Using TMS to study the role of the articulatory motor system in speech perception

Background: The ability to communicate using speech is a remarkable skill, which requires precise coordination of articulatory movements and decoding of complex acoustic signals. According to the traditional view, speech production and perception rely on motor and auditory brain areas, respectively. However, there is growing evidence that auditory-motor circuits support both speech production and perception.Aims: In this article we provide a review of how transcranial magnetic stimulation (TMS) has been used to investigate the excitability of the motor system during listening to speech and the contribution of the motor system to performance in various speech perception tasks. We also discuss how TMS can be used in combination with brain-imaging techniques to study interactions between motor and auditory systems during speech perception.Main contribution: TMS has proven to be a powerful tool to investigate the role of the articulatory motor system in speech perception.Conclusions: TMS studies have provided support for the view that the motor structures that control the movements of the articulators contribute not only to speech production but also to speech perception.     

Seeing and hearing speech excites the motor system involved in speech production

The perception of action is associated with increased activity in motor regions, implicating such regions in the recognition, understanding and imitation of actions. We examined the possibility that perception of speech, both auditory and visual, would also result in changes in the excitability of the motor system underlying speech production. Transcranial magnetic stimulation was applied to the face area of primary motor cortex to elicit motor-evoked potentials in the lip muscles. The size of the motor-evoked potentials was compared under the following conditions: listening to speech, listening to non-verbal sounds, viewing speech-related lip movements, and viewing eye and brow movements. Compared to control conditions, listening to and viewing speech enhanced the size of the motor-evoked potential. This effect was only seen in response to stimulation of the left hemisphere; stimulation of the right hemisphere produced no changes in motor-evoked potentials in any of the conditions. In a control experiment, the size of the motor-evoked potentials elicited in the muscles of the right hand did not differ among conditions, suggesting that speech-related changes in excitability are specific to the lip muscles. These results provide evidence that both auditory and visual speech perception facilitate the excitability of the motor system involved in speech production.     

When sounds become actions: higher-order representation of newly learned action sounds in the human motor system

In the absence of visual information, our brain is able to recognize the actions of others by representing their sounds as a motor event. Previous studies have provided evidence for a somatotopic activation of the listener's motor cortex during perception of the sound of highly familiar motor acts. The present experiments studied (a) how the motor system is activated by action-related sounds that are newly acquired and (b) whether these sounds are represented with reference to extrinsic features related to action goals rather than with respect to lower-level intrinsic parameters related to the specific movements. TMS was used to measure the correspondence between auditory and motor codes in the listener's motor system. We compared the corticomotor excitability in response to the presentation of auditory stimuli void of previous motor meaning before and after a short training period in which these stimuli were associated with voluntary actions. Novel cross-modal representations became manifest very rapidly. By disentangling the representation of the muscle from that of the action's goal, we further showed that passive listening to newly learnt action-related sounds activated a precise motor representation that depended on the variable contexts to which the individual was exposed during testing. Our results suggest that the human brain embodies a higher-order audio-visuo-motor representation of perceived actions, which is muscle-independent and corresponds to the goals of the action.     

Motor cortex hand area and speech: implications for the development of language

Recently a growing body of evidence has suggested that a functional link exists between the hand motor area of the language dominant hemisphere and the regions subserving language processing. We examined the excitability of the hand motor area and the leg motor area during reading aloud and during non-verbal oral movements using transcranial magnetic stimulation (TMS). During reading aloud, but not before or afterwards, excitability was increased in the hand motor area of the dominant hemisphere. This reading effect was found to be independent of the duration of speech. No such effect could be found in the contralateral hemisphere. The excitability of the leg area of the motor cortex remained unchanged during reading aloud. The excitability during non-verbal oral movements was slightly increased in both hemispheres. Our results are consistent with previous findings and may indicate a specific functional connection between the hand motor area and the cortical language network.     

