Recovery of movement-related potentials in the temporal course after prefrontal traumatic brain injury: a follow-up study

OBJECTIVE: The movement-related potential (MRP) is an EEG measure related to self-initiated movements, consisting of the Bereitschaftspotential (BP), the negative slope, and the motor potential. Since in a former study the BP was reduced in acute prefrontal traumatic brain injury (TBI) patients, the present study examined the MRPs' course in follow-up examinations. METHODS: Right index finger MRPs of 22 patients with contusions of the prefrontal cortex were recorded 12, 26, and 52 weeks after TBI and compared to controls. RESULTS: Within the patient group, a significant increase of the BP in the temporal course after TBI was observed. MRPs 12 and 26 weeks after TBI did not differ significantly from the control group. One year after TBI, significantly enhanced BPs were found. CONCLUSIONS: In the temporal course after prefrontal TBI, a recovery of the initially reduced BP was observed. The enhanced BP areas 1 year after TBI might represent the need for increased cognitive resources during movement preparation, supporting a recovered, but less effective neuronal network. SIGNIFICANCE: The present study represents the first longitudinal follow-up study of MRPs after prefrontal brain lesion. The observed changes reflect the plastic capacity of the brain, reorganizing the neuronal network function.     

Frontal lobe contribution to voluntary movements in humans

We assessed the contribution of human prefrontal cortex to movement related potentials (MRPs) generated prior to voluntary movements. MRPs were recorded during self-paced movements of the right thumb (experimental condition I), the left thumb (experimental condition II) and both thumbs (experimental condition III) from patients with focal lesions centered in dorsolateral frontal association cortex (PFCx, n = 11) and in age matched controls (n = 11). Controls generated a slowly rising readiness potential (RP) beginning at about 1000 ms prior to movement. A negative shift (NS') began at about 450 ms and a motor potential (MP) appeared at about 100 ms prior to movement. Both the NS' and MP were maximal over scalp sites contralateral to movements. Unilateral PFCx lesions preferentially reduced the RP and NS' components of the MRP. This indicates that PFCx is involved in a neural network beginning at least 1000 ms prior to movement. The differential PFCx effects on the early (RP, NS') and late components (MP) suggest that these MRPs index different movement-related circuits.     

Abnormal premovement brain potentials in schizophrenia.

We assessed scalp-recorded movement related potentials (MRPs) generated prior to voluntary movements in chronic, medicated schizophrenics (n = 9) and age matched normal controls (n = 9). MRPs were recorded in a self-paced button press task in which subjects pressed a button with either their right, left or both thumbs (experimental condition I, II and III respectively). Controls generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The initial MRP components (RP and NS') were reduced in schizophrenics indicating an impairment of the voluntary preparatory process in schizophrenia. Results of the present study indicate a similarity of MRP findings in schizophrenics and reported MRPs (Singh and Knight, 1990) in patients with unilateral lesions of the dorsolateral prefrontal cortex. These findings provide further support for frontal lobe dysfunction in schizophrenia.     

Movement-related cortical potentials in aged subjects]

Cortical potentials related to freely-executed voluntary wrist flexion (MRPs) were studied in 35 subjects aged 23-80 years. The characteristics of the MPRs in aged subjects were determined in comparison data from 14 young subjects aged 23-40 years. The analysis concerned 3 components of the MRPs: the slow negative shifts (NS1 and NS2) before the movement onset and the motor potential (MP). In the aged subject, the latencies measured at Cz show a significant lengthening of the NS1 and of the duration of NS2 (NS' of Shibasaki et al, 1980). The mean amplitude of the NS1 peak at Cz is decreased, and those of N1 (the negative peak before the movement) and MP are not significantly different from those of the young subjects. The NS2 component in the aged subject (between NS1 and N1) is thus increased. In contrast to the young subjects, who present a predominance of N1 and MP amplitudes of the contralateral motor cortex over the ipsilateral cortex, the aged subjects lose lateralization of these components. Recording of MRPs with subdural electrodes (Neshige et al, 1988) shows taht NS1 results from the activity of the supplementary motor area and from the ipsi-contralateral primary motor cortex. The increase in NS2 might be interpreted as an expression of activity coming from other structures to compensate for the reduction in NS1 in the aged subject and to maintain the level of the motor potential MP.     

