Distinct neural mechanisms support inner speaking and inner hearing.

Humans have the ability to mentally examine speech. This covert form of speech production is often accompanied by sensory (e.g., auditory) percepts. However, the cognitive and neural mechanisms that generate these percepts are still debated. According to a prominent proposal, inner speech has at least two distinct phenomenological components: inner speaking and inner hearing. We used transcranial magnetic stimulation to test whether these two phenomenologically distinct processes are supported by distinct neural mechanisms. We hypothesised that inner speaking relies more strongly on an online motor-to-sensory simulation that constructs a multisensory experience, whereas inner hearing relies more strongly on a memory-retrieval process, where the multisensory experience is reconstructed from stored motor-to-sensory associations. Accordingly, we predicted that the speech motor system will be involved more strongly during inner speaking than inner hearing. This would be revealed by modulations of TMS evoked responses at muscle level following stimulation of the lip primary motor cortex. Overall, data collected from 31 participants corroborated this prediction, showing that inner speaking increases the excitability of the primary motor cortex more than inner hearing. Moreover, this effect was more pronounced during the inner production of a syllable that strongly recruits the lips (vs. a syllable that recruits the lips to a lesser extent). These results are compatible with models assuming that the primary motor cortex is involved during inner speech and contribute to clarify the neural implementation of the fundamental ability of silently speaking in one's mind.

Effective connectivity of the left-ventral occipito-temporal cortex during visual word processing: Direct causal evidence from TMS-EEG co-registration.

As an interface between the visual and language system, the left ventral occipito-temporal cortex (left-vOT) plays a key role in reading. This functional role is supported by anatomical and functional connections between the area and other brain regions within and outside the language network. Nevertheless, only a few studies have investigated how the functional state of this area, which is dependent upon the nature of the task demand and the stimulus being processed, could influence the activity of the connected brain regions. In the present combined TMS-EEG study, we studied the left-vOT effective connectivity by adopting a direct, causal intervention approach. Using TMS, we probed left-vOT activation in different processing contexts and measured the neural propagation of activity from this area to other brain regions. A comparison of neural propagation measured during low-level visual detection of language versus non-language stimuli showed that processing language stimuli reduced neural propagation from the left-vOT to the right occipital cortex. Additionally, compared to the low-level visual detection of language stimuli, performing semantic judgments on the same stimuli further reduced neural propagation to the posterior part of the corpus callosum, right superior parietal lobule and the right anterior temporal lobe. This reduction of cross-hemispheric neural propagation was accompanied by an increase in the collaboration between areas within the left-hemisphere language network. Together, this first evidence from a direct causal intervention approach suggests that processing language stimuli and performing a high-level language task reduce effective connectivity from the left-vOT to the right hemisphere, and may contribute to the left-hemisphere lateralization typically observed during language processing.

Cerebellar and Cortical Correlates of Internal and External Speech Error Monitoring.

An event-related functional magnetic resonance imaging study examined how speakers inspect their own speech for errors. Concretely, we sought to assess 1) the role of the temporal cortex in monitoring speech errors, linked with comprehension-based monitoring; 2) the involvement of the cerebellum in internal and external monitoring, linked with forward modeling; and 3) the role of the medial frontal cortex for internal monitoring, linked with conflict-based monitoring. In a word production task priming speech errors, we observed enhanced involvement of the right posterior cerebellum for trials that were correct, but on which participants were more likely to make a word as compared with a nonword error (contrast of internal monitoring). Furthermore, comparing errors to correct utterances (contrast of external monitoring), we observed increased activation of the same cerebellar region, of the superior medial cerebellum, and of regions in temporal and medial frontal cortex. The presence of the cerebellum for both internal and external monitoring indicates the use of forward modeling across the planning and articulation of speech. Dissociations across internal and external monitoring in temporal and medial frontal cortex indicate that monitoring of overt errors is more reliant on vocal feedback control.

The Extrastriate Body Area and identity processing: An fMRI guided TMS study.

