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Introduction Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. Recommendations This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. Conclusions The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online (https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf).

Background and Purpose: Neuroplastic alterations of cortical excitability and activity represent the likely neuro- physiological foundation of learning and memory formation. Beyond their induction, alterations of these processes by subsequent modification of cortical activity, termed metaplasticity, came into the focus of interest recently. Animal slice experiments demon- strated that neuroplastic excitability enhancements, or diminutions, can be abolished by consecutive subthreshold stimulation. These processes, termed de-potentiation, and de-depression, have so far not been explored in humans. Methods: We combined neuroplasticity induction by transcranial direct current stimulation (tDCS) applied to the hand area of primary motor cortex (M1), which can be used to induce long-lasting excitability enhancements or reductions, dependent on the polarity of stimulation, with short-lasting voluntary muscle contraction (VMC), which itself does not induce plastic cortical excitability changes. Corticospinal and intra-cortical M1 excitability were monitored by different transcranial magnetic stimulation (TMS) protocols. Results: VMC reduced or tended to reverse the anodal tDCS-driven motor cortical excitability enhancement and the cathodal tDCS-induced excitability diminution. Our findings thus demonstrate de-potentiation- and de-depression-like phenomena at the system level in the human motor cortex. Conclusion: This neurophysiological study may contribute to a better understanding of the balance between induction and reversal of plasticity associated with motor learning and rehabilitation processes.

Recent work has demonstrated that overt reading influences the excitability of the language-dominant hand motor cortex. However, this effect was related to speech output, whereas results on silent reading have been inconsistent, and have not allowed for systematic investigation of the different stages of word recognition. To investigate a possible modulation of the cortical excitability mediating hand movements through different stages of covert reading, motor evoked potentials (MEP) from hand muscles in right-handed subjects were recorded. We showed a significant increase of the excitability of the hand motor cortex of the dominant hemisphere during late stages of covert word reading, whereas processing of abstract shapes had no effect and covert articulation induced a decrease in hand motor cortex excitability. There was no significant change of MEP amplitudes during earlier stages of covert reading in the dominant hemisphere or in the non-dominant hemisphere. Our results demonstrate a functional connection between cortical networks mediating linguistic processing and hand movements without concurrent activation of the motor cortex through overt articulation at late stages of word reading, which have been shown to involve converging activation of classic left frontal language regions. We speculate that the effect reported here is related to a cortical network mediating gestures which are a part of verbal communication. This supports recent theories on language evolution which postulate that language emerged through manual gestures.

Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS M1 vs. TMS vertex ) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation within the same experiment: subjects indicated with their left foot when they (i) had finished reading, (ii) had judged whether the corresponding movement involved a hand rotation after simulating the hand movement, and (iii) had judged whether they would frequently encounter the action verb in a newspaper (TASK: silent reading, motor imagery, and frequency judgment). Response times were compared between TMS M1 and TMS vertex , both applied at different time points after stimulus onset (DELAY: 150, 300, 450, 600, and 750 ms). TMS M1 differentially modulated task performance: there was a significant facilitatory effect of TMS M1 for the imagery task only (about 88 ms), with subjects responding about 10% faster (compared to TMS vertex ). In contrast, response times for silent reading and frequency judgments were unaffected by TMS M1 . No differential effect of the time point of TMS M1 was observed. The differential effect of TMS M1 when subjects performed a motor imagery task (relative to performing silent reading or frequency judgments with the same set of verbs) suggests that the primary motor cortex is critically involved in processing action verbs only when subjects are simulating the corresponding movement. This task-dependent effect of hand motor cortex TMS on the processing of hand-related action verbs is discussed with respect to the notion of embodied cognition and the associationist theory.

Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.

In humans, transcranial direct current stimulation (tDCS) can be used to induce, depending on polarity, increases or decreases of cortical excitability by polarization of the underlying brain tissue. Cognitive enhancement as a result of tDCS has been reported. The purpose of this study was to test whether weak tDCS (current density, 57 microA/cm(2)) can be used to modify language processing. Fifteen healthy subjects performed a visual picture naming task before, during and after tDCS applied over the posterior perisylvian region (PPR), i.e. an area which includes Wernicke's area [BA 22]. Four different sessions were carried out: (1) anodal and (2) cathodal stimulation of left PPR and, for control, (3) anodal stimulation of the homologous region of the right hemisphere and (4) sham stimulation. We found that subjects responded significantly faster following anodal tDCS to the left PPR (p

Performance in a semantic task is speeded up for repeated stimuli compared to novel stimuli. This conceptual priming effect is related to a decrease in functional activation within the left inferior prefrontal cortex for repeated stimulus exposure (repetition suppression). However, in contrast to perceptual priming which is known to be very robust over long periods of time, previous studies on semantic priming focused on short-term effects. The present study combined a behavioral and functional imaging experiment to investigate long-term conceptual repetition priming (retention interval 3 days). We found a highly significant decrease of reaction time for word stimuli which were presented repeatedly after 3 days both compared to initial presentation and to a matched word list. The functional magnetic resonance imaging data showed a repetition suppression within the left inferior (BA45, BA47) and middle (BA9) frontal gyrus for the comparison of known with unknown words. These data demonstrate that even over a period as long as 3 days, a repetition suppression within the left frontal network involved in semantic decision can be found. Thus, priming-related mechanisms in the semantic network may be robust over several days.

