Hans-Otto Karnath

Magnetic resonance imaging (MRI) offers detailed diagnostic insights but also unintentionally induces vestibular side effects by its static magnetic field. Magnetic vestibular stimulation (MVS) may cause dizziness and confound behavioral and physiological measures in fMRI by introducing an unavoidable mixture of neural activation in vestibular projection areas, driven both by the signal of interest and by vestibular system activation. This study investigated how different head orientations within a 3T MRI scanner influence the MVS-induced vestibulo-ocular reflex (VOR) in complete darkness, with the goal of identifying a head position that minimizes or eliminates MVS effects. Results revealed a linear relationship between head pitch and the horizontal VOR (Experiment 1), as well as between head roll and the vertical VOR (Experiment 2). Across participants, the horizontal VOR was eliminated at a median forward head pitch of 24.4°, while the vertical VOR was nullified at an average roll angle of 15.9° towards the right shoulder. A head position combining this forward pitch with this rightward roll effectively minimized both horizontal and vertical VOR components across subjects (Experiment 3). No conclusions can be drawn regarding torsional eye movements, as those were not recorded. The findings provide a practical solution to reduce the impact of MVS effects in MRI with important implications for improving data quality in neuroscientific fMRI studies and patient comfort during clinical imaging.

Background and Aim: Unilateral spatial neglect (UN) impairs patients’ ability to detect and respond to stimuli on the contralesional side, severely limiting functional recovery after right-hemispheric stroke. Neck muscle vibration (NMV) has been shown to be a bottom-up, proprioceptive intervention to modulate spatial neglect. Although preliminary studies found promising effects, the isolated efficacy of NMV for neglect rehabilitation has not yet been tested in a randomized, blinded controlled trial. This study aimed to evaluate whether NMV alone improves neglect symptoms and activities of daily living (ADL). Methods: Twenty patients with right-hemispheric stroke and UN were randomly assigned to receive either active or placebo NMV (combined, but not simultaneously with computer-based training) over 2 weeks (5 sessions/week, 20 minutes/day). In the computer training, the placebo NMV group completed neglect-specific modules (standard neglect therapy [SNT], e.g., visual exploration training), while the active NMV group performed only general cognitive tasks unrelated to neglect. This allowed the isolated effect of NMV to be examined. Assessments included standard neglect diagnostics (e.g., Letter Cancellation), the Free Exploration Test (FET), and 2 ADL-based measures (NET, CBS), conducted before, immediately after, and (NMV group only) 1 month post-treatment. Results: The active NMV group showed significant improvements in 3 of 4 standard neglect tests, exploration behavior (FET), and ADL performance, with effects remaining stable at 1-month follow-up. The SNT group with placebo NMV showed comparable gains in ADL outcomes but improved in 1 standard neglect test only. Between-group analyses revealed no statistically significant differences, suggesting similar efficacy of both interventions. Conclusion: NMV alone yields clinically meaningful and lasting improvements in neglect symptoms and ADL, comparable to SNT. Its passive nature makes it a promising tool, particularly for early rehabilitation.

Pusher syndrome is a disorder of postural control, characterized by an altered perception of upright body orientation. While visual verticality perception remains intact, patients incorrectly perceive their tilted body posture as upright, resulting in active resistance to posture correction. This perceptual mismatch offers a potential target for therapeutic interventions. We evaluated a newly developed Tilted Reality Device (TRD) designed to recalibrate body verticality perception by subtly tilting the patient’s real-time visual environment towards the ipsilesional side in a series of four patients with pusher syndrome. We implemented a three-phase experimental design: pre-manipulation (normal view), manipulation (TRD tilted 20° ipsilesionally), and post-manipulation (normal view). Passive body tilts were performed while we recorded body orientation. Fifteen healthy older adults served as controls. The behavioral changes were assessed via tilt angle analysis and were statistically compared using Crawford-Garthwaite Bayesian methods. Two of the four patients showed reduced resistance to ipsilesional body tilts during the TRD manipulation. Two patients also demonstrated an aftereffect. Our findings only partly confirmed our expectations; possible limitations are discussed. Further research is needed to evaluate our TRD in its potential treatment effects in pusher syndrome and better understand the mechanisms involved in the recalibration of upright body orientation perception in patients with pusher syndrome.

