Motor Resonance meets Motor Performance: Neurocognitive investigations with transcranial magnetic stimulation

The classical mirror neuron theory of action understanding asserts that when we observe an action, the representations that are engaged for performing it, are automatically activated. In order to do gain information about the role of the simulation in action understanding a state dependent TMS experiment has been carried out. The fundamental idea is to adapt a neural population in the motor system and then testing the effects of this adaptation when participants categorize visually presented actions. The second aim of the present work is to find a paradigm, or a particular cognitive set, that does not allow the simulation process to take place when the participants are observing actions. This step will be important in testing whether the simulation process is necessary in order to understand a visually presented action

Motor resonance meets motor performance

The aim of the present work is to explore which of two different models better explains facilitation/interference effects when participants have to conditionally react to an observed action with a movement. The Dimensional Overlap model assumes two parallel routes, an automatic route and a rule-based one, that interact only when the stimulus-set and the response-set share some dimensions. In the alternative model, a motor resonance for rule-based reaction, the automatic visuo-motor transformation is always an obligatory step that provides the correct categorization of the observed action as the input for the rule-based route, thus linking the two routes in a serial fashion. We explicitly tested which of the hypotheses fits better the data by asking participants to perform one of two different actions in a two-choice reaction paradigm. In one condition participants were required to perform the opposite action compared to the one they saw (COUNTER task: see A→do B, see B→do A), while in the other they were required to perform two actions that did not share any dimension with the stimulus-set (NEUTRAL task: see A→do C, see B→do D). We predicted an advantage for the NEUTRAL task if the Dimensional Overlap model was correct, while a similar performance was foreseen if the motor resonance-based model was correct. Since the interpretation of these results was not straightforward, we conducted a distributional analysis of participants' response accuracies in order to understand whether a serial or a general parallel model explained better the data. We found clear evidence that participants responded above chance before the motor representation of the action observed was activated. We conclude that two separate systems in the human brain can transform observed actions in own motor representations. One is stimulus-driven, while the second is rule-driven. Likely, their activity is mutually independent along parallel pathways

Transcranial Magnetic Mapping of the Short-Latency Modulations of Corticospinal Activity from the Ipsilateral Hemisphere during Rest

Skilled hand function relies heavily on the integrity of the primary motor cortex (M1) and on a web of cortico-cortical connections projecting onto it. We used a novel explorative paradigm to map the origin of cortico-M1 pathways assessed by dual transcranial magnetic stimulation (TMS) in three healthy participants. Subthreshold conditioning TMS (cTMS) was delivered over a grid of ≈100 spots. Covering the left hemisphere, and was followed by suprathreshold test (tTMS) delivered over the ipsilateral M1. Grid points were tested eight times, with inter-stimulus intervals between cTMS and tTMS of 4 and 7 ms. Participants were asked to stay relaxed with no particular task. Motor evoked potentials (MEPs) from cTMS + tTMS were normalized to MEPs from tTMS alone and were compared to the value expected from tTMS alone using t-statistics. The t-values from each grid point were then used to plot statistical maps. Several foci of significant cortico-M1 interactions were found in the dorsal–medial frontal cortex, in the ventral frontal cortex, in the superior and inferior parietal lobules and in the parietal operculum. The majority of active foci had inhibitory effects on corticospinal excitability. The spatial location of the network of different subjects overlapped but with some anatomical variation of single foci. TMS statistical mapping during the resting state revealed a complex inhibitory cortical network. The explorative approach to TMS as a brain mapping tool produced results that are self-standing in single subjects overcoming inter-individual variability of cortical active sites

The dorsal premotor cortex exerts a powerful and specific inhibitory effect on the ipsilateral corticofacial system: a dual-coil transcranial magnetic stimulation study

A rich pattern of connectivity is present in non-human primates between the dorsal premotor cortex (PMCd) and the motor cortex (M1). By analogy, similar connections are hypothesized in humans between the PMCd and the ipsilateral hand-related M1. However, the technical difficulty of applying transcranial magnetic stimulation (TMS) with a dual-coil paradigm to two cortical regions in such close spatial proximity renders their in vivo demonstration difficult. The present work aims at assessing in humans the existence of short-latency influences of the left PMCd on the ipsilateral corticofacial system by means of TMS. A dual-coil TMS paradigm was used with 16 participants. Test TMS pulses were applied to the left orofacial M1, and conditioning TMS pulses were applied to three distinct points of the ipsilateral PMCd along the caudal part of the superior frontal sulcus. The inter-stimulus interval (ISI) between condTMS and testTMS varied in 2-ms steps between 2 and 8 ms. Motor evoked potentials (MEPs) in the active orbicularis oris muscle were recorded. CondTMS exerted a robust effect on the corticofacial system only when applied to one specific portion of the PMCd and only at one specific ISI (6 ms). The effect consisted in a systematic suppression of facial MEPs compared to those obtained by testTMS alone. No other effect was found. We provide evidence for a specific short-latency inhibitory effect of the PMCd on the ipsilateral M1, likely witnessing direct corticocortical connectivity in humans. We also describe a novel paradigm to test ipsilateral PMCd-M1 in humans

