Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology.

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 ).

Modulation of attention functions by anodal tDCS on right PPC.

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.

Transcranial direct current stimulation (tDCS) of left parietal cortex facilitates gesture processing in healthy subjects.

Gesture processing deficits constitute a key symptom of apraxia, a disorder of motor cognition frequently observed after left-hemispheric stroke. The clinical relevance of apraxia stands in stark contrast to the paucity of therapeutic options available. Transcranial direct current stimulation (tDCS) is a promising tool for modulating disturbed network function after stroke. Here, we investigate the effect of parietal tDCS on gesture processing in healthy human subjects. Neuropsychological and imaging studies suggest that the imitation and matching of hand gestures involve the left inferior parietal lobe (IPL). Using neuronavigation based on cytoarchitectonically defined anatomical probability maps, tDCS was applied over left IPL-areas PF, PFm, or PG in healthy participants (n = 26). Before and after tDCS, subjects performed a gesture matching task and a person discrimination task for control. Changes in error rates and reaction times were analyzed for the effects of anodal and cathodal tDCS (compared with sham tDCS). Matching of hand gestures was specifically facilitated by anodal tDCS applied over the cytoarchitectonically defined IPL-area PFm, whereas tDCS over IPL-areas PF and PG did not elucidate significant effects. Taking into account tDCS electrode size and the central position of area PFm within IPL, it can be assumed that the observed effect is rather the result of a combined stimulation of the supramarginal and angular gyrus than an isolated PFm stimulation. Our data confirm the pivotal role of the left IPL in gesture processing. Furthermore, anatomically guided tDCS of the left IPL may constitute a promising approach to neurorehabilitation of apraxic patients with gesture processing deficits.

Modulation of top-down control of visual attention by cathodal tDCS over right IPS.

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.

Multi-session transcranial direct current stimulation (tDCS) elicits inflammatory and regenerative processes in the rat brain.

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.

Isometric contraction interferes with transcranial direct current stimulation (tDCS) induced plasticity: evidence of state-dependent neuromodulation in human motor cortex.

BACKGROUND AND PURPOSE: Neuroplastic alterations of cortical excitability and activity represent the likely neurophysiological 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 demonstrated 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.

Functional localization in the human brain: Gradient-Echo, Spin-Echo, and arterial spin-labeling fMRI compared with neuronavigated TMS.

A spatial mismatch of up to 14 mm between optimal transcranial magnetic stimulation (TMS) site and functional magnetic resonance imaging (fMRI) signal has consistently been reported for the primary motor cortex. The underlying cause might be the effect of magnetic susceptibility around large draining veins in Gradient-Echo blood oxygenation level-dependent (GRE-BOLD) fMRI. We tested whether alternative fMRI sequences such as Spin-Echo (SE-BOLD) or Arterial Spin-Labeling (ASL) assessing cerebral blood flow (ASL-CBF) may localize neural activity closer to optimal TMS positions and primary motor cortex than GRE-BOLD. GRE-BOLD, SE-BOLD, and ASL-CBF signal changes during right thumb abductions were obtained from 15 healthy subjects at 3 Tesla. In 12 subjects, tissue at fMRI maxima was stimulated with neuronavigated TMS to compare motor-evoked potentials (MEPs). Euclidean distances between the fMRI center-of-gravity (CoG) and the TMS motor mapping CoG were calculated. Highest SE-BOLD and ASL-CBF signal changes were located in the anterior wall of the central sulcus [Brodmann Area 4 (BA4)], whereas highest GRE-BOLD signal changes were significantly closer to the gyral surface. TMS at GRE-BOLD maxima resulted in higher MEPs which might be attributed to significantly higher electric field strengths. TMS-CoGs were significantly anterior to fMRI-CoGs but distances were not statistically different across sequences. Our findings imply that spatial differences between fMRI and TMS are unlikely to be caused by spatial unspecificity of GRE-BOLD fMRI but might be attributed to other factors, e.g., interactions between TMS-induced electric field and neural tissue. Differences between techniques should be kept in mind when using fMRI coordinates as TMS (intervention) targets.

