Changes in movement-related cortical potentials in Parkinson's patients before and after treatment with levodopa

Cortical potentials associated with voluntary, self-paced wrist flexion (MRPs) were recorded from 3 scalp locations (Cz and psi contralateral hand motor area) in patients with Parkinson's disease (9 de novo patients and 30 L-Dopa treated patients). The analysis concerned 3 components of the MRPs: the 2 slow negative shifts (NS1 and N1) before the movement onset and the motor potential (MP). The NSI amplitude was measured at Cz, the peak negativity N1 and MP from contralateral hand motor area location. The potential distribution was also studied. The amplitude of the MRPs components was the same as in the normals. But in de novo patients, the potential distribution of the NS1 component was different; a Cz preponderance of the NS1 amplitude was not found. In patients treated with L-Dopa, there is a negative correlation between the changes in amplitude and the changes in clinical rating for NS1, N1 and MP components. The decrease in the MRPs components was significant from stage III and IV of the Hoehn and Yahr scales. After L-Dopa therapy, the NS1 component from de novo patients was increased in amplitude. The amplitude of the MRPs components from patients with L-Dopa induced clinical fluctuations was reduced during "off" period in comparison to "on" period. The findings suggest that the NS1 potential and the N1 and MP components share 2 distinct systems for the control of voluntary movement. Their mechanism in Parkinson's disease is discussed.     

Movement-Related Potentials Associated with Motor Timing Errors as Determined by Internally Cued Movement Onset

ObjectiveAccurate motor timing is critical for efficient motor control of behaviors; however, the effect of motor timing abilities on movement-related neural activities has rarely been investigated. The current study aimed to examine the electrophysiological correlates of motor timing errors. MethodsTwenty-two healthy volunteers performed motor timing tasks while their electroencephalographic and electromyographic (EMG) activities were simultaneously recorded. The average of intervals between consecutive EMG onsets was calculated separately for each subject. Motor timing error was calculated as an absolute discrepancy value between the subjects’ produced and given time interval. A movement-related potential (MRP) analysis was conducted using readings from Cz electrode. ResultsMotor timing errors and MRPs were significantly correlated. Our principal finding was that only Bereitschaftpotential (BP) and motor potential (MP), not movement monitoring potential, were significantly attenuated in individuals with motor timing errors. Motor timing error had a significant effect on the amplitude of the late BP and MP. ConclusionThe findings provide electrophysiological evidence that motor timing errors correlate with the neural processes involved in the generation of self-initiated voluntary movement. Alterations in MRPs reflect central motor control processes and may be indicative of motor timing deficits.     

Impaired movement-related potentials in acute frontal traumatic brain injury.

OBJECTIVE: Focal brain lesions due to traumatic brain injury (TBI) do not only lead to functional deficits in the lesion area, but also disturb the structurally intact neuronal network connected to the lesion site. Therefore we hypothesized dysfunctions of the cortical motor network after frontal TBI. The movement related potential (MRP) is an EEG component related to voluntary movement consisting of the Bereitschaftspotential (BP), the negative slope (NS), and the motor potential (MP). The aim of our study was to demonstrate alterations in the movement related cortical network in the acute stage after TBI by comparing our patients' MRPs to those of a healthy control group. METHODS: EEGs of 22 patients with magnetic resonance imaging defined contusions of the prefrontal cortex were recorded within 8 weeks after TBI. We further recruited a healthy control group. The paradigm consisted of self-paced abductions of the right index finger. RESULTS: Compared to healthy controls, the BP in the patient group was significantly reduced and its onset delayed. Moreover, an enhanced contribution of the postrolandic hemisphere ipsilateral to the movement and a reduced contribution of the left frontal cortex, ipsilateral to the lesion in the majority of the patients, were observed during motor execution (MP). CONCLUSIONS: Anatomical connections between the prefrontal cortex and the supplementary motor area (SMA) are known to exist. We suggest that prefrontal lesions lead to reduced neuronal input into the SMA. This deficit in the preparatory motor network may cause the reduced BPs in our patients. Moreover, an increased need for attentional resources might explain the enhanced motor potentials during movement execution. In conclusion, we demonstrated altered MRPs in the acute stage after frontal TBI, which are a consequence of disturbed neuronal networks involved in the preparation and execution of voluntary movements.     