Spatial and temporal characteristics of set-related inhibitory and excitatory inputs from the dorsal premotor cortex to the ipsilateral motor cortex assessed by dual-coil transcranial magnetic stimulation

The capacity to produce movements only at appropriate times is fundamental in successful behavior and requires a fine interplay between motor inhibition and facilitation. Evidence in humans indicates that the dorsal premotor cortex (PMCd) is involved in such preparatory and inhibitory processes, but how PMCd modulates motor output in humans is still unclear. We investigated this issue in healthy human volunteers, using a variant of the dual-coil transcranial magnetic stimulation (TMS) technique that allows testing the short-latency effects of conditioning TMS to the left PMCd on test TMS applied to the ipsilateral orofacial primary motor cortex (M1). Participants performed a delayed cued simple reaction time task. They were asked to produce a lip movement cued by an imperative GO-signal presented after a predictable SET-period, during which TMS was applied at different intervals. Results showed that the area of motor evoked potentials (MEPs) to test TMS was modulated by conditioning TMS. A transient inhibition cortico-bulbar excitability by PMCd stimulation was observed around the middle of the SET-period. Conversely, a ramping excitatory effect of PMCd stimulation appeared towards the end of the SET-period, as the time of the predicted GO-signal approached. The time-course of PMCd-M1 activity scaled to the varying SET-period duration. Our data indicate that inhibition and excitation of motor output during a delayed reaction time task are two distinct neural phenomena. They both originate in PMCd and are conveyed via cortico-cortical connections to the ipsilateral M1, where they are integrated to produce harmonic fluctuations of motor output

Haptic working memory for grasping: the role of the parietal operculum

We investigated how haptic information on object geometry is encoded in the parietal operculum (OP) and is used for guiding object-directed motor acts in humans. We tested the effects of conditioning single-pulse transcranial magnetic stimulation (spTMS) applied to the left OP on corticospinal excitability assessed by a test spTMS applied to the ipsilateral motor cortex (M1) 5 ms after conditioning spTMS. Participants explored the size of a graspable object visually or haptically and waited for a go-signal to grasp it in the dark. They received TMS during the delay phase. In a separate group of participants performing the same task, conditioning spTMS was applied to the ventral premotor cortex (vPM) 7 ms before test spTMS. Results showed that conditioning TMS over OP modulated M1 output according to the information on object size that had been acquired haptically but not visually. Vice versa, conditioning TMS over vPM modulated M1 output according to information on object size acquired by vision but not haptically. Moreover spTMS over OP produced a significant modulation of the upcoming reaching behavior only when the object had been explored haptically. We show that OP contains a haptic memory of objects' macrogeometry and the appropriate motor plan for grasping them

The role of medial prefrontal cortex in processing emotional self-referential information: a combined TMS/fMRI study

In this study we investigate the neural basis of emotional content in self-referential processing by using a combination of off-line repetitive Transcranial Magnetic Stimulation (rTMS) applied to the medial prefrontal cortex (mPFC) and whole-brain functional Magnetic Resonance Imaging (fMRI).We applied effective or ineffective (sham) 1-Hz rTMS to the mPFC of 14 healthy participants who immediately thereafter underwent fMRI while performing a personality attribution task to self or to others. rTMS produced an increase in the participants' reaction time ( 48 60 msec) when processing negative attributes. The neuroimaging findings indicated the involvement of a network of cortical nodes distant from those at the stimulation site; these distant nodes showed task-specific changes in blood oxygen level-dependent (BOLD) activity after effective TMS. The posterior cingulate cortex seemingly encoded the negative dimension of stimuli, but it did not differentiate between self or other. On the contrary the left angular gyrus and the left anterior temporal cortex showed changes indicating encoding of negative self-directed categorization. The mPFC region did not show effects of rTMS along the self-other dimension, but only along the affective dimension. The results indicate that the mPFC is a pivotal node in a cortical network that supports affective referential reasoning. Therefore, a key function of mPFC seems to be related to the processing of negative attributes. In the other nodes of the network the two dimensions of self-other attribution and affective attribution are partially independent, but largely overlapping with different degrees of local specialization