Progressive Supranuclear Palsy in a family with TDP-43 pathology

The discovery of mirror neurons in macaque has led to a resurrection of motor theories of speech perception. Although the majority of lesion and functional imaging studies have associated perception with the temporal lobes, it has also been proposed that the ‘human mirror system’, which prominently includes Broca's area, is the neurophysiological substrate of speech perception. Although numerous studies have demonstrated a tight link between sensory and motor speech processes, few have directly assessed the critical prediction of mirror neuron theories of speech perception, namely that damage to the human mirror system should cause severe deficits in speech perception. The present study measured speech perception abilities of patients with lesions involving motor regions in the left posterior frontal lobe and/or inferior parietal lobule (i.e., the proposed human ‘mirror system’). Performance was at or near ceiling in patients with fronto-parietal lesions. It is only when the lesion encroaches on auditory regions in the temporal lobe that perceptual deficits are evident. This suggests that ‘mirror system’ damage does not disrupt speech perception, but rather that auditory systems are the primary substrate for speech perception.     

Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia

Auditory verbal hallucinations (AVHs) have a high prevalence in schizophrenic patients. An array of studies have explored the neural correlates of AVHs by means of functional neuroimaging and have associated AVHs with diverse brain regions, some of which have been shown to be involved in speech generation, speech perception, and auditory stimulus processing. We divided these studies into "state" studies comparing periods of presence and absence of AVHs within-subject and "trait" studies comparing patients experiencing AVHs with patients without AVHs or healthy controls during tasks with verbal material. We set out to test the internal consistency and possible dissociations of the neural correlates of AVHs. We used activation likelihood estimation to perform quantitative meta-analyses on brain regions reported in state and trait studies on AVHs to assess significant concordance across studies. State studies were associated with activation in bilateral inferior frontal gyrus, bilateral postcentral gyrus, and left parietal operculum. Trait studies on the other hand showed convergence of decreases in hallucinating subjects in left superior temporal gyrus, left middle temporal gyrus, anterior cingulate cortex, and left premotor cortex activity. Based on the clear dissociation of brain regions that show convergence across state in comparison to trait studies, we conclude that the state of experiencing AVHs is primarily related brain regions that have been implicated in speech production ie, Broca's area, whereas the general trait that makes humans prone to AVHs seems to be related to brain areas involved in auditory stimuli processing and speech perception, ie, auditory cortex.     

Temporal dynamics of motor cortex excitability during perception of natural emotional scenes

Although it is widely assumed that emotions prime the body for action, the effects of visual perception of natural emotional scenes on the temporal dynamics of the human motor system have scarcely been investigated. Here, we used single-pulse transcranial magnetic stimulation (TMS) to assess motor excitability during observation and categorization of positive, neutral and negative pictures from the International Affective Picture System database. Motor-evoked potentials (MEPs) from TMS of the left motor cortex were recorded from hand muscles, at 150 and 300 ms after picture onset. In the early temporal condition we found an increase in hand motor excitability that was specific for the perception of negative pictures. This early negative bias was predicted by interindividual differences in the disposition to experience aversive feelings (personal distress) in interpersonal emotional contexts. In the later temporal condition, we found that MEPs were similarly increased for both positive and negative pictures, suggesting an increased reactivity to emotionally arousing scenes. By highlighting the temporal course of motor excitability during perception of emotional pictures, our study provides direct neurophysiological support for the evolutionary notions that emotion perception is closely linked to action systems and that emotionally negative events require motor reactions to be more urgently mobilized.     

Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: an interleaved TMS/functional magnetic resonance imaging study.

BACKGROUND: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. METHODS: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. RESULTS: Both TMS (110% motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected post-task "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant differences between TMS- and volition-induced effects. Differences were detectable, however, in primary data time-intensity profiles. CONCLUSIONS: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation.     

