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Biomedical subjects

Alfons Schnitzler

Publications and source records attributed to Alfons Schnitzler.

At least 37 records · Page 2Linked to original sources

Cortical dynamics and synchronization related to multiple target consolidation under rapid-serial-visual-presentation conditions.

The present report reviews behavioural, electroencephalographic, and especially magnetoencephalographic findings on the cortical mechanisms underlying attentional processes that separate targets from distractors and that ensure durable target representations for goal-directed action. A common way of investigation is to observe the system's overt and covert behaviour when capacity limitations are reached. Here we focus on the aspect of temporally enhanced processing load, namely on performance deficits occurring under rapid-serial-visual-presentation (RSVP) conditions. The most prominent of these deficits is the so-called "attentional blink" (AB) effect. We first report MEG findings with respect to the time course of activation that shows modulations around 300 ms after target onset which reflect demands and success of target consolidation. Then, findings regarding long-range inter-area phase synchronization are reported that are hypothesized to mediate communication within the attentional network. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioural performance. Furthermore, enhanced vigilance of the system elicits systematically increased synchronization indices. A hypothetical framework is sketched out that aims at explaining limitations in multiple target consolidation under RSVP conditions.

Animals↗

Target consolidation under high temporal processing demands as revealed by MEG.

We investigated the nature of resource limitations during visual target processing by imposing high temporal processing demands on the cognitive system. This was achieved by embedding target stimuli into rapid-serial-visual-presentation-streams (RSVP). In RSVP streams, it is difficult to report the second of two targets (T2) if the second follows the first (T1) within 500 ms. This effect is known as the attentional blink (AB). For the AB to occur, it is essential that T1 is followed by a mask, as without such a stimulus, the AB is significantly attenuated. Usually, it is thought that T1 processing is delayed by the mask, which in turn delays T2 processing, increasing the likelihood for T2 failures (AB). Predictions regarding amplitudes and latencies of cortical responses (M300, the magnetic counterpart to the P300) to targets were tested by investigating the neurophysiological effects of the post-T1 item (mask) by means of magnetoencephalography (MEG). Cortical M300 responses to targets drawn from prefrontal sources--areas associated with working memory--revealed accelerated T1 yet delayed T2 processing with an intervening mask. The explanation we are proposing assumes that "protection" of ongoing T1 processing necessitated by the occurrence of the mask suppresses other activation patterns, which boosts T1 yet also hinders further processing. Our data shed light on the mechanisms employed by the human brain for ensuring visual target processing under high temporal processing demands, which is hypothesized to occur at the expense of subsequently presented information.

Adult↗

Right rolandic activation during speech perception in stutterers: a MEG study.

The focus of our magnetoencephalographic (MEG) study was to obtain further insight into the neuronal organization of language processing in stutterers. We recorded neuronal activity of 10 male developmental stutterers and 10 male controls, while they listened to pure tones, to words in order to repeat them, and to sentences in order to either repeat or transform them into passive form. Stimulation with pure tones resulted in similar activation patterns in the two groups, but differences emerged in the more complex auditory language tasks. In the stutterers, the left inferior frontal cortex was activated for a short while from 95 to 145 ms after sentence onset, which was not evident in the controls nor in either group during the word task. In both subject groups, the left rolandic area was activated when listening to the speech stimuli, but in the stutterers, there was an additional activation of the right rolandic area from 315 ms onwards, which was more pronounced in the sentence than word task. Activation of areas typically associated with language production was thus observed also during speech perception both in controls and in stutterers. Previous research on speech production in stutterers has found abnormalities in both the amount and timing of activation in these areas. The present data suggest that activation in the left inferior frontal and right rolandic areas in stutterers differs from that in controls also during speech perception.

Adolescent↗

Neural synchronization in hepatic encephalopathy.

