First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain.

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.

Rapid screening for neglect following stroke: A systematic search and European Academy of Neurology recommendations.

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.

Prehospital triage optimization of patients with large vessel occlusion by Austrian Prehospital Stroke Scale.

OBJECTIVES: 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. MATHERIAL & METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Avoid or seek light - a randomized crossover fMRI study investigating opposing treatment strategies for photophobia in migraine.

BACKGROUND: Photophobia, the aberrantly increased sensitivity to light, is a common symptom in migraine patients and light discomfort is frequently found as a trigger for migraine attacks. In behavioral studies, planned exposure to light was found to reduce headache in migraine patients with photophobia, potentially by increasing habituation to this migraine trigger. Here, we aimed to elucidate neurophysiological mechanisms of light exposure versus light deprivation in migraine patients using functional magnetic resonance imaging (fMRI). METHODS: Ten migraine patients (9 female, age = 28.70 ± 8.18 years) and 11 healthy controls (9 female, age = 23.73 ± 2.24 years) spent one hour on 7 consecutive days exposed to flashing light (Flash) or darkness (Dark) using a crossover design with a wash-out period of 3 months. Study participants kept a diary including items on interictal and ictal photophobia, presence and severity of headache 7 days before, during and 7 days after the interventions. One week before and one day after both interventions, fMRI using flickering light in a block design was applied. Functional activation was analyzed at whole-brain level and habituation of the visual cortex (V1) was modeled with the initial amplitude estimate and the corrected habituation slope. RESULTS: Mean interictal photophobia decreased after both interventions, but differences relative to the baseline did not survive correction for multiple comparisons. At baseline, flickering light induced activation in V1 was higher in the patients compared to the controls, but activation normalized after the Flash and the Dark interventions. V1 habituation indices correlated with headache frequency, headache severity and ictal photophobia. In the Flash condition, the individual change of headache frequency relative to the baseline corresponded almost perfectly to the change of the habituation slope compared to the baseline. CONCLUSIONS: On average, light exposure did not lead to symptom relief, potentially due to the short duration of the intervention and the high variability of the patients' responses to the intervention. However, the strong relationship between visual cortex habituation and headache symptoms and its modulation by light exposure might shed light on the neurophysiological basis of exposure treatment effects. TRIAL REGISTRATION: NCT05369910 (05/06/2022, retrospectively registered).

Design and Derivation of the Austrian Prehospital Stroke Scale (APSS) to Predict Severe Stroke with Large Vessel Occlusion.

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 developed using critical synthesis of previously published LVO-scores. The aim of this study was to investigate the accuracy of the APSS and compare it to other LVO-scores. Methods: APSS consists of 5 items: "facial palsy," "motor arm," "language," "motor leg" and "gaze deviation." The score ranges from 0 to 9 points. Data from 741 consecutive stroke patients with acute vessel imaging admitted to an independent comprehensive stroke center was used to test the predictive performance of the APSS in context of other LVO-scores (CPSS, FAST-ED, G-FAST, sNIHSS-EMS and RACE). Results: In the prediction of treatable LVO the APSS showed the highest area under the curve (0.834) with significant difference to CPSS (p = 0.010) and G-FAST (p = 0.006) and showed highest sensitivity (69%) as compared to other LVO scores. Specificity (85%), positive predictive value (75%), negative predictive value (81%) and accuracy (79%) were comparable to other LVO scores. Receiver operating curve analysis revealed an optimal cutoff for LVO prediction at APSS equal to 4 points. Conclusions: The easy assessable 5-item APSS score tended to outperform other LVO scores. Real-life prospective evaluation in prehospital setting is ongoing.

Recent developments in imaging of epilepsy.

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.

The clinical relevance of distortion correction in presurgical fMRI at 7T.

Presurgical planning with fMRI benefits from increased reliability and the possibility to reduce measurement time introduced by using ultra-high field. Echo-planar imaging suffers, however, from geometric distortions which scale with field strength and potentially give rise to clinically significant displacement of functional activation. We evaluate the effectiveness of a dynamic distortion correction (DDC) method based on unmodified single-echo EPI in the context of simulated presurgical planning fMRI at 7T and compare it with static distortion correction (SDC). The extent of distortion in EPI and activation shifts are investigated in a group of eleven patients with a range of neuropathologies who performed a motor task. The consequences of neglecting to correct images for susceptibility-induced distortions are assessed in a clinical context. It was possible to generate time series of EPI-based field maps which were free of artifacts in the eloquent brain areas relevant to presurgical fMRI, despite the presence of signal dropouts caused by pathologies and post-operative sites. Distortions of up to 5.1mm were observed in the primary motor cortex in raw EPI. These were accurately corrected with DDC and slightly less accurately with SDC. The dynamic nature of distortions in UHF clinical fMRI was demonstrated via investigation of temporal variation in voxel shift maps, confirming the potential inadequacy of SDC based on a single reference field map, particularly in the vicinity of pathologies or in the presence of motion. In two patients, the distortion correction was potentially clinically significant in that it might have affected the localization or interpretation of activation and could thereby have influenced the treatment plan. Distortion correction is shown to be effective and clinically relevant in presurgical planning at 7T.

