Generation Of Voluntary Movements Research Articles

We Move or Are We Moved? Unpicking the Origins of Voluntary Movements to Better Understand Semivoluntary Movements.

The capacity for voluntary control is seen as essential to human movements; the sense that one intended to move (willing) and those actions were self-generated (self-agency) gives the sense of voluntariness and of being in control. While the mechanisms underlying voluntary movement have long been unclear, recent neuroscientific tools have identified networks of different brain areas, namely, the prefrontal cortex, supplementary motor area, and parietal cortex, that underlie voluntary action. Dysfunction in these brain areas can result in different forms of semivoluntary movement as the borderland of voluntary and involuntary movement where a person may experience a disordered sense of will or agency, and thus the movement is experienced as unexpected and involuntary, for an otherwise voluntary-appearing movement. Tics, functional movement disorders, stereotypies, perseveration, compulsions, utilization behaviors, and motor mannerism have been described elsewhere in the context of psychoses, and are often mistaken for each other. Yet, they reflect an impairment of prefrontal cortices and related circuits rather than simple motor systems, which results in the absence of subjective recognition of the movements, in contrast to other neurological movement disorders where principal abnormalities are located within the basal ganglia and its connections. Therefore, their recognition is clinically important since they are usually associated with neurodevelopmental and neurodegenerative disorders. In this review, we first defined a conceptual framework, from both a neuroanatomical and a neurophysiological point of view, for the generation of voluntary movement. We then examined the evidence linking dysfunctions in different motor pathways to each type of movement disorder. We looked at common semivoluntary movement disorders providing an overview, where possible, of their phenomenology and brain network abnormalities for each condition. We also emphasized important clinical feature similarities and differences to increase recognition of each condition in practice.

Sensory Coding of Limb Kinematics in Motor Cortex across a Key Developmental Transition.

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements-especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptive-field properties of individual units within the forelimb region of M1. At postnatal day 8 (P8), nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich representation of movement long before M1 develops its motor functionality.SIGNIFICANCE STATEMENT Primary motor cortex (M1) plays a fundamental role in the generation of voluntary movements and motor learning in adults. In early development, however, M1 functions as a prototypical sensory structure. Here, we demonstrate in infant rats that M1 codes for the kinematics of self-generated limb movements long before M1 develops its capacity to drive movements themselves. Moreover, we identify a key transition during the second postnatal week in which M1 activity becomes more informationally complex. Together, these findings further delineate the complex developmental path by which M1 develops its sensory functions in support of its later-emerging motor capacities.

P149. Suppression of LTP-like associative plasticity in the human SMA–M1 network by simultaneous tDCS

Introduction Excitability and connectivity in the human motor network comprising the supplementary motor area (SMA) and primary motor cortex (M1) are important for voluntary movement generation and rehabilitation of lost motor function after stroke. Previously, we demonstrated that paired associative stimulation of SMA and M1 (SMA–M1-PAS) by dual coil transcranial magnetic stimulation (TMS) may induce LTP-like plasticity in this network (Arai et al., 2011. J Neurosci 31:15376–83). Here, we tested the influence of simultaneous modulation of general network excitability by transcranial direct current stimulation (tDCS) on associative SMA–M1 plasticity. Methods 12 healthy right-handed male subjects took part in this pseudo-randomized,single-blinded, crossover study. Subjects received two blocks (spaced by 5 min) of 50 pairs of neuronavigated SMA-before-M1 PAS at an interstimulus interval of 6 ms and intertrial interval of 5 s. Simultaneously we applied anodal, cathodal, or sham tDCS over the left M1 in three different sessions, at least 1 week apart. Associative SMA–M1 plasticity was quantified by changes in (i) motor-evoked potentials (MEP) in the right first dorsal interosseus muscle, and (ii) SMA-to-M1 connectivity (ratio of SMA-conditioned/unconditioned MEPs), at baseline versus for up to two hours after the intervention. Results SMA–M1-PAS resulted in an expected LTP-like MEP amplitude increase in 9 of 12 subjects in the sham tDCS condition. In 7 of these 9 SMA–M1-PAS responders, the LTP-like MEP amplitude increase was suppressed or even turned into depression both in the anodal and cathodal tDCS condition. In contrast, in all three non-responders anodal and cathodal tDCS led to less MEP suppression or even turned it into facilitation. Likewise, in 7 (anodal tDCS) and 6 (cathodal tDCS) of the 8 subjects who showed a facilitation of SMA-to-M1 connectivity in the sham tDCS condition this connectivity was reduced in the anodal and cathodal tDCS conditions, whereas it was less reduced or even facilitated in 2 (anodal tDCS) and all (cathodal tDCS) of the 4 subjects showing a reduction of SMA-to-M1 connectivity in the sham condition. Conclusion Our results demonstrate a reversing interaction between general network excitability modulation by tDCS and associative plasticity in the human SMA–M1 network, independent of the polarity of tDCS.

