Jens Volkmann

University of Wuerzburg | JMU · Department of Neurology

Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%) and the identification of several disease-linked genes, the etiology in most patients remains elusive. Moreover, understanding the correlations between clinical manifestation and gen...

Deep brain stimulation (DBS) is an established treatment for motor disorders like Parkinson’s disease, but its mechanisms and effects on neurons and networks are not fully understood, limiting research-driven progress. This review presents a framework that combines neurophysiological insights and translational research to enhance DBS therapy, empha...

Introduction: The use of ciltacabtagen autoleucel (cilta-cel) in RRMM patients within the CARTITUDE-1 study has exposed previously unknown late onset neurotoxicities, referred to as movement, neurocognitive treatment emergent events (MNT) (Cohen, A et al., 2022). In addition to their late occurrence, MNTs are characterized by their failure to respo...

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson’s disease (PwPD), the size and duration of the effects of STN-DBS on motor axial (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait – FOG) are still ambiguous. Physical therapy (PT) e...

Background Despite considerable heritability, previous smaller genome‐wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia. Objective The objective of this study was to perform a large‐scale GWAS in a well‐characterized, multicenter sample of >6000 individuals to identify genetic risk factors f...

Deep brain stimulation (DBS) has emerged as a revolutionary technique for accessing and modulating brain circuits. DBS is used to treat dysfunctional neuronal circuits in neurological and psychiatric disorders. Despite over two decades of clinical application, the fundamental mechanisms underlying DBS are still not well understood. One reason is th...

Frontal-eyed species use a combination of conjugate and vergence eye movements, termed 3-D gaze, to scan their environment 1–3 . The neural circuits mediating conjugate gaze have been extensively characterized, but those governing vergence remain disproportionately obscure ⁴ . Here, we combine lesion and deep brain stimulation data from 67 humans a...

Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for granular phenotyping. Instrumented neurophysiological analyses have proven useful, but are highly resource-intensive and lack broad accessibility. In contrast, bedside scores are simple to administer, but lack the gr...

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson’s disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the...

Pupillary assessment is a quintessential part of the clinical examination in neuro-intensive care patients because it provides insight into the integrity of midbrain reflex arcs. Abnormal pupils, particularly anisocoria and later bilateral fixed mydriasis, are classically used to assess expansive intracranial processes because they are frequently c...

Background Re‐emergent tremor is characterized as a continuation of resting tremor and is often highly therapy refractory. This study examines variations in brain activity and oscillatory responses between resting and re‐emergent tremors in Parkinson's disease. Methods Forty patients with Parkinson's disease (25 males, mean age, 66.78 ± 5.03 years...

Analysis of coupling between the phases and amplitudes of neural oscillations has gained increasing attention as an important mechanism for large-scale brain network dynamics. In Parkinson's disease (PD), preliminary evidence indicates abnormal beta-phase coupling to gamma-amplitude in different brain areas, including the subthalamic nucleus (STN)....

The reliable differentiation of tremor disorders poses a significant challenge, largely depending on the subjective interpretation of subtle signs and symptoms. Given the absence of a universally accepted bio-marker, diagnostic differentiation between the most prevalent tremor disorders, Essential Tremor (ET) and tremor-dominant Parkinsons Disease...

Parkinson’s disease (PD) is a neurodegenerative condition that is frequently associated with cognitive disorders. These can arise directly from the primary disease, or be triggered by external factors in susceptible individuals due to PD or other predisposing factors. The cognitive disorders encompass PD-associated cognitive impairment (PD-CI), del...

Mapping circuits for DBS. Within the enigmatic depths of an aquatic universe, divers use flashlights to reveal the hidden contours of an uncharted seabed that teems with wondrous vegetation. In an analogous exploration, Hollunder et al. describe how invasive brain stimulation delivered to deep-seated brain nuclei may act as a beacon. Using deep br...

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By anal...

In our prospective cross-sectional study, we comprehensively characterized Parkinson disease (PD)–related pain in monocentrically recruited patients with PD using standardized tools of pain assessment and categorization. One hundred fifty patients were systematically interviewed and filled in questionnaires for pain, depression, motor, and nonmotor...

Background Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co‐occurring movement disorders such as Parkin...

Background: Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for deep and granular phenotyping. Instrumented neurophysiological analyses have proven useful for clinical management, but are highly resource-intensive and lack broad accessibility. Simplified bedside score...

Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson’s disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics....

The pathophysiology of tremor in Parkinson’s disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the devel...

Studies have shown that beta band activity is not tonically elevated but comprises exaggerated phasic bursts of varying durations and magnitudes, for Parkinson’s disease (PD) patients. Current methods for detecting beta bursts target a single frequency peak in beta band, potentially ignoring bursts in the wider beta band. In this study, we propose...

(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used...

Background Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hind...

Re-emergent tremor (RET) during stable posture in Parkinson’s disease (PD) is characterized as a continuation of resting tremor (RT) and is often highly therapy refractory. The pathophysiology of both RT and RET is linked to deficits in cerebello-cortical circuits and dopaminergic depletion. However, it remains unclear how these two types of tremor...