Regulation of motor output between young and elderly subjects.

OBJECTIVES: Considerable information exists concerning the differences in motoneuron pool (MP) excitability between young and elderly subjects. A recent study demonstrated decreased heteronymous Ia facilitation with aging, suggesting increased presynaptic inhibition (PI) with increasing age as a mechanism for this change (Morita et al., Exp Brain Res 104 (1995) 167). It has been suggested that during voluntary movement, supraspinal, and possibly, segmental mechanisms (Hultborn et al., J Physiol 389 (1987) 757) modulate this inhibition. It is theorized that PI can modulate the recruitment gain of the MP during movement without altering the excitability of the motoneurons. Therefore, the purpose of this study was to examine the roles of PI and volitional volleys in modulating MP output in young and elderly subjects. METHODS: Twenty apparently healthy females participated in this study, 10 college aged (mean age, 22.4+/-2.8 years) and 10 independent, community dwelling elderly (mean age, 77.6+/-5.4 years). All subjects were tested in a semi-recumbent position. H-reflexes were elicited at rest, and at 10 and 20% of maximal voluntary contraction. To assess MP output, background electromyography (EMG) was monitored prior to stimulation. The stimulus intensity was adjusted during volitional contractions to ensure similar control reflexes (25% of the maximal motor response (M-max)) at each level of contraction. RESULTS: Control reflexes at each level of volitional contraction (rest, 10 and 20%) were similar for both groups. To assess PI and to estimate the extent to which a change in the H-reflex amplitude reflects a change in MP gating, the common peroneal nerve was stimulated at 1.5 times the motor threshold 100 ms prior to stimulation of the tibial nerve. Significantly greater PI was observed for the young subjects at rest (5 vs. 13% M-max). At both 10 and 20% levels of voluntary contraction, the conditioned reflex was significantly different from rest for the young subjects. The elderly subjects, in contrast, failed to modulate the conditioned reflex until the 20% of maximal voluntary contraction (MVC) condition. When examining the recruitment gain in the MP during the PI condition (H-reflex amplitude as a function of EMG levels), a significant group effect was observed, with the young subjects demonstrating significantly higher PI gain. CONCLUSIONS: These results indicate differential control of MP output (e.g. PI vs. volitional volleys) in young and elderly subjects.     

Frontal lobe contribution to voluntary movements in humans

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

Abnormal premovement brain potentials in schizophrenia.

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

Cortical potential shifts preceding voluntary movement are normal in parkinsonism

We have recorded movement-related cortical potentials (MRCPs) preceding voluntary finger extension from 10 subjects with Parkinson's disease and compared the results with those obtained from groups of young and old subjects described in the previous paper in this volume (Barrett et al. 1986). Three separate potential shifts preceding voluntary movement were identified in the wave forms of all subjects. There were no differences between the healthy aged subjects and those with Parkinson's disease in terms of the onset latencies or gradients of these potential shifts. The potential shift associated with the final phase of preparation (NS') was significantly less widespread over central scalp for the older subjects compared with the young. Equivalent results for a 35-year-old subject with Parkinson's disease were indistinguishable from those obtained from the young subjects suggesting that this restriction in the distribution of NS' is related to normal ageing rather than the disease process of parkinsonism. There were no differences within the group of parkinsonian subjects with respect to potential shifts associated with differing degrees of movement disability between the two hands. Our results contradict previous reports of abnormal MRCPs in Parkinson's disease (Deecke et al. 1977; Deecke and Kornhuber 1978; Shibasaki et al. 1978). We attribute this primarily to an improved method of recording MRCP which compensates for time jitter between EMG onset and the production of a trigger pulse for averaging (Barrett et al. 1985).     