Spike firing and IPSPs in layer V pyramidal neurons during beta oscillations in rat primary motor cortex (M1) in vitro.

Beta frequency oscillations (10–35 Hz) in motor regions of cerebral cortex play an important role in stabilising and suppressing unwanted movements, and become intensified during the pathological akinesia of Parkinson's Disease. We have used a cortical slice preparation of rat brain, combined with concurrent intracellular and field recordings from the primary motor cortex (M1), to explore the cellular basis of the persistent beta frequency (27–30 Hz) oscillations manifest in local field potentials (LFP) in layers II and V of M1 produced by continuous perfusion of kainic acid (100 nM) and carbachol (5 µM). Spontaneous depolarizing GABA-ergic IPSPs in layer V cells, intracellularly dialyzed with KCl and IEM1460 (to block glutamatergic EPSCs), were recorded at −80 mV. IPSPs showed a highly significant (P< 0.01) beta frequency component, which was highly significantly coherent with both the Layer II and V LFP oscillation (which were in antiphase to each other). Both IPSPs and the LFP beta oscillations were abolished by the GABAA antagonist bicuculline. Layer V cells at rest fired spontaneous action potentials at sub-beta frequencies (mean of 7.1+1.2 Hz; n = 27) which were phase-locked to the layer V LFP beta oscillation, preceding the peak of the LFP beta oscillation by some 20 ms. We propose that M1 beta oscillations, in common with other oscillations in other brain regions, can arise from synchronous hyperpolarization of pyramidal cells driven by synaptic inputs from a GABA-ergic interneuronal network (or networks) entrained by recurrent excitation derived from pyramidal cells. This mechanism plays an important role in both the physiology and pathophysiology of control of voluntary movement generation.

Reappraisal of field dynamics of motor cortex during self‐paced finger movements

BackgroundThe exact origin of neuronal responses in the human sensorimotor cortex subserving the generation of voluntary movements remains unclear, despite the presence of characteristic but robust waveforms in the records of electroencephalography or magnetoencephalography (MEG).AimsTo clarify this fundamental and important problem, we analyzed MEG in more detail using a multidipole model during pulsatile extension of the index finger, and made some important new findings.ResultsMovement-related cerebral fields (MRCFs) were confirmed over the sensorimotor region contralateral to the movement, consisting of a temporal succession of the first premovement component termed motor field, followed by two or three postmovement components termed movement evoked fields. A source analysis was applied to separately model each of these field components. Equivalent current diploes of all components of MRCFs were estimated to be located in the same precentral motor region, and did not differ with respect to their locations and orientations. The somatosensory evoked fields following median nerve stimulation were used to validate these findings through comparisons of the location and orientation of composite sources with those specified in MRCFs. The sources for the earliest components were evoked in Brodmann's area 3b located lateral to the sources of MRCFs, and those for subsequent components in area 5 and the secondary somatosensory area were located posterior to and inferior to the sources of MRCFs, respectively. Another component peaking at a comparable latency with the area 3b source was identified in the precentral motor region where all sources of MRCFs were located.ConclusionThese results suggest that the MRCF waveform reflects a series of responses originating in the precentral motor area.

P 71. The effects of cathodal transcranial direct current stimulation of the supplementary motor area on the function of anticipatory postural adjustments