Robust presurgical functional MRI at 7 T using response consistency.

Functional MRI is valuable in presurgical planning due to its non-invasive nature, repeatability, and broad availability. Using ultra-high field MRI increases the specificity and sensitivity, increasing the localization reliability and reducing scan time. Ideally, fMRI analysis for this application should identify unreliable runs and work even if the patient deviates from the prescribed task timing or if there are changes to the hemodynamic response due to pathology. In this study, a model-free analysis method-UNBIASED-based on the consistency of fMRI responses over runs was applied, to ultra-high field fMRI localizations of the hand area. Ten patients with brain tumors and epilepsy underwent 7 Tesla fMRI with multiple runs of a hand motor task in a block design. FMRI data were analyzed with the proposed approach (UNBIASED) and the conventional General Linear Model (GLM) approach. UNBIASED correctly identified and excluded fMRI runs that contained little or no activation. Generally, less motion artifact contamination was present in UNBIASED than in GLM results. Some cortical regions were identified as activated in UNBIASED but not GLM results. These were confirmed to show reproducible delayed or transient activation, which was time-locked to the task. UNBIASED is a robust approach to generating activation maps without the need for assumptions about response timing or shape. In presurgical planning, UNBIASED can complement model-based methods to aid surgeons in making prudent choices about optimal surgical access and resection margins for each patient, even if the hemodynamic response is modified by pathology. Hum Brain Mapp 38:3163-3174, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Psychiatric comorbidities and photophobia in patients with migraine.

BACKGROUND: Based on recent findings and our own impressions we took a closer look at the relationship between (inter)ictal photophobia and psychometric variables in migraine patients with photophobia. FINDINGS: For this study we included 29 (27 female) migraine patients and 31 (18 female) controls with a mean age of 31.6 ± 12.5 years and 24.0 ± 4.1 years, respectively. All participants filled out the Depression Anxiety Stress Scale (DASS). Interictal photophobia in patients was significantly higher than photophobia in controls (p = .001). Patients showed statistically significantly higher levels of depressive symptoms (p < .001), anxiety symptoms (p < .001) and stress (p < .001) than controls. Among all participants, (interictal) photophobia correlated positively with age (rho = .318, p = .013) as well as with the levels of depressive symptoms (rho = .459, p < .001), anxiety symptoms (rho = .346, p = .008) and stress (rho = .368, p = .005), but not with gender. In the patients, ictal photophobia correlated positively with age (rho = .473, p = .01) and interictal photophobia (rho = .423, p = .022). Linear regression analysis revealed only a trend towards statistical significance for (interictal) photophobia as a predictor for the level of depressive symptoms (rho = .457, p = 0.056) in the whole sample. CONCLUSIONS: Considering higher levels of photophobia in depression and the comorbidity of migraine and depression, it might be possible that depression contributes to interictal photophobia in patients with migraine. The same may be true for anxiety and stress. Both are also related to migraine and their possible impact on photophobia in migraine may be explained by pupillary dysfunction.

Between- and within-site variability of fMRI localizations.

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.

Improving the clinical potential of ultra-high field fMRI using a model-free analysis method based on response consistency.

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.

Neuromagnetic cortical activation during initiation of optokinetic nystagmus: an MEG pilot study.

PURPOSE: To investigate the spatiotemporal evolution of cortical activation during the initiation of optokinetic nystagmus using magnetoencephalography. BACKGROUND: Previous imaging studies of optokinetic nystagmus in humans using positron emission tomography and functional magnetic resonance imaging discovered activation of a large set of cortical and subcortical structures during steady-state optokinetic stimulation, but did not provide information on the temporal dynamics of the initial response. Imaging studies have shown that cortical areas responsible for vision in occipital and temporo-occipital areas are involved, i.e. cortical areas control optokinetic stimulation in humans. Magnetoencephalography provides measures that reflect neural ensemble activity in the millisecond time scale, allowing the identification of early cortical components of visuomotor integration. DESIGN/METHODS: We studied neuromagnetic cortical responses during the initiation of optokinetic nystagmus in 6 right-handed healthy subjects. Neuromagnetic activity was recorded with a whole-head magnetoencephalograph, consisting of 143 planar gradiometers. RESULTS: The mean (±SD) latency between stimulus onset and initiation of optokinetic nystagmus was 177.7 ± 59 ms. Initiation of optokinetic nystagmus evoked an early component in the primary visual cortex starting at 40-90 ms prior to the onset of the slow phase of nystagmus. Almost simultaneously an overlapping second component occurred bilaterally in the temporo-occipital area (visual motion areas), pronounced in the right hemisphere, starting at 10-60 ms prior to the slow-phase onset. Both components showed long-duration activity lasting for up to 100 ms after slow-phase onset. CONCLUSIONS: Our findings suggest that the initiation of optokinetic nystagmus induces early cortical activation in the occipital cortex and almost simultaneously bilaterally in the temporo-occipital cortex. These cortical regions might represent essential areas for the monitoring of retinal slip.

