Roland Beisteiner

• Medical University of Vienna

Background Novel ultrasound neuromodulation techniques allow therapeutic brain stimulation with unmet precision and non-invasive targeting of deep brain areas. Transcranial pulse stimulation (TPS), a multifrequency sonication technique, is approved for the clinical treatment of Alzheimer’s disease (AD). Here, we present the largest real-world retro...

Importance Given the increasing prevalence of dementia and the limited treatment options available, ultrasound neuromodulation could serve as a novel add-on therapy to standard treatments for Alzheimer disease (AD). As ultrasound neuromodulation is still in its early stages, further research is essential to fully explore its potential in treating b...

Spin‐lock (SL) pulses have been proposed to directly detect neuronal activity otherwise inaccessible through standard functional magnetic resonance imaging. However, the practical limits of this technique remain unexplored. Key challenges in SL‐based detection include ultra‐weak signal variations, sensitivity to magnetic field inhomogeneities, and...

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...

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 clin...

Transcranial pulse stimulation has been proven effective to improve cognition, memory and depressive symptoms of Alzheimer’s disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of transcranial pulse stimulation on the right temporoparietal junctio...

Background Traditional treatment alone might not effectively control the severity of attention deficit hyperactivity disorder (ADHD) symptoms. Transcranial pulse stimulation (TPS) is a non-invasive brain stimulation (NIBS) technology used on older adults with mild neurocognitive disorders and adults with major depressive disorder. However, there ha...

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 t...

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...

Transcranial pulse stimulation (TPS) is a recent development in non-invasive brain stimulations (NIBS) that has been proven to be effective in terms of significantly improving Alzheimer patients’ cognition, memory, and execution functions. Nonetheless, there is, currently, no trial evaluating the efficacy of TPS on adults with major depression diso...

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...

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 c...

Transcranial ultrasound holds much potential as a safe, non-invasive modality for navigated neuromodulation, with low-intensity focused ultrasound (FUS) and transcranial pulse stimulation (TPS) representing the two main modalities. While neuroscientific and preclinical applications have received much interest, clinical applications are still relati...

Abstract Melodic Intonation Therapy (MIT) is a prominent rehabilitation programme for individuals with post-stroke aphasia. The present meta-analysis investigated the efficacy of MIT while considering outcome measure quality, experimental design, influence of spontaneous recovery, MIT protocol, and level of generalisation. An extensive literature s...

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 6...

Introduction: 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 di...

Question Clinical effects of current therapies for neurodegeneration are limited. Very recently, a novel therapeutic approach has been developed as non-invasive add-on therapy: Transcranial Pulse Stimulation TPS (Beisteiner et al. 2019, Beisteiner & Lozano 2020, Popescu et al. 2021). This presentation intends to give an overview about clinical add-...

Background: 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...

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...

Background Since the emergence of the COVID-19 pandemic, there have been lots of published work examining the association between COVID-19 and mental health, particularly, anxiety and depression in the general populations and disease subpopulations globally. Depression is a debilitating disorder affecting individuals' level of bio-psychological-soc...

Introduction: Ultrasound-based brain stimulation is a novel, non-invasive therapeutic approach to precisely target regions of interest. Data from a first clinical trial of patients with Alzheimer's disease (AD) receiving 2-4 weeks transcranial pulse stimulation (TPS) have shown memory and cognitive improvements for up to 3 months, despite ongoing...

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 Europea...

The first human applications of ultrasound in medicine date back to 1939, when Reimar Pohlmann (Berlin, Germany) published data on therapy of neuralgia with ultrasound [...]

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...

This chapter gives an overview of the type of neuroplastic information that can be generated by functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) after damage of the central or peripheral nervous system. After an introductory overview about clinical neuroplasticity, benefits of neuroplastic investigations are demonstra...

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 br...

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 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 mor...

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...