Modulation of sensory and motor cortex activity during speech preparation

Previous studies have shown that speaking affects auditory and motor cortex responsiveness, which may reflect the influence of motor efference copy. If motor efference copy is involved, it would also likely influence auditory and motor cortical activity when preparing to speak. We tested this hypothesis by using auditory event-related potentials and transcranial magnetic stimulation (TMS) of the motor cortex. In the speech condition subjects were visually cued to prepare a vocal response to a subsequent target, which was compared to a control condition without speech preparation. Auditory and motor cortex responsiveness at variable times between the cue and target were probed with an acoustic stimulus (Experiment 1, tone or consonant-vowels) or motor cortical TMS (Experiment 2). Acoustic probes delivered shortly before targets elicited a fronto-central negative potential in the speech condition. Current density analysis showed that auditory cortical activity was attenuated at the beginning of the slow potential in the speech condition. Sensory potentials in response to probes had shorter latencies (N100) and larger amplitudes (P200) when consonant-vowels matched the sound of cue words. Motor cortex excitability was greater in the speech than in the control condition at all time points before picture onset. The results suggest that speech preparation induces top-down regulation of sensory and motor cortex responsiveness, with different time courses for auditory and motor systems.     

Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits

Recent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo-planar imaging with blood-oxygenation-level-dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high-frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra- and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI-detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re-afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.     

Hallucination‐ and speech‐specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task‐based fMRI data: An fBIRN study

Hypercoupling of activity in speech‐perception‐specific brain networks has been proposed to play a role in the generation of auditory‐verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task‐based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI‐CPCA), which allowed for comparison of task‐related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory‐motor, (b) language processing, and (c) default‐mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory‐motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non‐AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech‐perception‐related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation.     

Are mirror neurons the basis of speech perception? Evidence from five cases with damage to the purported human mirror system

The discovery of mirror neurons in macaque has led to a resurrection of motor theories of speech perception. Although the majority of lesion and functional imaging studies have associated perception with the temporal lobes, it has also been proposed that the 'human mirror system', which prominently includes Broca's area, is the neurophysiological substrate of speech perception. Although numerous studies have demonstrated a tight link between sensory and motor speech processes, few have directly assessed the critical prediction of mirror neuron theories of speech perception, namely that damage to the human mirror system should cause severe deficits in speech perception. The present study measured speech perception abilities of patients with lesions involving motor regions in the left posterior frontal lobe and/or inferior parietal lobule (i.e., the proposed human 'mirror system'). Performance was at or near ceiling in patients with fronto-parietal lesions. It is only when the lesion encroaches on auditory regions in the temporal lobe that perceptual deficits are evident. This suggests that 'mirror system' damage does not disrupt speech perception, but rather that auditory systems are the primary substrate for speech perception.     

Visual cortex excitability increases during visual mental imagery--a TMS study in healthy human subjects

Previous neuroimaging studies provided evidence that visual mental imagery relies, in part, on the primary visual cortex. We hypothesized that, analogous to the finding that motor imagery increases the excitability of motor cortex, visual imagery should increase visual cortex excitability, as indexed by a decrease in the phosphene threshold (PT). In order to test visual cortex excitability, the primary visual cortex was stimulated with transcranial magnetic stimulation (TMS), so as to elicit phosphenes in the right lower visual quadrant. Subjects performed a visual imagery task and an auditory control task. We applied TMS with increasing intensity to determine the PT for each subject. Independent of the quadrant in which subjects placed their visual images, imagery decreased PT compared to baseline PT; in contrast, the auditory task did not change PT. These findings demonstrate for the first time a short-term, task-dependent modulation of PT. These results constitute evidence that early visual areas participate in visual imagery processing.     

