Functional specificity of human premotor-motor cortical interactions during action selection

Functional connections between dorsal premotor cortex (PMd) and primary motor cortex (M1) have been revealed by paired-pulse transcranial magnetic stimulation (TMS). We tested if such connections would be modulated during a cognitive process (response selection) known to rely on those circuits. PMd-M1 TMS applied 75 ms after a cue to select a manual response facilitated motor-evoked potentials (MEPs). MEPs were facilitated at 50 ms in a control task of response execution, suggesting that PMd-M1 interactions at 75 ms are functionally specific to the process of response selection. At 100 ms, PMd-M1 TMS delayed choice reaction time (RT). Importantly, the MEP (at 75 ms) and the RT (at 100 ms) effects were correlated in a way that was hand-specific. When the response was made with the M1-contralateral hand, MEPs correlated with slower RTs. When the response was made with the M1-ipsilateral hand, MEPs correlated with faster RTs. Paired-pulse TMS confined to M1 did not produce these effects, confirming the causal influence of PMd inputs. This study shows that a response selection signal evolves in PMd early during the reaction period (75-100 ms), impacts on M1 and affects behaviour. Such interactions are temporally, anatomically and functionally specific, and have a causal role in choosing which movement to make.     

The differential modulation of the ventral premotor-motor interaction during movement initiation is deficient in patients with focal hand dystonia

A major feature of focal hand dystonia (FHD) pathophysiology is the loss of inhibition. One inhibitory process, surround inhibition, for which the cortical mechanisms are still unknown, is abnormal in FHD. As the ventral premotor cortex (PMv) plays a key role in the sensorimotor processing involved in shaping finger movements and has many projections onto the primary motor cortex (M1), we hypothesized that the PMv-M1 connections might play a role in surround inhibition. A paired-pulse transcranial magnetic stimulation paradigm was used in order to evaluate and compare the PMv-M1 interactions during different phases (rest, preparation and execution) of an index finger movement in patients with FHD and controls. A sub-threshold conditioning pulse (80% resting motor threshold) was applied to the PMv at 6 ms before M1 stimulation. The right abductor pollicis brevis, a surround muscle, was the target muscle. In healthy controls, the results showed that PMv stimulation induced an ipsilateral ventral premotor-motor inhibition at rest. This cortico-cortical interaction changed into an early facilitation (100 ms before movement onset) and turned back to inhibition 50 ms later. In patients with FHD, this PMv-M1 interaction and its modulation were absent. Our results show that, although the ipsilateral ventral premotor-motor inhibition does not play a key role in the genesis of surround inhibition, PMv has a dynamic influence on M1 excitability during the early steps of motor execution. The impaired cortico-cortical interactions observed in patients with FHD might contribute, at least in part, to the abnormal motor command.     

Charting the excitability of premotor to motor connections while withholding or initiating a selected movement

In 19 healthy volunteers, we used transcranial magnetic stimulation (TMS) to probe the excitability in pathways linking the left dorsal premotor cortex and right primary motor cortex and those linking the left and right motor cortex during the response delay and the reaction time period while subjects performed a delayed response [symbol 1 (S1) - symbol 2 (S2)] Go-NoGo reaction time task with visual cues. Conditioning TMS pulses were applied to the left premotor or left motor cortex 8 ms before a test pulse was given to the right motor cortex at 300 or 1800 ms after S1 or 150 ms after S2. S1 coded for right-hand or left-hand movement, and S2 for release or stopping the prepared movement. Conditioning of the left premotor cortex led to interhemispheric inhibition at 300 ms post-S1, interhemispheric facilitation at 150 ms post-S2, and shorter reaction times in the move-left condition. Conditioning of the left motor cortex led to inhibition at 1800 ms post-S1 and 150 ms post-S2, and slower reaction times for move-right conditions, and inhibition at 300 and 1800 ms post-S1 for move-left conditions. Relative motor evoked potential amplitudes following premotor conditioning at 150 ms post-S2 were significantly smaller in 'NoGo' than in 'Go' trials for move-left instructions. We conclude that the excitability in left premotor/motor right motor pathways is context-dependent and affects motor behaviour. Thus, the left premotor cortex is engaged not only in action selection but also in withholding and releasing a preselected movement generated by the right motor cortex.     

Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys

Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl‐stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5‐C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto‐Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non‐primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality.     

Frontal and parietal cortical ensembles predict single-trial muscle activity during reaching movements in primates

Previously we have shown that the kinematic parameters of reaching movements can be extracted from the activity of cortical ensembles. Here we used cortical ensemble activity to predict electromyographic (EMG) signals of four arm muscles in New World monkeys. The overall shape of the EMG envelope was predicted, as well as trial-to-trial variations in the amplitude and timing of bursts of muscle activity. Predictions of EMG patterns exhibited during reaching movements could be obtained not only from primary motor cortex, but also from dorsal premotor, primary somatosensory and posterior parietal cortices. These results suggest that these areas represent signals correlated to EMGs of arm muscles in a distributed manner, and that the larger the population sampled, the more reliable the predictions. We propose that, in the future, recordings from multiple cortical areas and the extraction of muscle patterns from these recordings will help to restore limb mobility in paralysed patients.     

Ipsilateral corticotectal projections from the primary,premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study

The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non‐human primates, previous studies reported that cortical projections to the superior colliculus (SC) originated from the premotor cortex (PM) and the primary motor cortex, whereas no projection originated from the supplementary motor area (SMA). The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n = 9). The anterograde tracer biotinylated dextran amine was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral SC. The data confirmed the presence of strong corticotectal projections from the PM. A new observation was that strong corticotectal projections were also found to originate from the SMA (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or SMAs. The corticotectal projection from each motor area was directed mainly to the deep layer of the SC, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non‐primary motor areas are in position to influence the preparation and planning of voluntary movements.     

Corticomotor representation to a human forearm muscle changes following cervical spinal cord injury

Functional imaging studies, using blood oxygen level-dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging-navigated transcranial magnetic stimulation (TMS) to non-invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1-weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma-related anatomical changes and TMS parameters. SCI participants had increased AMTs (P = 0.01) and increased CSP duration (P = 0.01). The CoG of the EDC motor-evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (P = 0.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r(2) ≥ 0.26, P < 0.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI.     

Dissociable substrates for body motion and physical experience in the human action observation network

Observation of human actions recruits a well-defined network of brain regions, yet the purpose of this action observation network (AON) remains under debate. Some authors contend that this network has developed to respond specifically to observation of human actions. Conversely, others suggest that this network responds in a similar manner to actions prompted by human and non-human cues, and that one's familiarity with the action is the critical factor that drives this network. Previous studies investigating human and non-human action cues often confound novelty and stimulus form. Here, we used a dance-learning paradigm to assess AON activity during observation of trained and untrained dance cues where a human model was present or absent. Results show that individual components of the AON respond differently to the human form and to dance training. The bilateral superior temporal cortex responds preferentially to videos with a human present, regardless of training experience. Conversely, the right ventral premotor cortex responds more strongly when observing sequences that had been trained, regardless of the presence of a human. Our findings suggest that the AON comprises separate and dissociable components for motor planning and observing other people's actions.     

Sensory input to the motor fields of the agranular frontal cortex: a comparison of the precentral, supplementary motor and premotor cortex

Arm displacements applied to the passive, but awake monkey are powerful stimuli for activating neurones in somatotopically appropriate areas of the precentral cortex. We have found that neurones in medial area 6 (SMA) and in lateral area 6 (PMC) may likewise be activated by such kinesthetic stimuli, at latencies which are only slightly longer than in area 4. Confirming previous findings, PMC neurones were sometimes also responsive to visual stimuli. The 'somatosensory' cells in the SMA were found in the microexcitable zone of the more posterior part of the SMA from where motor effects were elicited in arm and trunk muscles. These sensory neurones tended to be clustered together and they were only exceptionally excited antidromically by peduncular stimulation. Thus, somatosensory signals have access to both the PMC and SMA suggesting that both areas may be implicated in sensory-guided or sensory-triggered movements.     