Hepatic encephalopathy (HE) is clinically characterized by a large variety of symptoms including motor symptoms, cognitive deficits, as well as changes in the level of alertness up to hepatic coma. A number of pathological processes affecting glial and neuronal function have been identified, including hyper-ammonia, changes within the excitatory and inhibitory transmitter systems, as well as osmolytic changes with consecutive cell swelling. One explanation how these pathological processes result in neurological deficits in HE is the concept of pathologically synchronized oscillations within and between relevant brain regions. A number of studies suggest that the cognitive deficits and the reduced level of alertness in patients with HE can be attributed to a significantly slowed and pathologically synchronized spontaneous oscillatory brain activity, depending on the grade of HE. Moreover, HE motor symptoms, like postural tremor called"mini asterixis," have recently been shown to be associated with abnormal thalamo-cortical and cortico-muscular synchronization. Indirect evidence exists from studies of processing and recognition of flicker stimuli that in HE slowing of oscillations also occurs in the visual system. Taken together, pathological synchronization of neuronal activity may turn out to be a promising pathophysiological concept for linking neuronal dysfunction to the diversity of clinical deficits in HE.

Animals↗

The oscillatory network of simple repetitive bimanual movements.

Bimanual synchronization relies on the precisely coordinated interplay of both hands. It is assumed that during temporal bimanual coordination, timing signals controlling each hand might be integrated. Although a specific role of the cerebellum for this integration process has been suggested, its neural foundations are still poorly understood. Since dynamic interactions between spatially distributed neural activity are reflected in oscillatory neural coupling, the aim of the present study was to characterize the dynamic interplay between participating brain structures. More specifically, the study aimed at investigating whether any evidence for the integration of bilateral cerebellar hemispheres could be found. Seven right-handed subjects synchronized bimanual index finger-taps to a regular pacing signal. We recorded continuous neuromagnetic activity using a 122-channel whole-head neuromagnetometer and surface EMGs of the first dorsal interosseus (FDI) muscle of both hands. Coherence analysis revealed that an oscillatory network coupling at 8-12 Hz subserves task execution. The constituents are bilateral primary sensorimotor and premotor areas, posterior-parietal and primary auditory cortex, thalamus and cerebellum. Coupling occurred at different cortical and subcortical levels within and between both hemispheres. Coupling between primary sensorimotor and premotor areas was observed directly and indirectly via the thalamus. Coupling direction suggests that information was integrated within the left premotor cortex corroborating a specific role of the left premotor cortex for motor control in right-handers. Most importantly, our data indicate strong coupling between both cerebellar hemispheres substantiating the hypothesis that cerebellar signals might be integrated during task execution.

Adult↗

Normal and pathological oscillatory communication in the brain.

The huge number of neurons in the human brain are connected to form functionally specialized assemblies. The brain's amazing processing capabilities rest on local communication within and long-range communication between these assemblies. Even simple sensory, motor and cognitive tasks depend on the precise coordination of many brain areas. Recent improvements in the methods of studying long-range communication have allowed us to address several important questions. What are the common mechanisms that govern local and long-range communication and how do they relate to the structure of the brain? How does oscillatory synchronization subserve neural communication? And what are the consequences of abnormal synchronization?

Animals↗

Cortical mechanisms of attention in time: neural correlates of the Lag-1-sparing phenomenon.

If humans monitor streams of rapidly presented (approximately 100-ms intervals) visual stimuli, which are typically specific single letters of the alphabet, for two targets (T1 and T2), they often miss T2 if it follows T1 within an interval of 200-500 ms. If T2 follows T1 directly (within 100 ms; described as occurring at 'Lag 1'), however, performance is often excellent: the so-called 'Lag-1 sparing' phenomenon. Lag-1 sparing might result from the integration of the two targets into the same 'event representation', which fits with the observation that sparing is often accompanied by a loss of T1-T2 order information. Alternatively, this might point to competition between the two targets (implying a trade-off between performance on T1 and T2) and Lag-1 sparing might solely emerge from conditional data analysis (i.e. T2 performance given T1 correct). We investigated the neural correlates of Lag-1 sparing by carrying out magnetoencephalography (MEG) recordings during an attentional blink (AB) task, by presenting two targets with a temporal lag of either 1 or 2 and, in the case of Lag 2, with a nontarget or a blank intervening between T1 and T2. In contrast to Lag 2, where two distinct neural responses were observed, at Lag 1 the two targets produced one common neural response in the left temporo-parieto-frontal (TPF) area but not in the right TPF or prefrontal areas. We discuss the implications of this result with respect to competition and integration hypotheses, and with respect to the different functional roles of the cortical areas considered. We suggest that more than one target can be identified in parallel in left TPF, at least in the absence of intervening nontarget information (i.e. masks), yet identified targets are processed and consolidated as two separate events by other cortical areas (right TPF and PFC, respectively).

