Walter Paulus

Universitätsmedizin Göttingen · Department of Clinical Neurophysiology

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) has been firmly established; however, the entity of diabetic myocardial disorder (previously called diabetic cardiomyopathy) remains a matter of debate. Diabetic myocardial disorder was originally described as the occurrence of myocardial structural/functional abnormalit...

Titin‐dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure‐overload hyper...

In heart failure with preserved ejection fraction (HFpEF), natriuretic peptide (NP) levels are frequently lower. In several trials, the outcome differed between patients with low and high NP levels. This suggests that NP could be used to identify distinct stages of left ventricular (LV) remodeling and myocardial tissue composition. This study inves...

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in...

Repetitive transcranial magnetic stimulation (rTMS) is a widely used non-invasive neuromodulatory technique. When applied in sleep medicine, the main hypothesis explaining its effects concerns the modulation of synaptic plasticity and the strength of connections between the brain areas involved in sleep disorders. Recently, there has been a signifi...

Background Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuro-modulation technique. Most studies show that anodal tDCS increases cortical excitability, however, with variable outcomes. Previously, we have shown in computer simulations that our multi-channel tDCS (mc-tDCS) approach, the distributed constrained maximum...

Objective Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome metho...

Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field an...

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial m...

Heart failure with preserved ejection fraction (HFpEF) represents a complex and heterogeneous clinical syndrome, which is increasingly prevalent and associated with poor outcome. In contrast to heart failure with reduced EF (HFrEF), modern heart failure pharmacotherapy does not improve outcome in HFpEF, which is related to incomplete understanding...

Taking the reader from an understanding of the basic mechanisms of heart failure through to an appreciation of the complexities of heart failure management and the remarkable improvements possible with good treatment, the Oxford Textbook of Heart Failure 2e covers all aspects necessary to manage a patient with heart failure. The new edition has bee...

Persistent stuttering is a prevalent neurodevelopmental speech disorder, which presents with involuntary speech blocks, sound and syllable repetitions, and sound prolongations. Affected individuals often struggle with negative feelings, elevated anxiety, and low self-esteem. Neuroimaging studies frequently link persistent stuttering with cortical a...

Interindividual anatomical differences in the human cortex can lead to suboptimal current directions and may result in response variability of transcranial electrical stimulation methods. These differences in brain anatomy require individualized electrode stimulation montages to induce an optimal current density in the targeted area of each individ...

Objective The neurophysiological dynamics of the occurrence of a stuttering event are largely unknown. This sensor-level EEG study investigated whether already the intention to speak alters the formation of the speech production network in stuttering. Methods We studied alpha (8-13 Hz), low beta (15-25 Hz) and high beta (25-30 Hz) power modulation...

This study aimed to evaluate the diagnostic performance of echocardiographic markers of heart failure with preserved ejection fraction (HFpEF) and left ventricular diastolic dysfunction (LVDD) in comparison with the gold standard of cardiac catheterization. Diagnosing HFpEF is challenging, as symptoms are non-specific and often absent at rest. A cl...

Introduction: High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse du...

Fluency-shaping enhances the speech fluency of persons who stutter, yet underlying conditions and neuroplasticity-related mechanisms are largely unknown. While speech production-related brain activity in stuttering is well studied, it is unclear whether therapy repairs networks of altered sensorimotor integration, imprecise neural timing and sequen...

Through neuromodulation of neural activity, transcranial alternating current stimulation (tACS) interacts with neural oscillations in a frequency- and phase-specific manner, thereby influencing human brain function. Currents are applied at the scalp with intensities up to 4 mA peak to peak (except for electroconvulsive therapy with much higher inte...

Introduction. After-effects induced by repetitive transcranial magnetic stimulation (rTMS) at the primary motor cortex (M1) are usually indexed by the amplitude of the motor evoked potential (MEP). They depend on various parameters, in particular on the temporal pattern. Quadripulse stimulation (QPS; high-frequency train of four pulses delivered ev...

Pathogenic variants in HECW2 are extremely rare. So far, only 19 cases have been reported. They were associated with epilepsy, intellectual disability, absent language, hypotonia, and autism. As these cases were all de novo mutations, mostly presenting without identical variants, variable expressivity has never been investigated. Here, we describe...

Introduction: 1) During tES, increasing intracellular Ca2+ levels beyond those needed for inducing LTP may collapse aftereffects. 2) State-dependent plastic aftereffects are reduced when applied during muscle activation as compared to rest. 3) Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. O...

