Biomedical subjects

Alfons Schnitzler

Publications and source records attributed to Alfons Schnitzler.

At least 19 recordsLinked to original sources

PubMed2006

Pallidal deep-brain stimulation in primary generalized or segmental dystonia.

BACKGROUND: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial. METHODS: Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment. RESULTS: Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria. CONCLUSIONS: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].).

Adult↗

PubMed2006

Pain processing is faster than tactile processing in the human brain.

Pain signals threat and drives the individual into a behavioral response that significantly depends on a short stimulus-response latency. Paradoxically, the peripheral and spinal conduction velocities of pain are much slower than of tactile information. However, cerebral processing times and reaction times of touch and pain have not yet been fully assessed. Here we show that reaction times to selective nociceptive cutaneous laser stimuli are substantially faster than expected from the peripheral conduction velocities. Furthermore, by using magnetoencephalography, we found that latencies between earliest stimulus-evoked cortical responses and reaction times are approximately 60 ms shorter for nociceptive than for tactile stimuli. These findings reveal that cerebral processing of pain is substantially faster than processing of tactile information and relatively compensates for the slow peripheral and spinal conduction velocities of pain. Our observation shows how the cerebral organization of pain processing enhances motor responses to potentially harmful stimuli and thereby subserves the particular behavioral demands of pain.

Adult↗

PubMed2006

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

Activities of Daily Living↗

PubMed2006

Asymmetry of interhemispheric interaction in left-handed subjects.

In right-handed subjects the execution of a simple finger-tapping task is associated with an asymmetry of interhemispheric interaction, probably suggesting that the dominant left hemisphere inhibits the right one. The present study investigated the left-handed subjects in order to elucidate whether this asymmetry is related to handedness. Nineteen healthy subjects performed unimanual left, right, and bimanual auditorily paced finger-tapping tasks while neuromagnetic activity was recorded with a 122-channel whole-head neuromagnetometer (MEG). Simultaneously, we recorded activity of the first dorsal interosseus (FDI) muscle of both hands. By using the analysis tool dynamic imaging of coherent sources (DICS), oscillatory activity at alpha as well as at beta frequency within the primary sensorimotor (S1/M1) and premotor (PMC) cortex was localized. As expected, we observed oscillatory coupling between S1/M1 and PMC contralateral to the moving hand. Furthermore, coupling between left PMC and bilateral S1/M1 occurred in each movement condition, suggesting that the left PMC modulates neural activity in bilateral primary sensorimotor cortices independent of the moving hand. Coupling between bilateral S1/M1 occurred more frequently and significantly stronger during the right hand condition. This result demonstrates the same interhemispheric coupling pattern as in right-handed subjects, suggesting that the asymmetry of this interaction is not due to hand dominance. A specialization of the left premotor cortex either for superior motor control per se or for the execution of sequential tasks might account for these results.

Adult↗

PubMed2006

Investigating the human mirror neuron system by means of cortical synchronization during the imitation of biological movements.

The human mirror neuron system (MNS) has recently been a major topic of research in cognitive neuroscience. As a very basic reflection of the MNS, human observers are faster at imitating a biological as compared with a non-biological movement. However, it is unclear which cortical areas and their interactions (synchronization) are responsible for this behavioural advantage. We investigated the time course of long-range synchronization within cortical networks during an imitation task in 10 healthy participants by means of whole-head magnetoencephalography (MEG). Extending previous work, we conclude that left ventrolateral premotor, bilateral temporal and parietal areas mediate the observed behavioural advantage of biological movements in close interaction with the basal ganglia and other motor areas (cerebellum, sensorimotor cortex). Besides left ventrolateral premotor cortex, we identified the right temporal pole and the posterior parietal cortex as important junctions for the integration of information from different sources in imitation tasks that are controlled for movement (biological vs. non-biological) and that involve a certain amount of spatial orienting of attention. Finally, we also found the basal ganglia to participate at an early stage in the processing of biological movement, possibly by selecting suitable motor programs that match the stimulus.

Adult↗

PubMed2006

Oscillatory activity reflects the excitability of the human somatosensory system.