Adult↗

The cerebral oscillatory network associated with auditorily paced finger movements.

Motor tasks involve neural activity in a spatially distributed network. It is assumed that coherent activity between these brain structures reflects functional connectivity. The aim of the present study was to investigate brain areas associated with a unimanual auditorily paced finger-tapping task and to characterize their dynamic interplay. We examined cerebromuscular and cerebrocerebral coupling in 10 right-handed subjects using recordings of continuous brain activity with a 122-channel whole-head neuromagnetometer while subjects performed the task with both hands consecutively. Additionally, surface EMG of the first dorsal interosseus was measured. Our data demonstrate that an oscillatory network composed of primary sensorimotor cortex, lateral as well as mesial premotor areas, the posterior parietal cortex and thalamus contralateral, and cerebellum and primary auditory cortex ipsilateral to the tapping hand subserves task execution. Connectivity between these areas and direction of coupling agree well with anatomical findings. During the right-hand condition, additional oscillatory activity in the primary sensorimotor cortex ipsilateral to the tapping hand was evident. This result suggests an asymmetric motor control in right-handers. Cerebrocerebral coupling predominantly occurs at 8-12 Hz. Therefore, our data support the hypothesis that coupling at 8-12 Hz in a cerebello-thalamic-cortical network represents a fundamental characteristic of the motor system and provides evidence for the significance of 8-12 Hz oscillations in a large scale network during the execution of simple motor tasks.

Acoustic Stimulation↗

Shrinkage of somatosensory hand area in subjects with upper extremity dysmelia revealed by magnetoencephalography.

The effect of peripheral lesions on cerebral somatosensory representations is well studied for experimentally induced amputations and deafferentations acquired later in life. However, few studies have investigated the brain's capacity for plastic changes in congenital malformations. We studied somatosensory-evoked fields to electrical stimulation of the bordering fingers in 10 subjects with upper extremity dysmelia in comparison with 10 control subjects using a 122-channel whole-head magnetometer. The number of developed fingers varied between two and four in the affected subjects. We localized finger representations in the primary somatosensory cortex and calculated Euclidian distances to estimate the size of the somatosensory hand area. Euclidian distances were significantly smaller in dysmelic subjects (5.7 mm) than in control subjects (11.6 mm) and were related to the number of the developed fingers on the contralateral hand. In contrast, individual finger representations were not found to be reduced. We suggest that the shrinkage of the somatosensory hand area might be related to the congenital nature of the malformation, to the smaller anatomical hand size in the affected subjects, and/or to use-dependent effects due to impaired hand function.

Adult↗

Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans.

Because of attentional limitations, the human visual system can process for awareness and response only a fraction of the input received. Lesion and functional imaging studies have identified frontal, temporal, and parietal areas as playing a major role in the attentional control of visual processing, but very little is known about how these areas interact to form a dynamic attentional network. We hypothesized that the network communicates by means of neural phase synchronization, and we used magnetoencephalography to study transient long-range interarea phase coupling in a well studied attentionally taxing dual-target task (attentional blink). Our results reveal that communication within the fronto-parieto-temporal attentional network proceeds via transient long-range phase synchronization in the beta band. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioral performance. Thus, we show how attentional limitations arise from the way in which the subsystems of the attentional network interact.

Attention↗

Pain facilitates tactile processing in human somatosensory cortices.

