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Alfons Schnitzler

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29 papers
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29

YNICL Journal 2025 Journal Article

Longitudinal changes of resting-state networks in Parkinson‘s disease

  • Matthias Sure
  • Rasha Hyder
  • Levent Kandemir
  • Jan Vesper
  • Alfons Schnitzler
  • Esther Florin

Deep brain stimulation (DBS), but also the sole implantation of the electrodes and dopaminergic medication, can reduce symptoms in Parkinson's disease (PD) patients. Furthermore, an effect on network activity is known for all three options separately. However, long-term effects have rarely been investigated. Therefore, in the present study, we focus on the long-term impact of dopaminergic medication on whole-brain network activity following DBS electrode implantation. Therefore, we extracted resting state networks (RSNs) of 20 PD patients (4 females, (59.00 ± 9.72 years) from magnetoencephalography data. We recorded 30 min of resting-state activity two days before and one year after implantation of the electrodes with and without dopaminergic medication, but DBS was turned off. RSNs were obtained based on the phase-amplitude coupling between a low-frequency phase and a high gamma amplitude and examined for differences between conditions (i.e., pre- vs. post-surgery). We identified three RSNs across all conditions: sensory-motor, visual, and frontal. Each RSN was selectively altered due to a year of disease progression - while patients being treated with dopaminergic medication and DBS. In line with previous literature, we focus on longitudinal changes in RSNs over time after electrode implantation, acknowledging that chronic DBS treatment and other factors may confound the interpretation of these changes. In addition, the alterations found were RSN specific, as dopaminergic medication showed a greater impact on the frontal RSN, and the longitudinal factor expressed by the disease progression was more severe in alterations in the SMN and the visual RSN.

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YNICL Journal 2025 Journal Article

Modulations of thalamo-cortical coupling during voluntary movement in patients with essential tremor

  • Alexandra Steina
  • Sarah Sure
  • Markus Butz
  • Jan Vesper
  • Alfons Schnitzler
  • Jan Hirschmann

The ventral intermediate nucleus of the thalamus (VIM) is the main thalamic hub for cerebellar inputs and the primary deep brain stimulation target in essential tremor (ET). As such, it presumably plays a critical role in motor control. However, this structure is rarely studied in humans, and existing studies mostly focus on tremor. Here, we studied neural oscillations in the VIM and their coupling to cortical oscillations during voluntary movement. We investigated thalamo-cortical coupling, combining recordings of thalamic local field potentials and magnetoencephalography, in 10 ET patients with externalized deep brain stimulation electrodes. During the recording, patients repeatedly pressed a button in response to a visual cue. In a whole-brain analysis of VIM-cortex coherence, we contrasted activity during pre-movement baseline and button pressing. Button pressing was associated with a bilateral decrease of thalamic alpha (8-12 Hz) and beta (13-21 Hz) power and a contralateral gamma (35-90 Hz) power increase. Alpha/low-beta (8-20 Hz) coherence decreased during movement. This effect localized to the supplementary motor area and premotor cortex. A high-beta (21-35 Hz) coherence increase occurred in the same region but was more focal than the suppression. Pre-movement levels of thalamo-cortex low-beta coherence correlated with reaction time. Our results demonstrate that voluntary movement is associated with modulations of behaviourally relevant thalamic coupling, primarily to premotor areas. We observed a clear distinction between low- and high-beta frequencies and our results suggest that the concept of "antikinetic" beta oscillations, originating from research on Parkinson's disease, is transferable to ET.

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YNICL Journal 2023 Journal Article

Alterations of resting-state networks of Parkinson‘s disease patients after subthalamic DBS surgery

  • Matthias Sure
  • Sean Mertiens
  • Jan Vesper
  • Alfons Schnitzler
  • Esther Florin