Intracranial recordings of movement-related potentials to voluntary saccades

Movement-related potentials evoked by voluntary and self-initiated horizontal saccades were recorded from subdural electrodes placed over the lateral (premotor and motor cortex) and the mesial (supplementary motor area) surfaces of the frontal lobe, in four patients with intractable focal seizures. An extremely localized bereitschaftspotential showing approximately the same latencies and amplitudes was simultaneously recorded from the frontal eye field and supplementary motor area (SMA). Our data suggest that both regions are equally active prior to saccades and do not support the view that the SMA acts as a supramotor cortex, being activated during the planning of the movement and the primary motor cortex only later on, close to the execution of the movement. In addition, we never observed the spike potential in our intracranial recordings, thus supporting the hypothesis of its extracerebral origin.     

Neurophysiology of unimanual motor control and mirror movements.

In humans, execution of unimanual motor tasks requires a neural network that is capable of restricting neuronal motor output activity to the primary motor cortex (M1) contralateral to the voluntary movement by counteracting the default propensity to produce mirror-symmetrical bimanual movements. The motor command is transmitted from the M1 to the contralateral spinal motoneurons by a largely crossed system of fast-conducting corticospinal neurons. Alteration or even transient dysfunction of the neural circuits underlying movement lateralization may result in involuntary mirror movements (MM). Different models exist, which have attributed MM to unintended motor output from the M1 ipsilateral to the voluntary movement, functionally active uncrossed corticospinal projections, or on a combination of both. Over the last two decades, transcranial magnetic stimulation (TMS) proved as a valuable, non-invasive neurophysiological tool to investigate motor control in healthy volunteers and neurological patients. The contribution of TMS and other non-invasive electrophysiological techniques to characterize the neural network responsible for the so-called 'non-mirror transformation' of motor programs and the various mechanisms underlying 'physiological' mirroring, and congenital or acquired pathological MM are the focus of this review.     

Motor execution and imagination networks in post-stroke dystonia

Reorganization of motor execution and imagination networks was studied in six patients with unilateral dystonia secondary to a subcortical stroke and compared with seven control subjects using fMRI. Patients performed imagined and real auditory-cued hand movements. Movements of the dystonic hand resulted in overactivity in bilateral motor, premotor, and prefrontal cortex, insula, precuneus, and cerebellum, in parietal areas and the striatum contralateral to the lesion. Movements of the unaffected hand resulted in overactivity in bilateral preSMA, prefrontal, and parietal areas, insula and cerebellum, the ipsilateral premotor cortex and the contralateral striatum to the lesion. Mental representation of movements with each hand resulted in overactivity in bilateral parietal, premotor and prefrontal areas. These results suggest that execution and mental representation of movement are altered in these patients.     

Decoding movement intent from human premotor cortex neurons for neural prosthetic applications.

Primary motor cortex (M1), a key region for voluntary motor control, has been considered a first choice as the source of neural signals to control prosthetic devices for humans with paralysis. Less is known about the potential for other areas of frontal cortex as prosthesis signal sources. The frontal cortex is widely engaged in voluntary behavior. Single-neuron recordings in monkey frontal cortex beyond M1 have readily identified activity related to planning and initiating movement direction, remembering movement instructions over delays, or mixtures of these features. Human functional imaging and lesion studies also support this role. Intraoperative mapping during deep brain stimulator placement in humans provides a unique opportunity to evaluate potential prosthesis control signals derived from nonprimary areas and to expand our understanding of frontal lobe function and its role in movement disorders. This study shows that recordings from small groups of human prefrontal/premotor cortex neurons can provide information about movement planning, production, and decision-making sufficient to decode the planned direction of movement. Thus, additional frontal areas, beyond M1, may be valuable signal sources for human neuromotor prostheses.     

The role of the supplementary motor area in externally timed movement: the influence of predictability of movement timing

A significant role in the planning and preparation for voluntary movement has been ascribed to secondary motor areas located on the medial wall of the cerebral hemispheres, and in particular to the supplementary motor area (SMA). Within the SMA, rostral and caudal subdivisions have been described, and differential roles have been attributed to these regions in relation to movement planning, preparation and execution. We have used functional magnetic resonance imaging (fMRI) to investigate the role of the SMA in the timing of movement execution, by recording the fMRI signal from mesial pre-motor areas and primary sensorimotor cortex (SM1) during the execution of a simple motor task externally cued at predictable (regular) and unpredictable (irregular) time intervals. The mean rate of movement was matched in both experiments. There was a greater activation of caudal than rostral SMA with both predictably and unpredictably cued movements, and a doubling of the signal when the timing of the motor response was unpredictable. In contrast, there was no difference in the activation of primary sensorimotor cortex with the two tasks. The data demonstrate that the caudal SMA has an important role in the execution of externally cued movements. The results also suggest a greater role for this region in the performance of unpredictably timed compared with predictably timed movements, however a model is proposed (based on electrophysiological data) which shows how the difference in functional signal in these two situations can be explained on the basis of a difference in the time course of neuronal activation in the SMA, rather than in the overall degree of activation.     