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson's disease (PD). Clinical outcomes after DBS can be limited by poor programming, which remains a clinically driven, lengthy and iterative process. Electrophysiological recordings in PD patients undergoing STN-DBS have shown an associati...

Background: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with a...

Background: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. Objectives: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. Methods: The STIM-CP trial was a prospective, single-arm, multicente...

Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson’s disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution wit...

Disturbed motor control is a hallmark of Parkinson's disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modul...

Mental rotation (mR) bases on imagination of actual movements. It remains unclear whether there is a specific pattern of mR impairment in focal dystonia. We aimed to investigate mR in patients with cervical dystonia (CD) and blepharospasm (BS) and to assess potential confounders. 23 CD patients and 23 healthy controls (HC) as well as 21 BS and 19 h...

Deep brain stimulation (DBS) is a well-established symptomatic treatment for patients with Parkinson’s disease (PD). However, cellular mechanisms are not well understood. To close this knowledge gap, animal experiments are currently indispensable. However, basic research is hampered by the fact that only stationary DBS setups are readily available....

Introduction: Dystonia is a movement disorder of variable etiology and clinical presentation and is accompanied by tremor in about 50% of cases. Monogenic causes in dystonia are rare, but also in the group of non-monogenic dystonias 10-30% of patients report a family history of dystonia. This points to a number of patients currently classified as...

Research on the mental rotation task has sparked debate regarding the specific processes that underly the capability of humans to mentally rotate objects. The spread of reported brain activations suggests that mental rotation is subserved by a neural network circle. However, no common network has yet been found that uncovers the crucial processes u...

Tremor is the most frequent human movement disorder, and its diagnosis is based on clinical assessment. Yet finding the accurate clinical diagnosis is not always straightforward. Fine-tuning of clinical diagnostic criteria over the past few decades, as well as device-based qualitative analysis, has resulted in incremental improvements to diagnostic...

Neuroinflammation has been suggested as a pathogenetic mechanism contributing to Parkinson’s disease (PD). However, anti-inflammatory treatment strategies have not yet been established as a therapeutic option for PD patients. We have used a human α-synuclein mouse model of progressive PD to examine the anti-inflammatory and neuroprotective effects...

The frontal cortex is involved in motor, cognitive, and affective brain functions. In humans, however, neuroanatomy-function mappings are predominantly derived from correlative neuroimaging studies. Hence, exactly which frontal domains causally mediate which function remains largely elusive. Herein, we leverage a strategy that allows for causal inf...

Background: Skin biopsy is a potential tool for the premortem confirmation of an α-synucleinopathy. Objective: The aim was to assess the aggregation assay real-time quaking-induced conversion (RT-QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α-synucleinopathy. Methods: Skin biopsies of...

Background: Deep brain stimulation of the subthalamic nucleus is an effective treatment of Parkinson's disease, yet it is often associated with a general deterioration of speech intelligibility. Clustering the phenotypes of dysarthria has been proposed as a strategy to tackle these stimulation-induced speech problems. Methods: In this study, we...

The relationship between genotype and phenotype in DYT-TOR1A dystonia as well as the associated motor circuit alterations are still insufficiently understood. DYT-TOR1A dystonia has a remarkably reduced penetrance of 20-30%, which has led to the second-hit hypothesis emphasizing an important role of extragenetic factors in the symptomatogenesis of...

The deep brain stimulation (DBS) Think Tank X was held on August 17–19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation . Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was fou...

Background Regulatory CD4 ⁺ CD25 ⁺ FoxP3 ⁺ T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson’s disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create...

Recovery of upper limb (UL) impairment after stroke is limited in stroke survivors. Since stroke can be considered as a network disorder, neuromodulation may be an approach to improve UL motor dysfunction. Here, we evaluated the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in rats on forelimb grasping using the single...

Objective Gait disturbances causing impaired mobility are common in Parkinson’s disease after bilateral deep brain stimulation of the subthalamic nucleus. We describe subthalamic subregions where neurostimulation had a positive effect on gait or provoked gait disturbances. Methods Sixty-eight patients were classified according to postoperative gai...

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility asse...

Background Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography cap...

Freezing of gait (FOG) is a sudden episodic inability to produce effective stepping despite the intention to walk. It typically occurs during gait initiation (GI) or modulation and may lead to falls. We studied the anticipatory postural adjustments (imbalance, unloading, and stepping phase) at GI in 23 patients with Parkinson’s disease (PD) and FOG...

Background Pain is a common non-motor symptom of Parkinson`s disease (PD), however, its pathomechanism remains elusive. Objective We aimed to investigate the local gene expression of selected proinflammatory mediators in patients with PD and correlated our data with patients`pain phenotype. Methods We recruited 30 patients with PD and 30 healthy...

Seeding assays, such as real-time quaking-induced conversion (RT-QuIC), are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson’s disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight i...

Background Subthalamic nucleus (STN) deep brain stimulation (DBS) is regarded as an effective treatment for patients with advanced Parkinson’s disease (PD). Clinical benefit, however, varies significantly across patients. Lead location has been hypothesized to play a critical role in determining motor outcome and may account for much of the observe...

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modul