Mental movement simulation affects the N30 frontal component of the somatosensory evoked potential.

It is known that somatosensory evoked potentials can be influenced by several centripetal and centrifugal factors which modify their amplitude. The present study shows for the first time that the frontal waves N30 and to a lesser extent N23 are specifically attenuated during mental movement simulation (MMS) activity. This gating phenomenon, tested on 16 normal subjects, occurred when repeated fast finger movements on the stimulated side are mentally simulated. In contrast, no significant modification appeared when the subject performed the MMS activity with the hand contralateral to that receiving electrical stimuli or when the subject performed a mental operation unrelated to the MMS. The MMS was shown by Roland et al. (1980) to increase the regional blood flow exclusively in the supplementary motor area (SMA). Our experimental data therefore indicate that the SMA could play an important role in the generation of the frontal N30.     

Deafferentation of neighbouring motor cortex areas does not further enhance saturated practice-dependent plasticity in healthy adults

OBJECTIVE: To assess effects of deafferentation of the arm representation of primary motor cortex (M1) on practice-dependent plasticity in healthy adults. METHODS: Twelve healthy, right-handed adults (18-48 years, median 20.2 years) performed two consecutive experiments (exp. 1 and exp. 2). Exp. 1 consisted of a motor practice (MP) of repeated ballistic flexion movements of the left thumb. This was followed by exp. 2 consisting of selective anaesthesia of the upper brachial plexus (SPA) to disinhibit the training M1 and a second period of the same MP. Peak acceleration of the trained thumb movement and the motor evoked potential (MEP) amplitude in the flexor pollicis brevis muscle elicited by single-pulse transcranial magnetic stimulation of the training M1 were studied before and after exp. 1 and after exp. 2. RESULTS: After exp. 1 all subjects demonstrated an increase of peak acceleration (baseline: 19.23+/-3.81ms(-2); after exp. 1: 43.28+/-17.63ms(-2), p=0.008) and MEP amplitude (from 0.46+/-0.23mV to 1.26+/-0.77mV, p=0.03). There was no additional increase of these measures after exp. 2 (44.37+/-19.56ms(-2), p=0.78, 1.69+/-1.21mV (p=0.07)). CONCLUSIONS: Training of ballistic thumb movements leads to behavioural improvement as well as to an increased excitability of the corresponding M1 representation. These effects do not increase further during deafferentation of the training M1. In contrast to stroke patients [Muellbacher W, Richards C, Ziemann U, Wittenberg G, Weltz D, Boroojerdi B, et al. Improving hand function in chronic stroke. Arch Neurol 2002;59:1278-82], practice-dependent plasticity in healthy subjects cannot be enhanced by deafferentation of neighbouring motor cortex areas. SIGNIFICANCE: Healthy subjects, in contrast to patients with central motor lesions, are capable of saturating practice-dependent plasticity to a level that cannot be further enhanced by experimental manipulation.     

Abnormal movement related potentials in patients with lesions of basal ganglia and anterior thalamus.

Movement-related cortical potentials (MRCPs) were recorded from scalp electrodes during wrist flexion in 15 dystonic patients with bilateral (nine) or unilateral (six) circumscribed lesions in the striatum (eight), pallidum (six), or anterior thalamus (one). The results were compared with those of 10 age-matched healthy volunteers. The early (BP) and late (NS') MRCP components were assessed in terms of their gradients and distribution on the scalp in Cz, C3', and C4'. The gradients of both BP and NS' components were significantly flatter in the patients with bilateral lesions than in the control subjects. Also, the BP gradient was maximum at Cz, and the NS' component was contralaterally predominant in the control subjects but not in the patients. In patients with unilateral lesions, the gradients were flatter (p < 0.05) during movement of the dystonic wrist than during movement of the normal wrist. This difference was significant for BP and NS', regardless of the location of the electrodes. Also, the normal topographic predominance of BP at Cz and of contralateral NS' disappeared. The BP and NS' components of the MRCPs are thought to reflect preparatory activity in the supplementary motor area and the primary motor cortex before movement. Reduced BP and NS' gradients in patients with both bilateral and unilateral lesions of the basal ganglia, which project towards the supplementary motor area, are consistent with this hypothesis. The bilateral nature of these reductions suggests that both the ipsilateral and the contralateral motor cortex are involved in the genesis of the MRCPs and that the dystonia in these patients is associated with impaired motor preparation.     

