Cortical activation during fast repetitive finger movements in humans: dipole sources of steady-state movement-related cortical potentials

Fast repetitive finger movements are associated with characteristic EEG patterns described in humans as steady-state movement-related cortical potentials (ssMRCPs). The objective of the present study was to determine the electrical generators of ssMRCPs (movement rate, 2 Hz) by dipole modelling. The generators for the initial ssMRCP phase (peak approximately 60 msec before EMG onset) were located in the central region bilaterally, with largely radial orientation, consistent with activation of the crown of the precentral gyrus. The generator of the next phase (peak approximately 10 msec after EMG onset) was located in the contralateral central region with tangential posterior orientation, consistent with activation of the anterior wall of the central sulcus. The postmovement phase (peak approximately 95 msec after EMG onset) was explained by another source in the contralateral central region with tangential anterior orientation, consistent with activation of the posterior wall of the central sulcus. This pattern probably corresponds to a sequence of activation of the bilateral dorsal premotor cortex, contralateral primary motor, and primary somatosensory cortex that takes place within approximately 200 msec around EMG onset. Steady-state movement-related cortical potentials in combination with dipole modelling provide a novel, noninvasive approach to assessing changes of human cortical premotor, motor, and somatosensory activation in the millisecond range.     

Cellular biology of human intimal hyperplastic stenosis

We studied the topographic distribution of scalp-recorded, averaged movement-related cortical potentials occurring immediately before and after the onset of voluntary movements in six patients with cerebellar degenerative disease. We placed 26 electrodes on the scalp overlying the sensorimotor area and recorded cortical potentials related to abduction of the index finger. The amplitudes and latencies of the potentials were normal in all patients except two, in whom the negative slope (NS') was absent. All patients had an abnormal topographic pattern of potentials compared with normal subjects. The initial slope of motor potential (isMP), which was focal and contralateral in the normal subjects, was diffuse and bilateral in the patients. The topography of the frontal peak of motor potential (fpMP) was more posterior in the patients than in normal subjects. The patterns found in this preliminary study indicate a derangement of sensorimotor cortex activity in voluntary movement as a consequence of cerebellar dysfunction.     

Movement-related cortical potentials preceding repetitive and random-choice hand movements in Parkinson's disease

The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self-paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.     

Management of caustic esophagitis in adults

We investigated whether a cortical potential exists, that is similar to the Bereitschaftspotential, preceding postural adjustment followed by voluntary ballistic rising on tiptoe in 10 healthy subjects. On the basis of the electromyogram (EMG) activities of the soleus muscle, the onsets of the premotion silent period (PMSP) and EMG discharge were determined. The negative potentials associated with a voluntary rise-on-tiptoe movement with respect to EMG onset were similar to the readiness potential associated with voluntary foot movement. The slopes of the slow negative potential associated with the PMSP onset were significantly more negative than those of the potential associated with rise-on-tiptoe movement, particularly over the frontal electrode positions. The results suggest that a cortical potential precedes postural adjustment that is followed by voluntary rising on tiptoe.     

Polysomnographic sleep measures in patients with uremic and idiopathic restless legs syndrome

In the present study, the nocturnal electroencephalographic sleep pattern, the number of periodic leg movements (PLM) during sleep and wakefulness, and the subjective sleep parameters of patients with uremic (n = 10) and idiopathic (n = 17) restless legs syndrome (RLS) were compared. The main finding was that the total number of PLM (p = 0.019), the PLM index (p = 0.018), and the PLM index while awake (p = 0.003) were significantly higher in patients with uremic RLS compared with patients who had idiopathic RLS. Additionally, both groups showed a distinct time-of-night pattern of PLM activity. Polysomnographic measures of sleep continuity (total sleep time, sleep efficiency, sleep onset latency, time awake) and sleep architecture (amount of nonrapid eye movement sleep stages 1, 2, 3, and 4 and the amount of rapid eye movement sleep) did not differ between uremic and idiopathic RLS patients. With regard to subjective parameters, sleep quality was estimated to be worse in uremic RLS (p = 0.033), whereas other parameters (for example, severity of RLS, quality of life) did not differ between the two groups. It is suggested that uremia itself worsens the motor symptoms of RLS, probably as a result of increased excitability.     

