Motor-cortical interaction in Gilles de la Tourette syndrome

Background

In Gilles de la Tourette syndrome (GTS) increased activation of the primary motor cortex (M1) before and during movement execution followed by increased inhibition after movement termination was reported. The present study aimed at investigating, whether this activation pattern is due to altered functional interaction between motor cortical areas.

Methodology/Principal Findings

10 GTS-patients and 10 control subjects performed a self-paced finger movement task while neuromagnetic brain activity was recorded using Magnetoencephalography (MEG). Cerebro-cerebral coherence as a measure of functional interaction was calculated. During movement preparation and execution coherence between contralateral M1 and supplementary motor area (SMA) was significantly increased at beta-frequency in GTS-patients. After movement termination no significant differences between groups were evident.

Conclusions/Significance

The present data suggest that increased M1 activation in GTS-patients might be due to increased functional interaction between SMA and M1 most likely reflecting a pathophysiological marker of GTS. The data extend previous findings of motor-cortical alterations in GTS by showing that local activation changes are associated with alterations of functional networks between premotor and primary motor areas. Interestingly enough, alterations were evident during preparation and execution of voluntary movements, which implies a general theme of increased motor-cortical interaction in GTS.     

Some circuit operations in the mammalian brain

There is an account of the basis neuronal connectivities of the spinal cord with the Sherringtonian principles of divergence and convergence. Neurones act synaptically either as excitatory or as inhibitory, depending on the specific transmitter substances liberated. Inhibitory neurones usually act either in a feedback or a feedforward manner. Voluntary movement is considered in relation to the instructions delivered to the motor cortex in order to produce the discharges down the pyramidal tract that evoke the required movement. There is an account of the three lines of evidence which indicate that in voluntary movements the primary neural event arises in discharges of neurones of the supplementary motor area (SMA). There are three main circuits from the SMA that activate subroutines concerned in the preprogramming of movements: (1) SMA to the basal ganglia, thence to the thalamus with a collateral line through the substantia nigra, thence to the association cortex; (2) SMA to cerebellar hemisphere via the pontine nuclei, thence to the nucleus dentatus, to the thalamus, to the association cortex, and (3) SMA to association cortex both frontal and parietal. According to the SMA hypothesis the liaison brain for intention is located in the SMA, there being reciprocity of informational flow from the mental events of intention to the neuronal events in the SMA.     

An optimisation-based model for full-body upright reaching movements

An optimal simulation 3D model for full-body upright reaching movements was developed using graphic-based modelling tools (SimMechanics) to generate an inverse dynamics model of the skeleton and using parameterisation methods for a sensory motor controller. The adaptive weight coefficient of the cost function based on the final motor task error (i.e. distance between end-effector and target at the end of movement) was used to correct motor task error and physiological measurements (e.g. joint power, centre of mass displacement, etc.). The output of the simulation models using various cost functions were compared to experimental data from 15 healthy participants performing full-body upright reaching movements. The proposed method can reasonably predict full-body voluntary movements in terms of final posture, joint power, and movement of the centre of mass (COM) using simple algebraic calculations of inverse dynamics and forward kinematics instead of the complicated integrals of the forward dynamics. We found that the combination of several control strategies, i.e. minimising end-effector error, total joint power and body COM produced the best fit of the full-body reaching task.     

Alien hand syndrome: neural correlates of movements without conscious will

Background

The alien hand syndrome is a striking phenomenon characterized by purposeful and autonomous movements that are not voluntarily initiated. This study aimed to examine neural correlates of this rare neurological disorder in a patient with corticobasal degeneration and alien hand syndrome of the left hand.

Methodology/Principal Findings

We employed functional magnetic resonance imaging to investigate brain responses associated with unwanted movements in a case study. Results revealed that alien hand movements involved a network of brain activations including the primary motor cortex, premotor cortex, precuneus, and right inferior frontal gyrus. Conscious and voluntary movements of the alien hand elicited a similar network of brain responses but lacked an activation of the inferior frontal gyrus. The results demonstrate that alien and unwanted movements may engage similar brain networks than voluntary movements, but also imply different functional contributions of prefrontal areas. Since the inferior frontal gyrus was uniquely activated during alien movements, the results provide further support for a specific role of this brain region in inhibitory control over involuntary motor responses.