Introduction Although the supplementary motor area (SMA) is thought to contribute to the generation of anticipatory postural adjustments (APAs), which act to stabilize supporting body segments prior to movement, its precise role remains unclear ( Jacobs et al., 2009 ). Non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), over the primary motor cortex (M1) has been shown to modulate cortical excitability, thereby influencing motor behaviour and learning. However, only a few studies have reported that application of tDCS over the SMA changes the excitability of the M1 ( Kirimoto et al., 2011 ) and motor learning process ( Vollmann et al., 2012 ). Objectives This study was performed to elucidate whether cathodal tDCS applied over the SMA modifies the function of APAs. Materials and Methods Cathodal tDCS and sham tDCS (2 mA) were applied over the SMA or left of the leg area of the M1 of 11 healthy subjects for 15 min. Subjects performed the task of self-paced rapid shoulder flexion before, immediately after, and 15 min after tDCS. Electromyographic (EMG) activity was recorded from the deltoid anterior (DEL_A), as the prime mover muscle, and biceps femoris (BF), as the postural muscle during tasks. Latency differences (ΔEMG onset) with the two types of stimuli were calculated by subtracting the EMG burst onset of the BF from that of the DEL_A. Results Fig. 1 shows the EMG waveforms obtained from a representative subject before, immediately after, and 15 min after cathodal tDCS over the SMA. Following cathodal tDCS over the SMA, the ΔEMG onset was significantly shortened compared to after sham tDCS, while tDCS over the M1 did not produce any significant effect. Conclusion These results suggest that the SMA may play a critical role in the generation of voluntary movement accompanied by APAs. As the application of cathodal tDCS over the SMA could modulate EMG activity, anodal tDCS over the SMA could have beneficial effects in patients with Parkinson’s disease who have deficient APAs [Latash et al., 1995] . Acknowledgement of funding sources This work was supported in part by a Grant-in-Aid for Scientific Research (C) No. 08042773 from the Japan Society for the Promotion of Science and a research grant from Niigata University of Health and Welfare.

P1-12. The effects of cathodal transcranial direct current stimulation of the supplementary motor area on the function of anticipatory postural adjustments

Objective: Although the supplementary motor area (SMA) is thought to contribute to the generation of anticipatory postural adjustments (APAs), which act to stabilize supporting body segments prior to movement, its precise role remains unclear. This study was performed to elucidate whether cathodal transcranial direct current stimulation (tDCS) applied over the SMA modifies the function of APAs. Method: Cathodal tDCS and sham tDCS were applied over the SMA or left of the leg area of the M1 of 11 healthy subjects for 15 min. Subjects performed the task of self-paced rapid shoulder flexion before, immediately after, and 15 min after tDCS. Electromyographic (EMG) activity was recorded from the deltoid anterior (DEL_A), as the prime mover muscle, and biceps femoris (BF), as the postural muscle during tasks. Results: Following cathodal tDCS over the SMA, the ΔEMG onset between DEL_A and BF was significantly shortened compared to after sham tDCS, while tDCS over the M1 did not produce any significant effect. Conclusions: These results suggest that the SMA may play a critical role in the generation of voluntary movement accompanied by APAs. Application of cathodal tDCS over the SMA could modulate the function and timing of these APAs.

Prefrontal hyperactivity in older people during motor planning

The aim of this study was to assess the influence of age-related changes in cortical activity related to the motor preparation involved in simple- and discriminative-reaction tasks. To distinguish between age effects on motor planning and stimulus processing, both movement- and stimulus-locked event related potentials (ERPs) were investigated in 14 younger, 14 middle-aged, and 14 older adults (mean ages 24.4, 49, and 70 years, respectively). The novel results of the present study are the prefrontal over-recruitment observed in older adults in movement-related cortical potentials (MRCPs) and the differential pattern of aging effects observed at behavioral and at electrophysiological level between middle-aged and older adults. Overall, the following results were observed: (i) behavioral results confirmed the well-known slowing of responses in aging people, which were associated with optimal accuracy; (ii) the age-related differences in cortical activity underlying the generation of voluntary movements in response to external stimuli were more pronounced for the motor planning than the stimulus processing stage; (iii) the source and the time-course analysis of the over-recruitment in the older adults indicated tonic involvement of prefrontal areas regardless of task complexity; and (iv) middle-aged adults showed a 'young adult-like' behavioral speed, but an 'older adult-like' overactivation of prefrontal areas. In summary, to reach the same accuracy, older subjects prepared the action with greater anticipation and higher cost, as indexed by the earlier latency onset and larger prefrontal cortical activation.

