Papers by Alfons Schnitzler
New England Journal of Medicine, 2013
Subthalamic stimulation reduces motor disability and improves quality of life in patients with ad... more Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.
Brain Structure and Function, 2015
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms o... more Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms of Parkinson's disease. A tripartite system of STN subdivisions serving motoric, associative, and limbic functions was proposed, mainly based on tracing studies, which are limited by low numbers of observations. The evidence is compelling and raises the question as to what extent these functional zones are anatomically segregated. The majority of studies indicate that there is anatomical overlap between STN functional zones. Using ultrahigh-resolution magnetic resonance imaging techniques it is now possible to visualize the STN with high spatial resolution, and it is feasible that in the near future stereotactic guided placement of electrical stimulators aided by high-resolution imaging will allow for more specific stimulation of the STN. The neuroanatomical and functional makeup of these subdivisions and their level of overlap would benefit from clarification before serving as surgical targets. We discuss histological and imaging studies, as well as clinical observations and electrophysiological recordings in DBS patients. These studies provide evidence for a topographical organization within the STN, although it remains unclear to what extent functionally and anatomically distinct subdivisions overlap.
European Urology Supplements, 2006
Brain Sciences, 2022
Background: Current approaches to detect the positions and orientations of directional deep-brain... more Background: Current approaches to detect the positions and orientations of directional deep-brain stimulation (DBS) electrodes rely on radiative imaging data. In this study, we aim to present an improved version of a radiation-free method for magnetic detection of the position and the orientation (MaDoPO) of directional electrodes based on a series of magnetoencephalography (MEG) measurements and a possible future solution for optimized results using emerging on-scalp MEG systems. Methods: A directional DBS system was positioned into a realistic head–torso phantom and placed in the MEG scanner. A total of 24 measurements of 180 s each were performed with different predefined electrode configurations. Finite element modeling and model fitting were used to determine the position and orientation of the electrode in the phantom. Related measurements were fitted simultaneously, constraining solutions to the a priori known geometry of the electrode. Results were compared with the results ...
Neuromodulation : journal of the International Neuromodulation Society, 2018
Target localization for deep brain stimulation (DBS) is a challenging step that determines not on... more Target localization for deep brain stimulation (DBS) is a challenging step that determines not only the correct placement of stimulation electrodes, but also influences the success of the DBS procedure as reflected in the desired clinical outcome of a patient. We report on the feasibility of DBS target localization in the subthalamic nucleus (STN) by long-latency somatosensory evoked potentials (LL-SSEPs) (>40Â msec) in Parkinson's disease (PD) patients. Micro-macroelectrode recordings were performed intraoperatively on seven PD patients (eight STN hemispheres) who underwent DBS treatment. LL-SSEPs were elicited by ipsi- and contralateral median nerve stimulation to the wrist. Four distinctive LL-SSEP components were elicited ("LL-complex" consisting of P80, N100, P140, and N200). The P80 appeared as the most visible and reliable intraoperative component. Localization of the "LL-complex" within the target was approved with typical microelectrode firing acti...
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2018
To assess whether high frequency oscillations (HFOs, >150 Hz), known to occur in basal ganglia... more To assess whether high frequency oscillations (HFOs, >150 Hz), known to occur in basal ganglia nuclei, can be observed in the thalamus. We recorded intraoperative local field potentials from the ventral intermediate nucleus (VIM) of the thalamus in patients with Essential Tremor (N = 16), Parkinsonian Tremor (3), Holmes Tremor (2) and Dystonic Tremor (1) during implantation of electrodes for deep brain stimulation. Recordings were performed with up to five micro/macro-electrodes that were simultaneously advanced to the stereotactic target. Thalamic HFOs occurred in all investigated tremor syndromes. A detailed analysis of the Essential Tremor subgroup revealed that medial channels recorded HFOs more frequently than other channels. The highest peaks were observed 4 mm above target. Macro- but not microelectrode recordings were dominated by peaks in the slow HFO band (150-300 Hz), which were stable across several depths and channels. HFOs occur in the thalamus and are not specific ...