Pathophysiologies of dystonia and myoclonus--consideration from the standpoint of treatment

Pathophysiologies of disorders with dystonia or myoclonus were studied by evaluating the effects of treatment. Naturally, the main lesion of the dystonia responding to levodopa is in the nigrostriatal dopamine neuron. The target of stereotaxic operations is ventrolateral palladium for postural dystonia and the nucleus ventralis oralis posterior (Vop) thalamus for action dystonia. Torsion dystonia with lesion in the striatum and/or the pallidum causes axial torsion, it may be postural through the descending pathway and action through Vop. Stereotaxic operations on these pathways have shown to be effective. Focal dystonia is a reflection of abnormal co-activation of cortical motor neurons, occurring in a particular voluntary movement. Botulinus toxin injected into the affected muscle should be effective. Of myoclonus with epilepsy, cortical reflex myoclonus or cortical induced reticular myoclonus responds to valproic acid. However, no antiepileptic drugs are effective on those with primary brainstem lesion. Reticular reflex myoclonus due to asphyxia responds to ventralis intermedius thalamotomy. Idiopathic myoclonus associated with dystonia is particular because it responds to ventrolateral thalamotomy. Myoclonus except for idiopathic myoclonus with dystonia is associated with atonic NREM suggesting dysfunction of the dorsal raphe serotonergic neuron or the brainstem nucleus reticularis gigantocellularis, the causative neuron for experimental uremic myoclonus. Treatment for these neurons is necessary.     

A case of cortical reflex positive-negative myoclonus--electrophysiological study

An 11-year-old girl who had the positive-negative myoclonus and the history of the generalized tonic clonic seizure was electrophysiologically studied. She had no siblings with either myoclonus or epilepsy, and her intellectual level was normal. She had no other neurological deficits including ataxia, pyramidal and extrapyramidal signs. Surface EMG showed a brief increase in the EMG activity followed by the silent period associated with positive and negative myoclonus during sustained wrist extension. Giant SEP and C reflex (38.6 ms) following electric stimulation of the median nerve at the wrist were obtained in the resting condition and the silent period (about 180 ms) following C reflex was obtained during voluntary contraction. Jerk-locked back averaging of the EEG time-locked to the onset of the myoclonic discharge recorded from the right biceps muscle showed a cortical spike at the left central region preceding the myoclonus onset by 12.6 ms. The latency of C reflex in this case was very short compared with that of previously reported cortical reflex myoclonus. The estimated cortical delay between the arrival of the somatosensory volley and the motor cortex discharge responsible for the C reflex was -1.0 ms and this value was shorter than that in patients with typical cortical reflex myoclonus (mean 3.7 +/- 1.1 ms). Conditioning stimuli (C) of the right median nerve at the wrist started to facilitate the amplitude of the motor evoked potential recorded from the right abductor pollicis brevis muscle after magnetic test stimuli (T) of the left motor cortex at 20 ms of the C-T interval. This C-T interval was shorter than that (24.6 +/- 1.6 ms) in patients with the typical cortical myoclonus. These electrophysiological findings suggested the shorter reflex pathway of the cortical reflex myoclonus in this case than in typical cortical reflex myoclonus. We speculated that the myoclonus was based upon the direct sensory projection from the thalamus to the motor cortex in this case.     

Weak Extensive Measurement without Translation-Invariance Axioms

A neural model of voluntary movement and proprioception is developed that offers an integrated interpretation of the functional roles of diverse cell types in movement-related areas of primate cortex. The model circuit maintains accurate proprioception while controlling voluntary reaches to spatial targets, exertion of force against obstacles, posture maintenance despite perturbations, compliance with an imposed movement, and static and inertial load compensations. Computer simulations show that properties of model elements correspond to the properties of many known cells types in areas 4 and 5. Among these properties are delay period activation, response profiles during movement, kinematic and kinetic sensitivities, and latency of activity onset. In particular, area 4 phasic and tonic cells, respectively, compute velocity and position commands that are capable of activating alpha and gamma motor neurons, thereby shifting the mechanical equilibrium point. Anterior area 5 cells compute the position of the limb using corollary discharges from area 4 and feedback from muscle spindles. Posterior area 5 neurons use the position perception signal and a target position signal to compute a desired movement vector. The cortical loop is closed by a volition-gated projection of this movement vector to the area 4 phasic cells. An auxiliary circuit allows phasic-tonic cells in area 4 to incorporate force command components needed to compensate for static and inertial loads. After reporting simulations of prior experimental results, predictions are made for both motor and parietal cell types under novel experimental protocols.     