The implantation of deep brain stimulation (DBS) electrodes in Parkinson's disease (PD) patients can lead to a temporary improvement in motor symptoms, known as the stun effect. However, the network alterations induced by the stun effect are not well characterized. As therapeutic DBS is known to alter resting-state networks (RSN) and subsequent motor symptoms in patients with PD, we aimed to investigate whether the DBS-related stun effect also modulated RSNs. Therefore, we analyzed RSNs of 27 PD patients (8 females, 59.0 +- 8.7 years) using magnetoencephalography and compared them to RSNs of 24 age-matched healthy controls (8 females, 62.8 +- 5.1 years). We recorded 30 min of resting-state activity two days before and one day after implantation of the electrodes with and without dopaminergic medication. RSNs were determined by use of phase-amplitude coupling between a low frequency phase and a high gamma amplitude and examined for differences between conditions (i.e., pre vs post surgery). We identified four RSNs across all conditions: sensory-motor, visual, fronto-occipital, and frontal. Each RSN was altered due to electrode implantation. Importantly, these changes were not restricted to spatially close areas to the electrode trajectory. Interestingly, pre-operative RSNs corresponded better with healthy control RSNs regarding the spatial overlap, although the stun effect is associated with motor improvement. Our findings reveal that the stun effect induced by implantation of electrodes exerts brain wide changes in different functional RSNs.

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YNICL Journal 2023 Journal Article

Neuroimaging-based analysis of DBS outcomes in pediatric dystonia: Insights from the GEPESTIM registry

  • Bassam Al-Fatly
  • Sabina J. Giesler
  • Simon Oxenford
  • Ningfei Li
  • Till A. Dembek
  • Johannes Achtzehn
  • Patricia Krause
  • Veerle Visser-Vandewalle

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment in patients of various ages with pharmaco-resistant neurological disorders. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures, and on electrode connectivity to a specific distribution pattern within brain networks. Such information is usually collected using group-level analysis, which relies on the availability of normative imaging resources (atlases and connectomes). Analysis of DBS data in children with debilitating neurological disorders such as dystonia would benefit from such resources, especially given the developmental differences in neuroimaging data between adults and children. We assembled pediatric normative neuroimaging resources from open-access datasets in order to comply with age-related anatomical and functional differences in pediatric DBS populations. We illustrated their utility in a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources. METHODS: An average pediatric brain template (the MNI brain template 4.5-18.5 years) was implemented and used to localize the DBS electrodes in 20 patients from the GEPESTIM registry cohort. A pediatric subcortical atlas, analogous to the DISTAL atlas known in DBS research, was also employed to highlight the anatomical structures of interest. A local pallidal sweetspot was modeled, and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcomes. Additionally, a pediatric functional connectome of 100 neurotypical subjects from the Consortium for Reliability and Reproducibility was built to allow network-based analyses and decipher a connectivity fingerprint responsible for the clinical improvements in our cohort. RESULTS: We successfully implemented a pediatric neuroimaging dataset that will be made available for public use as a tool for DBS analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46, permuted p = 0.019). The functional connectivity fingerprint of DBS outcomes was determined to be a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30, permuted p = 0.003). CONCLUSIONS: Local sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcomes in dystonia using pediatric neuroimaging surrogate data. Implementation of this pediatric neuroimaging dataset might help to improve the practice and pave the road towards a personalized DBS-neuroimaging analyses in pediatric patients.

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YNIMG Journal 2022 Journal Article

Cortical network formation based on subthalamic beta bursts in Parkinson's disease

  • Matthias Sure
  • Jan Vesper
  • Alfons Schnitzler
  • Esther Florin

Recent evidence suggests that beta bursts in subthalamic nucleus (STN) play an important role in Parkinsonian pathophysiology. We studied the spatio-temporal relationship between STN beta bursts and cortical activity in 26 Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Postoperatively, we simultaneously recorded STN local field potentials (LFP) from externalized DBS leads and cortical activity using whole-brain magnetoencephalography. Event-related magnetic fields (ERF) were averaged time-locked to STN beta bursts and subjected to source localization. Our results demonstrate that ERF exhibiting activity significantly different from baseline activity were localized within areas functionally related to associative, limbic, and motor systems as well as regions pertinent for visual and language processing. Our data suggest that STN beta bursts are involved in network formation between STN and cortex. This interaction is in line with the idea of parallel processing within the basal ganglia-cortex loop, specifically within the functional subsystems of the STN (i.e., associative, limbic, motor, and the related cortical areas). ERFs within visual and language-related cortical areas indicate involvement of beta bursts in STN-cortex networks beyond the associative, limbic, and motor loops. In sum, our results highlight the involvement of STN beta bursts in the formation of multiple STN - cortex loops in patients with PD.

