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Biomedical subjects

P Praamstra

Publications and source records attributed to P Praamstra.

At least 19 recordsLinked to original sources

Brain activity correlates differentially with increasing temporal complexity of rhythms during initialisation, synchronisation, and continuation phases of paced finger tapping.

Activity in parts of the human motor system has been shown to correlate with the complexity of performed motor sequences in terms of the number of limbs moved, number of movements, and number of trajectories. Here, we searched for activity correlating with temporal complexity, in terms of the number of different intervals produced in the sequence, using an overlearned tapping task. Our task was divided into three phases: movement selection and initiation (initiate), synchronisation of finger tapping with an external auditory cue (synchronise), and continued tapping in absence of the auditory pacer (continue). Comparisons between synchronisation and continuation showed a pattern in keeping with prior neuroimaging studies of paced finger tapping. Thus, activation of bilateral SMA and basal ganglia was greater in continuation tapping than in synchronisation tapping. Parametric analysis revealed activity correlating with temporal complexity during initiate in bilateral supplementary and pre-supplementary motor cortex (SMA and preSMA), rostral dorsal premotor cortex (PMC), basal ganglia, and dorsolateral prefrontal cortex (DLPFC), among other areas. During synchronise, correlated activity was observed in bilateral SMA, more caudal dorsal and ventral PMC, right DLPFC and right primary motor cortex. No correlated activity was observed during continue at P<0.01 (corrected, cluster level), though left angular gyrus was active at P<0.05. We suggest that the preSMA and rostral dorsal PMC activities during initiate may be associated with selection of timing parameters, while activation in centromedial prefrontal cortex during both initiate and synchronise may be associated with temporal error monitoring or correction. The absence of activity significantly correlated with temporal complexity during continue suggests that, once an overlearned timed movement sequence has been selected and initiated, there is no further adjustment of the timing control processes related to its continued production in absence of external cues.

Adult↗

Absence of gaze direction effects on EEG measures of sensorimotor function.

OBJECTIVE: Gaze direction is known to modulate the activation patterns of sensorimotor areas as seen at the single cell level and in functional magnetic resonance imaging (fMRI). To determine whether such gaze direction effects can be observed in scalp-recorded electroencephalogram (EEG) measures of sensorimotor function we investigated somatosensory evoked potentials (SEPs) and steady state movement related cortical potentials (MRPs). METHODS: In two separate experiments, SEPs were elicited by electrical stimulation of the median nerve (experiment 1) and steady state MRPs were induced by 2 Hz tapping paced by an auditory cue (experiment 2), while subjects directed their gaze 15 degrees to the left or to the right. RESULTS: Gaze direction failed to produce any appreciable differences in the waveforms of the SEPs or MRPs. In particular, there was no effect on peak amplitude, peak latency and peak scalp topography measures of SEP and MRP components, or on spatial or temporal parameters of dipole models of the underlying cortical generators. Additional frequency domain analyses did not reveal reliable gaze-related changes in induced power at electrode sites overlying somatosensory and motor areas, or in coherence between pairs of parietal, central and frontal electrodes, across a broad range of frequencies. CONCLUSIONS: EEG measures of sensorimotor function, obtained in a non-visual motor task, are insensitive to modulatory effects of gaze direction in sensorimotor areas that are observable with fMRI.

Electric Stimulation↗

Attention and movement-related motor cortex activation: a high-density EEG study of spatial stimulus-response compatibility.

