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The Austrian Prehospital Stroke Scale (APSS) score was developed to predict large vessel occlusion (LVO) and improve prehospital transportation triage. Its accuracy has been previously analyzed retrospectively. We now aimed to investigate the accuracy, as well as the impact of the implementation of a triage strategy using this score on treatment times and outcome in a prospective study.Prospective diagnostic test accuracy and before-after interventional study. EMS prospectively evaluated APSS in patients suspected of stroke. Accuracy was compared with other LVO scores. Patients with APSS ≥4 points were brought directly to the comprehensive stroke center. Treatment time frames, neurological, and radiological outcome before and after the APSS implementation were compared.A total of 307 patients with suspected stroke were included from October 2018 to February 2020. Treatable LVO was present in 79 (26%). Sensitivity of APSS to detect those was 90%, specificity 79%, positive predictive value 66%, negative predictive value 95%, and area under the curve 0.87 (95% CI 0.83-0.91). This was similar to in-hospital NIHSS (AUC 0.89 95% CI 0.89-0.92, p = .06) and superior to CPSS (AUC 0.83 95% CI 0.78-0.87, p = .01). Implementation of APSS triage increased direct transportation rate for LVO patients (21% before vs. 52% after; p .001) with a significant time benefit (alert to groin puncture time benefit: 51 min (95% CI 28-74; p .001). Neurological and radiological outcome did not differ significantly.Austrian Prehospital Stroke Scale triage showed an accuracy comparable with in-hospital NIHSS, and lead to a significant optimization of prehospital workflows in patients with potential LVO.

After cardiac arrest (CA), some patients report impressions with highly realistic features, often referred to as near-death experience (NDE). The frequency of such episodes seems to be variable, with various types of content. In a prospective study, we subjected 126 CA cases treated at the Department of Emergency Medicine of the Medical University of Vienna under carefully controlled conditions to a structured interview. We included all patients admitted due to CA, whose communicative abilities were restored and who agreed to participate in the study. The questionnaire inquired as to living conditions, attitudes towards issues of life and death, and last recollections before and first impressions after the CA. The majority of the subjects (91 = 76%) replied to inquiries concerning impressions during CA with “nothing” or “blackout”, but 20 (16%) gave a detailed account. A German version of the Greyson questionnaire specifically addressing NDE phenomena (included towards the end of the interview) resulted in ≥7 points in five patients (4%). Three patients reported a meeting with deceased relatives (one with 6 Greyson points), one an out-of-body episode, and one having been sucked into a colorful tunnel. Eleven of these twenty cases had their cardiopulmonary resuscitation (CPR) started within the first min of CA, a higher fraction than cases without experience. Reported experience after CA was of high significance for the patients; many of them changed their point of view on issues of life and death.

Objectives: Prediction of large vessel occlusion (LVO) is highly relevant for accurate prehospital transportation triage. The Austrian Prehospital Stroke Scale (APSS) score for LVO prediction was d...

Transcranial pulse stimulation (TPS) has been recently introduced as a novel clinical brain stimulation technique based on highly focused ultrasound pressure pulses. In a first pilot study on clinical effects of navigated and focused ultrasound neuromodulation, a dichotomy of functional effects was found: patients with Alzheimer's disease improved cognition and language but deteriorated with visuo-constructive functions.We analyzed changes in functional connectivity measured with functional magnetic resonance imaging (fMRI) using graph analysis of a visuo-constructive network in 18 patients with Alzheimer's disease. We calculated the network's global efficiency and tested for correlation with visuo-constructive test scores to explain this dichotomy.Important visuo-constructive network nodes were not stimulated in the pilot setting and correspondingly global efficiency of a visuo-constructive network was decreased after TPS therapy, compatible with a natural progress of the disease. A correlation between visuo-constructive scores and changes in global efficiency was found.Results argue for a high functional specificity of ultrasound-based neuromodulation with TPS.Over the last decade, there has been growing interest in ultrasound-based non-invasive brain stimulation techniques in neuroscience and as a potential therapy for disorders of the brain. Transcranial pulse stimulation (TPS) has been introduced as an innovative neuromodulation technique, applying ultrashort pressure pulses through the skull into neural tissue with 3D navigation in real time. In the first clinical pilot study, patients suffering from Alzheimer’s disease showed an increase in memory and language functions for up to 3 months after TPS therapy. However, visuo-constructive capacities (e.g., copying a geometrical figure) worsened. Notably, brain areas relevant for such processes had been left out during stimulation. This begged the question whether the brain areas that were targeted for brain stimulation as well as functional changes could explain this diverse response pattern. We therefore analyzed functional magnetic resonance data from patients. Specifically, we compared graph theoretical functional connectivity measures in a visuo-constructive network before and after TPS therapy. We found a decrease in connectivity in a central network node, which also correlated with visuo-constructive test scores. This deterioration is likely associated with normal disease progression. Together with the already reported improvement in global cognitive functions, these results argue for a functional specific effect of TPS.