The extrastriate body area (EBA) is a body-selective focal region located in the lateral occipito-temporal cortex that responds strongly to images of human bodies and body parts in comparison with other classes of stimuli. Whether EBA contributes also to the body recognition of self versus others remains in debate. We investigated whether EBA contributes to self-other distinction and whether there might be a hemispheric-side specificity to that contribution using double-pulse transcranial magnetic stimulation (TMS) in right-handed participants. Prior to the TMS experiment, all participants underwent an fMRI localizer task to determine individual EBA location. TMS was then applied over either right EBA, left EBA or vertex, while participants performed an identification task in which images of self or others' right, or left hands were presented. TMS over both EBAs slowed responses, with no identity-specific effect. However, TMS applied over right EBA induced significantly more errors on other's hands than noTMS, TMS over left EBA or over the Vertex, when applied at 100-110 ms after image onset. The last three conditions did not differ, nor was there any difference for self-hands. These findings suggest that EBA participates in self/other discrimination.

Spoken language coding neurons in the Visual Word Form Area: Evidence from a TMS adaptation paradigm.

While part of the left ventral occipito-temporal cortex (left-vOT), known as the Visual Word Form Area, plays a central role in reading, the area also responds to speech. This cross-modal activation has been explained by three competing hypotheses. Firstly, speech is converted to orthographic representations that activate, in a top-down manner, written language coding neurons in the left-vOT. Secondly, the area contains multimodal neurons that respond to both language modalities. Thirdly, the area comprises functionally segregated neuronal populations that selectively encode different language modalities. A transcranial magnetic stimulation (TMS)-adaptation protocol was used to disentangle these hypotheses. During adaptation, participants were exposed to spoken or written words in order to tune the initial state of left-vOT neurons to one of the language modalities. After adaptation, they performed lexical decisions on spoken and written targets with TMS applied to the left-vOT. TMS showed selective facilitatory effects. It accelerated lexical decisions only when the adaptors and the targets shared the same modality, i.e., when left-vOT neurons had initially been adapted to the modality of the target stimuli. Since this within-modal adaptation was observed for both input modalities and no evidence for cross-modal adaptation was found, our findings suggest that the left-vOT contains neurons that selectively encode written and spoken language rather than purely written language coding neurons or multimodal neurons encoding language regardless of modality.

Do Words Stink? Neural Reuse as a Principle for Understanding Emotions in Reading.

How do we understand the emotional content of written words? Here, we investigate the hypothesis that written words that carry emotions are processed through phylogenetically ancient neural circuits that are involved in the processing of the very same emotions in nonlanguage contexts. This hypothesis was tested with respect to disgust. In an fMRI experiment, it was found that the same region of the left anterior insula responded whether people observed facial expressions of disgust or whether they read words with disgusting content. In a follow-up experiment, it was found that repetitive TMS over the left insula in comparison with a control site interfered with the processing of disgust words to a greater extent than with the processing of neutral words. Together, the results support the hypothesis that the affective processes we experience when reading rely on the reuse of phylogenetically ancient brain structures that process basic emotions in other domains and species.

Resting state brain dynamics and its transients: a combined TMS-EEG study.

The brain at rest exhibits a spatio-temporally rich dynamics which adheres to systematic behaviours that persist in task paradigms but appear altered in disease. Despite this hypothesis, many rest state paradigms do not act directly upon the rest state and therefore cannot confirm hypotheses about its mechanisms. To address this challenge, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study brain's relaxation toward rest following a transient perturbation. Specifically, TMS targeted either the medial prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was triggered by a given brain state, namely an increase in occipital alpha rhythm power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the induced occipital alpha rhythm, called Event Related Synchronisation, with a longer transient lifetime than TMS at SPL, and a higher amplitude. Our findings show a strong coupling between MPFC and the occipital alpha power. Although the rest state is organized around a core of resting state networks, the DMN functionally takes a special role among these resting state networks.

Internal modeling of upcoming speech: A causal role of the right posterior cerebellum in non-motor aspects of language production.