Visual spatial attentional activation of motor areas has been documented in single cell neurophysiology and functional imaging studies of the brain. Here, we investigate a candidate event-related brain potential representing visuospatial attentional activity in motor areas of the cortex. The investigation aimed to elucidate the neural origin and the functional characteristics of this brain potential, which has been labelled N2cc and is typically observed in spatial stimulus-response compatibility tasks. High-density EEG was recorded in 10 subjects while they performed a Simon-type spatial stimulus-response compatibility task and a control task where the same stimuli were assigned to Go-Nogo response alternatives. The N2cc showed a time course parallel to the posteriorly distributed N2pc, associated with visuospatial selection. Scalp distribution and current source density reconstructions allowed a spatial separation of N2pc and centrally distributed N2cc and were compatible with a source for the N2cc in the lateral premotor cortex. Comparisons across tasks demonstrated that the N2cc depends on bilateral response readiness, ruling out an exclusively attentional interpretation. Instead, the activity appears associated with visuospatial attentional processes that serve the selection and suppression of competing responses, in accord with a function of the dorsal premotor cortex in response selection. Together, the results consolidate the N2cc as a new ERP component relevant to the investigation of visuospatial motor processes.

Adult↗

Neurophysiological correlates of error correction in sensorimotor-synchronization.

In a sensorimotor synchronization task requiring subjects to tap in synchrony with an auditory stimulus, occasional perturbations (i.e., interval changes) in an otherwise isochronous sequence of auditory metronome stimuli are known to be compensated remarkably swift and with surprising precision, even when they are too small to be consciously perceived. To investigate the neural substrate and the informational basis of error correction in sensorimotor synchronization, we recorded movement-related, auditory-evoked, and error-related EEG potentials. Experiment 1 confirmed rapid adjustment to stimulus phase shifts, with faster correction of large (50 ms) compared to small (15 ms) shifts. In addition to being corrected faster, there was overcorrection of the 50 ms shifts, attributed to engagement of period correction mechanisms. For +50 ms shifts, a neural correlate of period correction was identified in the form of medial frontal cortex activation, preceded by an error-related brain potential (ERN). Auditory-evoked potential (AEP) amplitudes were sensitive to stimulus phase shifts of both large and small magnitude. Further experiments with a smaller magnitude 10 ms phase shift (Experiment 2) and passive auditory stimulation (Experiment 3) provided evidence that the modulation of AEP amplitudes is not due to metronome interval changes, but may represent auditory-somatosensory activation. Together, behavioral and neurophysiological data support the hypothesis that phase correction is a largely automatic process, not dependent on conscious perception of changes in timing. By contrast, perceivable phase shifts may invoke timekeeper adjustments accompanied by medial frontal cortex activity.

Acoustic Stimulation↗

Proprioceptive sensory function in Parkinson's disease and Huntington's disease: evidence from proprioception-related EEG potentials.

In both Parkinson's disease and Huntington's disease, proprioceptive sensory deficits have been suggested to contribute to the motor manifestations of the disease. Here, proprioceptive sensory function was investigated in Parkinson's disease patients, Huntington's disease patients, and healthy control subjects (each group n=8), using proprioception-related evoked potentials. Proprioception-related potentials were elicited by passive index finger movements and measured with high-density EEG. Conventional median nerve somatosensory evoked potentials (mnSEPs) were recorded in the same session. Analysis included amplitude and latency measures from selected scalp electrodes and dipole source reconstruction. We found a proprioception-related N90 component of normal latency in both Parkinson's disease and Huntington's disease. The source strength of the underlying cortical generator was normal in Parkinson's disease, but marginally reduced in Huntington's disease. Using the source location of the N20-P20 component of the mnSEP as a landmark for postcentral area 3b, the N90 was localized to the precentral motor cortex. At a latency around 170-180 ms proprioception-related potentials were explained by bilateral sensory cortex activation with an altered distribution in Parkinson's disease and a reduction of ipsilateral activation in Huntington's disease. Together, the results show largely normal early proprioception-related potentials, but changes in the cortical processing of kinaesthetic signals at longer latencies in both diseases.

Adult↗

Proprioception-related evoked potentials: origin and sensitivity to movement parameters.