The neuronal activity of the resting human brain is dominated by spontaneous oscillations in primary sensory and motor areas. These oscillations are thought to reflect the excitability of sensory and motor systems that can be modulated according to the actual behavioral demands. However, so far, evidence for an association between oscillatory activity and excitability has been inconsistent. Here, we used magnetoencephalography to reinvestigate the relationship between oscillatory activity and excitability in the somatosensory system on a single trial basis. Brief painful stimuli were applied to relate pain-induced suppressions of oscillatory activity to pain-induced increases in excitability. The analysis reveals a significant negative correlation between sensorimotor oscillatory activity, particularly in the alpha-band, and excitability of somatosensory cortices. Oscillatory activity outside the somatosensory system did not correlate with somatosensory excitability. These findings demonstrate that modulations of sensorimotor oscillatory activity specifically reflect modulations in excitability of the somatosensory system and thus provide direct evidence for the basic tenet of an association between oscillatory activity and cortical excitability.

Adult↗

PubMed2006

Resource sharing in the attentional blink.

Humans have difficulty processing more than one event at a time, as is evidenced by the attentional blink ('blink') phenomenon: the second of two targets in a visual stream of events cannot be reported accurately if it appears between 100 and 500 ms after the first. By using whole-head magnetoencephalography, we show that the probability of behaviourally failing to correctly identify the second target can be predicted from the amount of attentional resources devoted to processing the first target, as indexed by T1 activation. This important finding supports resource sharing accounts of divided attention tasks such as the 'blink'; that is, such tasks may reflect an individual processing strategy rather than an immutable structural processing bottleneck.

Adult↗

PubMed2006

Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation.

BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in those with Parkinson disease but may worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency DBS leads to deterioration of motor functions. It is not known whether low-frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine whether low-frequency STN DBS in contrast to high-frequency STN DBS has a positive effect on frontal functions on the basis of VF test results. DESIGN: A double-blind randomized crossover experiment to compare performance in 4 VF subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING: University hospitals in Düsseldorf and Cologne, Germany. PATIENTS: Twelve patients with Parkinson disease 3 months or more after bilateral electrode implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at different stimulation frequencies. RESULTS: The VF was significantly better at 10 Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These results were consistent across all subtests. CONCLUSIONS: The study provides evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may be caused by activating neural pathways projecting to the frontal cortex. In addition, the study reproduces the negative effect of therapeutic high-frequency STN DBS on VF. The study results provide evidence for a frequency-dependent modulation of cognitive circuits involving the STN.

Aged↗

PubMed2006

Synchronized brain network underlying postural tremor in Wilson's disease.

Common neurological manifestation of Wilson's disease (WD) is a postural tremor of the upper extremities. Recently, the primary sensorimotor cortex (S1/M1) has been shown to be involved in WD postural tremor generation. However, neuropathological changes in WD are mostly observed in subcortical structures. We therefore aimed to investigate whether S1/M1 may be functionally interconnected with other brain areas. In five WD patients, we used magnetoencephalography and surface electromyography (EMG) to record simultaneously cerebral neuronal activity and muscular activity during sustained posture of the right forearm. As demonstrated previously, the strongest coupling to tremor EMG was observed in the contralateral S1/M1. This area was taken as reference in order to identify and localize cerebro-cerebral coherence at tremor frequency and its first harmonic. The analysis revealed significant coherence within an oscillatory network including S1/M1, higher cortical motor areas (premotor cortex, PM; supplementary motor area, SMA), posterior parietal cortex (PPC) and thalamus contralateral as well as the cerebellum ipsilateral to the tremor forearm. Flow of information was mainly of bidirectional nature. Taken together, our results indicate that WD postural tremor is generated within a synchronized cerebello-thalamo-cortical network, comprising S1/M1, higher cortical motor areas (SMA, PM), and PPC.

Adult↗

PubMed2006

Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.

Adult↗

PubMed2006

Coupling between cerebellar hemispheres: behavioural, anatomic, and functional data.

Although the cerebellum has been related to emotional, cognitive, and sensory processes, its outstanding significance for motor behaviour has attracted a vast variety of studies. Specifically, the role of cerebellar activity for appropriate movement timing has been investigated intensively. Behavioural studies, particularly of patients following cerebellar lesions, gave rise to the hypothesis that each hand is controlled by separate timing mechanisms most likely localized within lateral portions of each cerebellar hemisphere. Reduced timing variability during simultaneous bimanual tasks implies that both timing signals are integrated prior to movement execution, probably by information transfer between both cerebellar hemispheres. However, this raises the question for functional and anatomic fundamentals of such an integration process. The present article reviews behavioural, functional, and anatomic data to shed light on possible interactions between both cerebellar hemispheres during the execution of timed motor behaviour.

