Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements – a PET study

The purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right-handed healthy male volunteers using positron emission tomography during a two-ball-rotation task using the right hand, the same task using the left hand and two control tasks. In the two-ball-rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.     

Changes in brain activation during the acquisition of a new bimanual coodination task

Motor skill acquisition is associated with the development of automaticity and induces neuroplastic changes in the brain. Using functional magnetic resonance imaging (fMRI), the present study traced learning-related activation changes during the acquisition of a new complex bimanual skill, requiring a difficult spatio-temporal relationship between the limbs, i.e., cyclical flexion-extension movements of both hands with a phase offset of 90 degrees. Subjects were scanned during initial learning and after the coordination pattern was established. Kinematics of the movements were accurately registered and showed that the new skill was acquired well. Learning-related decreases in activation were found in right dorsolateral prefrontal cortex (DLPFC), right premotor, bilateral superior parietal cortex, and left cerebellar lobule VI. Conversely, learning-related increases in activation were observed in bilateral primary motor cortex, bilateral superior temporal gyrus, bilateral cingulate motor cortex (CMC), left premotor cortex, cerebellar dentate nuclei/lobule III/IV/Crus I, putamen/globus pallidus and thalamus. Accordingly, bimanual skill learning was associated with a shift in activation among cortico-subcortical regions, providing further evidence for the existence of differential cortico-subcortical circuits preferentially involved during the early and advanced stages of learning. The observed activation changes account for the transition from highly attention-demanding task performance, involving processing of sensory information and corrective action planning, to automatic performance based on memory representations and forward control.     

Motor awareness without perceptual awareness

The control of action has traditionally been described as "automatic". In particular, movement control may occur without conscious awareness, in contrast to normal visual perception. Studies on rapid visuomotor adjustment of reaching movements following a target shift have played a large part in introducing such distinctions. We suggest that previous studies of the relation between motor performance and perceptual awareness have confounded two separate dissociations. These are: (a) the distinction between motoric and perceptual representations, and (b) an orthogonal distinction between conscious and unconscious processes. To articulate these differences more clearly, we propose a new measure of motor awareness, based on subjects' ability to reproduce the spatial details of reaching movements they have just made. Here we focus on the dissociation between motor awareness and perceptual awareness that may occur when subjects make rapid visuomotor adjustments to reaching movements following a target shift. In experiment 1, motor awareness was dissociated from perceptual awareness of a target shift during reaching movement. Participants' reproduction of movement endpoints following visuomotor adjustment was independent of whether they saw the target shift or not. Experiment 2 replicated this result, and further showed that neither motor awareness nor motor performance were disrupted by TMS over the parietal cortex. The neural mechanisms underlying motor awareness, and the implications for theories of consciousness, are discussed.     

Overflow movements and white matter abnormalities in ADHD

Multiple motor abnormalities have been identified in some children with Attention Deficit/Hyperactivity Disorder (ADHD). These include persistence of overflow movements, impaired timing of motor responses and deficits in fine motor abilities. Motor overflow is defined as co-movement of body parts not specifically needed to efficiently complete a task. The presence of age-inappropriate overflow may reflect immaturity of the cortical systems involved in automatic motor inhibition. Theories on overflow movements consistently implicate impairments in white matter (WM) tracts, including the corpus callosum. WM connections might be altered selectively in brain networks and thus influence motor behaviours. We reviewed the scientific contributions on overflow movements and WM abnormalities in ADHD. They suggest that WM abnormalities in motor/premotor circuits, which are important for motor response inhibition, might be responsible for overflow movements in patients with ADHD.     