Although language functions are, in general, attributed to the left hemisphere, it is still a matter of debate to what extent the cognitive functions underlying the processing of music are lateralized in the human brain. To investigate hemispheric specialization we evaluated the effect of different overt musical and linguistic tasks on the excitability of both left and right hand motor cortices using transcranial magnetic stimulation (TMS). Task-dependent changes of the size of the TMS-elicited motor evoked potentials were recorded in 12 right-handed, musically naive subjects during and after overt speech, singing and humming, i.e. the production of melody without word articulation. The articulation of meaningless syllables served as control condition. We found reciprocal lateralized effects of overt speech and musical tasks on motor cortex excitability. During overt speech, the corticospinal projection of the left (i.e. dominant) hemisphere to the right hand was facilitated. In contrast, excitability of the right motor cortex increased during both overt singing and humming, whereas no effect was observed on the left hemisphere. Although the traditional concept of hemispheric lateralization of music has been challenged by recent neuroimaging studies, our findings demonstrate that right-hemisphere preponderance of music is nevertheless present. We discuss our results in terms of the recent concepts on evolution of language and gesture, which hypothesize that cerebral networks mediating hand movement and those subserving language processing are functionally linked. TMS may constitute a useful tool to further investigate the relationship between cortical representations of motor functions, music and language using comparative approaches.

The combination of transcranial magnetic stimulation (TMS) with functional neuroimaging has expanded the potential of TMS for human brain mapping. The precise and reliable positioning of the TMS coil is not a simple task, however. Modern frameless stereotaxic systems allow investigators to base navigation either on the subject's structural magnetic resonance imaging (MRI), functional MRI data, or the use of functional neuroimaging data from the literature, so‐called “probabilistic approach.” The latter assumes consistency across individuals in the location of task‐related “activations” in standardized stereotaxic space. Conventional nonstereotaxic localization of brain areas is also a common method for defining the coil position. Our aim was to evaluate the accuracy of five different localization strategies in one single study. The left primary motor cortex (left M1‐Hand) was used as target region. Three approaches were based on real‐time frameless stereotaxy using information based on either anatomical or functional MRI. The remaining two strategies relied either on standard cranial landmarks (i.e., the International 10–20 EEG system) or a standardized function‐guided procedure (i.e., the spatial relationship between the left and right M1‐Hand). The results were compared to a TMS‐based mapping of the primary motor cortex; center of gravity of motor‐evoked potentials (MEP‐CoG) was calculated for each subject (n = 10). Our findings suggest that highest precision can be achieved with fMRI‐guided stimulation, which was accurate within the range of millimeters. Very consistent results were also obtained with the “probabilistic” approach. In view of these findings, we discuss the methods and special characteristics of each localization strategy. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.

Whereas it is widely accepted that the parietal cortex is crucial for visual attention, the role of the temporal cortex and the temporo-parietal junction (TPJ) is less clear. There are clinical reports of patients with lesions in different posterior temporal areas which exhibit contralateral visual neglect but this syndrome seems to be less frequent than in patients with parietal lesions. In a previous study, we could show that single-pulse transcranial magnetic stimulation (TMS) over the right inferior parietal cortex is capable to induce both neglect-like and extinction-like impairments of performance in normal subjects. In the present study, we used this method to examine the functional role of the superior temporal gyrus (STG) and the TPJ of the right hemisphere for visuo-spatial attention. Healthy volunteers were asked to detect small dots appearing for 40 ms unilaterally on right or left side or bilaterally on a computer screen. TMS was applied over the TPJ or STG. TMS over the TPJ induced an extinction-like behavioral pattern to the contralateral hemifield. TMS over the STG had no effect. The results demonstrate a functional involvement of the TPJ in visuo-attentional processing of competing stimuli in both hemifields. This region is part of the cortical network mediating stimulus-driven attention which is relevant for processing of competing stimuli.

We used single-pulse transcranial magnetic stimulation (TMS) to study visuospatial attention. TMS was applied over one hemisphere, or simultaneously over both the right and left posterior parietal cortex (PPC), at two different interstimulus intervals (ISI) during a visual detection task. Unilateral TMS over the right and left PPC, respectively, impaired detection of contralateral presented visual stimuli at an ISI of 150 ms. By contrast, simultaneous biparietal TMS induced no significant changes in correct stimulus detection. TMS at an ISI of 250 ms evoked no changes for magnetic stimulation over either the right or the left parietal cortex. These results suggest that both PPC play a crucial role at a relatively early stage in the widely distributed brain network of visuospatial attention. The abolition of behavioral deficits during simultaneous biparietal TMS underlines the common hypothesis that an interhemispheric imbalance might underlie the disorders of neglect and extinction seen following unilateral brain damage.

Causes of stroke in young adults include a variety of disorders that are less frequently seen in older patients. We report the case of a young patient, who suffered recurrent mild embolic infarctions from a free-floating thrombus formation of the internal carotid artery bulb. During preoperative preparation, the thrombus dislodged and led to middle cerebral artery occlusion and major stroke. Both during preoperative work-up and after thrombus displacement balanced fast field echo sequences were able to demonstrate thrombus with a high signal-to-noise ratio and a superior delineation of thrombus and flowing blood. The high contrast between blood and thrombus helped to establish the diagnosis, to plan subsequent treatment strategies and to follow closely the clinical course. Further studies have to show whether this technique might help in thrombus characterization.