Background and purpose Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments. Methods Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations. Results A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible. Conclusions This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.

The ability to generate complex hierarchical structures is a crucial component of human cognition which can be expressed in the musical domain in the form of hierarchical melodic relations. The neural underpinnings of this ability have been investigated by comparing the perception of well-formed melodies with unexpected sequences of tones. However, these contrasts do not target specifically the representation of rules generating hierarchical structure. Here, we present a novel paradigm in which identical melodic sequences are generated in four steps, according to three different rules: The Recursive rule, generating new hierarchical levels at each step; The Iterative rule, adding tones within a fixed hierarchical level without generating new levels; and a control rule that simply repeats the third step. Using fMRI, we compared brain activity across these rules when participants are imagining the fourth step after listening to the third (generation phase), and when participants listened to a fourth step (test sound phase), either well-formed or a violation. We found that, in comparison with Repetition and Iteration, imagining the fourth step using the Recursive rule activated the superior temporal gyrus (STG). During the test sound phase, we found fronto-temporo-parietal activity and hippocampal de-activation when processing violations, but no differences between rules. STG activation during the generation phase suggests that generating new hierarchical levels from previous steps might rely on retrieving appropriate melodic hierarchy schemas. Previous findings highlighting the role of hippocampus and inferior frontal gyrus may reflect processing of unexpected melodic sequences, rather than hierarchy generation per se. Electronic supplementary material The online version of this article (10.1007/s00429-020-02105-7) contains supplementary material, which is available to authorized users.

Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post-stroke aphasia. Our meta-analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies-overall 129 participants-met all eligibility criteria. Multi-level mixed- and random-effects models served to separately meta-analyze randomized controlled trial (RCT) and non-RCT data. RCT evidence on validated outcomes revealed a small-to-moderate standardized effect in noncommunicative language expression for MIT-with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non-RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non-Communicative Language Expression measures). Effect size for non-RCT data decreased with number of months post-stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.

Autistic spectrum disorder (ASD) is a common developmental disorder in children. The latest non-intrusive brain stimulation (NIBS) technology—transcranial pulse stimulation (TPS)—has been proven effective in older adults with mild neurocognitive disorders and adults with major depressive disorder. Nonetheless, there is so far no robust randomized controlled trial (RCT) conducted on adolescents with ASD nationwide. This study proposes a two-armed (verum TPS group vs. sham TPS group), double-blinded, randomized, sham-controlled trial. Both groups will be measured at four timepoints, namely, baseline (T1), 2 weeks immediately after post-TPS intervention (T2), and at the 1-month (T3) and 3-month (T4) follow-ups. Thirty-four subjects, aged between 12 and 17, diagnosed with ASD will be recruited in this study. All subjects will be computerized randomised into the verum TPS group or the sham TPS group on a 1:1 ratio. All subjects will undertake functional MRI (fMRI) before and after the 2-weeks TPS interventions, which will be completed in 2 weeks’ time. This will be the first RCT evaluating the efficacy of TPS adolescents with ASD in Hong Kong. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05408793.

