroanatomy from fMRI and lesion studies using TMS

Prosody conveys information about the emotional state and intention of others. Lesion studies have shown that damage to the right posterior temporal region is associated with prosody decoding deficits. Dissimilarly to findings from lesion studies, neuroimaging data show substantial bilateral peri-Sylvian activation. This study aimed to investigate the involvement of the left and right superior temporal gyrus (STG) in prosodic and semantic processing using transcranial magnetic stimulation (TMS). These two regions of interest were chosen for their correspondence to Wernicke's area in the left hemisphere and its analog in the right. Offline TMS with a stimulation frequency of 1 Hz and intensity of 60% of stimulator output (approximately 1.1 Tesla) with one pulse applied per second for 10 minutes (600 pulses) was performed. Directly after TMS on the right STG, the left STG or sham-stimulation, participants completed a prosody decoding or a semantic judgment task (whether the tone/meaning was happy or sad). Reaction times (RT) for the prosodic task were significantly slower when TMS was applied in the right STG in comparison to left STG and sham conditions. TMS over both right and left STG delayed RT in the semantic task, significantly when the tone of voice was incongruent with the meaning. Our data strongly suggests that left temporal regions are not crucial to the basic task of prosody decoding per se; however, the analogous region on the right is. Hence, involvement of the left STG in prosodic decoding revealed in previous imaging data is incidental.

On the role of the SMA in the discrete sequence production task: a TMS study

Participants practiced two discrete six-key sequences for a total of 420 trials. The 1×6 sequence had a unique order of key presses while the 2×3 sequence involved repetition of a three-key segment. Both sequences showed a long interkey interval halfway the sequence indicating hierarchical sequence control in that not only the 2×3 but also the 1×6 sequence was executed as two successive motor chunks. Besides, the second part of both sequences was executed faster than the first part. This supports the earlier notion of a motor processor executing the elements of familiar motor chunks and a cognitive processor triggering either these motor chunks or individual sequence elements. Low-frequency, off-line transcranial magnetic stimulation (TMS) of the supplementary motor area (SMA) counteracted normal improvement with practice of key presses at all sequence positions. Together, these results are in line with the notion that with moderate practice, the SMA executes short sequence fragments that are concatenated by other brain structures.