Mycoplasma pneumoniae (M. pn.) ist eine haufige Ursache respiratorischer Infekte beim Menschen. Es wird geschatzt, dass in bis zu 5% der Falle periphere und zentrale neurologische Sekundarkomplikationen auftreten konnen. Wir berichten uber den Fall eines 38-jahrigen, bislang gesunden Mannes, der mit Somnolenz und Hemiplegie aufgenommen wurde, nachdem er zuvor einen fieberhaften Atemwegsinfekt erlitten hatte. Anhand des klinischen Verlaufes und der Laborbefunde konnte die Diagnose einer akuten M.-pn.-assoziierten Meningoenzephalitis gestellt werden. Es erfolgte eine aggressive, antibiotische und immunmodulatorische Therapie uber mehrere Wochen auf einer neurologischen Intensivstation. Obwohl lebensbedrohlich erhohte intrakranielle Hirndruckwerte nur mittels dekompressiver Hemikraniektomie beherrscht werden konnten, bot der Patient nach 3 Monaten nur geringe neurologische Ausfalle und konnte beruflich wieder eingegliedert werden. Auf der Basis dieser Fallschilderung geben wir einen Literaturuberblick und diskutieren mogliche Pathomechanismen, Differenzialdiagnosen sowie diagnostische Moglichkeiten.

Cerivastatin wurde als ein reversibler HMGCoA- Reduktase-Hemmer (Statin) erfolgreich in der Behandlung der Hypercholesterinamie eingesetzt bis die Substanz vom Markt genommen wurde, nachdem 52 Todesfalle durch Rhabdomyolyse mit akutem Nierenversagen unter der Therapie berichtet worden waren. In den meisten dieser Falle wurde Cerivastatin zusammen mit anderen Pharmaka eingesetzt, die den Lebermetabolismus von Cerivastatin uber Isoenzyme der Cytochrom-Oxidase P450 beeinflussten.Wir prasentieren den gut dokumentierten Fall einer akuten Rhabdomyolyse unter einer Cerivastatin-Monotherapie, dessen Diagnose auch durch eine Muskelbiopsie gesichert wurde.Abschliesend geben wir einen aktuellen Uberblick zum gegenwartigen Kenntnisstand zur Therapie mit HMG-CoA-Reduktase-Hemmern, ein Jahr nachdem Cerviastatin vom Hersteller vom Markt genommen wurde.

Objectives : Phosphene thresholds (PTs) to transcranial magnetic stimulation over the occipital cortex and motor thresholds (MTs) have been used increasingly as measures of the excitability of the visual and motor cortex. MT has been utilized as a guide to the excitability of other, non-motor cortical areas such as dorsolateral prefrontal cortex. The aims of this study were to compare the PTs to MTs; to assess their stability across sessions; and to investigate their relation to MTs. Methods : PTs and MTs were determined using focal transcranial magnetic stimulation over the visual and motor cortex. Results : PTs were shown to be significantly higher than MTs. Both PTs and MTs were stable across sessions. No correlation between PTs and MTs could be established. Conclusions : Phosphene threshold is a stable parameter of the visual cortex excitability. MTs were not related to the excitability of non-motor cortical areas.

Objective: To investigate the modulatory effect of a subthreshold low frequency repetitive transcranial magnetic stimulation (rTMS) train on motor cortex excitability. Methods: The study consisted of two separate experiments. Subjects received a 10 min long subthreshold 1Hz rTMS train. In the first experiment, (single pulse paradigm), cortical excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) before and after the rTMS train. In the second experiment, a paired pulse paradigm was employed. Results: Corticospinal excitability, as measured by the MEP amplitude, was reduced by the rTMS train (experiment 1), with a significant effect lasting for about 10 min after the train completion. There was notable inter-individual as well as intra-individual variability in the effect. rTMS produced a significant decrease in intra-cortical facilitation as measured by the paired pulse paradigm (experiment 2). This effect lasted for up to 15 min following the train. Intra-cortical inhibition was not significantly affected. Conclusions: Subthreshold low frequency rTMS depresses cortical excitability beyond the duration of the train. This effect seems primarily due to cortical dysfacilitation. These results have implications on the therapeutic use of rTMS. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Attention is a complex construct that comprises at least three major subcomponents: alerting, spatial (re-)orienting, and executive functions, all of which have specific neural correlates along frontoparietal networks. Attention deficits are a common consequence of brain damage. Transcranial direct current stimulation (tDCS) has been shown to modulate spatial attention. We investigated whether tDCS of different stimulation targets differentially modulates alerting, spatial (re-)orienting, and executive functions. Twenty-four healthy participants were included in this randomized, double-blinded study, which employed a within-subject design. On four different days, the effects of 1.5 mA anodal tDCS (real and sham) on the left dorsolateral (EEG 10–20 point F3), left parietal (P3) and right parietal cortex (P4) were assessed using a modified attention network test. tDCS of the right parietal cortex enhanced spatial re-orienting, while tDCS of the other cortical targets did not modulate the assessed attention functions. With regard to visual field asymmetries in attentional processing, right parietal tDCS selectively enhanced mean network efficiency for targets presented in the contralateral left visual field. The observed visual field specific tDCS effects on reorienting suggest that systematic investigations into novel approaches for the treatment of patients suffering from spatial neglect patients are warranted.

