Kathrin S. Utz

Electrified minds: Transcranial direct current stimulation (tDCS) and Galvanic Vestibular Stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology—A review of current data and future implications

Transcranial direct current stimulation (tDCS) is a noninvasive, low-cost and easy-to-use technique that can be applied to modify cerebral excitability. This is achieved by weak direct currents to shift the resting potential of cortical neurons. These currents are applied by attaching two electrodes (usually one anode and one cathode) to distinct areas of the skull. Galvanic Vestibular Stimulation (GVS) is a variant of tDCS where the electrodes are attached to the mastoids behind the ears in order to stimulate the vestibular system. tDCS and GVS are safe when standard procedures are used. We describe the basic physiological mechanisms and application of these procedures. We also review current data on the effects of tDCS and GVS in healthy subjects as well as clinical populations. Significant effects of such stimulation have been reported for motor, visual, somatosensory, attentional, vestibular and cognitive/emotional function as well as for a range of neurological and psychiatric disorders. Moreover, both techniques may induce neuroplastic changes which make them promising techniques in the field of neurorehabilitation. A number of open research questions that could be addressed with tDCS or GVS are formulated in the domains of sensory and motor processing, spatial and nonspatial attention including neglect, spatial cognition and body cognition disorders, as well as novel treatments for various neuropsychological disorders. We conclude that the literature suggests that tDCS and GVS are exciting and easily applicable research tools for neuropsychological as well as clinical-therapeutic investigations.

Galvanic vestibular stimulation reduces the pathological rightward line bisection error in neglect-a sham stimulation-controlled study.

Patients with right hemisphere lesions often show left spatial neglect and the typical rightward deviation in horizontal line bisection. Previous studies have shown that sensory stimulation modulates line bisection. A less well-known but promising sensory stimulation method is galvanic vestibular stimulation (GVS). This non-invasive technique leads to activation of the vestibular cortices and adjacent cortical areas in the temporo-parietal cortex via polarization effects of the vestibular nerves. This is accomplished by application of weak direct currents, delivered by two electrodes attached to the mastoids. Despite the relative benefits of GVS its effects on line bisection have not yet been studied in neglect patients. Thus, the present study investigated the impact of GVS on performance in a modified line bisection task in right-brain damaged patients with versus without leftsided visual neglect. In neglect patients, but not in control patients, left-cathodal and right-cathodal GVS significantly reduced the rightward line bisection error as compared to Baseline (without GVS) and sham stimulation. A larger decrease of the rightward line bisection error was observed during right-cathodal GVS. Sham stimulation showed no specific effects on line bisection. The beneficial effects of GVS might be due to activation of preserved structures of the lesioned right posterior parietal cortex which is known to be involved in line bisection.

Minor adverse effects of galvanic vestibular stimulation in persons with stroke and healthy individuals

Objective: Galvanic vestibular stimulation (GVS) induces polarity-specific activations in the vestibular nerves and upstream in the vestibular and parietotemporal cortices as well as sub-cortical regions. This makes it an attractive technique for cognitive neuromodulation. However, systematic studies regarding adverse effects of GVS are unavailable. Thus, this study assessed adverse effects during and after sub-sensory GVS (mean: 0.6 mA) and GVS with 1.5 mA. Methods: Two hundred and fifty-five GVS sessions delivered to 55 persons with stroke and 30 healthy individuals were analysed using a 34-item-questionnaire including potential symptoms and rating scales for adverse effects. Results: The most frequent symptoms during and after GVS were slight itching (mean: 10.2%) and tingling (mean: 10.7%) underneath the electrodes. Healthy individuals and persons with stroke did not differ in their incidence and rated intensity of adverse effects, nor did persons with or without unilateral spatial neglect. Adverse effects were found more frequently with GVS with 1.5 mA as with sub-sensory GVS. Participants were unable to differentiate real from sham conditions during sub-sensory GVS. Importantly, neither seizures nor vertigo or nausea were observed. Conclusion: Sub-sensory GVS and GVS with 1.5 mA induce very few and mild adverse effects in healthy and persons with stroke and are safe when safety guidelines are followed.