Cortical hyperexcitability in progressive myoclonus epilepsy: a study with transcranial magnetic stimulation

In progressive myoclonus epilepsy (PME), responses to afferent input are frequently abnormal. It is unclear whether the abnormality lies at the cortical, subcortical, or segmental level. To obtain evidence for an exaggerated effect on motor cortical excitability, we used peripheral nerve and transcranial magnetic stimulation in controls and subjects with idiopathic generalized epilepsy and PME. Mean threshold intensity was higher in those with idiopathic generalized epilepsy and PME than in controls, probably as a result of anticonvulsant treatment. A long-latency response to peripheral stimulation and an exaggerated facilitatory effect of peripheral stimulation on the motor evoked potential was present in subjects with PME. Latency differences between the late responses in the upper and lower limbs provided evidence against a segmental reflex and implicated rapidly conducting fibers in the spinal cord. Both the late response and the facilitatory effect had onset latencies consistent with a transcortical pathway, suggesting an exaggerated effect of afferent input on motor cortical excitability in PME.     

The role of mast cells in mucosal permeability changes during ischemia-reperfusion injury of the small intestine

The ipsilateral primary motor cortex (M1) plays a role in voluntary movement. In our studies, we used repetitive transcranial magnetic stimulation (rTMS) to study the effects of transient disruption of the ipsilateral M1 on the performance of finger sequences in right-handed normal subjects. Stimulation of the M1 ipsilateral to the movement induced timing errors in both simple and complex sequences performed with either hand, but with complex sequences, the effects were more pronounced with the left-sided stimulation. Recent studies in both animals and humans have confirmed the traditional view that ipsilateral projections from M1 to the upper limb are mainly directed to truncal and proximal muscles, with little evidence for direct connections to distal muscles. The ipsilateral motor pathway appears to be an important mechanism for functional recovery after focal brain injury during infancy, but its role in functional recovery for older children and adults has not yet been clearly demonstrated. There is increasing evidence from studies using different methodologies such as rTMS, functional imaging and movement-related cortical potentials, that M1 is involved in ipsilateral hand movements, with greater involvement in more complex tasks and the left hemisphere playing a greater role than the right.     

Automatic alerting does not speed late motoric processes in a reaction-time task

When an irrelevant 'accessory' stimulus is presented at about the same time as the imperative signal in a choice reaction time-task, the latency of the voluntary response is markedly reduced. The most prominent cognitive theories agree that this effect is attributable to a brief surge in arousal ('automatic alerting'), but they disagree over whether the facilitation is localized to a late, low-level motoric process or to an earlier stage, the process of orienting to and then perceptually categorizing the reaction stimulus. To test these alternative hypotheses, we used the onset of the lateralized readiness potential (a movement-related brain potential) as a temporal landmark to partition mean reaction time into two time segments. The first segment included the time required to perceive the visual stimulus and decide which hand to react with; the second included only motoric processes. Presentation of an irrelevant acoustic stimulus shortened the first interval but had no effect on the second. We therefore rejected the motoric hypothesis.     

Generalisability of sensory gating during passive movement of the legs

Movement-related gating of somatosensory evoked potentials in the upper limb is restricted mainly to nerve stimulation supplying the moved limb segment. In the lower limb, this principle may not be followed. Tibial nerve (stimulation at the knee) somatosensory evoked potentials (SEPs) and soleus H reflexes exhibit quite similar patterns of modulation during movement. We hypothesised that movement-related gating of initial SEPs in the leg would be generalised from ipsilateral to contralateral leg movement and that such sensory gating would not be generalised to modalities with no functional relevance to the movement. Somatosensory, visual, and auditory evoked potentials (SEPs, VEPs, and AEPs) were recorded from scalp electrodes during unilateral passive movement. Short-latency tibial nerve SEPs, representing the first cortical components, and soleus H reflexes in both the moved leg and the stationary leg were attenuated compared to non-movement controls (p<0.05). Neither VEPs nor middle latency AEPs were modulated (p>0.05). We conclude that sensory gating occurs during contralateral movement. This gating is absent in other sensory modalities with no apparent functional relationship to the imposed movement.     