Objective : Simple reaction time (RT) can be influenced by transcranial magnetic stimulation (TMS) to the motor cortex. Since TMS differentially affects RT of ipsilateral and contralateral muscles a combined RT and TMS investigation sheds light on cortical motor control of bimanual movements. Methods : Ten normal subjects and one subject with congenital mirror movements (MM) were investigated with a RT paradigm in which they had to move one or both hands in response to a visual go-signal. Suprathreshold TMS was applied to the motor cortex ipsilateral or contralateral to the moving hand at various interstimulus intervals (ISIs) after presentation of the go-signal. EMG recordings from the thenar muscles of both hands were used to determine the RT. Results : TMS applied to the ipsilateral motor cortex shortened RT when TMS was delivered simultaneously with the go-signal. With increasing ISI between TMS and go-signal the RT was progressively delayed. This delay was more pronounced if TMS was applied contralateral to the moving hand. When normal subjects performed bimanual movements the TMS-induced changes in RT were essentially the same as if they had used the hand in an unimanual task. In the subject with MM, TMS given at the time of the go-signal facilitated both the voluntary and the MM. With increasing ISI, however, RT for voluntary movements and MM increased in parallel. Conclusions : Ipsilateral TMS affects the timing of hand movements to the same extent regardless of whether the hand is engaged in an unimanual or a bimanual movement. It can be concluded, therefore, that in normal subjects simple bimanual movements are controlled by each motor cortex independently. The results obtained in the subject with MM are consistent with the hypothesis that mirror movements originate from uncrossed corticospinal fibres. The alternative hypothesis that a deficit in transcallosal inhibition leads to MM in the contralateral motor cortex is not compatible with the presented data, because TMS applied to the motor cortex ipsilateral to a voluntary moved hand affected voluntary movements and MM to the same extent.

Study objectives To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) in patients with narcolepsy. Design Using rTMS, three patients with narcolepsy and cataplexy were investigated with and without their anticataplectic medication. rTMS of the motor cortex was performed at an intensity of 110% of resting motor threshold, a frequency of 20 Hz, and a duration of 2s. EMG activity was recorded for both the right and left first dorsal interosseous muscle (FDI). Eight healthy controls were also investigated under the same conditions. Setting The study was carried out in the sleep laboratory of the Neurology Department (University of Aachen). Patients One female and two male patients with narcolepsy/cataplexy. Interventions N/A. Measurements and results In three narcoleptic patients, after three days of not taking their usual anticataplectic medication, rTMS of the motorcortex induced an interruption of voluntary EMG activity in the FDI. EMG reduction lasted from 0.6 to 3.5s and was more pronounced in the hand contralateral to the stimulated hemisphere. This result was not observed in these patients when taking their regular medication nor in the normal controls. Stimulation of other cortical areas, as well as stimulation of the peripheral nervous system, did not induce muscle weakness episodes. Conclusions We postulate that rTMS of the descending voluntary motor pathway triggers muscle atonia similar to cataplexy by indirectly activating the mechanisms responsible for the generation of muscle atonia during REM sleep and cataplexy. We conclude that rTMS, in the future, might prove to be a useful addition to the diagnostic repertoire for narcolepsy.

We performed functional magnetic resonance imaging (MRI) in professional piano players and control subjects during an overtrained complex finger movement task using a blood oxygenation level dependent echo-planar gradient echo sequence. Activation clusters were seen in primary motor cortex, supplementary motor area, premotor cortex and superior parietal lobule. We found significant differences in the extent of cerebral activation between both groups with piano players having a smaller number of activated voxels. We conclude that, due to long-term motor practice a different cortical activation pattern can be visualized in piano players. For the same movements lesser neurons need to be recruited. The different volume of the activated cortical areas might therefore reflect the different effort necessary for motor performance in both groups.

Most cervical artery dissections occur spontaneously, but traumatic mechanisms can occasionally be identified. Traumatic internal carotid artery dissection has been attributed with several sports, but there are no reports of its occurrence in thriathlon. We report the case of a 63-year-old semi-professional triathlete, who noticed right-sided neck pain and parietooccipital headache after a triathlon competition. Neurological examination revealed an incomplete right Horner's syndrome. MRI and MR-angiography demonstrated a right-sided internal carotid artery dissection with segmental loss of flow-signal and a mural haematoma in the vessel wall. In this case two pathophysiological mechanisms may be considered. Our patient reported receiving several blows to the neck in a congested 50-metre pool during the triathlon swimming stage. Furthermore, the hyperextended position of the neck during the subsequent cycling stage may have contributed, to a large extent, to the arterial dissection. The risk factors, presenting symptoms, diagnosis of internal carotid artery dissection are reviewed.