Chronic dose effects of reboxetine on motor skill acquisition and cortical excitability

Summary Background. Enhancement of cortical excitability is thought to be beneficial for synaptic plasticity associated with motor skill acquisition. Single dose application of the selective norepinephrine reuptake inhibitor reboxetine (RBX) increases motor cortex excitability. In this study, we tested if a chronic dose application of RBX improved motor skill acquisition and modulated cortical excitability. Methods. The study was randomised, double blind and placebo-controlled. Twelve healthy subjects received four milligram RBX twice a day for four days preceded by two milligram RBX twice a day for two days. Each subject served as his own control. The time interval between the verum and the placebo session was 16 days or more. Measurement of cortical excitability by means of paired pulse transcranial magnetic stimulation (ppTMS) was conducted before and after the motor skill acquisition task in each session. The task was to lift two fingers of the right hand at once while the hand was positioned sprawled out on the table. The movements were self-paced and subjects had to perform as many moves as possible in 60 sec. Between seven blocks of self-paced movements six blocks with 60 single trials at a fixed interstimulus intervall were presented. Two equally difficult versions of the task using different finger combinations were established in order to avoid carry over effects in performance. The finger movements were recorded with a three-dimensional ultrasound movement analysis system (Zebris). Results. All subjects had substantial gain in performance across the selfpaced blocks. Average increase in number of correct moves was 87% (from 27.8 to 51.9). There was no significant difference neither between the versions of the task nor between placebo vs. verum. Also, there was no significant difference between first and second session, indicating that there was no carry over effect in performance. ppTMS revealed no significant differences in cortical excitability between groups. Conclusion. The newly developed skill acquisition task yields robust single subject gain of performance. As the two versions of the task do not interact, it is suitable to be used in cross-over designs. In contrast to studies using single doses of RBX, motor cortex excitability seems to be unaffected in a steady-state induced by repeated drug applications. This could explain why RBX did not modulate motor behavior.     

When emulation becomes reciprocity

It is well known that perceiving another''s body movements activates corresponding motor representations in an observer''s brain. It is nevertheless true that in many situations simply imitating another''s actions would not be an effective or appropriate response, as successful interaction often requires complementary rather than emulative movements. At what point does the automatic tendency to mirror another''s actions become the inclination to carry out appropriate, complementary movements? In the present study, single-pulse transcranial magnetic stimulation (TMS) was used to explore corticospinal excitability in participants observing action sequences evoking imitative or complementary movements. TMS was delivered at five time points corresponding to different moments in time when key kinematic landmarks characterizing an observed action occurred. A variation in motor evoked potentials (MEPs) confirmed that the motor system flexibly shifts from imitative to complementary action tendencies. That shift appears to take place very precociously in time. Observers are attuned to advance movement information and can use it to anticipate a future course of action and to prepare for an appropriate, complementary action. Altogether, these findings represent a step forward in research concerning social action-perception coupling mechanisms providing important data to better understand the role of predictive simulation in social contexts.     

Cortical plasticity and motor activity studied with transcranial magnetic stimulation

For decades cortical representations of the parts of the body have been considered to be unchangeable. This view has changed radically during the past 20 years using new tools designed to study plasticity in the adult human brain. Transcranial magnetic stimulation (TMS) is a valuable non-invasive technique for exploring the ability of the motor cortex to change during motor skill acquisition. Results obtained with TMS in neurological patients as well as in normal subjects demonstrate that cortical plasticity is a necessity for correct adaptation to the continuously changing environment. Topographical reorganization of the motor cortex depends on the types of movements performed by the subjects. During simple training, the cortical representation is enlarged, and it returns to its initial size when the task is overlearned. These transient modifications characterize simple motor training. Motor skills in which coordination of distal and proximal muscles, precision of the task and spatio-temporal constraints are associated, has a different impact on cortical reorganization. We propose that years of practice of a complex motor skill induces a new cortical topography that must be interpreted as structural plasticity which provides the capacity to execute a plastic behaviour instead of a stereotypical movement. We review the neuronal mechanisms underlying plasticity in different types of movement. We stress new emerging notions, such as overlap of cortical maps, and system dynamics at single neuron and network levels, to explain the reorganization of movement representations that encode motor skill. Dendritic arborizations as functional computing elements, newly generated neurons in adult brain, and plastic architectures of cortical networks operating as distributed functional modules are new hypotheses for structural plasticity.     

Impairments in the learning and performance of a new manual skill in patients with Parkinson''s disease.