Background With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior. Methods Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed. Results Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area. Conclusions TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSIMPORTANCEC_ST_ABSMelodic Intonation Therapy (MIT) is a prominent rehabilitation programme for individuals with post-stroke aphasia. Despite substantial progress in recent years, the efficacy of MIT remains not fully understood. OBJECTIVEBased on a-priori hypotheses, the present meta-analysis investigated the efficacy of MIT while considering quality of outcomes (psychometrically validated versus unvalidated measures), experimental design (presence versus absence of randomisation and control group), influence of spontaneous recovery (quantified as number of months post-stroke), MIT version applied (original versus modified protocol), and level of generalisation (performance on trained versus untrained items). DATA SOURCESAn extensive literature search in all major online databases, trials registers and the grey literature identified 606 studies (years searched: 1973-2021). STUDY SELECTIONInclusion criteria: randomised controlled trial (RCT) data or case reports on adults with aphasia; pre-post assessment of language performance. Exclusion criteria: substantial variation from original MIT protocol; unvalidated outcomes, unless both trained and untrained items were compared; essential information not indicated/retrievable. Final sample: 22 studies. DATA EXTRACTION AND SYNTHESISFollowing PRISMA guidelines, studies were double-coded. Multi-level mixed- and random-effects models were used to separately meta-analyse RCT and non-RCT data. MAIN OUTCOMES AND MEASURESMeasures of language performance focused on aphasia severity, everyday communication ability, domain-general function, language comprehension, non-communicative language expression, and speech-motor planning. RESULTSUnvalidated outcomes appeared to attenuate MITs effect size by a factor of 0.29-0.43 across study designs when compared to validated outcomes. Moreover, MITs effect size was 5.7 times larger for non-RCT data compared to RCT data. Effect size also decreased with number of months post-stroke, suggesting confound through spontaneous recovery primarily within the first year post-stroke. In contrast, variation of the original MIT protocol did not systematically alter benefit from treatment. Crucially, analyses demonstrated significantly improved performance on trained and untrained items. The latter finding arose mainly from gains in repetition tasks, rather than other domains of verbal expression including everyday communication ability. CONCLUSIONS AND RELEVANCEAccounting for various methodological aspects, the current results confirm the promising role of MIT in improving language performance on trained items and in repetition tasks, while highlighting possible limitations in promoting everyday communication ability. KO_SCPLOWEYC_SCPLOW PO_SCPLOWOINTSC_SCPLOWO_ST_ABSQUESTIONC_ST_ABSWhat determines the efficacy of Melodic Intonation Therapy (MIT), arguably the best-known treatment programme for individuals with neurological communication disorders? FINDINGSMITs effect size was modulated by the psychometric quality of outcomes, use of randomisation and control groups, and the number of months post-stroke at the time of testing. Language performance improved significantly on trained items, less for everyday communication ability on untrained items. MEANINGOur findings emphasise the importance of appropriate outcomes and rigorous study design to obtain realistic effect size estimates. While MIT promotes performance on trained items, it appears to have limited impact on everyday communication ability.

PURPOSE OF REVIEW Imaging constitutes one of the key pillars in the diagnostic workup after a first seizure as well as for the presurgical workup in epilepsy. The role of imaging in emergency situations, mainly to support the adequate diagnosis, as well as its role in planning of noninvasive image-guided therapies is less well established. Here, we provide an overview on peri-ictal imaging findings to support differential diagnosis in emergency situations and describe recent attempts toward minimal invasive therapy in the treatment of epilepsy and its comorbidities based on a combination of imaging techniques with ultrasound. RECENT FINDINGS Peri-ictal perfusion changes can differentiate ictal stroke mimics from acute ischemic stroke if focal areas of increased perfusion are depicted by computed tomography or MRI. Postictal perfusion patterns in patients with persisting neurological symptoms are frequently normal and do not reach enough diagnostic sensitivity to differentiate between stroke and its mimics. Noninvasive magnetic resonance-techniques as arterial spin labeling may provide a higher sensitivity, especially in combination with diffusion-weighted and susceptibility-weighted MRI. Imaging guided focused ultrasound (FUS) bears the potential to ablate epileptogenic tissue and allows suppression of epileptic activity. Imaging guided blood-brain-barrier opening with FUS offers new options for local drug administration. SUMMARY MRI should be considered the method of choice in the differential diagnosis of peri-ictal imaging findings and their differential diagnosis. A combination of various MRI techniques with FUS opens new avenues for treatment of epilepsy.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Introduction Ultrasound for the brain is a revolutionary therapeutic concept. The first clinical data indicate that 2–4 weeks of therapy with transcranial pulse stimulation (TPS) improve functional networks and cognitive performance of Alzheimer's disease (AD) patients for up to 3 months. No data currently exist on possible benefits concerning brain morphology, namely the cortical atrophy characteristic of AD. Methods We performed a pre‐/post‐therapy analysis of cortical thickness in a group of N = 17 AD patients. Results We found a significant correlation between neuropsychological improvement and cortical thickness increase in AD‐critical brain areas. Discussion AD patients who benefit from TPS appear to manifest reduced cortical atrophy within the default mode network in particular, whose memory‐related subsystems are believed to be disrupted in AD. TPS may therefore hold promise as a new add‐on therapy for AD.