In accordance with the comorbidity-inflammation paradigm, comorbidities and especially metabolic comorbidities are presumed to drive development and severity of heart failure with preserved ejection fraction through a cascade of events ranging from systemic inflammation to myocardial fibrosis. Recently, novel experimental and clinical evidence emer...

Dopamine is crucial for neuroplasticity, which is considered to be the neurophysiological foundation of learning and memory. The specific effect of dopamine on plasticity such as long-term potentiation (LTP) and long-term depression (LTD) is determined by receptor subtype specificity, concentration level, and the kind of plasticity induction techni...

This study was conducted to provide a better understanding of the role of electric field strength in the production of aftereffects in resting state scalp electroencephalography by repetitive transcranial magnetic stimulation (rTMS) in humans. We conducted two separate experiments in which we applied rTMS over the left parietal-occipital region. Pr...

The modulatory effects of non-invasive brain stimulation (NIBS) are highly variable between subjects. This variability may be due to uncontrolled caffeine consumption and circadian rhythms. Therefore, here we studied if caffeine consumption, systemically available caffeine measured in saliva, and daytime have effects on the excitability and plastic...

This handbook is currently in development, with individual articles publishing online in advance of print publication. At this time, we cannot add information about unpublished articles in this handbook, however the table of contents will continue to grow as additional articles pass through the review process and are added to the site. Please note...

Aims Echocardiographic predictors of outcomes in heart failure with preserved ejection fraction (HFpEF) have not been systematically or independently validated. We aimed at identifying echocardiographic predictors of cardiovascular events in a large cohort of patients with HFpEF and to validate these in an independent large cohort. Methods and res...

Objective We examined the effects of caffeine, time of day, and alertness fluctuation on plasticity effects after transcranial alternating current stimulation (tACS) or 25ms paired associative stimulation (PAS25) in caffeine-naïve and caffeine-adapted subjects. Methods In two randomised, double-blinded, cross-over or placebo-controlled (caffeine)...

Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used, non‐invasive brain stimulation technique in neuroscience research and clinical practice with a broad spectrum of suggested applications. Among other parameters, the choice of stimulus intensity and intracranial electric field strength substantially impact rTMS outcome. Thi...

Introduction Needle electromyography (EMG) is an essential part of electrodiagnosis (EDX) in neuromuscular disorders. As in all invasive procedures there is a risk of bleeding complications, but which is rare according to the current literature. Controlled, prospective studies that include patients under anticoagulation or antiplatelet therapy are...

Background Noradrenaline (NA) has an important role as a neuromodulator of the central nervous system. Noradrenergic enhancement was recently shown to enhance glutamate-dependent cortical facilitation, and long term potentiation-like plasticity. As cortical excitability and plasticity are closely linked to various cognitive processes, here we aimed...

Purpose Childhood onset speech fluency disorder (stuttering) is possibly related to dopaminergic dysfunction. Mesencephalic hyperechogenicity (ME) detected by transcranial ultrasound (TCS) might be seen as an indirect marker of dopaminergic dysfunction. We here determined whether adults who stutter since childhood (AWS) show ME. Methods We perform...

Recent studies have identified two distinct cortical representations of voice control in humans, the ventral and the dorsal laryngeal motor cortex. Strikingly, while persistent developmental stuttering has been linked to a white matter deficit in the ventral laryngeal motor cortex, intensive fluency shaping intervention modulated the functional con...

Background: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods: A total of 415 proteins were analyze...

Background Diagnosis of functional movement disorders and specifically functional tremor (FT) (representing 50% of them) remains demanding. Additionally, due to heterogeneity of the disorders, structured concepts and guidelines for diagnosis and therapy are difficult to establish. Ascertaining the state of knowledge to derive instructions for opera...

As the field of noninvasive brain stimulation (NIBS) expands there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three differ...

Background: Low intensity, high-frequency transcranial alternating current stimulation (tACS) applied over the motor cortex decreases the amplitude of motor evoked potentials. This double-blind, placebo-controlled parallel group study aimed to test the efficacy of this method for acute management of migraines. Methods: The patients received either...

s Sensorimotor mu-alpha rhythm reflects the state of cortical excitability. Repetitive transcranial magnetic stimulation (rTMS) can modulate neural synchrony by inducing periodic electric fields (E-fields) in the cortical networks. We hypothesized that the increased synchronization of mu-alpha rhythm would inhibit the corticospinal excitability ref...