Processing of auditory motion in inferior parietal lobule: evidence from transcranial magnetic stimulation.

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.

Inhibition of the anterior intraparietal area and the dorsal premotor cortex interfere with arbitrary visuo-motor mapping.

OBJECTIVE: The contribution of the human anterior intraparietal area and the dorsal premotor cortex to arbitrary visuo-motor mapping during grasping were tested. METHODS: Trained right-handed subjects reached for and pincer-grasped a cube with the right hand in the absence of visual feedback after the cube location had been displayed for 200ms. During the reaching movements, the colour of the cube changed and visual feedback about the change of colour was provided for 100ms at 500ms after movement onset (at the time of peak grasp aperture). Depending on colour, subjects were instructed to either pincer-grasp the cube in a horizontal or vertical grasp position with the latter necessitating wrist rotation (experiment 1) or to pincer-grasp and transport the cube to either a left or right target position (experiment 2). Within two consecutive 200ms time windows (TMS 1 and 2) starting 500ms and 700ms after movement onset, respectively, double pulses of supra-threshold transcranial magnetic stimulation (inter-stimulus interval: 100ms) were delivered over (i) the left primary motor cortex (90 degrees vertically angulated coil position, control stimulation), (ii) the left dorsal premotor cortex or (ii) the left anterior intraparietal area. RESULTS: Compared to control stimulation, stimulation of the anterior intraparietal area, but not of the dorsal premotor cortex, at TMS 1 delayed the times to wrist rotation (experiment 1) and hand transport (experiment 2). Compared to control stimulation, stimulation of the dorsal premotor cortex, but not of the anterior intraparietal area, at TMS 2 delayed both wrist rotation (experiment 1) and hand transport (experiment 2). CONCLUSIONS: We contend that the anterior intraparietal area and the dorsal premotor cortex are both involved albeit at different phases during the mapping of arbitrary visual cues with goal directed grasp and transport movements. SIGNIFICANCE: These data add to the current understanding of how human cortical areas work in concert during manual activities.

The dorsal premotor cortex orchestrates concurrent speech and fingertapping movements.

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.

End or means--the "what" and "how" of observed intentional actions.

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.

Transdermal dopaminergic stimulation with rotigotine in Parkinsonian akinetic crisis.

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.

On the role of the ventral premotor cortex and anterior intraparietal area for predictive and reactive scaling of grip force.

When lifting objects of different mass but identical visual appearance, we apply grip forces that match the expected mass of the object. Here we study the role of the primary motor cortex (M1), the ventral premotor cortex (PMv) and the anterior intraparietal area (AIP) for predictive and reactive scaling of grip forces. Participants performed a precision grip between the index finger and thumb of the right hand to lift two different masses of identical visual appearance in random order. Neuronavigated single pulse transcranial magnetic stimulation (TMS) over (i) left M1, (ii) left PMv, (iii) left AIP and (iv) the vertex (for control) was applied at two time points of the grasping movement after an unexpected change in mass had occurred: (a) at the time of movement onset and (b) at the time of peak grasp aperture. TMS over the PMv, but not over the vertex, M1 or the AIP, interfered with the predictive scaling of grip forces according to the most recent lift when applied at the time of peak grasp aperture. In contrast, TMS over AIP, but not over the vertex, M1 or PMv, disrupted the reactive adjustment of grip force to the novel mass of the object at hand. The findings highlight the differential involvement of PMv in the predictive scaling of grip force and of AIP in the reactive online adjustment of grip force during object manipulation.

Postinfectious focal necrotizing myopathy.

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.

The role of the anterior intraparietal sulcus in crossmodal processing of object features in humans: an rTMS study.

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.

Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction.

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.

Action verbs and the primary motor cortex: a comparative TMS study of silent reading, frequency judgments, and motor imagery.

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.

Transcranial magnetic stimulation and the challenge of coil placement: a comparison of conventional and stereotaxic neuronavigational strategies.

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.