Some language processing theories propose that, just as for other somatic actions, self-monitoring of language production is achieved through internal modeling. The cerebellum is the proposed center of such internal modeling in motor control, and the right cerebellum has been linked to an increasing number of language functions, including predictive processing during comprehension. Relating these findings, we tested whether the right posterior cerebellum has a causal role for self-monitoring of speech errors. Participants received 1 Hz repetitive transcranial magnetic stimulation during 15 min to lobules Crus I and II in the right hemisphere, and, in counterbalanced orders, to the contralateral area in the left cerebellar hemisphere (control) in order to induce a temporary inactivation of one of these zones. Immediately afterwards, they engaged in a speech production task priming the production of speech errors. Language production was impaired after right compared to left hemisphere stimulation, a finding that provides evidence for a causal role of the cerebellum during language production. We interpreted this role in terms of internal modeling of upcoming speech through a verbal working memory process used to prevent errors.

Contribution of writing to reading: Dissociation between cognitive and motor process in the left dorsal premotor cortex.

Functional brain imaging studies reported activation of the left dorsal premotor cortex (PMd), that is, a main area in the writing network, in reading tasks. However, it remains unclear whether this area is causally relevant for written stimulus recognition or its activation simply results from a passive coactivation of reading and writing networks. Here, we used chronometric paired-pulse transcranial magnetic stimulation (TMS) to address this issue by disrupting the activity of the PMd, the so-called Exner's area, while participants performed a lexical decision task. Both words and pseudowords were presented in printed and handwritten characters. The latter was assumed to be closely associated with motor representations of handwriting gestures. We found that TMS over the PMd in relatively early time-windows, i.e., between 60 and 160 ms after the stimulus onset, increased reaction times to pseudoword without affecting word recognition. Interestingly, this result pattern was found for both printed and handwritten characters, that is, regardless of whether the characters evoked motor representations of writing actions. Our result showed that under some circumstances the activation of the PMd does not simply result from passive association between reading and writing networks but has a functional role in the reading process. At least, at an early stage of written stimuli recognition, this role seems to depend on a common sublexical and serial process underlying writing and pseudoword reading rather than on an implicit evocation of writing actions during reading as typically assumed.

TMS reveals a direct influence of spinal projections from human SMAp on precise force production.

The corticospinal (CS) system plays an important role in fine motor control, especially in precision grip tasks. Although the primary motor cortex (M1) is the main source of the CS projections, other projections have been found, especially from the supplementary motor area proper (SMAp). To study the characteristics of these CS projections from SMAp, we compared muscle responses of an intrinsic hand muscle (FDI) evoked by stimulation of human M1 and SMAp during an isometric static low-force control task. Subjects were instructed to maintain a small cursor on a target force curve by applying a pressure with their right precision grip on a force sensor. Neuronavigated transcranial magnetic stimulation was used to stimulate either left M1 or left SMAp with equal induced electric field values at the defined cortical targets. The results show that the SMAp stimulation evokes reproducible muscle responses with similar latencies and amplitudes as M1 stimulation, and with a clear and significant shorter silent period. These results suggest that (i) CS projections from human SMAp are as rapid and efficient as those from M1, (ii) CS projections from SMAp are directly involved in control of the excitability of spinal motoneurons and (iii) SMAp has a different intracortical inhibitory circuitry. We conclude that human SMAp and M1 both have direct influence on force production during fine manual motor tasks.

Functional corticospinal projections from human supplementary motor area revealed by corticomuscular coherence during precise grip force control.

The purpose of the present study was to investigate whether corticospinal projections from human supplementary motor area (SMA) are functional during precise force control with the precision grip (thumb-index opposition). Since beta band corticomuscular coherence (CMC) is well-accepted to reflect efferent corticospinal transmission, we analyzed the beta band CMC obtained with simultaneous recording of electroencephalographic (EEG) and electromyographic (EMG) signals. Subjects performed a bimanual precise visuomotor force tracking task by applying isometric low grip forces with their right hand precision grip on a custom device with strain gauges. Concurrently, they held the device with their left hand precision grip, producing similar grip forces but without any precision constraints, to relieve the right hand. Some subjects also participated in a unimanual control condition in which they performed the task with only the right hand precision grip while the device was held by a mechanical grip. We analyzed whole scalp topographies of beta band CMC between 64 EEG channels and 4 EMG intrinsic hand muscles, 2 for each hand. To compare the different topographies, we performed non-parametric statistical tests based on spatio-spectral clustering. For the right hand, we obtained significant beta band CMC over the contralateral M1 region as well as over the SMA region during static force contraction periods. For the left hand, however, beta band CMC was only found over the contralateral M1. By comparing unimanual and bimanual conditions for right hand muscles, no significant difference was found on beta band CMC over M1 and SMA. We conclude that the beta band CMC found over SMA for right hand muscles results from the precision constraints and not from the bimanual aspect of the task. The result of the present study strongly suggests that the corticospinal projections from human SMA become functional when high precision force control is required.