Stop and go: the neural basis of selective movement prevention

Converging lines of evidence show that volitional movement prevention depends on the right prefrontal cortex (PFC), especially the right inferior frontal gyrus (IFG). Selective movement prevention refers to the rapid prevention of some, but not all, movement. It is unknown whether the IFG, or other prefrontal areas, are engaged when movement must be selectively prevented, and whether additional cortical areas are recruited. We used rapid event-related fMRI to investigate selective and nonselective movement prevention during performance of a temporally demanding anticipatory task. Most trials involved simultaneous index and middle finger extension. Randomly interspersed trials required the prevention of one, or both, finger movements. Regions of the right hemisphere, including the IFG, were active for selective and nonselective movement prevention, with an overlap in the inferior parietal cortex and the middle frontal gyrus. Selective movement prevention caused a significant delay in movement initiation of the other digit. These trials were associated with activation of the medial frontal cortex. The results provide support for a right-hemisphere network that temporarily "brakes" all movement preparation. When movement is selectively prevented, the supplementary motor cortex (SMA/pre-SMA) may participate in conflict resolution and subsequent reshaping of excitatory drive to the motor cortex.     

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.     

Alterations in voluntary movement execution in Huntington's disease are related to the dominant motor system — Evidence from event-related potentials

Huntington's disease is an autosomal dominant neurogenetic disorder leading to striatal atrophy, characterized by involuntary movements. Voluntary movements also deteriorate, but the neurophysiological mechanisms are less understood. We investigated voluntary movement execution and its neural correlates by means of movement-related potentials (MRPs) in symptomatic HD (HD), presymptomatic HD (pHD) and controls.Reaction times (RTs) revealed hand differences in controls and HD, but not in pHDs. Response-locked MRPs above the contralateral primary motor area (M1) were similar across all groups. Yet, the HD-group showed, selectively for the right hand, a second contralateral (left) activation after the response, followed by similar activation over the ipsilateral (right) motor area, which is normally inhibited. Similarly parietal processes were reversed for right hand movements. In strong contrast, pHDs showed an increased inhibition of the ipsilateral hemisphere.The results suggest modulations of inhibitory processes in HD dependent on disease stage. Importantly, these modulations occur after the response and are restricted to right-hand responses, or the dominant motor system (left hemisphere). Since also cognitive processes preceding the MRPs changed, the results suggest a cognitive contribution to the emergence of voluntary movement dysfunction. The pattern in the pHD-group, namely an increased inhibition of the ipsilateral hemisphere and similar RTs between the hands suggest compensatory mechanisms in presymptomatic stages of the disease. Despite neurophysiological alterations originating in the dominant left hemisphere in HDs, they also affect the right hemisphere, probably due to a dysfunction in interhemispheric inhibition in HD.     

Neural correlates of advance movement preparation: a dipole source analysis approach

This study examined cortical motor structures that are involved in preprogramming and execution of movements. In two independent experiments a response precuing task was employed that combined the recording of movement-related brain potentials (MRPs) with spatio-temporal source localization. Behavioral and MRP results indicated the utilization of advance information about movement direction and hand. Dipole source modeling of foreperiod MRPs revealed a reliable three-dipole solution with sources located in lateral and medial brain regions anterior to the precentral gyrus. These dipoles were located in the lateral premotor area (PMA) and supplementary/cingulate motor areas (SMA/CMA). Activity of the medial dipole increased with the extent of advance motor preparation, whereas lateral dipole activity revealed parallel preparation of both response hands when only partial information about movement direction was available. The dissociation in the strength and the onset of medial and lateral dipole activity indicated two phases of motor preparation. We propose that medial motor areas like SMA and CMA are involved in the assembling and selection of abstract movement programs, whereas lateral PMA and primary motor cortex are involved in effector-specific motor preparation.     

Gilles de la Tourette syndrome and voluntary movement: a functional MRI study

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.     

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation.     

State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network

The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.     