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YNIMG Journal 2020 Journal Article

Neuroimaging and electrophysiology meet invasive neurostimulation for causal interrogations and modulations of brain states

  • Gabriel Gonzalez-Escamilla
  • Muthuraman Muthuraman
  • Dumitru Ciolac
  • Volker A. Coenen
  • Alfons Schnitzler
  • Sergiu Groppa

Deep brain stimulation (DBS) has developed over the last twenty years into a highly effective evidenced-based treatment option for neuropsychiatric disorders. Moreover, it has become a fascinating tool to provide illustrative insights into the functioning of brain networks. New anatomical and pathophysiological models of DBS action have accelerated our understanding of neurological and psychiatric disorders and brain functioning. The description of the brain networks arose through the unique ability to illustrate long-range interactions between interconnected brain regions as derived from state-of-the-art neuroimaging (structural, diffusion, and functional MRI) and the opportunity to record local and large-scale brain activity at millisecond temporal resolution (microelectrode recordings, local field potential, electroencephalography, and magnetoencephalography). In the first part of this review, we describe how neuroimaging techniques have led to current understanding of DBS effects, by identifying and refining the DBS targets and illustrate the actual view on the relationships between electrode locations and clinical effects. One step further, we discuss how neuroimaging has shifted the view of localized DBS effects to a modulation of specific brain circuits, which has been possible from the combination of electrode location reconstructions with recently introduced network imaging methods. We highlight how these findings relate to clinical effects, thus postulating neuroimaging as a key factor to understand the mechanisms of DBS action on behavior and clinical effects. In the second part, we show how invasive electrophysiology techniques have been efficiently integrated into the DBS set-up to precisely localize the neuroanatomical targets of DBS based on distinct region-specific patterns of neural activity. Next, we show how multi-site electrophysiological recordings have granted a real-time window into the aberrant brain circuits within and beyond DBS targets to quantify and map the dynamic properties of rhythmic oscillations. We also discuss how DBS alters the transient synchrony states of oscillatory networks in temporal and spatial domains during resting, task-based and motion conditions, and how this modulation of brain states ultimately shapes the functional response. Finally, we show how a successful decoding and management of electrophysiological proxies (beta bursts, phase-amplitude coupling) of aberrant brain circuits was translated into adaptive DBS stimulation paradigms for a targeted and state-dependent invasive electrical neuromodulation.

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YNIMG Journal 2020 Journal Article

Spontaneous network activity <35 ​Hz accounts for variability in stimulus-induced gamma responses

  • Jan Hirschmann
  • Sylvain Baillet
  • Mark Woolrich
  • Alfons Schnitzler
  • Diego Vidaurre
  • Esther Florin

Gamma activity is thought to serve several cognitive processes, including attention and memory. Even for the simplest stimulus, the occurrence of gamma activity is highly variable, both within and between individuals. The sources of this variability, however, are largely unknown. In this paper, we address one possible cause: the cross-frequency influence of spontaneous, whole-brain network activity on visual stimulus processing. By applying Hidden Markov modelling to MEG data, we reveal that the trial-averaged gamma response to a moving grating depends on the individual network dynamics, inferred from slower brain activity (<35 ​Hz) in the absence of stimulation (resting-state and task baseline). In addition, we demonstrate that modulations of network activity in task baseline influence the gamma response on the level of trials. In summary, our results reveal a cross-frequency and cross-session association between gamma responses induced by visual stimulation and spontaneous network activity. These findings underline the dependency of visual stimulus processing on the individual, functional network architecture.

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YNICL Journal 2019 Journal Article

Chemical exchange saturation transfer imaging in hepatic encephalopathy

  • Helge Jörn Zöllner
  • Markus Butz
  • Markus Jördens
  • Nur-Deniz Füllenbach
  • Dieter Häussinger
  • Benjamin Schmitt
  • Hans-Jörg Wittsack
  • Alfons Schnitzler