Transcranial direct current stimulation (tDCS) is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16) were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min). Bromodeoxyuridine (BrdU) was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC). Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

The right intraparietal sulcus (rIPS) is a key region for the endogenous control of selective visual attention in the human brain. Previous studies suggest that the rIPS is especially involved in top-down control and spatial distribution of attention across both visual hemifields. We further explored these attentional functions using transcranial direct current stimulation (tDCS) of the rIPS to modulate behavioral performance in a partial report task. Performance was analyzed according to the theory of visual attention (TVA) (Bundesen, 1990), which provides a computational framework to investigate different parameters of visuo-attentional processing such as top-down control, attentional weighting, capacity of visual short term memory, and processing speed. We investigated the effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1 mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by a reduction of the α parameter of TVA, regardless of hemifield. This differential impact on the top-down control component of attentional processing suggests that the horizontal rIPS is mainly involved in attentional selection as none of the spatial or resource variables of TVA were altered. Furthermore, the data add evidence to previous work highlighting (1) the importance of using appropriate current strength in stimulation protocols, and (2) that the often reported inhibitory effect of cathodal stimulation in e.g., motor tasks might not extend to cognitive paradigms.

Neglect is a multifaceted, complex syndrome, in which patients fail to detect or respond to stimuli or parts thereof located contralesionally. Non-invasive brain stimulation by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) may not only be useful as diagnostic research tools to explore the pathophysiology of neglect, but also for ameliorating its symptoms. Current approaches for modulating neglect non-invasively are mainly based on the neurophysiological concept of interhemispheric inhibition, which suggests a pathological overactivation of the contralesional hemisphere due to reduced inhibitory influences from the lesioned one. Within this framework, non-invasive brain stimulation mainly aims to inhibit the contralesional hemisphere to allow for rebalancing the system. However, facilitatory protocols for enhancing the ipsilesional neural circuitry might also prove useful. In this review, we discuss the contribution of non-invasive brain stimulation to current pathological concepts of neglect, the promising results of the proof-of-principle studies currently available as well as the specific aspects to be systematically investigated before broader clinical trials may eventually suggest a routine clinical application.

The neural substrates of auditory motion processing are, at present, still a matter of debate. It has been hypothesized that motion information is, as in the visual system, processed separately from other aspects of auditory information, such as stationary location. Here we aimed to differentiate the location of auditory motion processing in human cortex using low-frequency repetitive transcranial magnetic stimulation (rTMS) in combination with a psychophysical task of motion discrimination. rTMS was applied offline to right posterior superior temporal gyrus, right inferior parietal lobule, right dorsal premotor cortex, or right primary somatosensory cortex (as reference site). A significant decrease in performance was obtained exclusively for sounds presented in left hemispace after rTMS over the right inferior parietal lobule (BA 40). This finding indicates that the inferior parietal lobule plays a crucial role in the analysis of moving sound, with an apparent contralaterality of cortical processing. Combined with previous studies which have demonstrated effects of rTMS on static sound localization for both inferior parietal and posterior temporal cortices, the results suggest a hierarchical processing of auditory spatial information, with higher-order functions of motion analysis, such as discrimination of motion direction, mainly taking place beyond the temporal lobe.

Transcranial direct current stimulation is a painless, non-invasive brain stimulation technique that allows one to induce polarity-specific excitability changes in the human brain. Here, we investigated, for the first time in a 'proof of principle' study, the behavioural effect of transcranial direct current stimulation on visuospatial attention in both healthy controls and stroke patients suffering from left visuospatial neglect. We applied anodal, cathoP:dal or sham transcranial direct current stimulation (57 microA/cm(2), 10 min) to the left or right posterior parietal cortex. Using a visual detection task in a group of right-handed healthy individuals (n = 20), we observed that transcranial direct current stimulation enhanced or impaired performance depending on stimulation parameters (i.e. current polarity) and stimulated hemisphere. These results are in good accordance with classic models of reciprocal interhemispheric competition ('rivalry'). In a second experiment, we investigated the potential of transcranial direct current stimulation to ameliorate left visuospatial neglect (n = 10). Interestingly, both the inhibitory effect of cathodal transcranial direct current stimulation applied over the unlesioned posterior parietal cortex and the facilitatory effect of anodal transcranial direct current stimulation applied over the lesioned posterior parietal cortex reduced symptoms of visuospatial neglect. Taken together, our findings suggest that transcranial direct current stimulation applied over the posterior parietal cortex can be used to modulate visuospatial processing and that this effect is exerted by influencing interhemispheric reciprocal networks. These novel findings also suggest that a transcranial direct current stimulation-induced modulation of interhemispheric parietal balance may be used clinically to ameliorate visuospatial attention deficits in neglect patients.

Human speech and hand use both involve highly specialized complex movement patterns. Whereas previous studies in detail characterized the cortical motor systems mediating speech and finger movements, the network that provides coordination of concurrent speech and hand movements so far is unknown. Using functional magnetic resonance imaging (fMRI), the present study investigated differential cortical networks devoted to speech or fingertapping, and regions mediating integration of these complex movement patterns involving different effectors. The conjunction contrasts revealing regions activated both during sole fingertapping and sole repetitive articulation or reading aloud showed contralateral regions at the border of ventral and dorsal motor cortex. In contrast, the analyses revealing regions showing a higher level of fMRI activation for concurrent movements of both effectors compared with sole hand movements or repetitive articulation or reading aloud showed distinct premotor activations, which were situated dorsal and caudal to the areas activated across speech and fingertapping tasks. These results indicate that the premotor cortex (PMC) subserves coordination of concurrent speech with hand movements. This integrative motor region is not identical with the area that shows overlapping activations for speech and fingertapping. Thus, concurrent performance of these complex movement patterns involving different effectors requires, in addition to somatotopic motor cortex activation, orchestration subserved by a distinct PMC area.