Preparing for a motor perturbation: early implication of primary motor and somatosensory cortices.

Although preparation of voluntary movement has been extensively studied, very few human neuroimaging studies have examined preparation of an intentional reaction to a motor perturbation. This latter type of preparation is fundamental for adaptive motor capabilities in everyday life because it allows a desired motor output to be maintained despite changes in external forces. Using fMRI, we studied how the sensorimotor cortical network is implicated in preparing to react to a mechanical motor perturbation. While maintaining a given wrist angle against a small force, subjects were instructed to prepare a reaction to a subsequent wrist angle displacement. This reaction consisted of, either resisting the imposed movement, or remaining passive. During the preparation of both reactions we found an early implication of M1 and S1 but no implication at all of the higher order motor area preSMA. This is clearly different from what has been found for voluntary movement preparation. These results show that the sensorimotor network activation during preparation of voluntary motor acts depends on whether one expects a motor perturbation to occur: when external forces can interfere with ongoing motor acts, the primary sensorimotor areas must be ready to react as quickly as possible to perturbations that could prevent the goal of the ongoing motor act from being achieved.

Corticospinal control of wrist muscles during expectation of a motor perturbation: a transcranial magnetic stimulation study.

Voluntary movement is often perturbed by the external forces in the environment. Because corticospinal (CS) control of wrist muscles during preparation of voluntary movement has been extensively studied without variation in the external forces, very little is known about the way CS control adapts when subjects expect motor perturbations. Here, we studied the CS control of wrist muscles during expectation of an imposed wrist extension. Subjects were instructed either to compensate (COMP) the perturbation (applied at variable delays) or not to intervene (NINT). In a quarter of all trials at random, in the time window when perturbation might occur, TMS was applied over contralateral M1. Motor evoked potentials (MEPs) were measured in the FCR (flexor carpi radialis) and ECR (extensor carpi radialis) muscles, as well as the silent period (SP) in the FCR. Following the perturbation, we found a larger long-latency stretch reflex in COMP than in NINT. During the expectation of the perturbation, MEP amplitudes did not differ across conditions in FCR. However, those evoked in ECR were greater in COMP than in NINT condition. Moreover in the FCR, the silent period lasted longer in NINT. Thus, we showed a selective effect of the prepared reaction on the anticipatory tuning of CS excitability and cortical inhibition in the agonist/antagonist muscles. This tuning clearly differed from the tuning during voluntary movement preparation without variation in the external forces. This shows that the tuning of the CS system during motor preparation depends on the dynamical context of movement production.

Error processing during online motor control depends on the response accuracy.

We investigated which brain areas show error-related activity during online motor control while errors occur independently from decision making. During motor tasks, error is a deviation from accuracy or correctness. The effect of the accuracy level on error-related brain activity is unclear. Using functional Magnetic Resonance Imaging (fMRI), we investigated how error-related brain activity, especially in fronto-medial wall areas, depended on motor accuracy (MA). Subjects performed a force tracking task with the thumb-index grip: to continuously follow a moving target on a monitor with a cursor which position was controlled by the force amount produced by the fingers. Task difficulty varied with changes in the cursor size (the smaller the cursor, the more difficult the task). We measured the motor accuracy (mean distance between the cursor center and the target) and the error amount (cursor out of the target). Errors were produced when motor accuracy was low and also when motor accuracy was high. For fMRI data processing, we defined a model based on both the error amount and the motor accuracy. The results showed that supplementary motor area (SMA) and dorsal anterior cingulate cortex (ACC) activation increased with error and task difficulty independent of the accuracy of motor control. Interestingly, activity in the rostral part of left ACC only increased with error when the motor accuracy was low, independently from task difficulty. These results suggest a clear functional dissociation between dorsal and rostral ACC in error processing which depends on the amount of attentional resources allocated to motor accuracy.