Touch and pain are intimately related modalities. Despite a substantial overlap in their cortical representations interactions between both modalities are largely unknown at the cortical level. We therefore used magnetoencephalography and selective nociceptive cutaneous laser stimulation to investigate the effects of brief painful stimuli on cortical processing of touch. Using a conditioning test stimulus paradigm, our results show that painful conditioning stimuli facilitate processing of tactile test stimuli applied 500 ms later. This facilitation applies to cortical responses later than 40 ms originating from primary (S1) and secondary (S2) somatosensory cortices but not to earlier S1 responses. By contrast, tactile conditioning stimuli yield a decrease of early as well as late responses to tactile test stimuli. Control experiments show that pain-induced facilitation of tactile processing is not restricted to the site of the painful conditioning stimulus, whereas auditory conditioning does not yield a comparable facilitation. Apart from a lack of spatial specificity, the facilitating effect of pain closely resembles attentional effects on cortical processing of tactile stimuli. Thus these findings may represent a physiological correlate of an alerting function of pain as a change in the internal state to prepare for processing signals of particular relevance.

Adult↗

The role of the primary somatosensory cortex in an auditorily paced finger tapping task.

It has been suggested that a simple auditorily paced finger tapping task is associated with three tap-related neuromagnetic sources in the primary sensorimotor cortex contralateral to the tapping hand. Since a first source peaking at approximately 100 ms before tap-onset most likely represents activation of the primary motor cortex (M1) due to the motor command, a second source localized in the primary somatosensory cortex (S1) peaking around tap-onset could be due to kinesthetic feedback of the finger movement. A third source peaking at approximately 100 ms after tap-onset is also localized in the primary somatosensory cortex but inferior to the first S1 source (S1 inferior). The functional meaning of this source is still under debate. On the one hand it has been argued that S1 inferior represents the neuromagnetic correlate of tactile-kinesthetic feedback due to finger-taps and movements. On the other hand the functional meaning of this source could go beyond the sole processing of somatosensory feedback monitoring the temporal distance between tap and pacer (click) to keep the subject in time with the external event. This hypothesis is based on the observation that (1). S1 inferior seems to be coupled equally well to tap and click and (2). that this source might be triggered by the last event (i.e. tap or click). In the present study we re-examined this hypothesis by using a 122-channel whole-head neuromagnetometer. Eight healthy subjects synchronized their right index finger taps to an auditory pacing signal presented with a constant interstimulus interval of 800 ms. To test the hypothesis that the last event triggers S1 inferior we compared neuromagnetic activity following the tap as the first and the last event. In the auditorily paced finger tapping task usually the tap leads over the click (negative asynchrony). Therefore, the tap usually occurs as the first event. Since it has been shown that delivering additional feedback at the time of tap-onset results in a reduced negative asynchrony, in a second run auditory feedback was presented at tap-onset to enhance the number of positive asynchronies (i.e. the tap is the last event). Since no latency differences of S1 inferior associated with positive and negative asynchronies were found, results from the present study do not support the assumption that S1 inferior is triggered by the last event. Moreover, the amplitude of S1 inferior is significantly reduced following positive asynchronies as compared to negative asynchronies. Additionally, tap duration (i.e. the time between tap-onset and tap-offset) is significantly reduced while subjects produce positive asynchronies. Therefore, the amplitude of S1 inferior seems to be modulated by movement kinematics. This observation agrees well with the idea that activation of S1 is solely associated with the processing of somatosensory information. To conclude, our data contradict the hypothesis of an evaluation process localized in the primary somatosensory cortex and substantiate the idea that S1 inferior exclusively represents the processing of somatosensory feedback information.

Acoustic Stimulation↗

Bimanual coordination: neuromagnetic and behavioral data.