Impairment of EEG desynchronisation before and during movement and its relation to bradykinesia in Parkinson's disease

OBJECTIVE: It has been suggested that the basal ganglia act to release cortical elements from idling (alpha) rhythms so that they may become coherent in the gamma range, thereby binding together those distributed activities necessary for the effective selection and execution of a motor act. This hypothesis was tested in 10 patients with idiopathic Parkinson's disease. METHODS: Surface EEG was recorded during self paced squeezing of the hand and elbow flexion performed separately, simultaneously, or sequentially. Recordings were made after overnight withdrawal of medication and, again, 1 hour after levodopa. The medication related improvement in EEG desynchronisation (in the 7.5-12.5 Hz band) over the 1 second before movement and during movement were separately correlated with the improvement in movement time for each electrode site. Correlation coefficients (r) > 0.632 were considered significant (p<0.05). RESULTS: Improvement in premovement desynchronisation correlated with reduction in bradykinesia over the contralateral sensorimotor cortex and supplementary motor area in flexion and squeeze, respectively. However, when both movements were combined either simultaneously or sequentially, this correlation shifted anteriorly, to areas overlying prefrontal cortex. Improvement in EEG desynchronisation during movement only correlated with reduction in bradykinesia in two tasks. Correlation was seen over the supplementary motor area during flexion, and central prefrontal and ipsilateral premotor areas during simultaneous flex and squeeze. CONCLUSIONS: The results are consistent with the idea that the basal ganglia liberate frontal cortex from idling rhythms, and that this effect is focused and specific in so far as it changes with the demands of the task. In particular, the effective selection and execution of more complex tasks is associated with changes over the prefrontal cortex.     

The initiation of voluntary movements by the supplementary motor area

The hypothesis is formulated that in all voluntary movements the initial neuronal event is in the supplementary motor areas (SMA) of both cerebral hemispheres. Experimental support is provided by three lines of evidence. 1. In voluntary movements many neurones of the SMA are activated probably up to 200 ms before the pyramidal tract discharge. 2. Investigations of regional cerebral blood flow by the radioactive Xenon technique reveal that there is neuronal activity in the SMA of both sides during a continual series of voluntary movements, and that this even occurs when the movement is thought of, but not executed. 3. With voluntary movement there is initiation of a slow negative potential (the readiness potential, RP) at up to 0.8 s before the movement. The RP is maximum over the vertex, i.e. above the SMA, and is large there even in bilateral Parkinsonism when it is negligible over the motor cortex. An account is given of the SMA, particularly its connectivities to the basal ganglia and the cerebellum that are active in the preprogramming of a movement. The concept of motor programs is described and related to the action of the SMA. It is proposed that each mental intention acts on the SMA in a specific manner and that the SMA has an 'inventory' and the 'addresses' of stored subroutines of all learnt motor programs. Thus by its neuronal connectivities the SMA is able to bring about the desired movement. There is a discussion of the manner in which the mental act of intention calls forth neural actions in the SMA that eventually lead to the intended movement. Explanation is given on the basis of the dualist-interactionist hypothesis of mind-brain liaison. The challenge is to the physicalists to account for the observed phenomena in voluntary movement.     

Contributions of the mesial frontal cortex to the premovement potentials associated with intermittent hand movements in humans

Two premovement potentials, the bereitschaftspotential (BP) and negative slope (NS'), can be recorded prior to the execution of self-paced hand movements using back-averaging of scalp electrical recordings. The contributions of the contralateral and ipsilateral primary motor cortex (M1) and the mesial dorsal frontal cortex (MFC) to the generation of the potentials were examined by simultaneously collecting positron emission tomography (PET) scans and scalp recorded electrical activity for dipole source analysis in eight right-handed normal subjects. Subjects performed simple unilateral thumb-finger opposition movements intermittently with an average inter-movement interval of 7.4 s. PET was also collected for the same movement performed repetitively with inter-movement intervals of 0.5 s such that finger movements were nearly continuous. PET studies of the intermittent movement revealed marked activation of the MFC in the region of the rostral supplementary motor area (SMA) and cingulate motor area, contralateral sensorimotor cortex and no activation of the ipsilateral sensorimotor cortex. When the same movements were performed in a continuous repetitive manner, PET revealed strong contralateral sensorimotor and caudal MFC activation, and no ipsilateral sensorimotor or rostral MFC activation. Dipole source solutions of the back-averaged potentials for the intermittent movements were analyzed by testing dipole vectors placed into the regions of PET activation. The premovement potentials were dominated by dipoles in the region of the MFC, with minimal contribution from either the contralateral or ipsilateral M1. Activation in the region of the contralateral M1 began near the onset of muscle activity. The orientation and timing of the MFC dipoles were consistent with both the BP and NS' potentials originating from neurons in the rostral SMA and dorsal tier of the cingulate sulcus and were appropriate for MFC activity to contribute to both the preparation for movement and the descending activation of spinal motor networks. © 1996 Wiley-Liss, Inc.     

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.