On-line flexibility of the cognitive tuning of corticospinal excitability: a TMS study in human gait.

Human subjects have been found to be able to cognitively prepare themselves to resist to a TMS-induced central perturbation by selectively modulating the corticospinal excitability (CS). The aim of this study was to investigate the on-line adaptability of this cognitive tuning of CS excitability during human gait. Transcranial magnetic stimulation (TMS) was used both as a central perturbation evoking a movement and as a tool for quantifying the CS excitability before the movement was evoked. TMS was applied at mid-stance (evoking additional hip extension) or at the beginning of the swing (evoking hip flexion) with a random phase, thus evoking unpredictable flexion or extension movement. This was compared to a condition of fixed phase, in which the subjects knew in advance the direction of the evoked movement. In both conditions, we compared the amplitude of the TMS-evoked movement and the motor-evoked potentials (MEPs) of the muscles acting at the hip joint (RF/BF) according to two opposite instructions, either to cognitively prepare to "let go", or to cognitively prepare to "compensate" for the evoked movements. The results showed that the subjects were able to compensate for random TMS-evoked movements, but with a lower performance level in comparison to the fixed TMS-evoked movements. When they succeeded in the random-phase condition, the subjects used the same preparation strategy as in the fixed-phase condition; preparing to compensate resulted in a selective increase in the CS excitability to those muscles which would be involved in counteracting the possible central perturbation. This requires continuous change in the tuning of CS excitability within the stride and thus reveals the high flexibility of the cognitive tuning of CS excitability during gait.

High level of dexterity: differential contributions of frontal and parietal areas.

In the present functional magnetic resonance imaging experiment, study participants performed a dynamic tracking task in a precision grip configuration. The precision level of the force control was varied while the mean force level of 5 N was kept constant. Contrasts cancelling error rate differences between the conditions showed activation of nonprimary motor areas and other frontal structures in response to increasing precision constraints when the precision of force control could still be increased, and of right primary and associative parietal areas when the precision of the produced force control reached its maximum. These results suggest that the network of frontal and parietal areas, usually working together in fine control of dexterity tasks, can be differentially involved when environmental constraints become very high.

Interactions between cognitive and sensorimotor functions in the motor cortex: evidence from the preparatory motor sets anticipating a perturbation.

The many signs of cognitive processes in the activation pattern of the primary motor cortex or in corticospinal (CS) excitability gave rise to the idea that the motor cortex is a crucial node in the processing of cognitive information related to sensorimotor functions. Moreover, it became clear that the preparatory motor sets offer a privileged window to investigate the interaction between cognitive and sensorimotor function in the motor cortex. In the present review, we examine how the study of the preparatory motor sets anticipating a mechanical movement perturbation contributes to enlightening this question. Following the initial observation made by Hammond that some components of the stretch reflex can be modulated by a prior intention either to resist or to relax in response to a subsequent perturbation, first evidence of the phenomenon was obtained in behaving monkeys. Moreover, this study related this peripheral fact to the observed anticipatory activity of motor cortex neurons after a prior instruction telling the animal how to respond to the subsequent perturbation, which triggered the instructed movement. Indeed, this anticipatory activity was found to be different according to the instruction. In the 1980s, this work inspired a lot of studies in human beings that brought support to the idea of a cognitive tuning of the long latency stretch response (LLSR). Specifically, the MI component of the response was shown to be modulated by a prior intent to resist versus to let go when faced with the perturbation. Recently, new approaches have been developed to obtain evidence of a cognitive tuning of CS excitability, thanks to transcranial magnetic stimulation (TMS). TMS has been used both as a reliable tool for quantifying the CS excitability via the motor evoked potentials (MEPs), and to centrally perturb the organization of movement. Such central perturbations offer the unique opportunity to activate the descending motor tracts while shunting, for a short time period, the ascending tracts assisting the movement. Thus, CS excitability was measured before the movement was perturbed. These studies demonstrated the readiness of the CS tract to be involved in anticipatory compensatory responses to central movement perturbations induced by TMS in relation to the subject's cognitive attitudes. The question of the cerebral regions upstream of the motor cortex that could be responsible for this modulation in CS excitability remains largely open.