It has been suggested that bimanual coordination is associated with stronger activation of the left motor cortex in right-handers. The aim of the present study was to investigate whether left motor cortex dominance constitutes a fundamental feature of bimanual coordination. We investigated neuromagnetic responses while subjects performed a bimanual tapping task using a 122-channel whole-head neuromagnetometer. Three neuromagnetic sources localized in the primary sensorimotor cortex of each hemisphere were found. Sources represent neuromagnetic correlates of the motor command and of somatosensory feedback. Since we found no differences of amplitudes or latencies of corresponding sources of both hemispheres, our data suggest that dominance of the left motor cortex is not a fundamental characteristic for bimanual coordination.

Adult↗

Perilesional pathological oscillatory activity in the magnetoencephalogram of patients with cortical brain lesions.

In the surrounding of focal ischemic brain lesions dysfunctional neuronal zones emerge often resulting in pathological oscillatory activity. Using whole-head magnetoencephalography we recorded brain activity during rest in 23 patients with ischemic cortical lesions to find out whether we can localise and characterise low-frequency oscillatory activity. We measured patients at different times after stroke and partly in a follow-up approach to determine the time course of slow-wave activity. Using the analysis tool Dynamic Imaging of Coherent Sources we computed tomographic maps of oscillatory power in the delta-band (0.5-3 Hz). Fifteen of 23 patients with cortical strokes showed delta-activity, which was localised in an area not more than 2 cm away from the lesion. We found this perilesional low-frequency activity in the acute as well as in the chronic stage of stroke. Follow-up measurements of individual patients revealed persistence of perilesional low-frequency activity for months and even years. No consistent relation between perilesional activity and clinical symptoms was observed. Our results indicate that perilesional delta activity is common after ischemic cortical stroke. However, the functional significance remains to be elucidated.

Action Potentials↗

Long-term results of bilateral pallidal stimulation in Parkinson's disease.

We followed up 11 patients for up to 5 years after bilateral pallidal deep brain stimulation for advanced Parkinson's disease. Dyskinesias remained significantly reduced until the last assessment. The initial improvement of off-period motor symptoms and fluctuations, however, was not sustained and gradually declined. Beneficial effects of pallidal deep brain stimulation on activities of daily living in the on- and off-period were lost after the first year. Replacement of pallidal electrodes into the subthalamic nucleus in four patients could restore the initial benefit of deep brain stimulation and allowed a significant reduction of dopaminergic drug therapy.

Activities of Daily Living↗

Ten-Hertz stimulation of subthalamic nucleus deteriorates motor symptoms in Parkinson's disease.

Recently, a pathological oscillatory network at 10 Hz including several motor areas was described in patients with idiopathic Parkinson's disease (PD). In 7 PD patients, we tested the clinical effect of subthalamic nucleus (STN) stimulation at varying frequencies 1 to 3 years after implantation of electrodes. STN stimulation at 10 Hz induced significant worsening of motor symptoms, especially akinesia, compared with no stimulation and therapeutic stimulation (> or =130 Hz). This finding indicates the clinical relevance of pathological 10 Hz synchronization in PD.

Aged↗

Postural tremor in Wilson's disease: a magnetoencephalographic study.

The following study included 5 Wilson's disease (WD) patients showing a right-sided postural forearm tremor (4-6 Hz) and addressed the question of whether the primary motor cortex (M1) is involved in tremor generation. Using a 122-channel whole-head neuromagnetometer and surface electromyogram (EMG), we investigated cerebromuscular coupling. Postural tremor was observed in a sustained 45-degree posture of the right-sided forearm. Data were analyzed using dynamic imaging of coherent sources (DICS), revealing cerebromuscular coupling between EMG and cerebral activity. Coherent sources were superimposed on individual high-resolution T1-weighted magnetic resonance images (MRI). Phase lags between EMG and cerebral areas showing strongest coherence were determined by means of a Hilbert transform of both signals. In all patients, postural tremor was associated with strong coherence between tremor EMG and activity in contralateral primary sensorimotor cortex (S1/M1) at tremor or double tremor frequency. Phase lag values between S1/M1 activity and EMG revealed efferent and afferent components in the corticomuscular coupling. Taken together, our results indicate that postural tremor in WD is mediated through a pathological oscillatory drive from the primary motor cortex.

Adult↗