Brain activation related to the change between bimanual motor programs

By using positron emission tomography, we aimed to identify cerebral foci of neuronal activation associated with the initiation of a specific motor program. To that end, a state of repeatedly alternating in- and antiphase of bimanual flexion and extension movements was compared with similar movement responses except phase changing. This comparison provided the opportunity to eliminate confounding effects of attention and simple movements. Change between the two bimanual motor programs was related with activation at the posterior border of the left angular gyrus, the right precuneus, and the right premotor and right medial prefrontal cortex. In a subsequent experiment, with attention and random movements as additional variables, activation at the posterior border of the left angular gyrus was found at the same significance level. This posterior parietal activation may indicate an equivalence with the coding of intention in monkey posterior parietal cortex. Lesion of the left posterior parietal cortex in human gives rise to left-right disorientation and ideomotor apraxia. Our results may support the view that these symptoms reflect the inability to transpose a motor plan to the representation of a personal body scheme. Activation of the right premotor and right medial prefrontal cortex was related both to the change between motor programs and to the condition with strictly regular movement in which no additional responses were made to randomly presented signals. This is consistent with the concept that motor preparation is associated with both the selection of internally instructed movements and the suppression of irrelevant environmental stimuli.     

Motor learning produces parallel dynamic functional changes during the execution and imagination of sequential foot movements

The aim of the present positron emission tomography study was to measure the dynamic changes in cerebral activity before and after practice of an explicitly known sequence of foot movements when executed physically and to compare them to those elicited during motor imagery of the same movements. Nine healthy volunteers were scanned while performing both types of movement at an early phase of learning and after a 1-h training period of a sequence of dorsiflexions and plantarflexions with the left foot. These experimental conditions were compared directly, as well as to a perceptual control condition. Changes in regional cerebral blood flow associated with physical execution of the sequence early in the learning process were observed bilaterally in the dorsal premotor cortex and cerebellum, as well as in the left inferior parietal lobule. After training, however, most of these brain regions were no longer significantly activated, suggesting that they are critical for establishing the cognitive strategies and motor routines involved in executing sequential foot movements. By contrast, after practice, an increased level of activity was seen bilaterally in the medial orbitofrontal cortex and striatum, as well as in the left rostral portion of the anterior cingulate and a different region of the inferior parietal lobule, suggesting that these structures play an important role in the development of a long lasting representation of the sequence. Finally, as predicted, a similar pattern of dynamic changes was observed in both phases of learning during the motor imagery conditions. This last finding suggests that the cerebral plasticity occurring during the incremental acquisition of a motor sequence executed physically is reflected by the covert production of this skilled behavior using motor imagery.     

Selective activation of a parietofrontal circuit during implicitly imagined prehension

It is generally held that motor imagery is the internal simulation of movements involving one's own body in the absence of overt execution. Consistent with this hypothesis, results from numerous functional neuroimaging studies indicate that motor imagery activates a large variety of motor-related brain regions. However, it is unclear precisely which of these areas are involved in motor imagery per se as opposed to other planning processes that do not involve movement simulation. In an attempt to resolve this issue, we employed event-related fMRI to separate activations related to hand preparation-a task component that does not demand imagining movements-from grip selection-a component previously shown to require the internal simulation of reaching movements. Our results show that in contrast to preparation of overt actions, preparation of either hand for covert movement simulation activates a large network of motor-related areas located primarily within the left cerebral and right cerebellar hemispheres. By contrast, imagined grip selection activates a distinct parietofrontal circuit that includes the bilateral dorsal premotor cortex, contralateral intraparietal sulcus, and right superior parietal lobule. Because these areas are highly consistent with the frontoparietal reach circuit identified in monkeys, we conclude that motor imagery involves action-specific motor representations computed in parietofrontal circuits.     

Building a motor simulation de novo: observation of dance by dancers

Research on action simulation identifies brain areas that are active while imagining or performing simple overlearned actions. Are areas engaged during imagined movement sensitive to the amount of actual physical practice? In the present study, participants were expert dancers who learned and rehearsed novel, complex whole-body dance sequences 5 h a week across 5 weeks. Brain activity was recorded weekly by fMRI as dancers observed and imagined performing different movement sequences. Half these sequences were rehearsed and half were unpracticed control movements. After each trial, participants rated how well they could perform the movement. We hypothesized that activity in premotor areas would increase as participants observed and simulated movements that they had learnt outside the scanner. Dancers' ratings of their ability to perform rehearsed sequences, but not the control sequences, increased with training. When dancers observed and simulated another dancer's movements, brain regions classically associated with both action simulation and action observation were active, including inferior parietal lobule, cingulate and supplementary motor areas, ventral premotor cortex, superior temporal sulcus and primary motor cortex. Critically, inferior parietal lobule and ventral premotor activity was modulated as a function of dancers' ratings of their own ability to perform the observed movements and their motor experience. These data demonstrate that a complex motor resonance can be built de novo over 5 weeks of rehearsal. Furthermore, activity in premotor and parietal areas during action simulation is enhanced by the ability to execute a learned action irrespective of stimulus familiarity or semantic label.     