There is a lack of consensus on how we define heart failure with preserved ejection fraction (HFpEF), with wide variation in diagnostic criteria across society guidelines. This lack of uniformity in disease definition stems in part from an incomplete understanding of disease pathobiology, phenotypic heterogeneity, and natural history. We review cur...

This study was conducted to provide a better understanding of the role of electric field strength in the production of aftereffects in resting state scalp electroencephalography by repetitive transcranial magnetic stimulation (rTMS) in humans. We conducted two separate experiments in which we applied rTMS over the left parietal-occipital region. Pr...

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical setti...

Aims: High myocardial stiffness in heart failure with preserved ejection fraction (HFpEF) is attributed to comorbidity-induced structural and functional remodelling through inflammation and oxidative stress affecting coronary microvascular endothelial cells and cardiomyocytes, which augments interstitial fibrosis and cardiomyocyte stiffness. In mu...

Background Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used, non-invasive brain stimulation technique in neuroscience research and clinical practice with a broad spectrum of suggested applications. Among other parameters, the choice of stimulus intensity and intracranial electric field strength substantially impact rTMS o...

Liquorzirkulationsstörungen stellen besondere Anforderungen an Neurologen, die es gewohnt sind, pathologische Veränderungen in den heutzutage ausgefeilten Schnittbildtechniken zu sehen. Dies ist auch bei den klassischen Hydrozephaluspatienten der Fall. Erkrankungen wie Liquorunterdrucksyndrom oder Pseudotumor cerebri lassen sich in der Regel kernsp...

Recent studies have identified two distinct cortical representations of voice control in humans, the ventral and the dorsal laryngeal motor cortex. Strikingly, while persistent developmental stuttering has been linked to a white matter deficit in the ventral laryngeal motor cortex, intensive fluency shaping intervention modulated the functional con...

Cognitive control is a mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the θ band and θ-γ cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. However, to date, the behavioral consequences of different forms of θ-γ CFC...

Developmental stuttering is a fluency disorder with anomalies in the neural speech motor system. Fluent speech requires multifunctional network formations. Currently, it is unclear which functional domain is targeted by speech fluency interventions. Here, we tested the impact of fluency-shaping on resting-state fMRI connectivity of the speech plann...

Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modulating endogenous oscillations in humans. The current standard method for rTMS defines the stimulation intensity based on the evoked liminal response in the visual or motor system (e.g., resting motor threshold). The key limitation of the current approach is that the magni...

Aim Diagnosing Heart Failure with Preserved Ejection Fraction (HFpEF) in the non‐acute setting remains challenging. Natriuretic peptides have limited value for this purpose, and a multitude of studies investigating novel diagnostic circulating biomarkers have not resulted in their implementation. This review aims to provide an overview of studies i...

Background: It has been proposed that diabetes and chronic kidney disease cause heart failure with preserved ejection fraction (HFpEF) through low-grade inflammation and microvascular endothelial dysfunction. We have previously shown that endothelial enhancement of cardiomyocyte contraction and relaxation is mediated by NO, impaired by cytokines, a...

Whether fluent-sounding utterances of adults who stutter (AWS) are normally articulated is unclear. We asked 15 AWS and 17 matched adults who do not stutter (ANS) to utter the pseudoword “natscheitideut” 15 times in a 3 T MRI scanner while recording real-time MRI videos at 55 frames per per second in a mid-sagittal plane. All stuttered or otherwise...

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodelin...

Cognitive control is a hypothetical mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the theta band and theta-gamma cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. Yet, to date the behavioral consequences of differ...

Understanding the mechanisms by which intermittent theta burst stimulation (iTBS) protocols exert changes in the default-mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. While a full session (3000 pulses) of 10 Hz repetitive transcranial magnetic stimulation (HF-rTMS) reduces the functional connect...

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF...

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently rev...

Heart failure (HF) with preserved ejection fraction (EF; HFpEF) currently accounts for greater than 50% of all HF cases, and its prevalence relative to HF with reduced EF (HFrEF) continues to rise. Outcomes in patients with HFpEF and HFrEF are equally poor. In contrast to HFrEF, modern HF pharmacotherapy did not improve outcome in HFpEF, which is r...

Transcranial direct current stimulation (tDCS) induces polarity‐ and dose‐dependent neuroplastic aftereffects on cortical excitability and cortical activity, as demonstrated by transcranial magnetic stimulation (TMS) and functional imaging (fMRI) studies. However, lacking systematic comparative studies between stimulation‐induced changes in cortica...