Hepatic encephalopathy (HE) is a common complication in liver cirrhosis and associated with an invasion of ammonia into the brain through the blood-brain barrier. Resulting higher ammonia concentrations in the brain are suggested to lead to a dose-dependent gradual increase of HE severity and an associated impairment of brain function. Amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) imaging has been found to be sensitive to ammonia concentration. The aim of this work was to study APTw CEST imaging in patients with HE and to investigate the relationship between disease severity, critical flicker frequency (CFF), psychometric test scores, blood ammonia, and APTw signals in different brain regions. Whole-brain APTw CEST images were acquired in 34 participants (14 controls, 20 patients (10 minimal HE, 10 manifest HE)) on a 3 T clinical MRI system accompanied by T1 mapping and structural images. T1 normalized magnetization transfer ratio asymmetry analysis was performed around 3 ppm after B0 and B1 correction to create APTw images. All APTw images were spatially normalized into a cohort space to allow direct comparison. APTw images in 6 brain regions (cerebellum, occipital cortex, putamen, thalamus, caudate, white matter) were tested for group differences as well as the link to CFF, psychometric test scores, and blood ammonia. A decrease in APTw intensities was found in the cerebellum and the occipital cortex of manifest HE patients. In addition, APTw intensities in the cerebellum correlated positively with several psychometric scores, such as the fine motor performance scores MLS1 for hand steadiness / tremor (r = 0. 466; p =. 044) and WRT2 for motor reaction time (r = 0. 523; p =. 022). Moreover, a negative correlation between APTw intensities and blood ammonia was found for the cerebellum (r = −0. 615; p =. 007) and the occipital cortex (r = −0. 478; p =. 045). An increase of APTw intensities was observed in the putamen of patients with minimal HE and correlated negatively with the CFF (r = −0. 423; p =. 013). Our findings demonstrate that HE is associated with regional differential alterations in APTw signals. These variations are most likely a consequence of hyperammonemia or hepatocerebral degeneration processes, and develop in parallel with disease severity.

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YNICL Journal 2018 Journal Article

Connecting occipital alpha band peak frequency, visual temporal resolution, and occipital GABA levels in healthy participants and hepatic encephalopathy patients

  • Thomas J. Baumgarten
  • Julia Neugebauer
  • Georg Oeltzschner
  • Nur-Deniz Füllenbach
  • Gerald Kircheis
  • Dieter Häussinger
  • Joachim Lange
  • Hans-Jörg Wittsack

Recent studies have proposed a connection between the individual alpha band peak frequency and the temporal resolution of visual perception in healthy human participants. This connection rests on animal studies describing oscillations in the alpha band as a mode of phasic thalamocortical information transfer for low-level visual stimuli, which critically relies on GABAergic interneurons. Here, we investigated the interplay of these parameters by measuring occipital alpha band peak frequency by means of magnetoencephalography, visual temporal resolution by means of behavioral testing, and occipital GABA levels by means of magnetic resonance spectroscopy. Importantly, we investigated a sample of healthy participants and patients with varying grades of hepatic encephalopathy, which are known to exhibit decreases in the investigated parameters, thus providing an increased parameter space. We found that occipital alpha band peak frequency and visual temporal resolution were positively correlated, i.e., higher occipital alpha band peak frequencies were on average related to a higher temporal resolution. Likewise, occipital alpha band peak frequency correlated positively with occipital GABA levels. However, correlations were significant only when both healthy participants and patients were included in the analysis, thereby indicating a connection of the measures on group level (instead of the individual level). These findings provide new insights into neurophysiological and neurochemical underpinnings of visual perception.

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YNIMG Journal 2018 Journal Article

Unilateral deep brain stimulation suppresses alpha and beta oscillations in sensorimotor cortices

  • Omid Abbasi
  • Jan Hirschmann
  • Lena Storzer
  • Tolga Esat Özkurt
  • Saskia Elben
  • Jan Vesper
  • Lars Wojtecki
  • Georg Schmitz

Deep brain stimulation (DBS) is an established therapy to treat motor symptoms in movement disorders such as Parkinson's disease (PD). The mechanisms leading to the high therapeutic effectiveness of DBS are poorly understood so far, but modulation of oscillatory activity is likely to play an important role. Thus, investigating the effect of DBS on cortical oscillatory activity can help clarifying the neurophysiological mechanisms of DBS. Here, we aimed at scrutinizing changes of cortical oscillatory activity by DBS at different frequencies using magnetoencephalography (MEG). MEG data from 17 PD patients were acquired during DBS of the subthalamic nucleus (STN) the day after electrode implantation and before implanting the pulse generator. We stimulated the STN unilaterally at two different stimulation frequencies, 130 Hz and 340 Hz using an external stimulator. Data from six patients had to be discarded due to strong artefacts and two other datasets were excluded since these patients were not able to finalize the paradigm. After DBS artefact removal, power spectral density (PSD) values of MEG were calculated for each individual patient and averaged over the group. DBS at both 130 Hz and 340 Hz led to a widespread suppression of cortical alpha/beta band activity (8–22 Hz) specifically over bilateral sensorimotor cortices. No significant differences were observed between the two stimulation frequencies. Our finding of a widespread suppression of cortical alpha/beta band activity is particularly interesting as PD is associated with pathologically increased levels of beta band activity in the basal ganglia-thalamo-cortical circuit. Therefore, suppression of such oscillatory activity might be an essential effect of DBS for relieving motor symptoms in PD and can be achieved at different stimulation frequencies above 100 Hz.