Brain diseases are one of the most important problems in our rapidly ageing society. Currently, there are not many effective medications and surgical options are limited due to invasiveness and non‐invasive brain stimulation techniques cannot be well targeted and cannot access deep brain areas. A novel therapy is transcranial ultrasound which allow...

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,...

One of the most important public issues in our rapidly ageing society are brain disorders and neurodegenerative diseases. Effective therapies are limited and therefore costs for public health systems rapidly increase in this sector. However, recently the first clinical evidence for a new class of therapies has emerged - ultrasound for the brain. Wi...

Homuncular organization, i.e., the neuronal representation of the human body within the primary motor cortex, is one of the most fundamental principles of the human brain. Despite this, in rare peripheral nerve surgery patients, the transformation of a monofunctional (diaphragm activation) into a bifunctional motor area (diaphragm and arm activatio...

In article number 1902583, Roland Beisteiner and co‐workers describe a brain activation technique for treatment of Alzheimer's disease. Transcranial pulse stimulation (TPS) applies ultrashort ultrasound pulses to activate neuronal resources. A therapeutic breakthrough is secure clinical targeting and access to deep brain areas. After 2 weeks of tre...

Ultrasound‐based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultr...

Functional imaging of the brainstem may open new avenues for clinical diagnostics. However, for reliable assessments of brainstem activation, further efforts improving signal quality are needed. Six healthy subjects performed four repeated functional magnetic resonance imaging (fMRI) sessions on different days with jaw clenching as a motor task to...

Apraxia is a deficit in central motor planning impairing praxis functions such as gesture production or tool use that affects a substantial number of patients with advanced Parkinson's disease. We investigated the functional connectivity of the praxis network in patients in early stages of Parkinson's disease having an increased risk for apraxia an...

Ultrasound-based brain stimulation techniques offer an exciting potential to modulate the human brain in a highly focal and precisely targeted manner. However, for clinical applications the current techniques have to be further developed. We introduce a new ultrasound stimulation technique, based on single ultrashort ultrasound pulses (transcranial...

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,...

Objectives: Gradients in the static magnetic field caused by tissues with differing magnetic susceptibilities lead to regional variations in the effective echo time, which modifies both image signal and BOLD sensitivity. Local echo time changes are not considered in the most commonly used metric for BOLD sensitivity, temporal signal-to-noise ratio...

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 o...

Cortical reorganization in response to peripheral nervous system damage is only poorly understood. In patients with complete brachial plexus avulsion and subsequent reconnection of the end of the musculocutaneous nerve to the side of a phrenic nerve, reorganization leads to a doubled arm representation in the primary motor cortex. Despite, homuncul...

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. FindingsFor 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 y...

Supporting Information

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 l...

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 t...

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 evaluat...

Background and purpose: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent...

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...

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 lo...

To investigate the spatiotemporal evolution of cortical activation during the initiation of optokinetic nystagmus using magnetoencephalography. 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 stru...

This chapter describes what kind of neuroplastic information may be generated by functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) after brain damage. Clinical neuroplasticity may be defined as an active reorganization contrary to loss of activation or connectivity simply due to brain damage. After giving an overview a...

Background: Cardiac arrest (CA) survivors experience cognitive deficits including post-traumatic stress disorder (PTSD). It is unclear whether these are related to cognitive/mental experiences and awareness during CPR. Despite anecdotal reports the broad range of cognitive/mental experiences and awareness associated with CPR has not been systemati...

Several investigations have shown limitations of fMRI reliability with current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language process...

Background / Purpose: We report results on brain activation patterns associated with recursive and iterative representations. Main conclusion: Recursive representations require the integration of the visual dorsal and ventral streams, while iterative representations require the recruitment of the dorsal stream only.

Crucial brain function can be localized via activation maps derived from fMRI. This approach is increasingly being used in presurgical planning in patients with brain tumors and epilepsy to facilitate resection of affected tissue without harming essential functional areas, minimizing the risk of post-surgical deficit [1]. The aim of this study was...