Oscillatory activity in the subthalamic nucleus during arm reaching in Parkinson's disease

Oscillatory activities in the brain within the beta (15–30Hz) and gamma (70–90Hz) ranges have been implicated in the generation of voluntary movement. However, their roles remain unclear. Here, we record local field potential activity from the region of the subthalamic nucleus during movement of the contralateral limb in 11 patients with Parkinson's disease. Patients were on their normal dopaminergic medication and were cued to perform arm-reaching movements after a delay period at three different speeds: ‘slow’, ‘normal’, and ‘fast’. Beta activity desynchronized earlier in response to the cue indicating an upcoming fast reach than to the cues for slow or normal speed movement. There was no difference in the degree of beta desynchronization between reaching speeds and beta desynchronization was established prior to movement onset in all cases. In contrast, synchronization in the gamma range developed during the reaching movement, and was especially pronounced during fast reaching. Thus the timing of suppression in the beta band depended on task demands, whereas the degree of increase in gamma oscillations depended on movement speed. These findings point to functionally segregated roles for different oscillatory frequencies in motor preparation and performance.

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.

How the Brain Generates Movement

In this study, we assume that the brain uses a general-purpose pattern generator to transform static commands into basic movement segments. We hypothesize that this pattern generator includes an oscillator whose complete cycle generates a single movement segment. In order to demonstrate this hypothesis, we construct an oscillator-based model of movement generation. The model includes an oscillator that generates harmonic outputs whose frequency and amplitudes can be modulated by external inputs. The harmonic outputs drive a number of integrators, each activating a single muscle. The model generates muscle activation patterns composed of rectilinear and harmonic terms. We show that rectilinear and fundamental harmonic terms account for known properties of natural movements, such as the invariant bell-shaped hand velocity profile during reaching. We implement these dynamics by a neural network model and characterize the tuning properties of the neural integrator cells, the neural oscillator cells, and the inputs to the system. Finally, we propose a method to test our hypothesis that a neural oscillator is a central component in the generation of voluntary movement.

Subthalamic Nucleus Deep Brain Stimulation Improves Saccades in Parkinson’s Disease

Objectives. The clinical efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) for major motor symptoms of Parkinson's disease (PD) is well established, but its effects on visually guided vs. internally generated eye movements in the medication off state need to be studied further. Since the basal ganglia are thought to be involved in the generation of voluntary movements under internal control, we hypothesized that voluntary saccades would show improvements with STN DBS. Materials and Methods. Seven PD patients with STN DBS performed visually guided and internally generated (anti- and memory-guided) saccades with STN DBS on and off following 12 hours of levodopa withdrawal. The change in saccade reaction time, first saccade gain, and final saccade gain with STN DBS were measured. Results. STN DBS improved the reaction time of visually guided saccades but not of anti- or memory-guided saccades. STN DBS also improved the first saccade gain of the anti- and memory-guided saccades, but not of the visually guided saccades. Conclusions. These results demonstrate that STN DBS has differential effects on the parameters of visually guided and internally generated saccades. These effects may be mediated by the influence of STN DBS on cortical ocular motor areas, the basal ganglia, ocular motor loop, or downstream structures such as the brainstem saccade generating circuits.

The onset of voluntary reactive movement is temporally influenced by the central oscillation in action tremor caused by multiple sclerosis

The influence of oscillatory activity in the motor system on the generation of voluntary movement has been previously studied by revealing temporal coupling between voluntary movements and associated physiological or pathological tremor. The present study aims to investigate whether there is any temporal correlation between the onset of a rapid reactive movement and the action tremor at the wrist in patients with multiple sclerosis (MS). In 13 MS patients, their reactive wrist movements and tremor were simultaneously recorded during a visually cued simple reaction time task. Significant correlation was found between the tremor-related and non-tremor-related measurements of the wrist movement. The onset of reactive movement was unevenly distributed over the tremor cycle peaking at 177° in the direction opposite to the reactive movement, suggesting a temporal coupling between the reactive movements and tremor. No significant difference in reaction time was found between voluntary flexion and extension movements, and no significant differences in the mean values or the standard deviations of the reaction time between the movements in-phase and out-of-phase with tremor were detected, suggesting that entrainment of the spinal motor neurons is not influenced by tremor activity. In conclusion, in MS action tremor, the timing of the initiation of a rapid voluntary movement may be influenced by the pathological oscillator at a supra-spinal level.

Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke?