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YNIMG Journal 2015 Journal Article

Language–motor interference reflected in MEG beta oscillations

  • Anne Klepp
  • Valentina Niccolai
  • Giovanni Buccino
  • Alfons Schnitzler
  • Katja Biermann-Ruben

The involvement of the brain's motor system in action-related language processing can lead to overt interference with simultaneous action execution. The aim of the current study was to find evidence for this behavioural interference effect and to investigate its neurophysiological correlates using oscillatory MEG analysis. Subjects performed a semantic decision task on single action verbs, describing actions executed with the hands or the feet, and abstract verbs. Right hand button press responses were given for concrete verbs only. Therefore, longer response latencies for hand compared to foot verbs should reflect interference. We found interference effects to depend on verb imageability: overall response latencies for hand verbs did not differ significantly from foot verbs. However, imageability interacted with effector: while response latencies to hand and foot verbs with low imageability were equally fast, those for highly imageable hand verbs were longer than for highly imageable foot verbs. The difference is reflected in motor-related MEG beta band power suppression, which was weaker for highly imageable hand verbs compared with highly imageable foot verbs. This provides a putative neuronal mechanism for language–motor interference where the involvement of cortical hand motor areas in hand verb processing interacts with the typical beta suppression seen before movements. We found that the facilitatory effect of higher imageability on action verb processing time is perturbed when verb and motor response relate to the same body part. Importantly, this effect is accompanied by neurophysiological effects in beta band oscillations. The attenuated power suppression around the time of movement, reflecting decreased cortical excitability, seems to result from motor simulation during action-related language processing. This is in line with embodied cognition theories.

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YNICL Journal 2014 Journal Article

Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

  • Bastian Cheng
  • Hanna Braass
  • Christos Ganos
  • Andras Treszl
  • Katja Biermann-Ruben
  • Friedhelm C. Hummel
  • Kirsten Müller-Vahl
  • Alfons Schnitzler

Gilles de la Tourette syndrome (GTS) is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico-striato-thalamo-cortical loops. We therefore applied structural diffusion tensor imaging (DTI) to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS). GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA) with basal ganglia (pre-SMA-putamen, SMA-putamen) and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.

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YNIMG Journal 2013 Journal Article

Audio–visual congruency alters power and coherence of oscillatory activity within and between cortical areas

  • Joachim Lange
  • Nadine Christian
  • Alfons Schnitzler

Dynamic communication between functionally specialized, but spatially distributed areas of the brain is essential for effective brain functioning. A candidate mechanism for effective neuronal communication is oscillatory neuronal synchronization. Here, we used magnetoencephalography (MEG) to study the role of oscillatory neuronal synchronization in audio–visual speech perception. Subjects viewed congruent audio–visual stimuli of a speaker articulating the vowels /a/ or /o/. In addition, we presented modified, incongruent versions in which visual and auditory signals mismatched. We identified a left hemispheric network for processing congruent audio–visual speech as well as network interaction between areas: low frequency (4–12Hz) power was suppressed for congruent stimuli at auditory onset around auditory cortex, while power in the high gamma (120–140Hz)-band was enhanced in the Broca's area around auditory offset. In addition, beta-power (20–30Hz) was suppressed in supramarginal gyrus for incongruent stimuli. Interestingly, coherence analysis revealed a functional coupling between auditory cortex and Broca's area for congruent stimuli demonstrated by an increase of coherence. In contrast, coherence decreased for incongruent stimuli, suggesting a decoupling of auditory cortex and Broca's area. In addition, the increase of coherence was positively correlated with the increase of high gamma-power. The results demonstrate that oscillatory power in several frequency bands correlates with the processing of matching audio-visual speech on a large spatio-temporal scale. The findings provide evidence that coupling of neuronal groups can be mediated by coherence in the theta/alpha band and that low frequency coherence and high frequency power modulations are correlated in audio–visual speech perception.