Primary auditory cortex activation by visual speech: an fMRI study at 3 T

Recent studies have yielded contradictory evidence on whether visual speech perception (watching articulatory gestures) can activate the human primary auditory cortex. To circumvent confounds due to inter-individual anatomical variation, we defined our subjects' Heschl's gyri and assessed blood oxygenation-dependent signal changes at 3 T within this confined region during visual speech perception and observation of moving circles. Visual speech perception activated Heschl's gyri in nine subjects, with activation in seven of them extending to the area of primary auditory cortex. Activation was significantly stronger during visual speech perception than during observation of the moving circles. Further, a significant hemisphere by stimulus interaction occurred, suggesting left Heschl's gyrus specialization for visual speech processing.     

MEG Intersubject Phase Locking of Stimulus-Driven Activity during Naturalistic Speech Listening Correlates with Musical Training

Musical training is associated with increased structural and functional connectivity between auditory sensory areas and higher-order brain networks involved in speech and motor processing. Whether such changed connectivity patterns facilitate the cortical propagation of speech information in musicians remains poorly understood. We here used magnetoencephalography (MEG) source imaging and a novel seed-based intersubject phase-locking approach to investigate the effects of musical training on the interregional synchronization of stimulus-driven neural responses during listening to naturalistic continuous speech presented in silence. MEG data were obtained from 20 young human subjects (both sexes) with different degrees of musical training. Our data show robust bilateral patterns of stimulus-driven interregional phase synchronization between auditory cortex and frontotemporal brain regions previously associated with speech processing. Stimulus-driven phase locking was maximal in the delta band, but was also observed in the theta and alpha bands. The individual duration of musical training was positively associated with the magnitude of stimulus-driven alpha-band phase locking between auditory cortex and parts of the dorsal and ventral auditory processing streams. These findings provide evidence for a positive relationship between musical training and the propagation of speech-related information between auditory sensory areas and higher-order processing networks, even when speech is presented in silence. We suggest that the increased synchronization of higher-order cortical regions to auditory cortex may contribute to the previously described musician advantage in processing speech in background noise.SIGNIFICANCE STATEMENT Musical training has been associated with widespread structural and functional brain plasticity. It has been suggested that these changes benefit the production and perception of music but can also translate to other domains of auditory processing, such as speech. We developed a new magnetoencephalography intersubject analysis approach to study the cortical synchronization of stimulus-driven neural responses during the perception of continuous natural speech and its relationship to individual musical training. Our results provide evidence that musical training is associated with higher synchronization of stimulus-driven activity between brain regions involved in early auditory sensory and higher-order processing. We suggest that the increased synchronized propagation of speech information may contribute to the previously described musician advantage in processing speech in background noise.     

Motor and phosphene thresholds: a transcranial magnetic stimulation correlation study

Objective: To investigate the stability of visual phosphene thresholds and to assess whether they correlate with motor thresholds. Background: Currently, motor threshold is used as an index of cortical sensitivity so that in transcranial magnetic stimulation (TMS) experiments, intensity can be set at a given percentage of this value. It is not known whether this is a reasonable index of cortical sensitivity in non-motor and hence whether it should be used in experiments where other cortical areas are targeted. Previous studies have indicated that phosphene threshold might be a suitable alternative in TMS studies of the visual system. Method: Using single pulse TMS visual phosphene and motor thresholds were measured in 15 subjects. Both thresholds were retested in seven of these subjects a week later. Result: Visual phosphene thresholds, though stable within subjects across the two sessions, showed greater variability than motor thresholds. There was no correlation between the two measures. Conclusion: TMS motor thresholds cannot be assumed to be a guide to visual cortex excitability and by extension are probably an inappropriate guide to the cortical excitability of other non-motor areas of the brain. Phosphene thresholds are proposed as a potential standard for inter-individual comparison in visual TMS experiments.     