Cortical potentials preceding voluntary movement: evidence for three periods of preparation in man

We have recorded movement-related cortical potentials (MRCPs) to voluntary middle finger extension from 10 young and 10 old subjects free of neurological disease using the method of detecting EMG onset associated with each movement described by Barrett et al. (1985). The slow potential shifts preceding movement were measured by fitting a linear regression line to the wave forms to obtain a measure of their slope. Three separate potential shifts were identified. The first had a scalp distribution and onset latency similar to the Bereitschaftspotential (BP) first reported by Kornhuber and Deecke (1964, 1965). The potential shift immediately preceding movement corresponded with the NS' of Shibasaki et al. (1980). We identified, for the first time, a third shift intervening between BP and NS' and named it the intermediate shift (IS). The onset of BP occurred about 1.6 sec before EMG onset and was followed by IS which began about 875 msec before movement. The onset of NS' occurred 300 msec before EMG onset and terminated about 90 msec before this event. The slope of BP preceding right finger movement was steeper than that preceding left hand movement in all our right-handed subjects. The distribution of BP was symmetric about the midline. The IS potential shift had a slope which was steeper on the average preceding left finger movement than right. The distribution of IS was symmetric about the midline preceding left finger movement but had a contralateral tendency preceding right hand movement. NS' had a maximum slope at contralateral electrodes over the hand motor area and parietal areas. It was suggested that the BP potential shift originates in the supplementary motor area on the medial surface of the cerebral cortex. The differing distribution of the IS shift for the two hands suggests that this potential may be generated bilaterally preceding left finger movement but from the contralateral hemisphere only preceding movement of the right finger. The most likely origin of this potential was thought to be superior premotor cortex. NS' was considered to originate in primary motor cortex with possible contributions from other cortical areas associated with movement.     

Prior intention can locally tune inhibitory processes in the primary motor cortex: direct evidence from combined TMS-EEG

Human subjects are able to prepare cognitively to resist an involuntary movement evoked by a suprathreshold transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) by anticipatory selective modulation of corticospinal excitability. Uncovering how the sensorimotor cortical network is involved in this process could reveal directly how a prior intention can tune the intrinsic dynamics of M1 before any peripheral intervention. Here, we used combined TMS-EEG to study the cortical integrative processes that are engaged both in the preparation to react to TMS (Resist vs. Assist) and in the subsequent response to it. During the preparatory period, the contingent negative variation (CNV) amplitude was found to be smaller over central electrodes (FC1, C1, Cz) when preparing to resist compared with preparing to assist the evoked movement whereas α-oscillation power was similar in the two conditions. Following TMS, the amplitude of the TMS evoked-N100 component was higher in the Resist than in the Assist condition for some central electrodes (FCz, C1, Cz, CP1, CP3). Moreover, for six out of eight subjects, a single-trial-based analysis revealed a negative correlation between CNV amplitude and N100 amplitude. In conclusion, prior intention can tune the excitability of M1. When subjects prepare to resist a TMS-evoked movement, the anticipatory processes cause a decreased cortical excitability by locally increasing the inhibitory processes.     