Current state of clinical ultrasound neuromodulation.

Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson's disease: a first retrospective analysis.

BACKGROUND: Transcranial Pulse Stimulation (TPS) has been recently introduced as a novel ultrasound neuromodulation therapy with the potential to stimulate the human brain in a focal and targeted manner. Here, we present a first retrospective analysis of TPS as an add-on therapy for Parkinson's disease (PD), focusing on feasibility, safety, and clinical effects. We also discuss the placebo response in non-invasive brain stimulation studies as an important context. METHODS: This retrospective clinical data analysis included 20 PD patients who received ten sessions of TPS intervention focused on the individual motor network. Safety evaluations were conducted throughout the intervention period. We analyzed changes in motor symptoms before and after TPS treatment using Unified Parkinson's Disease Rating Scale part III (UPDRS-III). RESULTS: We found significant improvement in UPDRS-III scores after treatment compared to baseline (pre-TPS: 16.70 ± 8.85, post-TPS: 12.95 ± 8.55; p < 0.001; Cohen's d = 1.38). Adverse events monitoring revealed no major side effects. CONCLUSION: These preliminary findings suggest that TPS can further improve motor symptoms in PD patients already on optimized standard therapy. Findings have to be evaluated in context with the current literature on placebo effects.

Efficacy and safety of transcranial pulse stimulation in young adolescents with attention-deficit/hyperactivity disorder: a pilot, randomized, double-blind, sham-controlled trial.

Background: This is the first study to evaluate the efficacy and safety of transcranial pulse stimulation (TPS) for the treatment of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Hong Kong. Methods: This double-blind, randomized, sham-controlled trial included a TPS group and a sham TPS group, encompassing a total of 30 subjects aged 12-17 years who were diagnosed with ADHD. Baseline measurements SNAP-IV, ADHD RS-IV, CGI and executive functions (Stroop tests, Digit Span) and post-TPS evaluation were collected. Both groups were assessed at baseline, immediately after intervention, and at 1-month and 3-month follow-ups. Repeated-measures ANOVAs were used to analyze data. Results: The TPS group exhibited a 30% reduction in the mean SNAP-IV score at postintervention that was maintained at 1- and 3-month follow-ups. Conclusion: TPS is an effective and safe adjunct treatment for the clinical management of ADHD. Clinical trial registration: ClinicalTrials.Gov, identifier NCT05422274.

Variability of clinical functional MR imaging results: a multicenter study.

PURPOSE: To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. MATERIALS AND METHODS: Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. RESULTS: Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). CONCLUSION: Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

FACET - a "Flexible Artifact Correction and Evaluation Toolbox" for concurrently recorded EEG/fMRI data.

BACKGROUND: In concurrent EEG/fMRI recordings, EEG data are impaired by the fMRI gradient artifacts which exceed the EEG signal by several orders of magnitude. While several algorithms exist to correct the EEG data, these algorithms lack the flexibility to either leave out or add new steps. The here presented open-source MATLAB toolbox FACET is a modular toolbox for the fast and flexible correction and evaluation of imaging artifacts from concurrently recorded EEG datasets. It consists of an Analysis, a Correction and an Evaluation framework allowing the user to choose from different artifact correction methods with various pre- and post-processing steps to form flexible combinations. The quality of the chosen correction approach can then be evaluated and compared to different settings. RESULTS: FACET was evaluated on a dataset provided with the FMRIB plugin for EEGLAB using two different correction approaches: Averaged Artifact Subtraction (AAS, Allen et al., NeuroImage 12(2):230-239, 2000) and the FMRI Artifact Slice Template Removal (FASTR, Niazy et al., NeuroImage 28(3):720-737, 2005). Evaluation of the obtained results were compared to the FASTR algorithm implemented in the EEGLAB plugin FMRIB. No differences were found between the FACET implementation of FASTR and the original algorithm across all gradient artifact relevant performance indices. CONCLUSION: The FACET toolbox not only provides facilities for all three modalities: data analysis, artifact correction as well as evaluation and documentation of the results but it also offers an easily extendable framework for development and evaluation of new approaches.

Ultrasound Neuromodulation as a New Brain Therapy.

Within the last decade, ultrasound has been "rediscovered" as a technique for brain therapies. Modern technologies allow focusing ultrasound through the human skull for highly focal tissue ablation, clinical neuromodulatory brain stimulation, and targeted focal blood-brain-barrier opening. This article gives an overview on the state-of-the-art of the most recent application: ultrasound neuromodulation as a new brain therapy. Although research centers have existed for decades, the first treatment centers were not established until 2020, and clinical applications are spreading rapidly.

Lapses of the Heart: Frequency and Subjective Salience of Impressions Reported by Patients after Cardiac Arrest.

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.