Conclusions/Significance

We discuss the outcome of this study as providing evidence for a distributed neural network associated with unwanted movements in alien hand syndrome, including brain regions known to be related to movement execution and planning as well as areas that have been linked to inhibition control (inferior frontal gyrus) and experience of agency (precuneus).     

The supplementary motor area is implicated in the coordination between posture and movement in man

The aim of the present experimental series was to investigate the central organization of the coordination between posture and movement in a bimanual load lifting task. The seated subject was instructed to maintain horizontal one forearm (postural arm) which was loaded with a 1 kg weight. The unloading was performed either by the experimenter (imposed unloading) or by a voluntary movement of the other arm (bimanual unloading). With the bimanual unloading, the movement control was accompanied by an anticipatory adjustment of the postural forearm flexors activity, which resulted in the maintenance of the forearm position despite the unloading. No change in the anticipatory postural adjustment was observed in one patient with complete callosal section. It was reduced in 5 patients with lesion of the SMA region, but only when the postural forearm was contralateral to the lesion. It is suggested that the SMA region contralateral to the postural forearm may select the circuits responsible for the phasic postural adjustments which are necessary to ensure postural maintenance, whereas the motor cortex contralateral to the voluntary movement controls both the movement and, via collaterals, the preselected circuits responsible for the associated postural adjustment.     

Functional organization of the cortex of the large hemispheres during voluntary movement performance: Age aspect

The method of estimation of the coherence (Coh) function values of EEG rhythmic components disclosed the specific features of functional associations of cortical regions during the performance of voluntary graphic cyclic movements under usual and unusual conditions. A significant increase in the Coh function values of the α-rhythm was observed both in the contralateral hemisphere and the symmetrical central and parietal cortical regions in adult subjects during right-hand movement performance with open eyes (usual conditions); in this case the resulting functional associations included motor zone and cortical regions responsible for visual information analysis and perception. During right- and left-hand movement performance with closed eyes (unusual conditions), the mature-type functional organization had a bilateral character with interrelated activity focused in the frontal regions that clearly demonstrated the function of these structures during formation of new motor programs. The significant changes in cortical mechanisms of voluntary graphic movements were disclosed in young 7- to 8- and 9- to 10-year-old schoolchildren.     

Evidence for a Role of a Cortico-Subcortical Network for Automatic and Unconscious Motor Inhibition of Manual Responses

It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, a key role of the medial frontal cortex has been suggested by administrating a subliminal masked prime task to a patient with a small lesion restricted to the supplementary motor area (SMA). In this task, invisible masked arrows stimuli were followed by visible arrow targets for a left or right hand response at different interstimuli intervals (ISI), producing a traditional facilitation effect for compatible trials at short ISI and a reversal inhibitory effect at longer ISI. Here, by using fast event-related fMRI and a weighted parametric analysis, we showed BOLD related activity changes in a cortico-subcortical network, especially in the SMA and the striatum, directly linked to the individual behavioral pattern. This new imaging result corroborates previous works on subliminal priming using lesional approaches. This finding implies that one of the roles of these regions was to suppress a partially activated movement below the threshold of awareness.     

Supplementary motor area of the monkey: activity of neurones during performance of a learned motor task.

1. Recordings were made of the natural dischages of neurones in the supplementary motor area (SMA) of conscious monkeys trained to perform a stereotyped motor task with either hand. 2. Eighty % of the total population of cells showed modulation of their activity during particular movements of either limb. Two thirds of this group had a similar pattern of modulation regardless of whether the contralateral or ipsilateral hand was used. 3. The number of cells whose activity was related to movements of distal joints was approximately equal to that whose discharges occurred with proximal movements. 4. Only 5% of cells tested sent their axons into the pyramidal tract, and only 15% of units investigated showed responses to passive manipulation of the limbs. The effective afferent input usually was of a rather complex kind. 5. The findings suggest that the discharges of a large number of neurones in SMA are changing during particular movements of either arm, and that only a small number of cells receive afferent sensory input. These results contrast with those obtained in the primary motor area and suggest a different role for SMA the control of movement.     