Reafferent electroencephalography (EEG) potentials evoked by active or passive movement are largely dependent on muscle spindle input, which projects to postrolandic sensory areas as well as the precentral motor cortex. The origin of these proprioception-related evoked potentials has previously been studied by using N20-P20 source locations of the median nerve somatosensory evoked potential as an landmark for postcentral area 3b. As this approach has yielded contradictory findings, likely due to spatial undersampling, we applied dipole source analysis on two independently collected sets of high-density EEG data, containing the proprioception-related N90 elicited by passive finger movement, and the N20-P20 elicited by median nerve stimulation. In addition, the influence of movement parameters on the N90 was explored by varying amplitude/duration and direction of passive movements. The results showed that the proprioceptive N90 component was not influenced by movement direction, but had a duration that covaried with the duration of the movement. Sources were localized in the precentral cortex, located on average 10 mm anterior to the N20-P20 sources. The latter result supports earlier claims that the motor cortex is involved in the generation of proprioception-related EEG potentials.

Adult↗

Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations.

A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.

Aged↗

Failed suppression of direct visuomotor activation in Parkinson's disease.

The response times in choice-reaction tasks are faster when the relative spatial positions of stimulus and response match than when they do not match, even when the spatial relation is irrelevant to response choice. This spatial stimulus-response (S--R) compatibility effect (i.e., the Simon effect) is attributed in part to the automatic activation of spatially corresponding responses, which need to be suppressed when the spatial location of stimulus and correct response do not correspond. The present study tested patients with Parkinson's disease and healthy control subjects in a spatial S--R compatibility task in order to investigate whether basal ganglia dysfunction in Parkinson's disease leads to disinhibition of direct visuomotor activation. High-density event-related brain potential recordings were used to chart the cortical activity accompanying attentional orientation and response selection. Response time measures demonstrated a failure to inhibit automatic response activation in Parkinson patients, which was revealed by taking into account a sequence-dependent modulation of the Simon effect. Event-related potential (ERP) recordings demonstrated that visuospatial orientation to target stimuli was accompanied by signal-locked activity above motor areas of the cortex, with similar latencies but an enhanced amplitude in patients compared to control subjects. The results suggest that inhibitory modulation of automatic, stimulus-driven, visuomotor activation occurs after the initial sensory activation of motor cortical areas. The failed inhibition in Parkinson's disease appears therefore related to a disturbance in processes that prevent early attention-related visuomotor activation, within motor areas, from actually evoking a response.

Aged↗

Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype.

We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurological abnormalities are only present in 2. This family shows that intermediate repeat lengths can be pathogenic and may predispose for restless legs and peripheral nerve disorder.

Aged↗

Impaired motor cortical inhibition in Parkinson's disease: motor unit responses to transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS)-induced corticospinal volleys can be investigated in detail by analysing the firing pattern modulation of active motor units (MUs) at close to threshold stimulation strengths. In amyotropic lateral sclerosis (ALS) these volleys are dispersed and prolonged, attributed to altered motor cortical excitability. Impaired intracortical inhibition, as found in ALS, is not unique to this disease, but is also a well-established finding in Parkinson's disease (PD). The present study explored whether reduced inhibition in the motor cortex in PD is accompanied by similar changes in motor unit firing modulation by TMS as are found in ALS. TMS was applied to the contralateral motor cortex during a low-force voluntary elbow flexion while 126-channel surface electromyography (SEMG) was recorded from the brachial biceps muscle. A recently developed method for SEMG decomposition was used to extract the firing pattern of up to five simultaneously active MUs. Sixteen MUs in 7 PD patients and 17 MUs in 5 healthy control subjects were analysed and peristimulus time histograms (PSTHs) and interspike interval change functions (IICFs) were calculated. The IICF provides an estimate of the modulation of the postsynaptic membrane potential at the spinal motoneuron, evoked by the stimulus. In PD the duration of the PSTH peak was significantly increased and the synchrony was decreased. The excitatory phase at 20-50 ms of the IICF was broader in PD, reflecting a longer duration of the TMS-evoked excitatory postsynaptic potential. It is proposed that these results are due to prolonged corticospinal volleys resulting from impaired intracortical inhibition.