A long-lasting improvement of tactile extinction after galvanic vestibular stimulation: Two Sham-stimulation controlled case studies

Sensory extinction is frequent and often persistent after brain damage. Previous studies have shown the transient influence of sensory stimulation on tactile extinction. In the present two case studies we investigated whether subliminal galvanic vestibular stimulation (GVS) modulates tactile extinction. GVS induces polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas in the temporo-parietal cortex via polarization of the vestibular nerves. Two patients (DL, CJ) with left-sided tactile extinction due to chronic (5 vs. 6 (1/2) years lesion age) right-hemisphere lesions (right fronto-parietal in DL, right frontal and discrete parietal in CJ) were examined. Both showed normal tactile sensitivity to light touch and yielded 90-100% correct identifications in unilateral tactile stimulations for both hands. In Baseline investigations without GVS and Sham-GVS both showed stable left-sided tactile extinction rates of 40-55% (DL) and 49-72% (CJ). In contrast, one session of right-cathodal GVS (intensity: 0.6 mA, duration: 20 min) permanently improved tactile identification of identical stimuli, while a second session with left-cathodal GVS significantly reduced left-sided extinction rates for different stimuli in DL. Patient CJs left-sided tactile extinction was significantly improved by left-cathodal GVS (0.5 mA, 20 min) for different stimuli, while right-cathodal GVS induced a significant reduction for identical materials. In contrast, Sham-stimulation was ineffective. Improvements remained stable for at least 1 year (DL) resp. 3 weeks (CJ). Control experiments ruled out improvements in tactile extinction merely by retesting. In conclusion, chronic tactile extinction may be permanently improved by GVS in a polarity-specific way.

Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis

Objectives: With an increasing number of disease-modifying treatments (DMTs) for multiple sclerosis (MS), patient preferences will gain importance in the decision-making process. We assessed patients’ implicit preferences for oral versus parenteral DMTs and identified factors influencing patients’ treatment preference. Methods: Patients with relapsing–remitting MS (n = 156) completed a questionnaire assessing treatment preferences, whereby they had to decide between pairs of hypothetical treatment scenarios. Based on this questionnaire a choice-based conjoint analysis was conducted. Results: Treatment frequency and route of administration showed a stronger influence on patient preference compared with frequency of mild side effects. The latter attribute was more important for treatment-naïve patients compared with DMT-experienced patients. The higher the Extended Disability Status Scale score, the more likely pills, and the less likely fewer side effects were preferred. Pills were preferred over injections by 93% of patients, when treatment frequency and frequency of side effects were held constant. However, preference switched to injections when pills had to be taken three times daily and injections only once per week. Injections were also preferred when pills were associated with frequent side effects. Conclusions: Our results suggest that route of administration and treatment frequency play an important role in the patients’ preference for a given DMT.

Now You Feel both: Galvanic Vestibular Stimulation Induces Lasting Improvements in the Rehabilitation of Chronic Tactile Extinction

Tactile extinction is frequent, debilitating, and often persistent after brain damage. Currently, there is no treatment available for this disorder. In two previous case studies we showed an influence of galvanic vestibular stimulation (GVS) on tactile extinction. Here, we evaluated in further patients the immediate and lasting effects of GVS on tactile extinction. GVS is known to induce polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas. Tactile extinction was examined with the Quality Extinction Test (QET) where subjects have to discriminate six different tactile fabrics in bilateral, double simultaneous stimulations on their dorsum of hands with identical or different tactile fabrics. Twelve patients with stable left-sided tactile extinction after unilateral right-hemisphere lesions were divided into two groups. The GVS group (N = 6) performed the QET under six different experimental conditions (two Baselines, Sham-GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, and a Follow-up test). The second group of patients with left-sided extinction (N = 6) performed the QET six times repetitively, but without receiving GVS (control group). Both right-cathodal/left-anodal as well as left-cathodal/right-anodal GVS (mean: 0.7 mA) improved tactile identification of identical and different stimuli in the experimental group. These results show a generic effect of GVS on tactile extinction, but not in a polarity-specific way. These observed effects persisted at follow-up. Sham-GVS had no significant effect on extinction. In the control group, no significant improvements were seen in the QET after the six measurements of the QET, thus ruling out test repetition effects. In conclusion, GVS improved bodily awareness permanently for the contralesional body side in patients with tactile extinction and thus offers a novel treatment option for these patients.

Galvanic Vestibular Stimulation Improves Arm Position Sense in Spatial Neglect: A Sham-Stimulation-Controlled Study

Background. Disturbed arm position sense (APS) is a frequent and debilitating condition in patients with hemiparesis after stroke. Patients with neglect, in particular, show a significantly impaired contralesional APS. Currently, there is no treatment available for this disorder. Galvanic vestibular stimulation (GVS) may ameliorate neglect and extinction by activating the thalamocortical network. Objective. The present study aimed to investigate the immediate effects and aftereffects (AEs; 20 minutes) of subsensory, bipolar GVS (M = 0.6 mA current intensity) on APS in stroke patients with versus without spatial neglect and matched healthy controls. Methods. A novel optoelectronic arm position device was developed, enabling the precise measurement of the horizontal APS of both arms. In all, 10 healthy controls, 7 patients with left-sided hemiparesis and left-spatial neglect, and 15 patients with left hemiparesis but without neglect were tested. Horizontal APS was measured separately for both forearms under 4 experimental conditions (baseline without GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, sham GVS). The immediate effects during GVS and the AEs 20 minutes after termination of GVS were examined. Results. Patients with neglect showed an impaired contralateral APS in contrast to patients without neglect and healthy controls. Left-cathodal/right-anodal GVS improved left APS significantly, which further improved into the normal range 20 minutes poststimulation. GVS had no effect in patients without neglect but right-cathodal/left-anodal GVS worsened left APS in healthy participants significantly. Conclusions. GVS can significantly improve the impaired APS in neglect. Multisession GVS can be tested to induce enduring therapeutic effects.