Cognitive tuning of corticospinal excitability during human gait: adaptation to the phase.

The aim of this study was to investigate how the cognitive tuning of corticospinal (CS) excitability adapts to the type of evoked-movement (Flexion vs. Extension) during human gait. Transcranial magnetic stimulation (TMS) was used both as a central perturbation evoking a movement and as a tool for quantifying the CS excitability of the muscles under study (RF/BF). In the first condition (Dst), the TMS occurred at mid-stance, inducing hip extension, whereas in the second condition (Dsw), the TMS occurred at the beginning of the swing phase, inducing hip flexion. In both conditions, the subjects were asked to cognitively prepare to either not intervene (NINT) or to compensate (COMP) for the evoked-movements. The results showed that, regardless of the type of evoked-movement, preparing to compensate resulted in a selective increase in the CS excitability to those muscles that would be involved in counteracting the possible central perturbation, i.e. the hip extensor muscle (BF) to compensate for an evoked flexion during the swing phase or the hip flexor muscle (RF) to compensate for an evoked extension during the stance phase. This latter result offers the first evidence of a modulation in CS excitability to the proximal muscles during the stance phase. In conclusion, the cognitive tuning of CS excitability was found to adapt to the gait phases. Moreover, the same selective preparation strategy was observed whether the central perturbation occurred during the stance or the swing phase of the step cycle.

Awareness of muscular force during movement production: an fMRI study.

Awareness of the muscular forces we produce during voluntary movement must be distinguished from awareness of motor outcome itself. Indeed, there is no univocal relationship between produced muscle force and movement outcome because of external forces. In the present study, we performed a functional magnetic resonance imaging study to investigate the neural bases underlying the awareness we can have of the muscular forces we put into our voluntary movements. In reference conditions, subjects made rhythmical hand movements and knew they had to reproduce, in a subsequent condition in which the resistance to the movement was increased, either their muscular forces or their kinematics. The idea behind this (well established) reproduction paradigm is that, after an explicit verbal instruction, subjects can only reproduce what they are aware off. The main contrast, that is, between the condition during which the subjects had to gain awareness of their muscular forces and that during which they had to gain awareness of their kinematics (conditions in which the actual motor output was similar), shows that gaining awareness about muscular forces exerted during movement execution makes much higher demands on many brain structures, in particular posterior insula, primary sensorimotor areas and associative somatosensory areas. This indicates the important role of somesthetic information processing in awareness of produced muscular force. Therefore, the often-heard presumption that muscle force sense might be based on the outgoing motor command is not confirmed by the present results.

Effects of transcranial magnetic stimulation on muscle activation patterns and joint kinematics within a two-joint motor synergy.

We studied the effects of transcranial magnetic stimulation (TMS) on muscle activation patterns and joint kinematics during oscillatory movements of a joint within a two-joint (elbow-wrist) synergy. Healthy young adults (N=8) performed cyclic movements in one of the joints while the other joint was or was not involved into a postural task. TMS was applied unexpectedly at different phases of the movement cycle. TMS-induced motor evoked potentials (MEPs) showed a modulation within the movement cycle, partly related to changes in the background muscle activity. After normalization by the background activity, MEPs were higher in conditions involving maintenance of a posture by one of the joints. MEPs in a flexor-extensor muscle pair could show peaks at the same phase within the movement cycle while background EMG peaks were out of phase. TMS induced a phase shift in the ongoing movement, and the phase shift changed over the next cycles. It stabilized by the fourth cycle and could show both phase advances and phase delays, the latter dominated. The findings are interpreted as supporting two hypotheses: (1) TMS can activate cortical neurons interposed in a transcortical long-latency loop leading to pre-programmed reactions to perturbations; and (2) apparent effects of TMS on the timing of an ongoing cyclic movement are defined by an interaction between its effects on a central 'clock' and those induced by the peripheral mechanical response.