Multiple descending corticospinal volleys demonstrated by changes of the wrist flexor H-reflex to magnetic motor cortex stimulation in intact human subjects

To study noninvasively multiple descending volleys on alpha motoneurons, we used a 30–50% maximum H-reflex in the wrist flexor muscle conditioned by a subthreshold magnetic stimulus of the contralateral motor cortex as a parameter of motoneuronal excitability in seven neurologically healthy subjects. The time interval of the median nerve (test) stimulus and the magnetic (conditioning) stimulus was varied. In all subjects the conditioned H-reflex significantly (P < 0.05) enhanced at conditioning-test intervals between -1 ms and +10 ms. Superimposed on the overall facilitation there were at least two short duration periods of enhanced facilitation in all but one subject. These periods were separated by 2–4 ms and suggest increased excitability at the alpha motoneuronal pool brought on by the descending volleys. We conclude that with subthreshold magnetic cortical stimuli it is possible to produce multiple descending corticospinal volleys, which probably represent descending I waves. This should be taken into account when analyzing motor evoked potentials (MEPs) in clinical studies. © 1993 John Wiley & Sons, Inc.     

Terminal distribution of the corticospinal projection from the hand/arm region of the primary motor cortex to the cervical enlargement in rhesus monkey

To further our understanding of the corticospinal projection (CSP) from the hand/arm representation of the primary motor cortex (M1), high‐resolution anterograde tracing methodology and stereology were used to investigate the terminal distribution of this connection at spinal levels C5 to T1. The highest number of labeled terminal boutons occurred contralaterally (98%) with few ipsilaterally (2%). Contralaterally, labeled boutons were located within laminae I–X, with the densest distribution found in lamina VII and, to a lesser extent, laminae IX and VI. Fewer terminals were found in other contralateral laminae. Within lamina VII, terminal boutons were most prominent in the dorsomedial, dorsolateral, and ventrolateral subsectors. Within lamina IX, the heaviest terminal labeling was distributed dorsally. Ipsilaterally, boutons were found in laminae V–X. The most pronounced distribution occurred in the dorsomedial and ventromedial sectors of lamina VII and fewer labeled boutons were located in other ipsilateral laminae. Segmentally, contralateral lamina VII labeling was highest at levels C5–C7. In contrast, lamina IX labeling was highest at C7–T1 and more widely dispersed among the quadrants at C8–T1. Our findings suggest dominant contralateral influence of the M1 hand/arm CSP, a contralateral innervation pattern in lamina VII supporting Kuypers (1982) conceptual framework of a “lateral motor system,” and a projection to lamina IX indicating significant influence on motoneurons innervating flexors acting on the shoulder and elbow rostrally (C5–C7), along with flexors, extensors, abductors and adductors acting on the digits, hand and wrist caudally (C8–T1). J. Comp. Neurol. 521:4205–4235, 2013. © 2013 Wiley Periodicals, Inc.     

Separate ipsilateral and contralateral corticospinal projections in congenital mirror movements: Neurophysiological evidence and significance for motor rehabilitation.

The neurophysiological hallmark of congenital mirror movements (MM) are fast-conducting corticospinal projections from the hand area of one primary motor cortex to both sides of the spinal cord. It is still unclear whether the abnormal ipsilateral projection originates through branching fibres from the normal contralateral projection or constitutes a separate ipsilateral projection. To clarify this question, we used focal paired-pulse transcranial magnetic stimulation to test task-related modulation of short-interval intracortical inhibition (SICI) in the abductor pollicis brevis (APB) muscles of a 15-year-old girl (Patient 1) and a 40-year-old woman (Patient 2) with congenital MM. In both patients, during intended unilateral APB contraction, SICI decreased markedly in the "task" APB but remained unchanged in the "mirror" APB when compared to muscle rest. In contrast, spinal excitability as tested with H reflexes increased similarly in the task and mirror flexor carpi radialis muscles. This dissociation of task-related SICI modulation strongly supports the existence of a separate ipsilateral fast-conducting corticospinal projection. In Patient 1, we tested the functional significance of this separate ipsilateral projection during 7 months of motor rehabilitation training, which was designed to facilitate unilateral finger movements. A marked reduction of MM was observed after training, suggesting that unwanted mirror activity in the ipsilateral pathway can be suppressed by learning.     