Twelve patients with Parkinson's disease learned two novel skills in which they had to track a target by moving a joystick. In task 1 they had to learn to anticipate the movements of a semi predictable target. In task 2 they had to learn a novel control system in which the movements of the joystick were mirror reversed in relation to the computer screen. On each task they performed two sessions of three minutes continuous practice separated by a 10 minute rest. In both tasks the patients performed much worse than the controls, but showed clear evidence of learning, particularly after the ten minute rest. Detailed examination of their performance suggested that the skill was becoming automatic, releasing attention for aspects of the task that could not be learned. The major difference from the controls appeared during the first minute of each practice session when the controls showed a marked improvement in performance while the patients did not. We suggest that this rapid but temporary improvement in performance reflects the acquisition of a motor "set" whereby existing motor programs or skills are modified to suit the task currently in hand. We concluded that patients with Parkinson's disease have difficulty in maintaining such sets.     

Self-organizing continuous attractor networks and motor function.

Motor skill learning may involve training a neural system to automatically perform sequences of movements, with the training signals provided by a different system, used mainly during training to perform the movements, that operates under visual sensory guidance. We use a dynamical systems perspective to show how complex motor sequences could be learned by the automatic system. The network uses a continuous attractor network architecture to perform path integration on an efference copy of the motor signal to keep track of the current state, and selection of which motor cells to activate by a movement selector input where the selection depends on the current state being represented in the continuous attractor network. After training, the correct motor sequence may be selected automatically by a single movement selection signal. A feature of the model presented is the use of 'trace' learning rules which incorporate a form of temporal average of recent cell activity. This form of temporal learning underlies the ability of the networks to learn temporal sequences of behaviour. We show that the continuous attractor network models developed here are able to demonstrate the key features of motor function. That is, (i) the movement can occur at arbitrary speeds; (ii) the movement can occur with arbitrary force; (iii) the agent spends the same relative proportions of its time in each part of the motor sequence; (iv) the agent applies the same relative force in each part of the motor sequence; and (v) the actions always occur in the same sequence.     

Learning to move machines with the mind

Brain-computer interfaces (BCIs) extract signals from neural activity to control remote devices ranging from computer cursors to limb-like robots. They show great potential to help patients with severe motor deficits perform everyday tasks without the constant assistance of caregivers. Understanding the neural mechanisms by which subjects use BCI systems could lead to improved designs and provide unique insights into normal motor control and skill acquisition. However, reports vary considerably about how much training is required to use a BCI system, the degree to which performance improves with practice and the underlying neural mechanisms. This review examines these diverse findings, their potential relationship with motor learning during overt arm movements, and other outstanding questions concerning the volitional control of BCI systems.     

Development of reaching and grasping skills in infants with Down syndrome

Reaching and grasping skills have been described to emerge from a dynamic interaction between intrinsic and extrinsic factors. The aims of the study were to investigate the effect of such intrinsic factors as age and Down syndrome on the development of reaching and grasping skills and on overall gross motor skill, and to test the influence of the overall level of gross motor skill on the development of reaching and grasping. Seven infants with Down syndrome (DS) and seven infants with typical development were assessed at the ages of 4, 5 and 6 months. The following variables were analyzed: straightness index, mean velocity, movement units and deceleration time (for reaching movements), grasping frequency and AIMS scores. Intrinsic factors such as age and DS were found to influence the development of reaching, grasping, and of the overall level of gross motor skill. The overall level of gross motor skill was observed to influence grasping.     

Age-dependent modulation of motor network connectivity for skill acquisition,consolidation and interlimb transfer after motor practice

ObjectiveAge-related differences in neural strategies for motor learning are not fully understood. We determined the effects of age on the relationship between motor network connectivity and motor skill acquisition, consolidation, and interlimb transfer using dynamic imaging of coherent sources.MethodsHealthy younger (n = 24, 18–24 y) and older (n = 24, 65–87 y) adults unilaterally practiced a visuomotor task and resting-state electroencephalographic data was acquired before and after practice as well as at retention.ResultsThe results showed that right-hand skill acquisition and consolidation did not differ between age groups. However, age affected the ability to transfer the newly acquired motor skill to the non-practiced limb. Moreover, strengthened left- and right-primary motor cortex-related beta connectivity was negatively and positively associated with right-hand skill acquisition and left-hand skill consolidation in older adults, respectively.ConclusionAge-dependent modulations of bilateral resting-state motor network connectivity indicate age-specific strategies for the acquisition, consolidation, and interlimb transfer of novel motor tasks.SignificanceThe present results provide insights into the mechanisms underlying motor learning that are important for the development of interventions for patients with unilateral injuries.     