Investigating the human mirror neuron system by means of cortical synchronization during the imitation of biological movements

The human mirror neuron system (MNS) has recently been a major topic of research in cognitive neuroscience. As a very basic reflection of the MNS, human observers are faster at imitating a biological as compared with a non-biological movement. However, it is unclear which cortical areas and their interactions (synchronization) are responsible for this behavioural advantage. We investigated the time course of long-range synchronization within cortical networks during an imitation task in 10 healthy participants by means of whole-head magnetoencephalography (MEG). Extending previous work, we conclude that left ventrolateral premotor, bilateral temporal and parietal areas mediate the observed behavioural advantage of biological movements in close interaction with the basal ganglia and other motor areas (cerebellum, sensorimotor cortex). Besides left ventrolateral premotor cortex, we identified the right temporal pole and the posterior parietal cortex as important junctions for the integration of information from different sources in imitation tasks that are controlled for movement (biological vs. non-biological) and that involve a certain amount of spatial orienting of attention. Finally, we also found the basal ganglia to participate at an early stage in the processing of biological movement, possibly by selecting suitable motor programs that match the stimulus.     

Attention to action: specific modulation of corticocortical interactions in humans

The prefrontal cortex may exert cognitive control by a general mechanism of attentional selection of neuronal representations. We used functional magnetic resonance imaging to test this hypothesis in the motor system. Normal volunteers were scanned during performance of a simple motor task, with their attention either directed towards their actions, or diverted towards a visual search task, or neither. Attention to action increased activity in prefrontal, premotor and parietal cortex, compared with unattended performance of the same movements. Analysis of cortical activity by structural equation modelling of regional fMRI time series was used to measure effective connectivity among prefrontal, premotor and parietal cortices. Attention to action enhanced effective connectivity between dorsal prefrontal cortex and premotor cortex, whereas non-motor attention diminished it. These effects were not attributable to common inputs from parietal cortex to the prefrontal and premotor cortex. The results suggest a supra-modal role for the dorsal prefrontal cortex in attentional selection, operating within the motor system as well as sensory and mnemonic domains.     

The effect of switching between sequential and repetitive movements on cortical activation

We used whole-head functional magnetic resonance imaging (fMRI) to investigate the effect of switching between different sequential and repetitive movements in the context of conditional and fixed tasks. Four different movement tasks were applied: (1) unpredictable switching between two movement sequences comprising six submovements each according to visual cues (SEQ-VC); (2) unpredictable switching between repetitive movement of one finger according to visual cues (REP-VC); (3) performance of the same sequential movements used for SEQ-VC but in a fixed mode triggered by a visual stimulus (SEQ-FIX); (4) performance of the repetitive movements used for REP-FIX but in a fixed mode by a visual stimulus (REP-FIX). The statistical group analysis of the hemodynamic responses revealed the following results: (1) the SEQ-VC compared to the SEQ-FIX condition (switching between movement sequences) engendered stronger activations in the left rostral supplementary motor area (pre-SMA), bilaterally in the posterior parietal lobule, the left ventral premotor area, and the visual cortices; (2) the REP-VC compared to the REP-FIX condition (switching between repetitive movements) only revealed stronger activation in extra-striate areas. We hypothesize that during switching of movement sequences higher motor control aspects are involved including movement selection, updating of motor plans, as well as recalling and restoring motor plans. The repetitive movements are too simple in order to evoke additional activations in the medial and lateral premotor areas, as well as in parietal areas.     