Effects of reversible inactivation of the supplementary motor area (SMA) on unimanual grasp and bimanual pull and grasp performance in monkeys

Abstract The supplementary motor area (SMA) was reversibly inactivated by muscimol microinfusion in two monkeys while they were performing two motor tasks: (1) a delayed conditional bimanual drawer pulling and grasping sequence which was initiated on a self-paced basis; (2) a unimanual reach and grasp task (modified Kluver board task). Unilateral or bilateral inactivation of the SMA induced a prominent deficit in trial initiation of bimanual sequential movements, affecting the hand contralateral to the inactivated side or both hands, respectively. The deficit was a long lasting (10-15 min or more) inability of the monkey to place its hand (s) in the ready position on start touch-sensitive pads, a condition required to initiate the drawer task. However, if after such a deficit period, the experimenter put his hand on the start touch-sensitive pad to initiate the trial, then the monkey executed the drawer task without obvious motor deficit. SMA inactivation did not affect unimanual reaching and grasping movements in the board task. In contrast to the SMA, inactivation of other motor areas (primary, premotor dorsal, anterior intraparietal area) did not affect the initiation of movement sequences in the drawer task. These data thus indicate that the SMA plays a crucial and specific role in initiation of self-paced movement sequences. However, SMA inactivation did not prevent the monkeys to perform coordinated movements of the two forelimbs and hands, indicating that SMA is not necessary for bimanual coordination.     

Contribution of the frontal lobe secondary motor area to organization of postural components in human voluntary movement

A total of 225 patients with local verified brain lesions were investigated with a view to identifying the brain regions contributing to organizing postural aspects of voluntary movement. Impaired postural adjustment movements associated with voluntary deep breathing were found in patients with damage primarily to the posterior section of the frontal lobe inferior convolution. Impaired activation of leg and trunk muscles accompanying arm movements were revealed in patients with damage chiefly to the posterior section of the superior convolution of the lobe, including the accessory motor area. It was deduced that postural movements differing in their functional purpose are controlled, like other learned tasks, by different sections of the secondary motor zone of the frontal lobe of the brain.Institute for Information Transmission Studies, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 7–15, January–February, 1988.     

Neuronal activity in the primate supplementary motor area and the primary motor cortex in relation to spatio-temporal bimanual coordination

Single neuronal activity was recorded from the supplementary motor area (SMA-proper and pre-SMA) and primary motor cortex (M1) in two Macaca fascicularis trained to perform a delayed conditional sequence of coordinated bimanual pull and grasp movements. The behavioural paradigm was designed to distinguish neuronal activity associated with bimanual coordination from that related to a comparable motor sequence but executed unimanually (left or right arm only). The bimanual and unimanual trials were instructed in a random order by a visual cue. Following the cue, there was a waiting period until presentation of a "go-signal", signalling the monkey to perform the instructed movement. A total of 143 task-related neurons were recorded from the SMA (SMA-proper, 62; pre-SMA, 81). Most SMA units (87%) were active in both unimanual contralateral and unimanual ipsilateral trials (bilateral neurons), whereas 9% of units were active only in unimanual contralateral trials and 3% were active only in unimanual ipsilateral trials. Forty-eight per cent of SMA task-related units were classified as bimanual, defined as neurons in which the activity observed in bimanual trials could not be predicted from that associated with unimanual trials when comparing the same events related to the same arm. For direct comparison, 527 neurons were recorded from M1 in the same monkeys performing the same tasks. The comparison showed that M1 contains significantly less bilateral neurons (75%) than the SMA, whereas the reverse was observed for contralateral neurons (22% in M1). The proportion of M1 bimanual cells (53%) was not statistically different from that observed in the SMA. The results suggest that both the SMA and M1 may contribute to the control of sequential bimanual coordinated movements. Interlimb coordination may then take place in a distributed network including at least the SMA and M1, but the contribution of other cortical and subcortical areas such as cingulate motor cortex and basal ganglia remains to be investigated.     

Functional Near Infrared Spectroscopy of the Sensory and Motor Brain Regions with Simultaneous Kinematic and EMG Monitoring During Motor Tasks

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions.     