Multimodal and multispatial deficits of verticality perception in hemispatial neglect

Recent evidence suggests that patients with left-sided visuospatial neglect often show deviations in their visual and haptic perception of verticality in the frontal and sagittal plane. However, little is known about the multimodality of these impairments and the relationship between deviations in the frontal and the sagittal plane. Moreover, no previous study has combined investigations of verticality judgments in both modalities and both spatial planes within the same sample of subjects using the same apparatus. Thus, the aim of the present study was to investigate both subjective visual vertical (SVV) and subjective haptic vertical (SHV) judgments in the frontal and the sagittal plane in right-brain-damaged patients with visuospatial neglect (n=16), right-brain-damaged patients without neglect (n=18) and age-matched healthy individuals (n=16) using the same testing device for all tasks. This allowed for direct comparisons of visual vs. haptic and frontal vs. sagittal verticality judgments. Neglect patients showed significant counterclockwise tilts in their SVV and SHV judgments in the frontal plane as well as marked backward (upper end of the rod towards the observer) tilts in the sagittal plane. In contrast, right-brain-damaged patients without neglect and healthy individuals showed no marked deviations in the frontal plane, but small forward (upper end of the rod away from the observer) tilts in the sagittal plane. Moreover, neglect patients showed significantly higher unsigned errors in all tasks. These results demonstrate multimodal and multispatial deficits in the judgment of verticality in patients with visuospatial neglect which are most likely due to an altered representation of verticality caused by lesions of brain areas related to multisensory integration and space representation in the right temporo-parietal cortex.

Biomechanical factors may explain why grasping violates Weber’s law

For grasping, Ganel, Chajut, and Algom (2008) demonstrated that the variability of the maximum grip aperture (MGA) does not increase with the size of the target object. This seems to violate Webers law, a fundamental law of psychophysics. They concluded that the visual representations guiding grasping are distinct from representations used for perceptual judgments. Webers law is however only relevant for one component of the measurable variability of MGA, namely the variability in the sensory system. We argue that when looking at the relationship between object size and grasping, the gain (often called slope) governing the relationship between target size and MGA can be used as an approximation to estimate the contribution of sensory noise to MGA variability. To test the idea that differences in gain modulate the relationship between target size and MGA variability, we examined grasping under a variety of conditions. We found that gain varied quite significantly across different tasks, but irrespective of gain Webers law could not be found in any of the grasping tasks. Instead we repeatedly found an inverse relationship between variability and object size, i.e. variability decreased for bigger objects. This trend may reflect the reduced biomechanical freedom found for movements at the end an effectors effective range of motion. MGA variability may thus be dominated by non-sensory factors and therefore may constitute a poor choice to estimate the variability of the visual signals used by the brain to guide our grasping actions.

Visual context modulates the subjective vertical in neglect: evidence for an increased rod-and-frame-effect

Patients with spatial hemi-neglect display systematic deviations of the subjective vertical. The magnitude of such deviations was shown to be modulated by internal factors mediating the perception of verticality, including head-orientation. The present study investigated whether and how spatial orientation deficits are modulated by external, contextual changes in neglect patients. In a classic rod-and-frame task, we analyzed effects of frame orientation on the subjective visual vertical (SVV) in neglect patients, control patients with left- or right-sided brain damage without neglect and healthy participants. We found that neglect patients, but not brain-damaged control patients, generally display a systematic counterclockwise (CCW) tilt in their SVV judgments. Furthermore, all participant groups displayed a typical rod-and-frame effect (RFE), that is, a modulation of the SVV as a function of frame tilt. However, in the control groups, this modulation was only moderate whereas in the neglect group SVV judgments were substantially and systematically modulated by frame orientation: with CCW frame tilts, the spatial bias of neglect patients increased as a function of the magnitude of the tilt whereas with clockwise (CW) frame tilts, the spatial bias was decreased in case of moderate frame tilts and even reversed in case of stronger frame tilts, resulting in a substantial CW spatial bias. This dramatically enhanced RFE might be caused by a pathologically increased influence of contextual cues on the subjective vertical in neglect patients as a consequence of impaired processing of gravitational information. The results indicate a systematic bias of the subjective vertical along with an impairment of spatial orientation constancy which leads to severe perturbations of subjective space as well as an increased reliance on internal and external cues mediating the perception of verticality in neglect.