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, Jan 17, 2018
Magnetoencephalography (MEG) records weak magnetic fields outside the human head and thereby prov... more Magnetoencephalography (MEG) records weak magnetic fields outside the human head and thereby provides millisecond-accurate information about neuronal currents supporting human brain function. MEG and electroencephalography (EEG) are closely related complementary methods and should be interpreted together whenever possible. This manuscript covers the basic physical and physiological principles of MEG and discusses the main aspects of state-of-the-art MEG data analysis. We provide guidelines for best practices of patient preparation, stimulus presentation, MEG data collection and analysis, as well as for MEG interpretation in routine clinical examinations. In 2017, about 200 whole-scalp MEG devices were in operation worldwide, many of them located in clinical environments. Yet, the established clinical indications for MEG examinations remain few, mainly restricted to the diagnostics of epilepsy and to preoperative functional evaluation of neurosurgical patients. We are confident that ...
The Lancet. Neurology, 2018
Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson&#... more Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outc...
Frontiers in Human Neuroscience, 2017
Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF... more Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF) like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC) has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC) in 39 PD patients and 44 age-and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF) and under their regular dopaminergic medication (ON). We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC) and left dorsal premotor region (PMd) in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC) in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part.
BMC neurology, Jan 21, 2017
The introduction of deep brain stimulation (DBS) about 25Â years ago provided one of the major bre... more The introduction of deep brain stimulation (DBS) about 25Â years ago provided one of the major breakthroughs in the treatment of Parkinson's disease (PD). However, a high percentage of patients are reluctant to undergo DBS. Previous research revealed that the critical step on the patient's path to DBS is the decision whether to undergo further diagnostic assessment for surgery at a specialized DBS-center. The aims of the current study were to evaluate how effective the combination of an outpatient DBS screening tool, STIMULUS, with specially developed educational material was to enhance patient education on DBS and to identify motivational aspects which influenced the patients' willingness to undergo further assessment. In total, 264 patients were identified as appropriate candidates for DBS by general neurologists using the electronic preselection tool STIMULUS. Patient-centered information material was designed and handed out to support education on DBS. Further, severa...
Frontiers in Human Neuroscience, 2016
F1000 - Post-publication peer review of the biomedical literature, 2008
Cognitive deficits are very common in Parkinson's disease particularly for 'executive functions' ... more Cognitive deficits are very common in Parkinson's disease particularly for 'executive functions' associated with frontal cortico-striatal networks. Previous work has identified deficits in tasks that require attentional control like task-switching, and reward-based tasks like gambling or reversal learning. However, there is a complex relationship between the specific cognitive problems faced by an individual patient, their stage of disease and dopaminergic treatment. We used a bimodality continuous performance task during fMRI to examine how patients with Parkinson's disease represent the prospect of reward and switch between competing task rules accordingly. The task-switch was not separately cued but was based on the implicit reward relevance of spatial and verbal dimensions of successive compound stimuli. Nineteen patients were studied in relative 'on' and 'off' states, induced by dopaminergic medication withdrawal (Hoehn and Yahr stages 1^4). Patients were able to successfully complete the task and establish a bias to one or other dimension in order to gain reward. However the lateral prefrontal cortex and caudate nucleus showed a non-linear U-shape relationship between motor disease severity and regional brain activation. Dopaminergic treatment led to a shift in this U-shape function, supporting the hypothesis of differential neurodegeneration in separate motor and cognitive cortico^striato^thalamo^cortical circuits. In addition, anterior cingulate activation associated with reward expectation declined with more severe disease, whereas activation following actual rewards increased with more severe disease. This may facilitate a change in goal-directed behaviours from deferred predicted rewards to immediate actual rewards, particularly when on dopaminergic treatment. We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease.