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YNIMG Journal 2012 Journal Article

Increased sensory feedback in Tourette syndrome

  • Katja Biermann-Ruben
  • Anastasia Miller
  • Stephanie Franzkowiak
  • Jennifer Finis
  • Bettina Pollok
  • Claudia Wach
  • Martin Südmeyer
  • Melanie Jonas

Tourette syndrome (TS) is a neuro-psychiatric disorder being characterized by motor and phonic tics typically preceded by sensory urges. Given the latter the role of the sensory system and sensorimotor interaction in TS has recently gained increased attention. 12 TS patients and 12 matched control subjects performed two tasks, requiring simple finger movements: a Go/NoGo task and a self paced movement task. Neurophysiological data was recorded using magnetoencephalography (MEG). Event related responses around movement onset, i. e. motor field (MF) occurring directly prior to the movement and movement evoked field (MEF) immediately after movement onset were analyzed using dipole modeling. MF peak amplitudes did not differ between groups in either task. In contrast, in both tasks MEF peak amplitudes were increased in TS patients. Moreover, larger MEF amplitudes during self paced movements were inversely correlated with motor tic frequency and severity. Enlarged MEF amplitudes as a marker of early sensory feedback of one's own movements probably represent enlarged sensory input from the periphery resulting from altered subcortical gating. We conclude that TS patients exhibit altered sensory–motor processing involved in voluntary movement control, which might also be successful in tic control.

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YNIMG Journal 2012 Journal Article

Lowered frequency and impaired modulation of gamma band oscillations in a bimodal attention task are associated with reduced critical flicker frequency

  • Nina Kahlbrock
  • Markus Butz
  • Elisabeth S. May
  • Meike Brenner
  • Gerald Kircheis
  • Dieter Häussinger
  • Alfons Schnitzler

Visual attention is associated with occipital gamma band activity. While gamma band power can be modulated by attention, the frequency of gamma band activity is known to decrease with age. The present study tested the hypothesis that reduced visual attention is associated with a change in induced gamma band activity. To this end, 26 patients with liver cirrhosis and 8 healthy controls were tested. A subset of patients showed symptoms of hepatic encephalopathy (HE), a frequent neuropsychiatric complication in liver disease, which comprises a gradual increase of cognitive dysfunction including attention deficits. All participants completed a behavioral task requiring shifts of attention between simultaneously presented visual and auditory stimuli. Brain activity was recorded using magnetoencephalography (MEG). The individual critical flicker frequency (CFF) was assessed as it is known to reliably reflect the severity of HE. Results showed correlations of behavioral data and HE severity, as indexed by CFF. Individual visual gamma band peak frequencies correlated positively with the CFF (r=0. 41). Only participants with normal, but not with pathological CFF values showed a modulation of gamma band power with attention. The present results suggest that CFF and attentional performance are related. Moreover, a tight relation between the CFF and occipital gamma band activity both in frequency and power is shown. Thus, the present study provides evidence that a reduced CFF in HE, a disease associated with attention deficits, is closely linked to a slowing of gamma band activity and impaired modulation of gamma band power in a bimodal attention task.

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YNIMG Journal 2012 Journal Article

Pre- and post-stimulus alpha activity shows differential modulation with spatial attention during the processing of pain

  • Elisabeth S. May
  • Markus Butz
  • Nina Kahlbrock
  • Nienke Hoogenboom
  • Meike Brenner
  • Alfons Schnitzler