Humans generate recursive hierarchies in a variety of domains, including linguistic, social and visuo-spatial modalities. The ability to represent recursive structures has been hypothesized to increase the efficiency of hierarchical processing. Theoretical work together with recent empirical findings suggests that the ability to represent the self-similar structure of hierarchical recursive stimuli may be supported by internal neural representations that compress raw external information and increase efficiency. In order to explicitly test whether the representation of recursive hierarchies depends on internalized rules we compared the processing of visual hierarchies represented either as recursive or non-recursive, using task-free resting-state fMRI data. We aimed to evaluate the relationship between task-evoked functional networks induced by cognitive representations with the corresponding resting-state architecture. We observed increased connectivity within Default Mode Network (DMN) related brain areas during the representation of recursion, while non-recursive representations yielded increased connectivity within the Fronto-Parietal Control-Network. Our results suggest that human hierarchical information processing using recursion is supported by the DMN. In particular, the representation of recursion seems to constitute an internally-biased mode of information-processing that is mediated by both the core and dorsal-medial subsystems of the DMN. Compressed internal rule representations mediated by the DMN may help humans to represent and process hierarchical structures in complex environments by considerably reducing information processing load.

In recent years, the interest in clinical applications of functional neuroimaging techniques like functional Magnetic Resonance Imaging (fMRI) or modern Magneto- or Electro- Encephalography (MEG-EEG) has steadily grown as have discussions about possible standardizations of these methodologies. The modern techniques allow non-invasive localization of essential brain functions with the potential to extend or even replace invasive clinical technologies (1–4). The focus of this article is to discuss standardization options in using functional MRI for clinical cases, mostly in the context of medical decision aid for planning treatment (radiotherapy and surgery).

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

In Parkinson’s disease (PD) the prevalence of apraxia increases with disease severity implying that patients in early stages may already have subclinical deficits. The aim of this exploratory fMRI study was to investigate if subclinical aberrations of the praxis network are already present in patients with early PD. In previous functional imaging literature only data on basal motor functions in PD exists. Thirteen patients with mild parkinsonian symptoms and without clinically diagnosed apraxia and 14 healthy controls entered this study. During fMRI participants performed a pantomime task in which they imitated the use of visually presented objects. Patients were measured ON and OFF dopaminergic therapy to evaluate a potential medication effect on praxis abilities and related brain functions. Although none of the patients was apraxic according to De Renzi ideomotor scores (range 62–72), patients OFF showed significantly lower praxis scores than controls. Patients exhibited significant hyperactivation in left fronto-parietal core areas of the praxis network. Frontal activations were clearly dominant in patients and were correlated with lower individual praxis scores. We conclude that early PD patients already show characteristic signs of praxis network dysfunctions and rely on specific hyperactivations to avoid clinically evident apraxic symptoms. Subclinical apraxic deficits were shown to correlate with an activation shift from left parietal to left frontal areas implying a prospective individual imaging marker for incipient apraxia.

Objective To develop an analysis method that is sensitive to non-model-conform responses often encountered in ultra-high field presurgical planning fMRI. Using the consistency of time courses over a number of experiment repetitions, it should exclude low quality runs and generate activation maps that reflect the reliability of responses. Materials and methods 7 T fMRI data were acquired from six healthy volunteers: three performing purely motor tasks and three a visuomotor task. These were analysed with the proposed approach (UNBIASED) and the GLM. Results UNBIASED results were generally less affected by false positive results than the GLM. Runs that were identified as being of low quality were confirmed to contain little or no activation. In two cases, regions were identified as activated in UNBIASED but not GLM results. Signal changes in these areas were time-locked to the task, but were delayed or transient. Conclusion UNBIASED is shown to be a reliable means of identifying consistent task-related signal changes regardless of response timing. In presurgical planning, UNBIASED could be used to rapidly generate reliable maps of the consistency with which eloquent brain regions are activated without recourse to task timing and despite modified hemodynamics. Electronic supplementary material The online version of this article (doi:10.1007/s10334-016-0533-8) contains supplementary material, which is available to authorized users.

Brain activations in early-blind subjects during Braille reading indicate considerable cross-modal neuroplasticity in posterior brain areas. Up to now it is, however, not clear how far such neuroplastic reorganization processes reach and whether a specific brain activation pattern corresponds to a specific component of the Braille reading task. Therefore, this fMRI study investigates whether different cortical areas are functionally specialized for different aspects of Braille reading. The comprehensive Braille reading task was contrasted to three control tasks representing subcomponents of Braille reading (passive tactile stimulation, active tactile pattern recognition, Braille imagery). Results in 14 early-blind subjects indicate that only occipital and basal temporo-occipital brain areas show specific fMRI correlates for Braille reading. Central rolandic brain activations correlated with basic somatosensory processing and superior temporal activations were associated with higher level stimulus-independent language processing. In these latter areas no indications for neuroplastic reorganizations specific for Braille reading were found, despite strong activations during the Braille reading task.