Oscillatory interaction between the hand area of human primary motor cortex and finger muscles during steady-state isometric contraction

Objective

To compare the magnitudes of β-band coherence between the primary motor cortex (M1) and electromyogram (EMG) for finger muscles, and to determine whether M1–EMG coherence is related to the stability of muscle contraction.

Methods

Cortical signals and EMG during steady-state isometric contraction of right thumb muscle (flexor pollicis brevis (FPB)) or right little finger muscle (flexor digiti minimi brevis (FDMB)) were recorded simultaneously with magnetoencephalography system from 13 right-handed healthy subjects.

Results

The magnitudes of β-band M1–EMG coherence and spectral power in the M1 for the FPB muscle were greater than that for the FDMB muscle (P < 0.001 and P < 0.005, respectively). The stability of EMG for the FPB was higher than that for FDMB (P < 0.001). Greater levels of β-band M1–EMG coherence were associated with higher levels of EMG stability (P < 0.05). The mean dipole sources of the FPB muscle were located more laterally, inferiorly and anteriorly than that of FDMB in the M1 hand area (P < 0.005).

Conclusions

The strength of β-band M1–EMG coherence would play an important role in the stability level of finger-muscle contraction.

Significance

The β-band M1–EMG coherence may reflect effective oscillatory interaction between the M1 and finger muscle during steady-state motor output.     

Origins of callosal projections to the supplementary motor area (SMA): a direct comparison between pre-SMA and SMA-proper in macaque monkeys.

The two subdivisions of the supplementary motor area (SMA), the pre-SMA (rostrally) and SMA-proper (caudally), exhibit distinct functional properties and clear differences with respect to their connectivity with the spinal cord, the thalamus, and other homolateral motor cortical areas. The goal of the present study was to establish in monkeys whether these subdivisions also differ with regard to their callosal connectivity. Two fluorescent retrograde tracers (Fast Blue and Diamidino Yellow) were injected in each animal, one in the pre-SMA and the second in the SMA-proper. Tracer injections in the pre-SMA or in SMA-proper resulted in significant numbers of labeled neurons in the opposite SMA, premotor cortex (PM), cingulate motor areas (CMA), and cingulate gyrus. Labeled neurons in M1 were rare, being observed only after injection in the SMA-proper. The two subdivisions of the SMA differed in the proportion of labeled neurons found across areas providing their callosal inputs. The SMA-proper receives about half of its callosal inputs from its counterpart in the other hemisphere (42-65% across monkeys). A comparable proportion of neurons was found in the pre-SMA after injection in the opposite pre-SMA (32-47%). The pre-SMA receives more callosal inputs from the rostral halves of the dorsal PM, the ventral PM, and the CMA than from their caudal halves. In addition, the pre-SMA, but not the SMA-proper, receives callosal inputs from the prefrontal cortex. The SMA-proper receives more callosal inputs from the caudal halves of the dorsal PM and ventral PM than from their rostral halves. The two subdivisions of the SMA receive callosal inputs from the same cortical areas (except the prefrontal cortex and M1), but they differ with respect to the quantitative contribution of each area of origin. In conclusion, quantitative data now support the notion that pre-SMA receives more transcallosal inputs than the SMA-proper.     