Comparative study of cerebral cortical potentials associated with voluntary movements in monkey and man

Eight monkeys (Macaca mulatta) were taught to squeeze and release a handgrip. The movement simulated the brisk squeeze of a hand dynamometer performed by 7 human subjects. Monkey. During the performance of the voluntary movements, slow cortical potentials (motor potentials or MPs) were studied with monopolar, surface bipolar, transcortical and intracortical recordings. A survey of the dorsal expanse of cerebral cortex showed that the contralateral motor hand area, somatosensory hand area and area 6 adjacent to the supplementary motor area became active with movement. MPs also were seen in the motor and somatosensory cortex medial to the hand area, but we concluded that those potentials were probably related to adventitious movements in the arm and leg. That area 6 became active with movement was further verified with extracellular unit recording; the behavior of area 6 units was compared with that recorded from units in the motor hand area. Using simultaneous transcortical recordings a sequence of cortical activation was observed in those areas generating an MP. The motor hand area became active first, followed in turn by area 6 and the somatosensory hand area. The monosynaptic cortico-cortical connections of the motor hand area were studied with autoradiographic and horseradish peroxidase techniques and compared to the distribution of the MP. The hand area demonstrated reciprocal connectivity with portions of the somatosensory hand area, the supplementary motor area in area 6 and the cortex adjacent to the intraparietal sulcus. The distribution of the MPs correlated with the connectivity to the supplementary motor and somatosensory areas. Our physiologic studies did not adequately investigate the area adjacent to the intraparietal sulcus. Man. Motor potentials were studied using surface bipolar recordings with closely spaced electrodes (inter-electrode distances 1 cm or 2 cm). Recordings were made directly from the cortex in one subject studied under local anesthesia during an operation for epilepsy, and epidurally in 6 subjects in whom epidural electrode arrays had been inserted for the purpose of localizing an epileptogenic focus. Similar to the findings in the animals, MPs were recorded from the contralateral motor and somatosensory hand area with activity in motor cortex appearing first; area 6 just anterior to the motor hand area probably also generated a response. In addition, a locally generated potential not seen in monkey was recorded anterior to area 6. This difference in response distribution is viewed as possibly relating to the different significance which the seemingly comparable hand movements have for the animal and human subjects. No response was seen in motor and somatosensory hand area with ipsilateral movements. We have no information for the anteriorly recorded response with ipsilateral movement.     

Rapid rate transcranial magnetic stimulation – a safety study

We assessed the safety of repeated short trains (4 stimuli) of rapid-rate transcranial magnetic stimulation (rrTMS) over the left motor cortex in 6 healthy normal subjects. rrTMS involved two separate blocks of 50 consecutive trains of 4 stimuli at a frequency of 20 Hz and an intensity of 5–10% above active motor threshold. We monitored EEG, and assessed aspects of neurological (balance, gait, two-point discrimination, blood pressure, pulse rate), cognitive (attention, memory, executive function) and motor function (speed of movement initiation and execution and manual dexterity) before and after the two blocks of rrTMS. EMG was also recorded from a number of hand, forearm and arm muscles contralateral to the site of stimulation. Two blocks of repeated rrTMS at 20 Hz and 5–10% above active motor threshold did not produce any adverse effects. Measures of neurological, cognitive and motor function showed no change following rrTMS. From the EMG recording there was evidence of increase in the amplitude of the motor evoked potentials (MEPs) recorded from the biceps in one subject during the first block of rrTMS, but this did not occur in the second block. A similar magnification of MEPs was also observed in another subject only during the second block of stimulation. When applied using parameters falling within published guidelines (Pascual-Leone et al., 1993; Pascual-Leone et al., 1994), repeated rrTMS is a relatively safe technique in healthy normal subjects. As rrTMS allows disruption of cortical function for a longer period, it has the potential of becoming a particularly useful tool for the study of cognitive function as well as sensory or motor function.     

Movement-related potentials accompanying unilateral and bilateral finger movements with different inertial loads.