Role of cerebral cortex in voluntary movements. A review

Findings from studies using electrical stimulation of cortex, recording from single neurons in awake animals, and measuring regional cerebral blood flow in humans have revealed some specific motor functions for several cerebral cortical areas. These areas include primary motor cortex, supplementary motor area, premotor area, parietal areas 5 and 7, and prefrontal area. Execution of movement is a function of the primary motor cortex, which translates program instructions for movement from other parts of the brain into signals. These signals encode variables of movement, such as the muscles to contract and the force and timing of their contraction. Long-latency reflex responses of muscles to stretch and cutaneous stimulation are also mediated by the motor cortex; other motor areas seem to perform higher order motor functions. The supplementary motor area controls input-output coupling in motor cortex and the programming of complex sequences of rapidly occurring discrete movements, such as playing the piano. The premotor area participates in the assembly of new motor programs. The parietal areas 5 and 7 are involved in directing attention to objects of interest in visual space and issuing commands for arm movements and eye movements to these objects. The prefrontal cortex performs cognitive functions, such as short-term memory of correct motor responses in delayed response tests.     

Internal vs external generation of movements: differential neural pathways involved in bimanual coordination performed in the presence or absence of augmented visual feedback

It is commonly agreed that a functional dissociation with respect to the internal vs external control of movements exists for several brain regions. This has, however, only been tested in relation to the timing and preparation of motor responses, but not to ongoing movement control. Using functional magnetic resonance imaging (fMRI), the present study addressed the neuroanatomical substrate of the internal-external control hypothesis by comparing regional brain activation for cyclical bimanual movements performed in the presence or absence of augmented visual feedback. Subjects performed a bimanual movement pattern, either with the help of on-line visual feedback of the movements (externally guided coordination) or with the eyes closed on the basis of an internal representation of the movement pattern (internally generated coordination). Visual control and baseline rest conditions were also added. Results showed a clear functional dissociation within the network involved in movement coordination. The hMT/V5+, the superior parietal cortex, the premotor cortex, the thalamus, and cerebellar lobule VI showed higher activation levels when movements were guided by visual feedback. Conversely, the basal ganglia, the supplementary motor area, cingulate motor cortex, the inferior parietal, frontal operculum, and cerebellar lobule IV-V/dentate nucleus showed higher involvement when movements were internally generated. Consequently, the present findings suggest the existence of distinct cortico-cortical and subcortico-cortical neural pathways for externally (augmented feedback) and internally guided cyclical bimanual movements. This provides a neurophysiological account for the beneficial effect of providing augmented visual feedback to optimize movements in normal and motor disordered patients.     

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.     

Neural correlates of counting of sequential sensory and motor events in the human brain

Little is known about the ability to enumerate small numbers of successive stimuli and movements. It is possible that there exist neural substrates that are consistently recruited both to count sensory stimuli from different modalities and for counting movements executed by different effectors. Here, we identify a network of areas that was involved in enumerating small numbers of auditory, visual, and somatosensory stimuli, and in enumerating sequential movements of hands and feet, in the bilateral premotor cortex, presupplementary motor area, posterior temporal cortex, and thalamus. The most significant consistent activation across sensory and motor counting conditions was found in the lateral premotor cortex. Lateral premotor activation was not dependent on movement preparation, stimulus presentation timing, or number word verbalization. Movement counting, but not sensory counting, activated the anterior parietal cortex. This anterior parietal area may correspond to an area recruited for movement counting identified by recent single-neuron studies in monkeys. These results suggest that overlapping but not identical networks of areas are involved in counting sequences of sensory stimuli and sequences of movements in the human brain.     

A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 +/- 14 years) with H(2)(15)O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)--compared to the rest condition--were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor-cerebellar structures, reflecting their role in mediating sequence control.     

Gender Difference in Premotor Activity during Active Tactile Discrimination

To investigate possible gender differences in tactile discrimination tasks, we measured cerebral blood flow of seven men and seven women using positron emission tomography and ¹⁵O water during tactile tasks performed with the right index finger. A nondiscrimination, somatosensory control task activated the left primary sensorimotor cortex and the left parietal operculum extending to the posterior insula without any gender difference. Compared with the control task, discrimination tasks activated the superior and inferior parietal lobules bilaterally, right dorsal premotor cortex, and dorsolateral prefrontal cortex in both genders, consistent with the notion of right hemisphere involvement during exploratory attentional movements. In both genders, symmetric activation of the superior and inferior parietal lobules and asymmetric activation of the right dorsolateral prefrontal cortex were confirmed. The former is consistent with the spatial representation of the tactile input and the latter with the spatial working memory. However, activation of the dorsal premotor cortex was asymmetric in men, whereas it was symmetric in women, the gender difference being statistically significant. This may suggest gender differences in motor programs for exploration in manipulospatial tasks such as tactile discrimination with active touch, possibly by greater interhemispheric interaction through the dorsal premotor cortices in women than in men.     