Are interlimb interactions disturbed in patients with Parkinson’s disease? A study under unloading conditions

During natural human locomotion, neural connections are activated that are typical of regulation of the quadrupedal walking. The interaction between the neural networks generating rhythmic movements of the upper and lower limbs depends on tonic state of each of these networks regulated by motor signals from the brain. Distortion of these signals in patients with Parkinson’s disease (PD) may lead to disruption of the interlimb interactions. We examined the effect of movements of the limbs of one girdle on the parameters of the motor activity of another limb girdle at their joint cyclic movements under the conditions of arm and leg unloading in 17 patients with PD and 16 healthy subjects. We have shown that, in patients, the effect of voluntary and passive movements of arms, as well as the active movement of the distal parts of arms, on the voluntary movement of legs is weak, while in healthy subjects, the effect of arm movements on the parameters of voluntary stepping is significant. The effect of arm movements on the activation of the involuntary stepping by vibrational stimulation of-legs in patients was absent, while in healthy subjects, the motor activity of arms increased the possibility of involuntary rhythmic movements activation. Differences in the effect of leg movements on the rhythmic movements of arms were found in both patients and healthy subjects. The interlimb interaction appeared after drug administration. However, the effect of the drug was not sufficient for the recovery of normal state of the neural networks in patients. In PD patients, neural networks generating stepping rhythm have an increased tonic activity, which prevents the activation and appearance of involuntary rhythmic movements facilitating the effects of arms on legs.     

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10?ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500?ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of?movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission.     

Reorganizing the intrinsic functional architecture of the human primary motor cortex during rest with non-invasive cortical stimulation

The primary motor cortex (M1) is the main effector structure implicated in the generation of voluntary movements and is directly involved in motor learning. The intrinsic horizontal neuronal connections of M1 exhibit short-term and long-term plasticity, which is a strong substrate for learning-related map reorganization. Transcranial direct current stimulation (tDCS) applied for few minutes over M1 has been shown to induce relatively long-lasting plastic alterations and to modulate motor performance. Here we test the hypothesis that the relatively long-lasting synaptic modification induced by tDCS over M1 results in the alteration of associations among populations of M1 neurons which may be reflected in changes of its functional architecture. fMRI resting-state datasets were acquired immediately before and after 10 minutes of tDCS during rest, with the anode/cathode placed over the left M1. For each functional dataset, grey-matter voxels belonging to Brodmann area 4 (BA4) were labelled and afterwards BA4 voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal network parameters which characterize the architecture of functional networks (connectivity degree, clustering coefficient and characteristic path-length) were computed, transformed to volume maps and compared before and after stimulation. At the dorsolateral-BA4 region cathodal tDCS boosted local connectedness, while anodal-tDCS enhanced long distance functional communication within M1. Additionally, the more efficient the functional architecture of M1 was at baseline, the more efficient the tDCS-induced functional modulations were. In summary, we show here that it is possible to non-invasively reorganize the intrinsic functional architecture of M1, and to image such alterations.     

A Functional Magnetic Resonance Imaging Study of Pathophysiological Changes Responsible for Mirror Movements in Parkinson’s Disease

Mirror movements correspond to involuntary movements observed in the limb contralateral to the one performing voluntary movement. They can be observed in Parkinson’s disease (PD) but their pathophysiology remains unclear. The present study aims at identifying their neural correlates in PD using functional magnetic resonance imaging. Ten control subjects and 14-off drug patients with asymmetrical right-sided PD were included (8 with left-sided mirror movements during right-hand movements, and 6 without mirror movements). Between-group comparisons of BOLD signal were performed during right-hand movements and at rest (p<0.005 uncorrected). The comparison between PD patients with and without mirror movements showed that mirror movements were associated with an overactivation of the insula, precuneus/posterior cingulate cortex bilaterally and of the left inferior frontal cortex and with a deactivation of the right dorsolateral prefrontal cortex, medial prefrontal cortex, and pre-supplementary motor area and occipital cortex. These data suggest that mirror movements in Parkinson’s disease are promoted by: 1- a deactivation of the non-mirroring inhibitory network (dorsolateral prefrontal cortex, pre-supplementary motor area); 2- an overactivation of prokinetic areas (notably the insula). The concomitant overactivation of a proactive inhibitory network (including the posterior cingulate cortex and precuneus) could reflect a compensatory inhibition of mirror movements.     