Action Potentials↗

The five percent electrode system for high-resolution EEG and ERP measurements.

OBJECTIVE: A system for electrode placement is described. It is designed for studies on topography and source analysis of spontaneous and evoked EEG activity. METHOD: The proposed system is based on the extended International 10-20 system which contains 74 electrodes, and extends this system up to 345 electrode locations. RESULTS: The positioning and nomenclature of the electrode system is described, and a subset of locations is proposed as especially useful for modern EEG/ERP systems, often having 128 channels available. CONCLUSION: Similar to the extension of the 10-20 system to the 10-10 system ("10% system"), proposed in 1985, the goal of this new extension to a 10-5 system is to further promote standardization in high-resolution EEG studies.

Brain Mapping↗

Overlap of attention and movement-related activity in lateralized event-related brain potentials.

OBJECTIVE: In tasks that involve lateralized visuospatial attention and a lateralized motor response, the associated brain electrical potentials, i.e. the attention-related N2pc and the lateralized readiness potential, typically overlap at central scalp sites. The manifestation of the N2pc at central electrode sites is commonly attributed to electric volume conduction effects, assuming the N2pc to be generated in occipito-temporal brain areas. We evaluated this explanation in a simulation study. METHODS: Using a forward modeling approach with a realistically shaped volume conduction model, we calculated the range of amplitude ratios between occipital and central electrode sites when a single source is assumed in area V4 or in area TO, at the temporo-occipital convexity. RESULTS: A comparison of the simulated amplitude ratios with reported data indicates that volume conduction effects from the investigated source origins in the occipito-temporal region are insufficient to explain the experimental data. CONCLUSIONS: We conclude that the anterior spread of the N2pc from its occipito-temporal maximum to central electrode sites is probably due to simultaneous attention-related activity in posterior and central brain areas.

Attention↗

Magnetic stimulation-induced modulations of motor unit firings extracted from multi-channel surface EMG.

The noninvasive assessment of motor unit (MU) firing patterns on the basis of topographical information from 128-channel high-density surface electromyography (SEMG) is reported. First, multi-channel MU action potential (MUAP) templates are obtained by clustering detected firing events according to the surface topography of the MUAP. Second, a template-matching algorithm is used to find all firings of a MU, including the superimpositions of MUAPs. From a single recording, the firing pattern of up to five MUs could be derived. The modulation of MU firing by transcranial magnetic stimulation was analyzed in peri-stimulus time histograms. The results are similar to previous results of transcranial magnetic stimulation (TMS) obtained by needle electromyographic (EMG) recordings. The method can be used to investigate MU firing patterns in patients with central motor disorders. An additional advantage of the technique, apart from its noninvasiveness, is the structural and functional information that it provides on the MUs, which is not obtained by needle EMG.

Action Potentials↗

Redundant-signals effects on reaction time, response force, and movement-related potentials in Parkinson's disease.

Studies using transcranial magnetic stimulation have established that patients with Parkinson's disease have increased motor cortex excitability. Relying on current evidence that the redundant-signals effect has its source in the motor system, we investigated whether, as a result of cortical hyperexcitability, Parkinson's disease patients demonstrate an enhancement of this effect. Eight patients with moderately severe Parkinson's disease and nine healthy control subjects participated in a task requiring simple manual responses to visual, auditory, and combined auditory-visual signals. During the task, motor cortex activation was recorded by means of movement-related EEG potentials, while responses were measured via isometric force recordings. The movement-related potentials and the force measures both yielded support for the view that the redundant-signals effect is partially caused in the motor system. However, the facilitatory effect of bimodal as compared to unimodal stimulation (i.e. the redundant-signals effect) was of the same size in Parkinson's disease patients and control subjects, as expressed in latency measures of the movement-related potentials and the force signals. We conclude that the redundant-signals effect is not enhanced in Parkinson's disease and that the mechanisms underlying this effect are probably not influenced by the increased motor cortex excitability found in this disease.