Ipsilateral motor cortex activation on functional magnetic resonance imaging during unilateral hand movements is related to interhemispheric interactions

Distal, unilateral hand movements can be associated with activation of both sensorimotor cortices on functional MRI. The neurophysiological significance of the ipsilateral activation remains unclear. We examined 10 healthy right-handed subjects with and without activation of the ipsilateral sensorimotor area during unilateral index-finger movements, to examine ipsilateral, uncrossed-descending pathways and interhemispheric interaction between bilateral motor areas, using transcranial magnetic stimulation (TMS). No subject showed ipsilateral activation during right hand movement. Five subjects showed ipsilateral sensorimotor cortical activation during left hand movement (IpsiLM1). In these subjects, paired-pulse TMS revealed a significant interhemispheric inhibition of the left motor cortex by the right hemisphere that was not present in the 5 subjects without IpsiLM1. Neither ipsilateral MEPs nor ipsilateral silent periods were evoked by TMS in any subjects. Our observation suggests that IpsiLM1 is not associated with the presence of ipsilateral uncrossed-descending projections. Instead, IpsiLM1 may reveal an enhanced interhemispheric inhibition from the right hemisphere upon the left to suppress superfluous, excessive activation.     

Handedness-dependent and -independent cerebral asymmetries in the anterior intraparietal sulcus and ventral premotor cortex during grasp planning

When planning grasping actions, right-handers show left-lateralized responses in the anterior intraparietal sulcus (aIPS) and ventral premotor cortex (vPMC), two areas that are also implicated in sensorimotor control of grasp. We investigated whether a similar cerebral asymmetry is evident in strongly left-handed individuals. Fourteen participants were trained to grasp an object appearing in a variety of orientations with their left and right hands and with a novel mechanical tool (operated with either hand). BOLD fMRI data were then acquired while they decided prospectively whether an over- or under-hand grip would be most comfortable for grasping the same stimulus set while remaining still. Behavioral performances were equivalent to those recorded previously in right-handers and indicated reliance on effector-specific internal representations. In left-handers, however, grip selection decisions for both sides (left, right) and effectors (hand, tool) were associated with bilateral increases in activity within aIPS and vPMC. A direct comparison between left- and right-handers did reveal equivalent increases in left vPMC regardless of hand dominance. By contrast, aIPS and right vPMC activity were dependent on handedness, showing greater activity in the motor-dominant hemisphere. Though showing bilateral increases in both left- and right-handers, greater increases in the motor dominant hemisphere were also detected in the caudal IPS (cIPS), superior parietal lobule (SPL) and dorsal premotor cortex (dPMC). These findings provide further evidence that regions involved in the sensorimotor control of grasp also participate in grasp planning, and that for certain areas hand dominance is a predictor of the cerebral organization of motor cognitive functions.     

fMRI评价正常老年人腕关节被动运动下脑激活区

目的 用功能磁共振技术观察正常老年人双侧腕关节被动运动时脑区激活情况.方法 对30例正常的右利手老年受试者分别进行双侧腕关节被动运动的功能MR扫描,采用SPM2软件进行数据分析和脑功能区定位.结果 利手(右手)运动主要激活对侧感觉运动皮质、运动前区,双侧辅助运动区、后顶叶及同侧小脑;非利手运动时除激活上述脑区外,还激活了同侧运动感觉区和对侧小脑,且对侧运动前区、双侧辅助运动区和同侧小脑的激活体积明显大于利手腕关节运动.结论 被动运动依赖于大脑皮质和小脑等许多与运动相关的脑功能区的参与;与利手腕关节运动相比,非利手腕关节运动更依赖于对侧PMC、双侧SMA和同侧小脑等运动区.     

Neural substrates of visuomotor learning based on improved feedback control and prediction

Motor skills emerge from learning feedforward commands as well as improvements in feedback control. These two components of learning were investigated in a compensatory visuomotor tracking task on a trial-by-trial basis. Between-trial learning was characterized with a state-space model to provide smoothed estimates of feedforward and feedback learning, separable from random fluctuations in motor performance and error. The resultant parameters were correlated with brain activity using magnetic resonance imaging. Learning related to the generation of a feedforward command correlated with activity in dorsal premotor cortex, inferior parietal lobule, supplementary motor area and cingulate motor area, supporting a role of these areas in retrieving and executing a predictive motor command. Modulation of feedback control was associated with activity in bilateral posterior superior parietal lobule as well as right ventral premotor cortex. Performance error correlated with activity in a widespread cortical and subcortical network including bilateral parietal, premotor and rostral anterior cingulate cortex as well as the cerebellar cortex. Finally, trial-by-trial changes of kinematics, as measured by mean absolute hand acceleration, correlated with activity in motor cortex and anterior cerebellum. The results demonstrate that incremental, learning-dependent changes can be modeled on a trial-by-trial basis and neural substrates for feedforward control of novel motor programs are localized to secondary motor areas.     