Action understanding and learning are suggested to be mediated, at least in part, by the human mirror neuron system (hMNS). Static images as well as videos of actions with the outcome occluded have been shown to activate the hMNS. However, whether the hMNS preferentially responds to end or means of an action remains to be investigated. We, therefore, presented subjects with videos of intentional actions that were shown from two perspectives (factor 1, perspective: first vs. third person) while subjects directed their attention to the means or the end thereof (factor 2, task: means vs. end). End- or means-related changes in BOLD signal and corticospinal excitability (CSE) were assessed using fMRI and TMS, respectively. Judging the means of an action compared with its end differentially activated bilateral ventral premotor (vPMC) and inferior parietal cortex (IPL), that is, the core regions of the hMNS. The reverse contrast revealed left precuneus and bilateral superior frontal, angular, and middle temporal gyrus activity. In accordance, the two tasks, although identically in stimulus properties, modulated CSE differentially. Although recent studies suggest that the hMNS may prefer the presence of a goal or context, our data show that within the same context, it responds preferentially when attention is directed to the action means. Consequently, in addition to inferring action goals, a key function of the hMNS may be to anticipate the trajectories and dynamics of observed actions, which is a prerequisite for any timely interaction.

A 37-year-old woman was admitted to our department with general fatigue, fever, and asymmetric pain in her lower legs, 2 weeks after a common cold. Dynamic skeletal scintigraphy with 780 MBq (20 mCi) Tc-99m HDP revealed increased perfusion and tracer uptake in the soft tissue of the lower legs, suggesting an inflammatory etiology. A muscle biopsy revealed a vasculitic necrotizing myopathy predominantly affecting the small vessels of the lower legs. We diagnosed it as a postinfectious immunologic reaction.

Investigations in macaques and humans have shown that the anterior intraparietal sulcus (IPS) has an important function in the integration of information from tactile and visual object manipulation. The goal of this study was to investigate the special functional role of the anterior IPS in visuo-tactile matching in humans. We used the "virtual-lesion" technique of repetitive transcranial magnetic stimulation (rTMS) to test the functional relevance of anterior IPS for visuo-tactile crossmodal matching. Two crossmodal (visual encoding and tactile recognition and vice versa) and two unimodal delayed matching-to-sample tests with geometrical patterns were performed by 12 healthy subjects. We determined error rates before and after focal low-frequency rTMS applied over the left anterior IPS, right anterior IPS and vertex. During the manipulation of objects with the right hand, rTMS over the left anterior IPS induced a significant deterioration for visual encoding and tactile recognition, but not for tactile encoding and visual recognition. For the visual and tactile unimodal conditions, no significant alterations in task performance were found. rTMS application over right IPS when manipulating objects with the left hand did not affect crossmodal task performance. In conclusion, we have demonstrated an essential functional role of the left anterior IPS for visuo-tactile matching when manipulating objects with the right hand. However, we found no clear evidence for left IPS involvement in tactile encoding and visual recognition. The differential effect of rTMS on tactile and visual encoding and recognition are not consistently explained by previous concepts of visuo-tactile integration.

Akinetic crisis (AC) is a much-feared complication of Parkinson's disease (PD) which may appear upon abrupt cessation or malabsorption of dopaminergic medication due to gastrointestinal tract disorders or acute surgery. Intravenous infusion of amantadine sulphate or subcutaneous administration of apomorphine are established treatment strategies for AC. We speculate whether the use of a non-invasive transdermal application form (patch) of a dopaminergic drug (rotigotine) may represent a useful alternative treatment option. We describe the successful treatment of severe AC using rotigotine in a PD patient with gastro-oesophageal ulcers which precluded administration of any oral medication. This case demonstrates that a rotigotine patch might be effective in the treatment of AC. We suggest that rotigotine may represent a useful treatment option due to its favourable receptor profile and unique application form. In particular, it may be helpful in situations that might provoke AC, such as acute surgery. However, experience of the use of the rotigotine patch in this clinical setting is rather sparse and the patch is currently not approved for this indication.

In humans, hyperventilation (HV) has various effects on systemic physiology and, in particular, on neuronal excitability and synaptic transmission. However, it is far from clear how the effects of HV are mediated at the cortical level. In this study we investigated the effects of HV-induced hypocapnia on primary motor (M1) and visual cortex (V1) excitability. We used 1) motor threshold (MT) and phosphene threshold (PT) and 2) stimulus-response (S-R) curves (i.e., recruitment curves) as measures of excitability. In the motor cortex, we additionally investigated 3) the intrinsic inhibitory and facilitatory neuronal circuits using a short-interval paired-pulse paradigm. Measurements were performed before, during, and after 10 min of HV (resulting in a minimum end-tidal Pco2 of 15 Torr). HV significantly increased motor-evoked potential (MEP) amplitudes, particularly at lower transcranial magnetic stimulation (TMS) intensities. Paired-pulse stimulation indicated that HV decreases intracortical inhibition (ICI) without changing intracortical facilitation. The results suggestthat low Pco2 levels modulate, in particular, the intrinsic neuronal circuits of ICI, which are largely mediated by neurons containing γ-aminobutyric acid. Modulation of MT probably resulted from alterations of Na+ channel conductances. A significant decrease of PT, together with higher intensity of phosphenes at low stimulus intensities, furthermore suggested that HV acts on the excitability of M1 and V1 in a comparable fashion. This finding implies that HV also affects other brain structures besides the corticospinal motor system. The further exploration of these physiological mechanisms may contribute to the understanding of the various HV-related clinical phenomenona.