Gene therapy: targeting tumor cells for destruction

Sensory and motor symptoms of the limbs, motor restlessness and an urge to move only at rest are the characteristics of the restless legs syndrome (RLS), which often leads to severe sleep disturbances. The clinical diagnosis can be made on the basis of the typical history, normal neurological findings and, in some cases, a positive family history, and can be confirmed by polysomnography. The indication for treatment depends on the patient's discomfort and the severity of the sleep disturbances. L-DOPA is the treatment of first choice both in idiopathic and uremic RLS. A bedtime dose of 100-200 mg L-DOPA standard plus decarboxylase inhibitor is effective against mild and moderate sleep disturbances in RLS. Titration of the dosage and additional treatment with sustained-release preparations of L-DOPA should be applied individually. Opioids and dopamine agonists are effective alternative treatments in idiopathic RLS. Benzodiazepines are indicated only in individual cases. Besides L-DOPA, uremic RLS patients can be treated with opioids and benzodiazepines. Various approaches in the treatment of idiopathic and uremic RLS are reviewed and the practical management of therapy is outlined.     

Cortical activation during fast repetitive finger movements in humans: steady-state movement-related magnetic fields and their cortical generators

OBJECTIVE: To study the cortical physiology of fast repetitive finger movements. METHODS: We recorded steady-state movement-related magnetic fields (ssMRMFs) associated with self-paced, repetitive, 2-Hz finger movements in a 122-channel whole-head magnetometer. The ssMRMF generators were determined by equivalent current dipole (ECD) modeling and co-registered with anatomical magnetic resonance images (MRIs). RESULTS: Two major ssMRMF components occurred in proximity to EMG onset: a motor field (MF) peaking at 37+/-11 ms after EMG onset, and a postmovement field (post-MF), with inverse polarity, peaking at 102+/-13 ms after EMG onset. The ECD for the MF was located in the primary motor cortex (M1), and the ECD for the post-MF in the primary somatosensory cortex (S1). The MF was probably closely related to the generation of corticospinal volleys, whereas the post-MF most likely represented reafferent feedback processing. CONCLUSIONS: The present data offer further evidence that the main phasic changes of cortical activity occur in direct proximity to repetitive EMG bursts in the contralateral M1 and S1. They complement previous electroencephalography (EEG) findings on steady-state movement-related cortical potentials (ssMRCPs) by providing more precise anatomical information, and thereby enhance the potential value of ssMRCPs and ssMRMFs for studying human sensorimotor cortex activation non-invasively and with high temporal resolution.     

Evaluation of the effect of ivermectin administered topically at zero and six weeks after turnout on gastrointestinal nematode infection in first-season grazing cattle

OBJECTIVES: Slow potentials appearing during simple repetitive acral limb movement were investigated. Twenty-six patients suffering from drug resistant partial epilepsies and explored with implanted intracerebral electrodes were examined using two protocols. METHODS: In 18 patients, readiness potential (RP), in 13 patients contingent negative variation (CNV), and in 7 patients both protocols, were tested. The recordings from leads with evident pathological EEG activity were excluded from evaluation. The results concerning the slow potentials preceding the movements in RP and CNV protocols have already been published. RESULTS: The movement-accompanying slow potentials (MASP) were polyphasic or monophasic, started before or during the movement. In the primary motor cortex they followed the pre-movement potentials depending on the protocol: in the RP paradigm they were present only contralateral to the movement, but were bilateral in the CNV protocol. In other areas they either followed the potentials preceding the movement, in some cases with opposite polarity, or they occurred alone. MASP was recorded in motor and supplementary motor, premotor and prefrontal, midtemporal, somatosensory, superior parietal and cingular cortices. The cingular cortex was heavily involved in the self-paced movements but rarely in the cued movements. CONCLUSION: The major involvement of the cingular gyrus contrasted with the absence of slow potentials in temporal limbic structures. MASP is evidently a heterogenic phenomenon. Its genesis could be involved in a spread of information through the relevant structures.     

Noninvasive study of cortical neuronal mechanism in voluntary movements: role of basal ganglia and cerebellum

Voluntary movements can be classified into the two categories depending on how those are initiated; ones initiated internally, and others triggered or paced by external stimuli. Central neuronal mechanisms involved in those preparation and execution could be represented by movement-related cortical potentials (MRCP) or Bereitschaftspotential (BP), and contingent negative variation (CNV), respectively. The both potentials, as the field potentials, can be recorded with long time constant, and represent transient changes of the membrane potentials of the cortical neurons. In patients with the lesion at the cerebellar efferent system, the BP disappeared completely whereas the late CNV was normally seen. In patients with parkinsonism, in contrast, the late CNV was significantly smaller in amplitude in severe than in mild symptom group. Recent subdural recording in epilepsy patients demonstrated that the BP and late CNV were commonly generated from the primary and supplementary motor areas, and that late CNV also arose from the frontal association cortices (mesial, basal and lateral prefrontal areas). It is therefore suggested that subcortical generating mechanism is different for the late CNV and BP although both commonly share at least some cortical generators, and that the basal ganglia are most likely responsible for the generation of the late CNV and the cerebellar efferent system for the generation of the BP.     