Animals↗

PubMed2006

Anticipatory control of long-range phase synchronization.

Everyday human behaviour relies on our ability to predict outcomes on the basis of moment by moment information. Long-range neural phase synchronization has been hypothesized as a mechanism by which 'predictions' can exert an effect on the processing of incoming sensory events. Using magnetoencephalography (MEG) we have studied the relationship between the modulation of phase synchronization in a cerebral network of areas involved in visual target processing and the predictability of target occurrence. Our results reveal a striking increase in the modulation of phase synchronization associated with an increased probability of target occurrence. These observations are consistent with the hypothesis that long-range phase synchronization plays a critical functional role in humans' ability to effectively employ predictive heuristics.

Attention↗

PubMed2005

Image-to-sound conversion: experience-induced plasticity in auditory cortex of blindfolded adults.

The ability to adapt to environmental changes is based on the impressive capacity of the central nervous system for plasticity changes. A better understanding of the requirements of neuroplasticity will help to apprehend and predict the success of sensory prostheses. To investigate neuroplastic changes associated with (1) blindfolding and (2) the use of a mobile visual-auditory substitution system, five normally sighted adults underwent weekly measurements of neuromagnetic activity using a 122-channel whole head neuromagnetometer. The substitution device converted visual images into sound patterns. During measurements subjects listened to "geometric sounds" converted from images of geometric shapes, "natural sounds" representing photographs of everyday objects, as well as to original "environmental sounds". To assess the role of visual deprivation, three individuals were blindfolded throughout a 3-week testing period. To assess the effect of extended exposure to "visual sounds", three subjects-two blindfolded, one sighted-had free use of the substitution device. Neuromagnetic responses were restricted to the auditory cortex across all measurements. Activity at 100 ms after presentation of "natural sounds", but not other auditory stimuli, showed a significant enhancement over time only in blindfolded subjects using the substitution system, indicating that the combination of visual deprivation and practice facilitated intra-modal plasticity. The fact that changes occurred only in response to "natural sounds" probably reflects the increased behavioural relevance of this category evident only for blindfolded subjects using the substitution device.

Acoustic Stimulation↗

PubMed2005

How the brain blinks: towards a neurocognitive model of the attentional blink.

When people monitor a visual stream of rapidly presented stimuli for two targets (T1 and T2), they often miss T2 if it falls into a time window of about half a second after T1 onset-the attentional blink (AB). We provide an overview of recent neuroscientific studies devoted to analyze the neural processes underlying the AB and their temporal dynamics. The available evidence points to an attentional network involving temporal, right-parietal and frontal cortex, and suggests that the components of this neural network interact by means of synchronization and stimulus-induced desynchronization in the beta frequency range. We set up a neurocognitive scenario describing how the AB might emerge and why it depends on the presence of masks and the other event(s) the targets are embedded in. The scenario supports the idea that the AB arises from "biased competition", with the top-down bias being generated by parietal-frontal interactions and the competition taking place between stimulus codes in temporal cortex.

Attention↗

PubMed2005

Physiological and pathological oscillatory networks in the human motor system.

Human brain functions are heavily contingent on neural interactions both at the single neuron and the neural population or system level. Accumulating evidence from neurophysiological studies strongly suggests that coupling of oscillatory neural activity provides an important mechanism to establish neural interactions. With the availability of whole-head magnetoencephalography (MEG) macroscopic oscillatory activity can be measured non-invasively from the human brain with high temporal and spatial resolution. To localise, quantify and map oscillatory activity and interactions onto individual brain anatomy we have developed the 'dynamic imaging of coherent sources' (DICS) method which allows to identify and analyse cerebral oscillatory networks from MEG recordings. Using this approach we have characterized physiological and pathological oscillatory networks in the human sensorimotor system. Coherent 8 Hz oscillations emerge from a cerebello-thalamo-premotor-motor cortical network and exert an 8 Hz oscillatory drive on the spinal motor neurons which can be observed as a physiological tremulousness of the movement termed movement discontinuities. This network represents the neurophysiological substrate of a discrete mode of motor control. In parkinsonian resting tremor we have identified an extensive cerebral network consisting of primary motor and lateral premotor cortex, supplementary motor cortex, thalamus/basal ganglia, posterior parietal cortex and secondary somatosensory cortex, which are entrained in the tremor or twice the tremor rhythm. This low frequency entrapment of motor areas likely plays an important role in the pathophysiology of parkinsonian motor symptoms. Finally, studies on patients with postural tremor in hepatic encephalopathy revealed that this type of tremor results from a pathologically slow thalamocortical and cortico-muscular coupling during isometric hold tasks. In conclusion, the analysis of oscillatory cerebral networks provides new insights into physiological mechanisms of motor control and pathophysiological mechanisms of tremor disorders.