Exploring the contributions of premotor and parietal cortex to spatial compatibility using image-guided TMS

Functional brain imaging studies have demonstrated increased activity in dorsal premotor and posterior parietal cortex when performing spatial stimulus-response compatibility tasks (SRC). We tested the specific role of these regions in stimulus-response mapping using single-pulse transcranial magnetic stimulation (TMS). Subjects were scanned using functional magnetic resonance imaging (fMRI) prior to the TMS session during performance of a task in which spatial compatibility was manipulated. For each subject, the area of increased signal within the regions of interest was registered onto their own high-resolution T1-weighted anatomic scan. TMS was applied to these areas for each subject using a frameless stereotaxic system. Task accuracy and reaction time (RT) were measured during blocks of compatible or incompatible trials and during blocks of real TMS or sham stimulation. On each trial, a single TMS pulse was delivered at 50, 100, 150, or 200 ms after the onset of the stimulus in the left or right visual field. TMS over the left premotor cortex produced various facilitatory effects, depending on the timing of the stimulation. At short intervals, TMS appeared to prime the left dorsal premotor cortex to select a right-hand response more quickly, regardless of stimulus-response compatibility. The strongest effect of stimulation, however, occurred at the 200-ms interval, when TMS facilitated left-hand responses during the incompatible condition. Facilitation of attention to the contralateral visual hemifield was observed during stimulation over the parietal locations. We conclude that the left premotor cortex is one of the cortical regions responsible for overriding automatic stimulus-response associations.     

The human parietal cortex is involved in spatial processing of tongue movement-an fMRI study

The human tongue is so sensitive and dexterous that spatial representations of the inside of the oral cavity for the tongue movement are naturally expected to exist. In the present study, we examined the brain activity associated with spatial processing during tongue movements using a functional magnetic resonance imaging technique. Twenty-four normal subjects participated in the study, which consisted of a periodic series of three blocks; resting of the tongue, tongue movement (pressing the inside of a tooth with the tip of the tongue), and tongue retraction. The cerebral fields of activation during the tongue movement to the left and right side relative to those during rest were found in the primary sensorimotor area and supplementary motor area bilaterally, and in the left inferior parietal lobule (IPL). The activation areas during the tongue retraction relative to those during rest were almost the same, except that activation in the left IPL was not observed. The fields of activation during tongue movement to the left and right side relative to those during tongue retraction were found bilaterally in the dorsal premotor area, superior parietal lobule (SPL), and the IPL. The results indicate that the bilateral SPL and IPL were specifically involved in the processing for human tongue movement. Although no significant laterality was observed, the left parietal area tended to show greater activation in statistical values and area than the right parietal area, thus indicating the possibility that this processing for human tongue movement is related to that for language.     

fMRI investigation of unexpected somatosensory feedback perturbation during speech

Somatosensory feedback plays a critical role in the coordination of articulator movements for speech production. In response to unexpected resistance to lip or jaw movements during speech, fluent speakers can use the difference between the somatosensory expectations of a speech sound and the actual somatosensory feedback to adjust the trajectories of functionally relevant but unimpeded articulators. In an effort to investigate the neural substrates underlying the somatosensory feedback control of speech, we used an event-related sparse sampling functional magnetic resonance imaging paradigm and a novel pneumatic device that unpredictably blocked subjects' jaw movements. In comparison to speech, perturbed speech, in which jaw perturbation prompted the generation of compensatory speech motor commands, demonstrated increased effects in bilateral ventral motor cortex, right-lateralized anterior supramarginal gyrus, inferior frontal gyrus pars triangularis and ventral premotor cortex, and bilateral inferior posterior cerebellum (lobule VIII). Structural equation modeling revealed a significant increased influence from left anterior supramarginal gyrus to right anterior supramarginal gyrus and from left anterior supramarginal gyrus to right ventral premotor cortex as well as a significant increased reciprocal influence between right ventral premotor cortex and right ventral motor cortex and right anterior supramarginal gyrus and right inferior frontal gyrus pars triangularis for perturbed speech relative to speech. These results suggest that bilateral anterior supramarginal gyrus, right inferior frontal gyrus pars triangularis, right ventral premotor and motor cortices are functionally coupled and influence speech motor output when somatosensory feedback is unexpectedly perturbed during speech production.