Extensive work using magneto- and electroencephalography (M/EEG) suggests that cortical alpha activity represents a top-down controlled gating mechanism employed by processes like attention across different modalities. However, it is not yet clear to what extent this presumed gating function of alpha activity also applies to the processing of pain. In the current study, a spatial attention paradigm was employed requiring subjects to attend to painful laser stimuli on one hand while ignoring stimuli on the other hand. Simultaneously, brain activity was recorded with MEG. In order to disentangle pre- and post-stimulus effects of attention, alpha activity was analyzed during time windows in anticipation of and in response to painful laser stimulation. Painful laser stimuli led to a suppression of alpha activity over both ipsi- and contralateral primary somatosensory areas irrespective if they were attended or ignored. Spatial attention was associated with a lateralization of anticipatory pre-stimulus alpha activity. Alpha activity was lower over primary somatosensory areas when the contralateral hand was attended compared to when the ipsilateral hand was attended, in line with the notion that oscillatory alpha activity regulates the flow of incoming information by engaging and/or disengaging early sensory areas. On the contrary, post-stimulus alpha activity, for stimuli on either hand, was consistently decreased with attention over contralateral areas. Most likely, this finding reflects an increased cortical activation and enhanced alerting if a painful stimulus is attended. The present results show that spatial attention results in a modulation of both pre- and post-stimulus alpha activity associated with pain. This flexible regulation of alpha activity matches findings from other modalities. We conclude that the assumed functional role of alpha activity as a top-down controlled gating mechanism includes pain processing and most likely represents a unified mechanism used throughout the brain.

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YNIMG Journal 2012 Journal Article

Sustained gamma band synchronization in early visual areas reflects the level of selective attention

  • Nina Kahlbrock
  • Markus Butz
  • Elisabeth S. May
  • Alfons Schnitzler

Cortical gamma band synchronization is associated with attention. Accordingly, directing attention to certain visual stimuli modulates gamma band activity in visual cortical areas. However, gradual effects of attention and behavior on gamma band activity in early visual areas have not yet been reported. In the present study, the degree of selective visual attention was gradually varied in a cued bimodal reaction time paradigm using audio-visual stimuli. Brain activity was recorded with magnetoencephalography (MEG) and analyzed with respect to time, frequency, and location of strongest response. Reaction times to visual and auditory stimuli reflected three presumed graded levels of visual attention (high, medium, and low). MEG data showed sustained gamma band synchronization in all three conditions in early visual areas (V1 and V2), while the intensity of gamma band synchronization increased with the level of visual attention (from low to high). Differences between conditions were seen for up to 1600ms. The current results show that in early visual areas the level of gamma band synchronization is related to the level of attention directed to a visual stimulus. These gradual and long-lasting effects highlight the key role of gamma band synchronization in early visual areas for selective attention.

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YNIMG Journal 2010 Journal Article

Functional network interactions during sensorimotor synchronization in musicians and non-musicians

  • Vanessa Krause
  • Alfons Schnitzler
  • Bettina Pollok

Precise timing as determined by sensorimotor synchronization is crucial for a wide variety of activities. Although it is well-established that musicians show superior timing as compared to non-musicians, the neurophysiological foundations – in particular the underlying functional brain network – remain to be characterized. To this end, drummers, professional pianists and non-musicians performed an auditory synchronization task while neuromagnetic activity was measured using a 122-channel whole-head magnetoencephalography (MEG) system. The underlying functional brain network was determined using the beamformer approach Dynamic Imaging of Coherent Sources (DICS). Behaviorally, drummers performed less variably than non-musicians. Neuromagnetic analysis revealed a cerebello-thalamo-cortical network in all subjects comprising bilateral primary sensorimotor cortices (S1/M1), contralateral supplementary motor and premotor regions (SMA and PMC), thalamus, posterior parietal cortex (PPC), ipsilateral cerebellum and bilateral auditory cortices. Stronger PMC–thalamus and PPC–thalamus interactions at alpha and beta frequencies were evident in drummers as compared to non-musicians. In professional pianists stronger PMC–thalamus interaction as compared to non-musicians at beta frequency occurred. The present data suggest that precise timing is associated with increased functional interaction within a PMC–thalamus–PPC network. The PMC–thalamus connectivity at beta frequency might be related to musical expertise, whereas the PPC–thalamus interaction might have specific relevance for precise timing.

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YNIMG Journal 2006 Journal Article

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

  • Klaus Kessler
  • Katja Biermann-Ruben
  • Melanie Jonas
  • Hartwig Roman Siebner
  • Tobias Bäumer
  • Alexander Münchau
  • Alfons Schnitzler

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.

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YNIMG Journal 2006 Journal Article

Oscillatory activity reflects the excitability of the human somatosensory system

  • Markus Ploner
  • Joachim Gross
  • Lars Timmermann
  • Bettina Pollok
  • Alfons Schnitzler

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 α-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.

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