Efferent Pathways↗

PubMed2005

How the brain controls repetitive finger movements.

Adequate interaction with our physical and social environment requires accurate timing abilities. Since planning and control of movements is closely related to sensorimotor synchronization, the investigation of synchronization abilities may allow insights into fundamental principles of motor behaviour. The finger-tapping task has frequently been used to study the synchronization of one's own movements in relation to external events. Data from behavioural studies gave rise to the assumption that it is not the peripheral event (i.e., finger-tap or pacing signal) that is synchronized but its central representation. The neural foundations of sensorimotor synchronization have only recently been investigated and are still poorly understood. The present article reviews data from neurophysiological studies investigating sensorimotor synchronization to shed light on the neurophysiological processes associated with sensorimotor synchronization. This review focuses on studies investigating neuroelectric and neuromagnetic activity associated with simple repetitive synchronization tasks.

Brain↗

PubMed2005

Pain suppresses spontaneous brain rhythms.

The neuronal activity of the resting human brain is dominated by spontaneous oscillatory activity of primary visual, somatosensory and motor areas. These spontaneous brain rhythms are related to the functional state of a system. A higher amplitude of oscillatory activity is thought to reflect an idling state, whereas a lower amplitude is associated with activation and higher excitability of the specific system. Here, we used magnetoencephalography to investigate the effects of pain on spontaneous brain rhythms. Our results show that a focally applied brief painful stimulus globally suppresses spontaneous oscillations in somatosensory, motor and visual areas. This global suppression contrasts with the regionally specific suppressions of other modalities and shows that pain induces a widespread change in cortical function and excitability. This global change in excitability may reflect the alerting function of pain which opens the gates for processing of and reacting to stimuli of existential relevance.

Adult↗

PubMed2005

Oscillatory coupling in writing and writer's cramp.

Writing is a highly skilled and overlearned movement. In patients suffering from writer's cramp, a focal task-induced dystonia, writing is impaired or even impossible due to involuntary muscle contractions and abnormal posture, which occur as soon as the person picks up a pen or within writing a few words. The underlying pathophysiological mechanisms of this movement disorder are not fully understood up to now. The aim of the present study was to unravel the oscillatory network underlying physiological writing in healthy subjects and dystonic writing in writer's cramp patients. Using whole-head magnetoencephalography (MEG) and the analysis tool dynamic imaging of coherent sources (DICS) we studied oscillatory neural coupling during writing in eleven healthy subjects and eight patients suffering from writer's cramp. Simultaneous recording of brain activity with MEG and activity of forearm and hand muscles with surface electromyography (EMG) was performed while subjects were writing for five minutes with their dominant right hand. Applying DICS sources of strongest cerebro-muscular coherence and cerebro-cerebral coherence during writing were identified, which consistently included six brain areas in both, the control subjects and the patients: contralateral and ipsilateral sensorimotor cortex, ipsilateral cerebellum, contralateral thalamus, contralateral premotor and posterior parietal cortex. Coherence between cortical sources and muscles appeared primarily in the frequency of writing movements (3-7 Hz) while coherence between cerebral sources occurred primarily around 10 Hz (8-13 Hz). Interestingly, consistent coupling between both sensorimotor cortices was observed in patients only, whereas coupling between ipsilateral cerebellum and the contralateral posterior parietal cortex was found in control subjects only. These results are consistent with the often described bilateral pathophysiology and impaired sensorimotor integration in writer's cramp patients.

Adult↗