Areas around the horizontal part of the intraparietal sulcus (hIPS) have repeatedly been reported to participate in processing numerical magnitude. Using transcranial magnetic stimulation (TMS), we investigated the functional role of the hIPS by examining two effects from the domain of numerical cognition: in magnitude comparison tasks response latencies are inversely related to the numerical distance between two numbers. This distance effect indexes access to the mental number representation. In magnitude comparison tasks responses are faster when decade and unit comparison would lead to the same decision (e.g. 42_57, 45 and 27) than when they would not (e.g. 47_62, 46 but 72). This compatibility effect reflects unit-decade integration processes. Differential susceptibility of (fe)male participants to TMS was examined. We applied repetitive TMS (rTMS; 1Hz for 10 min) over the left hIPS in 12 participants (6 female). No stimulation and vertex stimulation served as control conditions. The effect of rTMS was mediated by gender: in male participants, the distance effect decreased after TMS over hIPS. For female participants distance and compatibility effect both increased. This modulation of the compatibility effect was limited in duration to no more than 4 min. The hIPS seems to be functionally involved both in number magnitude processing and in integrating unit-decade magnitude information of two-digit numbers. Relative hemispheric specialization of the hIPS with respect to two-digit magnitude comparison is discussed.

Previous data indicate that in healthy subjects, there is a connectivity between cortical areas for hand movement and language on the left hemisphere. This link is possibly mediated by the so-called mirror neuron system. The present study investigated the functional relationship between linguistic and hand movement processing in patients who were recovering from post-stroke aphasia. The excitability of the right- and left-hand motor cortex during language production in patients who were recovering from post-stroke aphasia and age-matched controls was investigated. As control, phonation was investigated. Hand motor cortex excitability was assessed with Motor Evoked Potentials which were elicited by Transcranial Magnetic Stimulation (TMS). In patients, reading aloud enhanced the excitability of the right hemispheric hand motor cortex, whereas phonation had no effect on hand motor cortex excitability. In the control group, an increased excitability of the left hemispheric hand motor system was found during reading aloud in accordance with previous data. The present data suggest a functional connectivity between regions mediating hand movements and reading. This may indicate that the right hemisphere participates in language processing as far as involved in single word reading in patients recovering from aphasia. The coactivation between cerebral representations of hand movements and language may be used therapeutically for aphasia rehabilitation.

Previous studies using short-interval paired-pulse TMS have provided valuable insights into physiology of human motor cortex. Depending on the interstimulus interval (ISI) between the two pulses intra-cortical facilitation (ICF) or intra-cortical inhibition (ICI) can be observed. Similar patterns of inhibition and facilitation have also been demonstrated in prefrontal and parietal cortices. In order to prove whether principles that govern cortical excitability in the motor system also extend to the visual system and to further characterize possible neural correlates of phosphene generation, we applied short-interval paired-pulse TMS to the occipital cortex. In addition, we examined the effect of different coil orientations on perception of phosphenes induced by paired-pulse TMS. In all of 10 healthy subjects, a general facilitation of phosphene perception could be observed for interstimulus intervals of 2–12 ms (conditioning stimulus (CS) 90% and test stimulus (TS) 100% of subject's phosphene threshold) compared to TS alone. With CS intensity decreasing to 80% or less, the effect diminished. No significant changes occurred when TS intensity was increased to 110%. Phosphene perception was enhanced with an induced current direction from lateral to medial at an ISI of 12 ms. Inhibition was not observed in any condition. Our results indicate that the mechanisms underlying phosphene induction in the visual cortex are different from those underlying intracortical inhibition and facilitation in the motor cortex.

upper eyelids (figure, A, arrows). She was seen by doctors who applied topical mydriatic drops, and examined her eyes thoroughly, but found nothing unusual, and made a working diagnosis of an allergic reaction. 3 days later, the patient developed a headache and consulted an orthopaedic specialist and a practitioner of alternative medicine, neither of whom made a specific diagnosis. On day 6, she presented to our hospital. Her medical history was unremarkable and she was not prone to headaches. Blood pressure, body temperature, and routine blood tests were in the normal range. The patient had a body mass index of 32·2. We did a neurological examination and found slightly exaggerated left-sided tendon jerks. A contrastenhanced angio-CT showed thrombosis of the sagittal superior sinus and both transverse sinuses (figure, B, arrows). We diagnosed an aseptic cerebral venous thrombosis, and gave her intravenous heparin. The eyelid oedema decreased the following day (figure, C) and a second ophthalmic examination showed bilateral papilloedema (figure, D). Tests for thrombophilia were negative. Following 6 months of oral anticoagulation, the veins partially recanalised. Eyelid oedema is a typical finding in cases of septic thrombosis of the cavernous sinus, but can also occur with aseptic thrombosis of the sagittal sinus. The venous drainage from the eyelids via the venae ophthalmicae into the cavernous sinus is probably impaired by elevated intracranial pressure as well as by the compensatory elevated flow in the emissary veins, through the diploe into the veins of the forehead. In this case the eyelid oedema preceded the more common symptoms of cerebral venous thrombosis—namely headache, neurological signs, and papilloedema, by a few days. Clinical Picture