Thalamic input to mesial and superior area 6 in the macaque monkey

The aim of the present study was to define the origin of the thalamocortical projections to each of the mesial and superior area 6 areas. To this purpose, restricted injections of neuronal tracers were made into areas F3, F6, F2, and F7 after physiological identification of the injection sites. The results showed that each of these areas receives afferents from a set of thalamic nuclei and that this set differs, qualitatively and quantitatively, according to the injected area. The main inputs to F3 [supplementary motor area properly defined (SMA-proper)] originate in the nuclei ventral lateral, pars oralis (VLo), ventral posterior lateral, pars oralis (VPLo), and ventral lateral, pars caudalis (VLc) as well as in caudal parts of the VPLo and VLc (VPLo/VLc complex). F6 (pre-SMA) is mainly the target of nucleus ventral anterior, pars parvocellularis (VApc), and area X of Olszewski. The input to F2 originates mainly in the VPLo/VLc complex, in VLc, and in VLo. The dorsal part of F7 (supplementary eye field) mainly receives from area X, VApc, and nucleus ventral anterior, pars magnocellularis (VAmc), whereas the ventral F7 is connected with VApc, area X, VLc, and the VPLo/VLc complex. All of the injected areas receive a strong projection from the medial dorsal nucleus (MD). It is concluded that each cortical area is a target of both cerebellar and basal ganglia circuits. F3 and F2 are targets of the so-called “motor” basal ganglia circuit and a cerebellar circuit originating in dorsorostral sectors of dentate and interpositus nuclei. In contrast, F6 and ventral F7 receive a basal ganglia input mainly from the so-called “complex” circuit and a cerebellar input originating in the ventrocaudal sectors of dentate and interpositus nuclei. Finally, with respect to the rest of F7, dorsal F7 also receives a basal ganglia input from the “oculomotor circuit.” © 1996 Wiley-Liss, Inc.     

Prefrontal and agranular cingulate projections to the dorsal premotor areas F2 and F7 in the macaque monkey

The superior sector of Brodmann area 6 (dorsal premotor cortex, PMd) of the macaque monkey consists of a rostral and a caudal architectonic area referred to as F7 and F2, respectively. The aim of this study was to define the origin of prefrontal and agranular cingulate afferents to F7 and F2, in the light of functional and hodological evidence showing that these areas do not appear to be functionally homogeneous. Different sectors of F7 and F2 were injected with neural tracers in seven monkeys and the retrograde labelling was qualitatively and quantitatively analysed. The dorsorostral part of F7 (supplementary eye field, F7-SEF) was found to be a target of strong afferents from the frontal eye field (FEF), from the dorsolateral prefrontal regions located dorsally (DLPFd) and ventrally (DLPFv) to the principal sulcus and from cingulate areas 24a, 24b and 24c. In contrast, the remaining part of F7 (F7-non SEF) is only a target of the strong afferents from DLPFd. Finally, the ventrorostral part of F2 (F2vr), but not the F2 sector located around the superior precentral dimple (F2d), receives a minor, but significant, input from DLPFd and a relatively strong input from the cingulate gyrus (areas 24a and 24b) and area 24d. Present data provide strong hodological support in favour of the idea that areas F7 and F2 are formed by two functionally distinct sectors.     

Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects

Objective

We studied the correlation between motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) from single-pulse TMS before and after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex (M1) in 17 healthy older participants.

The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis

Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension.     

Tuning‐in to the beat: Aesthetic appreciation of musical rhythms correlates with a premotor activity boost

Listening to music can induce us to tune in to its beat. Previous neuroimaging studies have shown that the motor system becomes involved in perceptual rhythm and timing tasks in general, as well as during preference‐related responses to music. However, the role of preferred rhythm and, in particular, of preferred beat frequency (tempo) in driving activity in the motor system remains unknown. The goals of the present functional magnetic resonance imaging (fMRI) study were to determine whether the musical rhythms that are subjectively judged as beautiful boost activity in motor‐related areas and if so, whether this effect is driven by preferred tempo, the underlying pulse people tune in to. On the basis of the subjects' judgments, individual preferences were determined for the different systematically varied constituents of the musical rhythms. Results demonstrate the involvement of premotor and cerebellar areas during preferred compared to not preferred musical rhythms and indicate that activity in the ventral premotor cortex (PMv) is enhanced by preferred tempo. Our findings support the assumption that the premotor activity increase during preferred tempo is the result of enhanced sensorimotor simulation of the beat frequency. This may serve as a mechanism that facilitates the tuning‐in to the beat of appealing music. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.