Given the vestibular system’s important role in the perception of upright, we investigated the possible effects of galvanic vestibular stimulation (GVS) on the perception of one’s own upright body orientation in relation to gravity, the so-called ‘Subjective Postural Vertical (SPV)’. Two groups of healthy participants with an average age of 25.4 years and 64.5 years respectively, each consisting of 28 healthy participants, sat (blindfolded) on a tilting chair. The subjects’ feeling of being upright was tested under three different conditions of GVS: right-sided anodal stimulation, left-sided anodal stimulation, and sham stimulation. Our findings revealed that right-sided anodal GVS significantly altered the SPV in both age groups, whereas left-sided anodal GVS did not. The observed effect of GVS on perceived upright body posture was numerically small (up to 0.87° on average) and not due to a loss of sensitivity to the perception of body verticality. The unexpected asymmetry of the behavioral effects of GVS could be related to the known right hemispheric asymmetry of cortical activation in vestibular projection areas, which would need to be further clarified in future studies.

Magnetic resonance imaging (MRI) offers detailed diagnostic insights but also unintentionally induces vestibular side effects by its static magnetic field. Magnetic vestibular stimulation (MVS) may cause dizziness and confound behavioral and physiological measures in fMRI by introducing an unavoidable mixture of neural activation in vestibular projection areas, driven both by the signal of interest and by vestibular system activation. This study investigated how different head orientations within a 3T MRI scanner influence the MVS-induced vestibulo-ocular reflex (VOR) in complete darkness, with the goal of identifying a head position that minimizes or eliminates MVS effects. Results revealed a linear relationship between head pitch and the horizontal VOR (Experiment 1), as well as between head roll and the vertical VOR (Experiment 2). Across participants, the horizontal VOR was eliminated at an average forward head pitch of 24.4°, while the vertical VOR was nullified at an average roll angle of 15.9° towards the right shoulder. A head position combining this forward pitch with this rightward roll effectively minimized both horizontal and vertical VOR components across subjects (Experiment 3). The findings provide a practical solution to reduce the impact of MVS effects in MRI with important implications for improving data quality in neuroscientific fMRI studies and patient comfort during clinical imaging.

Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience. This perspective examines the factors that hinder clinical progress in translational neuroscience and provides solutions on how to overcome them. Editorial board members of Exploration of Neuroscience were interrogated about the most prominent challenges they see in translational neuroscience and about possible ways to overcome these issues. Key challenges were seen at the interface between experimental research and clinical studies by several members, both from the basic and applied neuroscience fields, which include the selection of appropriate study readouts and endpoints. The establishment of refined study endpoints, combined with biomarkers capable of predicting treatment responses in human patients, will be crucial for the successful clinical implementation of new therapies. Further obstacles were found in the standardization of experimental models, interventions, and assessments both in animals and humans, as well as in the development of personalized treatment strategies. These challenges can be addressed through more clearly defined experimental procedures that closely match clinical conditions and precision-based approaches that ensure efficient therapeutic responses. As a great opportunity, treatment options targeting pathophysiological processes in multiple brain diseases and disease processes in different organ systems were noted. Significant barriers remain in the funding of investigator-driven clinical trials through public research programs, as well as the education of translational and clinician scientists dedicated to clinical translation. Enhanced communication between experimental neuroscientists and clinicians, with a shared understanding and common language, will be essential for the success of future research endeavors.