Mycoplasma pneumoniae (M. pn.) commonly causes respiratory tract infections in humans. In a certain percentage of cases it may also be associated with various peripheral and central nervous system manifestations. We report a case of a 38-year-old previously healthy man who presented with hemiplegia and somnolence after he had suffered from a febrile respiratory infection 10 days earlier. Clinical features and laboratory investigations supported the diagnosis of an acute M. pneumoniae-associated meningoencephalitis. He was treated by an aggressive antibiotic and immunomodulatory regimen over the course of several weeks in the neurocritical care unit. Decompressive hemicraniectomy was performed due to life-threatening raised intracranial pressure. However, the patient recovered almost completely and presented with a mild neurological deficit after 3 months. Based on this case we give a review of the literature and discuss potential pathomechanisms and diagnostic approaches.

Neuroimaging studies have suggested an evolution of the brain activation pattern in the course of motor recovery after stroke. Initially poor motor performance is correlated with an recruitment of the uninjured hemisphere that continuously vanished until a nearly normal (contralateral) activation pattern is achieved and motor performance is good. Here we were interested in the early brain activation pattern in patients who showed a good and rapid recovery after stroke.Ten patients with first-ever ischemic stroke affecting motor areas had to perform self-paced simple or more complex movements with the affected or the unaffected hand during functional magnetic resonance imaging (fMRI). The location and number of activated voxels above threshold were determined. To study possible changes in the cortical motor output map the amplitude of the motor evoked potentials (MEP) and the extent of the excitable area were determined using transcranial magnetic stimulation (TMS).The pattern of activation observed with movements of the affected and the unaffected hand was similar. In the simple motor task significant (P0.05) increases were found in the primary motor cortex ipsilateral to the movement, the supplementary motor area and the cerebellar hemisphere contralateral to the movement during performance with the affected hand compared to movements with the unaffected hand. When comparing simple with more complex movements performed with either the affected or the unaffected hand, a further tendency to increased activation in motor areas was observed. The amplitude of MEPs obtained from the affected hemisphere was smaller and the extent of cortical output maps was decreased compared to the unaffected hemisphere; but none of the patients showed MEPs at the affected hand when the ipsilateral unaffected motor cortex was stimulated.Despite a rapid and nearly complete motor recovery the brain activation pattern was associated with increased activity in (bilateral) motor areas as revealed with fMRI. TMS revealed impaired motor output properties, but failed to demonstrate ipsilateral motor pathways. Successful recovery in our patients may therefore rely on the increased bilateral activation of existing motor networks spared by the injury.

Objective : Phantom pain is linked to a reorganization of the partially deafferented sensory cortex. In this study we have investigated whether the pain syndrome can be influenced by repetitive transcranial magnetic stimulation (rTMS). Methods : Two patients with a longstanding unilateral avulsion of the lower cervical roots and chronic pain in the arm were studied. As a control the acute effects of rTMS (15 Hz, 2 s duration) on pain were studied in 4 healthy subjects. Pain intensity was assessed with the Visual Analogue Scale. Results : Stimulation of the contralateral parietal cortex led to a reproducible reduction in pain intensity lasting up to 10 min. Stimulation of other cortical areas produced only minor alterations in the severity of the pain. Both 1 and 10 Hz rTMS trains applied to the contralateral parietal cortex on weekdays for 3 consecutive weeks did, however, not lead to permanent changes in the pain intensity. Experimentally induced pain (cold water immersion of the right hand) in normal subjects was not influenced by rTMS. Conclusions : These results do not favor the use of rTMS in the treatment of phantom limb pain. The results, however, support the concept that phantom pain is due to a dysfunctional activity in the parietal cortex. The transient rTMS-induced analgesic effect may be due to a temporary interference with the cerebral representation of the deafferented limb.

Electrophysiological studies have shown that forceful activation of the hand muscles (power grip) is accompanied by an increased excitability of the ipsilateral corticospinal system. This increase in excitability may be due to spinal or cortical mechanisms. Here we show with fMRI that this phenomenon is at least in part mediated at a cortical level. We used TMS to show that the increased ipsilateral excitability during a forceful maneuver leads to enhanced stimulus-response curves. fMRI was used to compare the activation during a repetitive hand movement with or without an accompanying power grip on the opposite site. The power grip reduced movement-related activation in the ipsilateral sensorimotor cortex. Peak deactivation was located in the left postcentral gyrus extending into the adjacent precentral gyrus. This finding suggests that a forceful activation of the hand muscles disinhibits a distinct functional representation in the ipsilateral sensorimotor cortex. Consequently, the excitability of the corticospinal system increases and less neuronal excitatory activity is needed to perform a given task. The results may be important for a variety of studies as they suggest that fMRI may show decreased hemodynamic response under conditions in which other neurophysiological methods have shown increased functional activity.