Sensorimotor regulation of movements: Novel strategies for the recovery of mobility

A series of observations have provided important insight into properties of the spinal as well as supraspinal circuitries that control posture and movement. We have demonstrated that spinal rats can regain full weight-bearing standing and stepping over a range of speeds and directions with the aid of electrically enabling motor control (eEmc), pharmacological modulation (fEmc), and training [1, 2]. Also, we have reported that voluntary control movements of individual joints and limbs can be regained after complete paralysis in humans [3, 4]. However, the ability to generate significant levels of voluntary weight-bearing stepping with or without epidural spinal cord stimulation remains limited. Herein we introduce a novel method of painless transcutaneous electrical enabling motor control (pcEmc) and sensory enabling motor control (sEmc) strategy to neuromodulate the physiological state of the spinal cord. We have found that a combination of a novel non-invasive transcutaneous spinal cord stimulation and sensory-motor stimulation of leg mechanoreceptors can modulate the spinal locomotor circuitry to state that enables voluntary rhythmic locomotor movements.     

Abnormal Movement Preparation in Task-Specific Focal Hand Dystonia

Electrophysiological and behavioral studies in primary dystonia suggest abnormalities during movement preparation, but this crucial phase preceding movement onset has not yet been studied specifically with functional magnetic resonance imaging (fMRI). To identify abnormalities in brain activation during movement preparation, we used event-related fMRI to analyze behaviorally unimpaired sequential finger movements in 18 patients with task-specific focal hand dystonia (FHD) and 18 healthy subjects. Patients and controls executed self-initiated or externally cued prelearnt four-digit sequential movements using either right or left hands. In FHD patients, motor performance of the sequential finger task was not associated with task-related dystonic posturing and their activation levels during motor execution were highly comparable with controls. On the other hand reduced activation was observed during movement preparation in the FHD patients in left premotor cortex / precentral gyrus for all conditions, and for self-initiation additionally in supplementary motor area, left mid-insula and anterior putamen, independent of effector side. Findings argue for abnormalities of early stages of motor control in FHD, manifesting during movement preparation. Since deficits map to regions involved in the coding of motor programs, we propose that task-specific dystonia is characterized by abnormalities during recruitment of motor programs: these do not manifest at the behavioral level during simple automated movements, however, errors in motor programs of complex movements established by extensive practice (a core feature of FHD), trigger the inappropriate movement patterns observed in task-specific dystonia.     

Human medial frontal cortex mediates unconscious inhibition of voluntary action

Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect--ocular or manual--corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action.     

Development of functional variability during the motor learning process of a complex cyclic movement

Traditionally, movement variability is considered an indicator for sensorimotor malfunctioning. However, functional movement variability is also a result of compensation mechanisms e.g. to account for prior movement deviations and is, therefore, crucial for stable movements. The aim of this study was to analyze functional variability during motor learning of a complex cyclic task.Thirteen young participants practised riding a Pedalo® slalom until they were able to complete the task without errors. Since trunk movements are controlled with high priority, we analyzed trunk kinematics as a result parameter. Since lower extremities affect the result parameter, foot, thigh and pelvis kinematics are considered execution parameters. The movement variability for result and execution parameters was determined for the first (poor performance), an intermediate (medium performance) and the last (good performance) training sessions. Furthermore, the variability ratio (execution/result parameter) was calculated as a measure of functional variability.Movement variability of the result parameter decreased significantly with increasing expertise. In contrast, movement variability of all execution parameters increased significantly from measurements representing poor to medium performance. No change from medium to good performance was found. Functional variability increased over time in all execution parameters.Since the movement variability of all execution parameters did not decrease with increasing Pedalo performance, applying a traditional interpretation approach of movement variability would have led to completely wrong conclusions. Possible mechanisms explaining the increased movement variability are discussed. The variability ratio seems to be the only parameter that can reveal improved sensorimotor functioning during all analyzed stages of motor learning.