Acoustic Stimulation↗

Magnetic stimulation of the dorsal premotor cortex modulates the Simon effect.

In choice reaction tasks, subjects typically respond faster when the relative spatial positions of stimulus and response match than when they do not match. A prominent explanation attributes this 'Simon effect' to automatic response activation elicited by spatial correspondence, which facilitates or competes with the controlled selection of the response demanded by the stimulus. To test this account, we applied repetitive transcranial magnetic stimulation (rTMS) on the dorsal premotor cortex (PMd), as this area may subserve the inhibitory control of automatic response activation. Temporary interference with PMd was predicted to release the automatic activation from inhibition and thereby enhance the Simon effect. The results confirmed a modulation for trials following an incompatible trial, providing new evidence for competition between automatic and controlled response activation as a mechanism underlying the Simon effect.

Adult↗

Magneto-encephalographic correlates of the lateralized readiness potential.

To determine the onset of movement-related EEG activity accompanying stimulus-induced movements, it is commonly isolated from overlapping stimulus-related activity by a subtraction procedure, yielding the lateralized readiness potential (LRP). In order to elucidate the generation of the LRP and to explore whether magnetoencephalographic (MEG) measures have advantages over the LRP as a measure of response selection, MEG activity was recorded in four healthy adults during self-paced and stimulus-induced hand movements. Self-paced movements were preceded by readiness fields in all subjects, explained by sources in contralateral and (for 2/8 response sides) also ipsilateral hemispheres. Movement-related activity preceding stimulus-induced movements could only be modeled adequately when stimulus-related activity was removed by subtracting MEG signals for left and right hand movements. Thus identified source locations showed no systematic deviation from the sources for readiness fields, supporting a generation of the movement-related activity in primary motor cortex. The corresponding source waveforms allowed latency determinations of motor cortex activity as markers for response-choice timing. MEG thus provides information on the time course of hand-specific motor cortex activation for each hemisphere separately, where the electro-encephalographic LRP provides a composite measure for both hemispheres.

Adult↗

Motor cortex activation in Parkinson's disease: dissociation of electrocortical and peripheral measures of response generation.

This study investigated characteristics of motor cortex activation and response generation in Parkinson's disease with measures of electrocortical activity (lateralized readiness potential [LRP]), electromyographic activity (EMG), and isometric force in a noise-compatibility task. When presented with stimuli consisting of incompatible target and distractor elements asking for responses of opposite hands, patients were less able than control subjects to suppress activation of the motor cortex controlling the wrong response hand. This was manifested in the pattern of reaction times and in an incorrect lateralization of the LRP. Onset latency and rise time of the LRP did not differ between patients and control subjects, but EMG and response force developed more slowly in patients. Moreover, in patients but not in control subjects, the rate of development of EMG and response force decreased as reaction time increased. We hypothesize that this dissociation between electrocortical activity and peripheral measures in Parkinson's disease is the result of changes in motor cortex function that alter the relation between signal-related and movement-related neural activity in the motor cortex. In the LRP, this altered balance may obscure an abnormal development of movement-related neural activity.

Aged↗

Genetic and environmental risk factors in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial disorder, caused by a combination of age, genetics and environmental factors. Nigral cells are susceptible to multiple causes of derangement of normal cell function, all of which may contribute to the same Parkinson phenotype. Autosomal dominant alpha-synuclein-gene PD represents one of the pure genetic forms, whereas cases of sporadic PD probably depend more on age and environmental factors, MPTP-Parkinsonism being the purest example of an environmentally caused Parkinson phenotype. This review suggests that pesticides-herbicides, smoking and head trauma probably represent the most eligible candidates for environmental factors involved in provoking PD or influencing its natural course.

Aging↗