Stereotactic and functional neurosurgery, 2009
Deep brain stimulation (DBS) of the globus pallidus internus (GPi) offers a very promising therap... more Deep brain stimulation (DBS) of the globus pallidus internus (GPi) offers a very promising therapy for medically intractable dystonia. However, little is known about the long-term benefit and safety of this procedure. We therefore performed a retrospective long-term analysis of 18 patients (age 12-78 years) suffering from primary generalized (9), segmental (6) or focal (3) dystonia (minimum follow-up: 36 months). Outcome was assessed using the Burke-Fahn-Marsden (BFM) scores (generalized dystonia) and the Tsui score (focal/segmental dystonia). Follow-up ranged between 37 and 90 months (mean 60 months). Patients with generalized dystonia showed a mean improvement in the BFM movement score of 39.4% (range 0-68.8%), 42.5% (range -16.0 to 81.3%) and 46.8% (range -2.7 to 83.1%) at the 3- and 12-month, and long-term follow-up, respectively. In focal/segmental dystonia, the mean reduction in the Tsui score was 36.8% (range 0-100%), 65.1% (range 16.7-100%) and 59.8% (range 16.7-100%) at the...
Acta neurobiologiae experimentalis, 2000
Oscillations are a prominent feature of macroscopic human sensorimotor cortical activity as recor... more Oscillations are a prominent feature of macroscopic human sensorimotor cortical activity as recorded non-invasively with electroencephalography (EEG) and magnetoencephalography (MEG). The advent of whole-scalp MEG systems allowing rapid non-invasive recording from the entire cortex and accurate localisation of neural sources, and the development of refined signal analysis methods are important factors that led to an increasing interest in studies of sensorimotor oscillations during the last 10 years. Investigations on healthy subjects revealed frequency-specific localisation and modality-specific reactivity of 10 Hz and 20 Hz sensorimotor oscillations. Task-specific coherence between motor cortical and electromyographic oscillations, reflecting cortico-motoneuronal coupling, point towards a functional role of precentral oscillations in the cortical control of voluntary movements. Furthermore, abnormal cortico-motoneuronal coupling may underlie clinical symptoms of motor disorders, s...
Frontiers in Human Neuroscience, 2013
The Journal of Physiology, 2004
It has recently been shown that resting tremor in Parkinson's disease is associated with oscillat... more It has recently been shown that resting tremor in Parkinson's disease is associated with oscillatory neural coupling in an extensive cerebral network comprising a cerebello-diencephalic-cortical loop and cortical motor, somatosensory and posterior parietal areas contralateral to the tremor hand. The aim of the present study was to investigate whether this oscillatory brain network exclusively reflects a pathophysiological state in parkinsonian resting tremor or whether it constitutes a fundamental feature of physiological motor control. We investigated cerebro-muscular and cerebro-cerebral coupling in 11 healthy subjects imitating typical antagonistic parkinsonian tremor. We recorded brain activity with a 122-channel whole-head neuromagnetometer and surface EMGs of the forearm extensor. Analysis of cerebro-muscular and cerebro-cerebral coherence revealed oscillatory coupling in the same brain structures that comprise the oscillatory network of parkinsonian resting tremor. Interestingly, similar to parkinsonian resting tremor, cerebro-cerebral coherences often showed a significant peak at twice the simulated tremor frequency. The most striking differences between parkinsonian patients, as investigated in a previous study and healthy subjects imitating the antagonistic resting tremor were a reduction of the coupling between primary sensorimotor cortex and a diencephalic structure-most likely the thalamus-and an enhancement of the coupling between premotor and primary sensorimotor cortex. Our results indicate that the coupling of oscillatory activity within a cerebello-diencephalic-cortical loop constitutes a basic feature of physiological motor control. Thus, our data are consistent with the hypothesis that parkinsonian resting tremor involves oscillatory cerebro-cerebral coupling in a physiologically pre-existing network.
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Papers by Alfons Schnitzler