Given the vestibular system’s important role in the perception of upright, we investigated the possible effects of galvanic vestibular stimulation (GVS) on the perception of one’s own upright body orientation in relation to gravity, the so-called ‘Subjective Postural Vertical (SPV)’. Two groups of healthy participants with an average age of 25.4 years and 64.5 years respectively, each consisting of 28 healthy participants, sat (blindfolded) on a tilting chair. The subjects’ feeling of being upright was tested under three different conditions of GVS: right-sided anodal stimulation, left-sided anodal stimulation, and sham stimulation. Our findings revealed that right-sided anodal GVS significantly altered the SPV in both age groups, whereas left-sided anodal GVS did not. The observed effect of GVS on perceived upright body posture was numerically small (up to 0.87° on average) and not due to a loss of sensitivity to the perception of body verticality. The unexpected asymmetry of the behavioral effects of GVS could be related to the known right hemispheric asymmetry of cortical activation in vestibular projection areas, which would need to be further clarified in future studies.

Background and Aim Unilateral spatial neglect (UN) impairs patients’ ability to detect and respond to stimuli on the contralesional side, severely limiting functional recovery after right-hemispheric stroke. Neck muscle vibration (NMV) has been shown as a bottom-up, proprioceptive intervention to modulate spatial neglect. Although preliminary studies found promising effects, the isolated efficacy of NMV for neglect rehabilitation has not yet been tested in a randomized, blinded controlled trial. This study aimed to evaluate whether NMV alone improves neglect symptoms and activities of daily living. Methods Twenty patients with right-hemispheric stroke and UN were randomly assigned to receive either active or placebo NMV over two weeks (5 sessions/week). Both groups received 20-minute daily vibration sessions. Standard neglect therapy was withheld in the active group but administered in the placebo group. Assessments included standard neglect diagnostics (e.g., Letter Cancellation, Bells Test), the Free Exploration Test (FET), and two ADL-based measures (NET, CBS), conducted before, immediately after, and (for the NMV group) one month post-treatment. Results The active NMV group showed significant improvements in three of four standard neglect tests, exploration behavior (FET), and ADL performance, with effects remaining stable at one-month follow-up. The placebo group showed comparable gains in ADL outcomes but improved in one standard neglect test only. Between-group analyses revealed no statistically significant differences, suggesting similar efficacy of both interventions. Conclusion NMV alone yields clinically meaningful and lasting improvements in neglect symptoms and daily functioning, comparable to standard active exploration therapy. Its passive nature makes it a promising tool, especially for early rehabilitation.

Spatial neglect is commonly attributed to lesions of a predominantly right-hemispheric cortical network. Although spatial neglect was also repeatedly observed after lesions to the basal ganglia and the thalamus, many anatomical network models omit these structures. We investigated if disruption of functional or structural connectivity can explain spatial neglect in subcortical stroke. We retrospectively investigated data of first-ever, acute stroke patients with right-sided lesions of the basal ganglia (n = 27) or the thalamus (n = 16). Based on lesion location, we estimated (i) functional connectivity via lesion-network mapping with normative resting state fMRI data, (ii) structural white matter disconnection using a white matter atlas and (iii) tract-wise disconnection of association fibres based on normative tractography data to investigate the association of spatial neglect and disconnection measures. Apart from very small clusters of functional disconnection observed in inferior/middle frontal regions in lesion-network symptom mapping for basal ganglia lesions, our analyses found no evidence of functional or structural subcortico-cortical disconnection. Instead, the multivariate consideration of lesion load to several association fibres predicted the occurrence of spatial neglect (p = 0.0048; AUC = 0.76), which were the superior longitudinal fasciculus, inferior occipitofrontal fasciculus, superior occipitofrontal fasciculus, and the uncinate fasciculus. Disconnection of long (cortico-cortical) association fibres can explain spatial neglect in subcortical stroke. Like the competing theory of remote cortical hypoperfusion, our finding does not support a genuine role for subcortical grey matter structures in spatial neglect.