Multiple sclerosis and canine pets

Spontaneous and associated hyperkinetic facial movements and contracture which follow injury to the seventh cranial nerve (postparalytic hemifacial spasm) or arise without known previous injury (cryptogenic hemifacial spasm) are pathological motor phenomena not found in the distribution of other cranial or somatic motor nerves. The commonly expressed hypotheses of pathogenesis—aberrant regeneration and fiber excitation by false synapse formation (ephapses) at the site of injury—cannot account for all aspects of these phenomena or for the uniqueness of such movements to the distribution of the seventh nerve. The suggestion is made that the existing diversity of facial motor behavior, which encompasses voluntary, emotional, and especially automatic, associated, and reflexive movements, is based on a unique central organization that sets it apart from other motor groups. I hypothesize that because of this organization, the changes following axonal injury—which include selective deafferentation, glial response, axonal sprouting, functional reconnection, and hyperexcitability from dendritic spike generation—can unmask and augment automatic, associated, and reflexive movements already present in the facial neuronal network to result in facial hyperkinesia.     

Different cortical potentials preceding self-paced and visually initiated hand movements and their reciprocal transition in the same monkey

With chronically implanted electrodes on the surface and in the depth of the cortex, field potentials preceding hand movements initiated at self-pace and by visual stimulus were recorded from the premotor cortex and the forelimb areas of motor and somatosensory cortices of the same monkey. A monkey trained with either self-paced or visually initiated movement of a common motor performance revealed the premovement cortical potentials characteristic of the movement, which were markedly distinguishable between the differently initiated movements. When a monkey well-trained with one of the two movements was subsequently trained with the other, it still showed the premovement cortical potentials characteristic of the previous movement at an early stage of training and then later came gradually to reveal the premovement potentials characterized with the latter movement. After sufficient sequential training with each type of movement, the monkey was able to elicit the two kinds of premovement cortical potentials respectively on self-paced and visually initiated movements in successive sessions of the same day. We suggest that the central nervous mechanisms (programs) of preparing self-paced (“voluntary”) and visually initiated (reaction) movements with a common motor performance are very different in the same monkey, and that they can be switched from one to the other after the mechanisms have been reliably established by sufficient training with the two types of movements.     

Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET.

The functional anatomy of motor skill acquisition was investigated in six normal human subjects who learned to perform a pursuit rotor task with their dominant right hand during serial positron emission tomography (PET) imaging of relative cerebral blood flow (relCBF). The effect of motor execution, rather than learning, was identified by a comparison of four motor performance scans with two control scans (eye movements only). Motor execution was associated with activation of a distributed network involving cortical, striatonigral, and cerebellar sites. Second, the effect of early motor learning was examined. Performance improved from 17% to 66% mean time on target across the four PET scans obtained during pursuit rotor performance. Across the same scans, significant longitudinal increases of relCBF were located in the left primary motor cortex, the left supplementary motor area, and the left pulvinar thalamus. The results demonstrate that changes of regional cerebral activity associated with early learning of skilled movements occur in sites that are a subset of a more widely distributed network that is active during motor execution.     

The importance of the dominant hemisphere in the organization of bimanual movements