Hierarchical structures play a central role in many aspects of human cognition, prominently including both language and music. In this study we addressed hierarchy in the visual domain, using a novel paradigm based on fractal images. Fractals are self-similar patterns generated by repeating the same simple rule at multiple hierarchical levels. Our...

Awareness during anesthesia is characterized by auditory perceptions, pain, and dream like states and associated with PTSD. Few studies have examined awareness during cardiac arrest. Although, these two phenomena share similarities, there are also differences. In particular during CA, patients may report visual perceptions (‘seeing’ and recalling e...

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 toolb...

Establishing a reliable correspondence between lesioned brains and a template is challenging using current normalization techniques. The optimum procedure has not been conclusively established, and a critical dichotomy is whether to use input data sets which contain skull signal, or whether skull signal should be removed. Here we provide a first in...

Increased BOLD sensitivity at 7 T offers the possibility to increase the reliability of fMRI, but ultra-high field is also associated with an increase in artifacts related to head motion, Nyquist ghosting, and parallel imaging reconstruction errors. In this study, the ability of independent component analysis (ICA) to separate activation from these...

In functional MRI it is desirable for the blood-oxygenation level dependent (BOLD) signal to be localized to the tissue containing activated neurons rather than the veins draining that tissue. This study addresses the dependence of the specificity of the BOLD signal – the relative contribution of the BOLD signal arising from tissue compared to veno...

The clinical significance of functional MR imaging is steadily increasing. At the latest annual meeting of the Organization for Human Brain Mapping ([www.humanbrainmapping.org][1]) in Seattle this year, the largest group of contributions concerned the category “Disorders of the Nervous System.”

Functional MRI is often used for presurgical planning in patients with brain tumors and epilepsy (Beisteiner et al., 2008). This application might benefit from the use of ultra-high field strength, with the associated increased time-series SNR, BOLD sensitivity and increased specificity to BOLD signal changes in the microvasculature (Beisteiner et...

Information theory-based metric such as mutual information (MI) is widely used as similarity measurement for multimodal registration. Nevertheless, this metric may lead to matching ambiguity for non-rigid registration. Moreover, maximization of MI alone does not necessarily produce an optimal solution. In this paper, we propose a segmentation-assis...

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...

The aim of this study was to develop an analysis method sensitive to activation in regions of pathology, where responses might deviate from predictions due to modified HRF [1]. The suggested method, which we call uN-BIASED, is an extension of the BIASLESS method of Levin et al. (2001) [2] to N runs (N>=2) [3] and is tested on 7T clinical data.

The General Linear Model (GLM) is the most commonly applied approach to the statistical analysis of fMRI data. Neuronal responses are presumed to be accurately predictable from stimulus timing, and the HRF is taken to be uniform throughout the brain. Both of these assumptions may not be valid in clinical populations, however. Task execution may not...

Neural activity preceding force-loaded voluntary finger movement (the Bereitschaftsfeld) was recorded using 143-channel whole-scalp magnetoencephalography (MEG) in order to determine how the level of force produced during voluntary finger movement is represented in activity over different premovement time intervals localized to different cortical a...

In brachial plexus avulsion, a recent technique connects the ending of the disrupted musculocutaneous nerve to the side of the intact phrenic nerve to regain elbow flexion. This requires the phrenic nerve to perform a new double function: independent control of breathing and elbow flexion. Neuroplastic changes associated with acquisition of double...

Despite there being an increasing number of installations of ultra high field MR systems (>3T) in clinical environments, no functional patient investigations have yet examined possible benefits for functional diagnostics. Here we performed presurgical localization of the primary motor hand area on 3T and 7T Siemens scanners with identical investiga...

Final outcome after surgical repair of peripheral nerve transections varies. Here, we present the first longitudinal functional magnetic resonance imaging (fMRI) observation of cortical somatosensory reorganization patterns after surgery. A 43-year-old man presented with isolated complete transection of the right median nerve and underwent immediat...