The present study was aimed at investigating the effect of inertial loading on movement-related potentials (MRPs) recorded from the scalps of normal subjects while performing finger movements. Two experiments were performed. Experiment 1. MRPs preceding and accompanying the execution of voluntary, unilateral finger movements were investigated in 8 subjects under the 3 experimental conditions of: no inertial load, small inertial load (250 g), and large inertial load (400 g). A significant effect of the inertial load on Bereitschaftspotential (BP) amplitude was observed for the 100 msec period preceding movement onset (BP -100 to 0) at precentral electrode sites and following movement onset (N0 to 100) at both precentral and parietal electrode sites. Pairwise comparisons revealed that significant effects were due to differences between the loading and non-loading conditions and not for different amounts of loading. No significant differences were observed for BP onset or early BP amplitudes, indicating that scalp negativity immediately prior to, and during, movement onset is primarily influenced by conditions of inertial loading. Experiment 2. This experiment examined the effect of inertial loading on MRPs for bilateral, simultaneous voluntary finger movements in 10 subjects under conditions of: no inertial load, inertial load applied separately to the left and right fingers, and with identical inertial loads applied to both fingers. No significant effect of inertial load on MRP amplitude was observed. These results are contrasted with those of experiment 1 which show significant effects of inertial loading for unilateral movements and are interpreted in terms of the hypothesis that bilateral movement organization involves 'higher' aspects of motor control than those reflecting adjustment to conditions of inertial loading.     

Movement-related potentials in high-functioning autism and Asperger's disorder

Autism and Asperger's disorder (AD) are neurodevelopmental conditions that affect cognitive and social-communicative function. Using a movement-related potential (MRP) paradigm, we investigated the clinical and neurobiological issue of 'disorder separateness' versus 'disorder variance' in autism and AD. This paradigm has been used to assess basal ganglia/supplementary motor functioning in Parkinson's disease. Three groups (high functioning autism [HFA]: 16 males, 1 female; mean age 12y 5mo [SD 4y 4mo]; AD: 11 males, 2 females; mean age 13y 5mo [SD 3y 8mo]; comparison group: 13 males, 8 females; mean age 13y 10mo [SD 3y 11mo]) completed a cued motor task during electroencephalogram recording of MRPs. The HFA group showed reduced peak amplitude at Cz, indicating less activity over the supplementary motor area during movement preparation. Although an overall significant between-group effect was found for early slope and peak amplitude, sub-analysis revealed that the group with AD did not differ significantly from either group. However, it is suggested that autism and AD may be dissociated on the basis of brain-behaviour correlations of IQ with specific neurobiological measures. The overlap between MRP traces for autism and Parkinson's disease suggests that the neurobiological wiring of motor functioning in autism may bypass the supplementary motor area/primary motor cortex pathway.     

The effect of sex differences on event-related potentials in young adults.

Female/male cognitive differences have been studied for some time; however, such differences in Turkish population is unknown. Evoked potentials (EPs) of the brain have been applied as an index of information processing in a wide variety of normal and cognitive impaired subjects. Scalp event-related potentials (ERP) evoked by auditory stimuli were recorded in 20 male and 18 female neurologically and audiologically normal young Turkish subjects of 18-25 years (Av. 20.6) of age. Standard auditory "Oddball" paradigm involving simple discrimination task of concentrating on infrequent (target) stimulus and ignoring frequent (non-target) stimulus was employed. EEG activity was recorded at the Fz, Cz, Pz and Oz electrode sites of the 10-20 system using Ag/AgCl electrodes. Wave forms were collected and averaged off-line by a Pentium 100 computer, which also controlled the stimulus presentation. In general, significant main effects of gender and electrode site on evoked potential components were found. The interpeak amplitudes N1-P2 and N2-P3 were higher in the male subjects than in the female subjects at Cz. N2-P3 were higher in the male subjects than in the female subjects at Oz. The latencies of N1, P2, N2, P3 components were not different between both sex. For both sexes we found that N1-P2 amplitude was higher at Fz and Cz than Pz and Oz. N2-P3 amplitude was higher at Fz than Oz for only female subject. In male subjects, latency of N2 was longer at Fz than Oz. There were no significant differences in the latencies of N1, P2, and P3 components between electrode sites in both sexes. We suggest that ERP components could be affected by sex, electrode site, and cognitive performance.     

Movement-related cortical potentials associated with progressive muscle fatigue in a grasping task.