Interaction of sound and sight during action perception: Evidence for shared modality-dependent action representations

Seeing or hearing manual actions activates the mirror neuron system, i.e., specialized neurons within motor areas which fire not only when an action is performed but also when it is passively perceived. Although it has been shown that mirror neurons respond to either action-specific vision or sound, it remains a topic of debate whether and how vision and sound interact during action perception.Here we used transcranial magnetic stimulation to explore multimodal interactions in the human motor system, namely at the level of the primary motor cortex (M1). Corticomotor excitability in M1 was measured while subjects perceived unimodal visual (V), unimodal auditory (A), or multimodal (V + A) stimuli of a simple hand action. In addition, incongruent multimodal stimuli were included, in which incongruent vision or sound was presented simultaneously with the auditory or visual action stimulus. A selective response increase was observed to the congruent multimodal stimulus as compared to the unimodal and incongruent multimodal stimuli.These findings speak in favour of ‘shared’ action representations in the human motor system that are evoked in a ‘modality-dependent’ way, i.e., they are elicited most robustly by the simultaneous presentation of congruent auditory and visual stimuli. Multimodality in the perception of hand movements bears functional similarities to speech perception, suggesting that multimodal convergence is a generic feature of the mirror system which applies to action perception in general.     

Transcranial Magnetic Stimulation in the investigation and treatment of schizophrenia: a review

Transcranial Magnetic Stimulation (TMS) is a non-invasive method of stimulating the brain that is increasingly being used in neuropsychiatric research and clinical psychiatry. This review examines the role of TMS in schizophrenia research as a diagnostic and a therapeutic resource. After a brief overview of TMS, we describe the application of TMS to schizophrenia in studies of cortical excitability and inhibition, and we discuss the potential confounding role of neuroleptic medications. Based on these studies, it appears that some impairment of cortical inhibition may be present in schizophrenic subjects. We then review attempts to employ TMS for treating different symptoms of schizophrenia. Some encouraging results have been obtained, such as the reduction of auditory hallucinations after slow TMS over auditory cortex and an improvement of psychotic symptoms after high frequency TMS over left prefrontal cortex. However, these results need to be confirmed using better placebo conditions. Future studies are likely to employ TMS in combination with functional brain imaging to examine the effects produced by the stimulated area on activity in other brain regions. Such studies may reveal impaired effective connectivity between specific brain areas, which could identify these regions as targets for selective stimulation with therapeutic doses of TMS.     

Task-dependent modulation of functional connectivity between hand motor cortices and neuronal networks underlying language and music: a transcranial magnetic stimulation study in humans

Although language functions are, in general, attributed to the left hemisphere, it is still a matter of debate to what extent the cognitive functions underlying the processing of music are lateralized in the human brain. To investigate hemispheric specialization we evaluated the effect of different overt musical and linguistic tasks on the excitability of both left and right hand motor cortices using transcranial magnetic stimulation (TMS). Task-dependent changes of the size of the TMS-elicited motor evoked potentials were recorded in 12 right-handed, musically naive subjects during and after overt speech, singing and humming, i.e. the production of melody without word articulation. The articulation of meaningless syllables served as control condition. We found reciprocal lateralized effects of overt speech and musical tasks on motor cortex excitability. During overt speech, the corticospinal projection of the left (i.e. dominant) hemisphere to the right hand was facilitated. In contrast, excitability of the right motor cortex increased during both overt singing and humming, whereas no effect was observed on the left hemisphere. Although the traditional concept of hemispheric lateralization of music has been challenged by recent neuroimaging studies, our findings demonstrate that right-hemisphere preponderance of music is nevertheless present. We discuss our results in terms of the recent concepts on evolution of language and gesture, which hypothesize that cerebral networks mediating hand movement and those subserving language processing are functionally linked. TMS may constitute a useful tool to further investigate the relationship between cortical representations of motor functions, music and language using comparative approaches.     

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non‐invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long‐lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS‐I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS‐I. TMS examinations also revealed that the nature of motor dysfunction in CRPS‐I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS‐I patients. Two studies have begun to therapeutically use rTMS. This non‐invasive brain stimulation technique could have therapeutic utility in CRPS, but further well‐designed studies are needed to corroborate initial findings.