Motor impairment resulting from chronic stroke can have extensive physical, psychological, financial, and social implications despite available neurorehabilitative treatments. Recent studies in animals showed that direct epidural stimulation of the primary motor cortex surrounding a small infarct in the lesioned hemisphere (M1(lesioned hemisphere)) elicits improvements in motor function. In human beings, proof of principle studies from different laboratories showed that non-invasive transcranial magnetic stimulation and direct current stimulation that upregulate excitability within M1(lesioned hemisphere) or downregulate excitability in the intact hemisphere (M1(intact hemisphere)) results in improvement in motor function in patients with stroke. Possible mechanisms mediating these effects can include the correction of abnormally persistent interhemispheric inhibitory drive from M1(intact hemisphere) to M1(lesioned hemisphere) in the process of generation of voluntary movements by the paretic hand, a disorder correlated with the magnitude of impairment. In this paper we review these mechanistically oriented interventional approaches. WHAT NEXT?: These findings suggest that transcranial magnetic stimulation and transcranial direct current stimulation could develop into useful adjuvant strategies in neurorehabilitation but have to be further assessed in multicentre clinical trials.

Ball experiments in 32 acute akinetic catatonic patients: deficits of internal initiation and generation of movements.

We undertook ball experiments in 32 akinetic catatonic patients in order to determine specific functional deficits in the motor system in akinetic catatonia. Standardized ball experiments (catching, throwing, stopping, kicking) were conducted in 32 acute akinetic catatonic patients (23 without neuroleptics on admission), diagnosed according to Lohr, Rosebush, and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) on days 0 and 21. Additionally, associated psychopathology was evaluated using different scales on days 0 and 21: the Global Assessment Scale, the Brief Psychiatric Rating Scale, the Hamilton-Anxiety Scale, the scale for the assessment of negative symptoms (SANS), and the Simpson scale for extrapyramidal side effects (SEPS). Significantly more patients were able to perform more externally guided tasks (catching, stopping) than internally guided tasks (throwing, kicking). Patients showed significantly more posturing and awkward movements on day 0 than on day 21. There was a significantly positive correlation between hypokinetic extrapyramidal features (SEPS) and negative symptoms with their cognitive alterations (SANS) on day 0. The findings suggest a deficit of internal initiation, as in parkinsonism, as well as a dysfunction in the generation of voluntary movements in akinetic catatonia. We assume an underactivity in the dorsolateral prefrontal cortex and the supplementary motor area with consecutive down-regulation of the cortical-striatal-thalamic circuit, the "motor loop," in catatonia.

PS-14-7 Movement-related cortical potentials upon forward stepping — difference by varied trigger points —

The aim of this study was to assess the influence of age-related changes in cortical activity related to the motor preparation involved in simple- and discriminative-reaction tasks. To distinguish between age effects on motor planning and stimulus processing, both movement- and stimulus-locked event related potentials (ERPs) were investigated in 14 younger, 14 middle-aged, and 14 older adults (mean ages 24.4, 49, and 70 years, respectively). The novel results of the present study are the prefrontal over-recruitment observed in older adults in movement-related cortical potentials (MRCPs) and the differential pattern of aging effects observed at behavioral and at electrophysiological level between middle-aged and older adults. Overall, the following results were observed: (i) behavioral results confirmed the well-known slowing of responses in aging people, which were associated with optimal accuracy; (ii) the age-related differences in cortical activity underlying the generation of voluntary movements in response to external stimuli were more pronounced for the motor planning than the stimulus processing stage; (iii) the source and the time-course analysis of the over-recruitment in the older adults indicated tonic involvement of prefrontal areas regardless of task complexity; and (iv) middle-aged adults showed a ‘young adult-like’ behavioral speed, but an ‘older adult-like’ overactivation of prefrontal areas. In summary, to reach the same accuracy, older subjects prepared the action with greater anticipation and higher cost, as indexed by the earlier latency onset and larger prefrontal cortical activation.

Changes in functionally determined order processes of the EEG in a motor task due to various dosages of biperidene.

Animal experiments have demonstrated that the cholinergic system plays an important role in the activation of the cerebral cortex in conjunction with motor activities. In order to study the significance of the cholinergic system in the generation of voluntary movements in man, the effects of the anticholinergic drug biperidene on EEG states were analyzed. The effects depend strongly on the dosage and are shown in various frequency bands, topographic loci and time periods. Different functional significances of various frequency bands were found. In the alpha band motoric control processes are seen as an expression of mechanisms which substitute the cholinergic system. A shift of functions from the theta to the delta band with the increase of the medication seems to parallel an enhancement of motivational or volitional effort. The emergence of highly ordered EEG states is seen to be meaningful in view of the underlying processes of voluntary movements.