Contributions of the dopaminergic system to voluntary and automatic orienting of visuospatial attention

Visuospatial attention can be directed by voluntary or involuntary control independent of eye movement. The involvement of cortical and subcortical neural structures in this covert orienting mechanism has been studied using neuroimaging and electrophysiological techniques. This study was designed to investigate the role of the dopaminergic system in both voluntary and automatic orienting mechanisms of visuospatial attention. We recorded event-related evoked potentials (ERPs) and reaction time (RT) during a cued priming task in both patients with idiopathic Parkinson's disease (PD) and control subjects. Voluntary and automatic shifts in attention were studied by using central and peripheral cues, respectively. In the experiment using a central cue, the RT data showed that when the cue-target interval was long, PD patients' responses were delayed, and cue validity effects were reduced, whereas in the peripheral cue experiment the validity effects persisted across all trials. The ERPs demonstrated reduced sustained negativities preceding the imperative targets in both the central and peripheral cue experiments in PD patients. Furthermore, during the long cue-target interval in the central cue experiment, PD patients showed reduced attention shift-related negativities (ARNs) at the anterior scalp sites, whereas ARNs were generated widely in the peripheral cue experiment. The ERP findings were consistent with the RT data. These findings suggest that the dopaminergic system may contribute to voluntary and sustained control of visuospatial attention as well as to the neural system for response preparation, whereas automatic control of visuospatial attention is relatively independent of the dopamine system.     

Cortical sensorimotor reorganization after spinal cord injury: an electroencephalographic study

The aim of this study was to determine if cortical motor representation and generators change after partial or complete paralysis after spinal cord injury (SCI). Previously reported evidence for a change in cortical motor function after SCI was derived from transcranial magnetic stimulation. These studies inferred a reorganization of the cortical motor system. We applied the new technique of high-resolution EEG to measure changes in cortical motor representation directly. We recorded and mapped the motor potential (MP) of the movement-related cortical potentials in 12 SCI patients and 11 control subjects. Results were analyzed using a distance metric to compare MP locations between patients and control subjects. EEG was coregistered with subject-specific MR images and a boundary element model created for dipole source analysis (DSA). When compared with normal control subjects, seven quadriparetics had posteriorly located MPs with finger movements. One paraparetic had a posterior MP with toe movements, but three who could not move the toes had normally located MPs on attempts to move. DSA confirmed the electrical field map distributions of the MPs. We are reporting a reorganization of cortical motor activity to a posterior location after SCI. These results suggest an important role of the somatosensory cortex (S1) in the recovery process after SCI.     

Enzyme histochemical and immunohistochemical localization of carbonic anhydrase as a marker of ductal differentiation in the developing rat parotid gland

Whether the two earliest cortical somatosensory evoked potentials (SEPs) to tibial nerve stimulation (N37 and P40) are generated by the same dipolar source or, instead, originate from different neuronal populations is still a debated problem. We recorded the early scalp SEPs to tibial nerve stimulation in 10 healthy subjects at rest and during voluntary movement of the stimulated foot. We found that the P40, which reached its highest amplitude on the vertex at rest, changed its topography during movement, since its amplitude was reduced much more in the central than in the parietal traces. These findings suggest that two different components contribute to the centro-parietal positivity at rest: (1) the P37 response, which is parietally distributed and is not modified by movement, and (2) the 'real' P40 SEP, which is focused on the vertex and is reduced in amplitude during voluntary movement. Since, also, the N37 response did not vary its amplitude under interference condition, it is possible that the N37 and P37 potentials are generated by the same dipolar source. Other later components, namely P50 and N50 were significantly reduced in amplitude during foot movement. Lastly, the subcortical P30 far-field remained unchanged and this suggests that the phenomenon of amplitude reduction during movement (i.e. gating) occurs above the cervico-medullary junction.     

Retinal arterial occlusions in young adults

Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical-basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement-related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement-related activity in motor association areas.