OBJECTIVE: The present research was aimed to further address the general empirical question regarding the behavioral and neurophysiological indices and mechanisms that contribute to and/or compensate for muscle fatigue. In particular, we examined isometric force production, EMG, and EEG correlates of progressive muscle fatigue while subjects performed a grasping task. METHODS: Six neurologically healthy subjects were instructed to produce and maintain 70% of maximum voluntary contraction (MVC) for a total of 5 s in a sequence of 120 trials using a specially designed grip dynamometer. Three components of movement-related potentials (Bereitschaftspotential, BP, Motor potential, MP, and Movement-monitoring potential, MMP) were extracted from continuous EEG records and analyzed with reference to behavioral indicators of muscle fatigue. RESULTS: Experimental manipulations induced muscle fatigue that was demonstrated by decreases in both MVC values and mean force levels produced concomitant to increases in EMG root mean square (RMS) amplitude with respect to baseline levels, and EMG slope. EEG data revealed a significant increase in MP amplitude at precentral (Cz and FCz) and contralateral (C3) electrode sites, and increases in BP amplitude at precentral (Cz and FCz) electrode sites. CONCLUSIONS: The increases in EMG amplitude, EMG slope, and MP amplitudes suggest a possible link between the control signal originating in the motor cortex and activity level of the alpha-motoneuron pool as a function of progressive muscle fatigue. Overall, the data demonstrate that progressive muscle fatigue induced a systematic increase in the electrocortical activation over the supplementary motor and contralateral sensorimotor areas as reflected in the amplitude of movement-related EEG potentials.     

Motor cortex inhibition is not impaired in patients with Alzheimer's disease: evidence from paired transcranial magnetic stimulation

Motor cortex excitability was studied by transcranial magnetic stimulation (TMS) in 17 patients with Alzheimer’s disease (AD). Resting and active thresholds for TMS were significantly reduced in AD patients compared to young and aged healthy subjects. The maximum amplitude of the motor response evoked by TMS was also significantly increased in AD patients. We have tested if these changes are related to a modification of the short-lasting intracortical inhibition of the motor cortex by paired conditioning-test TMS. We found no significant differences between AD patients and aged healthy subjects even if there is a slight but significant difference between aged and young normal subjects. We conclude that the modification of excitability of the motor cortex does not result from an impaired intracortical inhibition.     

Delayed onset of late movement-related cortical potentials and abnormal response to lorazepam in catatonia

Catatonia is a psychomotor syndrome with an inability to execute and terminate movements completely, leading consecutively to akinesia and posturing, which both respond almost immediately to benzodiazepines, i.e. gaba-potentiators like lorazepam. However, pathophysiological mechanisms of cortical motor and gaba-ergic dysfunction remain unclear. We therefore investigated movement-related cortical potentials (MRPs) and movement kinematics during a motor task before and after lorazepam.Ten akinetic catatonic patients were compared with 10 psychiatric (similar age, sex, medication, and underlying psychiatric disease but without catatonic syndrome) and 20 healthy controls. MRPs from frontal (F), central (C), and parietal (P) sites were recorded to obtain measures of early and late readiness potential and movement potential. Kinematic measures included parameters for amplitude of movements, peak velocity, average duration of movements, elevation angle, and angle velocity. The motor task consisted in self-initiated extension of the right index finger. All catatonic and psychiatric control patients received intravenous lorazepam (1mg), whereas healthy controls were subjected to a placebo-controlled (10 received lorazepam, 10 received placebo) double-blind study design.Catatonics showed a significantly delayed onset of late readiness and movement potential in central electrodes (Cz, C3) compared with psychiatric and healthy controls. This delayed onset correlated significantly with catatonic motor symptoms and movement duration. Lorazepam led to significantly stronger delays in onset of late readiness potential in left fronto-parietal (F3, C3, P3) electrodes in catatonic patients than in psychiatric and healthy controls.It is concluded that delayed latencies in late MRP components in catatonic patients may reflect their inability to execute and terminate movements completely. Differential and stronger response to lorazepam in catatonia suggests dysfunction in inhibitory control of cortical motor function with increased gaba-ergic sensitivity.