The successful control of upper limb movements is an essential skill of the human motor system. Yet, the neural organization of bimanual actions remains an issue of debate. Their control can be directed from both hemispheres, or, coordinated motion might be organized from the dominant (left) hemisphere. In order to unravel the neural mechanisms of bimanual behavior, we analyzed the standard task-related and directed coherence between EEG signals picked up over the primary sensorimotor cortices in right-handed subjects during unimanual as well as bimanual in-phase (symmetrical) and anti-phase (asymmetrical) movements. The interhemispheric coherence in the beta frequency band (>13-30 Hz) was increased in both unimanual and bimanual patterns, compared to rest. During unimanual actions, the drive in the beta band from one primary sensorimotor cortex to the other was greater during movement of the contralateral as opposed to ipsilateral hand. In contrast, during bimanual actions, the drive from the dominant to the non-dominant primary sensorimotor cortex prevailed, unless task constraints induced by an external perturbation resulted in a substantial uncoupling of the hand movements, when interhemispheric coherence would also drop. Together, these results suggest that the contralateral hemisphere predominantly organizes unimanual movements, whereas coupled bimanual movements are mainly controlled from the dominant hemisphere. The close association between changes in interhemispheric coupling and behavioral performance indicates that synchronization of neural activity in the beta band is exploited for the control of goal-directed movement.     

Motor learning in man: a positron emission tomographic study

We measured regional cerebral blood flow (rCBF) with positron emission tomography to study changes in anatomical structures during the course of learning a complicated finger sequence of voluntary movements. Motor learning was accompanied by rCBF increases in the cerebellum, decreases in all limbic and paralimbic structures, and striatal decreases which changed to striatal increases as the motor skill was learned. Simultaneously, activations of initially contributing non-motor parts of the cerebral cortex vanished. Both cerebellar circuits and striatal circuits appear important for the storage of motor skills in the brain.     

Motor complications in Parkinson's disease: Striatal molecular and electrophysiological mechanisms of dyskinesias

Long‐term levodopa (l ‐dopa) treatment in patients with Parkinson´s disease (PD) is associated with the development of motor complications (ie, motor fluctuations and dyskinesias). The principal etiopathogenic factors are the degree of nigro‐striatal dopaminergic loss and the duration and dose of l ‐dopa treatment. In this review article we concentrate on analysis of the mechanisms underlying l ‐dopa–induced dyskinesias, a phenomenon that causes disability in a proportion of patients and that has not benefited from major therapeutic advances. Thus, we discuss the main neurotransmitters, receptors, and pathways that have been thought to play a role in l ‐dopa–induced dyskinesias from the perspective of basic neuroscience studies. Some important advances in deciphering the molecular pathways involved in these abnormal movements have occurred in recent years to reveal potential targets that could be used for therapeutic purposes. However, it has not been an easy road because there have been a plethora of components involved in the generation of these undesired movements, even bypassing the traditional and well‐accepted dopamine receptor activation, as recently revealed by optogenetics. Here, we attempt to unify the available data with the hope of guiding and fostering future research in the field of striatal activation and abnormal movement generation. © 2017 International Parkinson and Movement Disorder Society     

Intact intracortical microstimulation (ICMS) representations of rostral and caudal forelimb areas in rats with quinolinic acid lesions of the medial or lateral caudate-putamen in an animal model of Huntington's disease

Neurotoxic, cell-specific lesions of the rat caudate-putamen (CPu) have been proposed as a model of human Huntington's disease and as such impair performance on many motor tasks, including skilled forelimbs tasks such as reaching for food. Because the CPu and motor cortex share reciprocal connections, it has been proposed that the motor deficits are due in part to a secondary disruption of motor cortex. The purpose of the present study was to examine the functionality of the motor cortex using intracortical microstimulation (ICMS) following neurotoxic lesions of the CPu. ICMS maps have been shown to be sensitive indicators of motor skill, cortical injury, learning, and experience. Long-evans hooded rats received a sham, a medial, or a lateral CPu lesion using the neurotoxin, quinolinic acid (2,3-pyridinedicarboxylic acid). Two weeks later the motor cortex was stimulated under light ketamine anesthesia. Neither lateral nor medial lesions of the CPu altered the stimulation threshold for eliciting forelimb movements, the type of movements elicited, or the size of the rostral forelimb (RFA) and caudal forelimb areas (CFA) from which movements were elicited. The preservation of ICMS forelimb movement representations (the forelimb map) in rats with cell-specific CPu lesions suggests motor impairments following lesions of the lateral striatum are not due to the disruption of the motor map. Therefore, the impairments that follow striatal cell loss are due either to alterations in circuitry that is independent of motor cortex or to alterations in circuitry afferent to the motor cortex projections.