Stefan Reinhart

Recovery from auditory and visual neglect after optokinetic stimulation with pursuit eye movements – Transient modulation and enduring treatment effects

Optokinetic stimulation (OKS) modulates many facets of the neglect syndrome. This sensory stimulation technique is known to activate multiple brain regions (temporo-parietal cortex, basal ganglia, brain stem, cerebellum) some of which are involved in auditory and visual space coding. Here, we evaluated whether OKS modulates auditory neglect transiently and induces a sustained effect (Study 1), and whether repetitive OKS permanently recovers auditory neglect (Study 2). In Study 1, 20 patients with visuospatial neglect and auditory neglect in an auditory midline task following rightsided stroke were randomly allocated to an experimental and a control group matched for neglect severity and socio-demographic factors. Both groups showed a stable, pathological shift of their auditory subjective median plane (ASMP) in front space to the right side. During leftward OKS the experimental group showed a complete normalization of the shift of the ASMP, which endured until 30 min poststimulation, and returned almost to baseline values 24h after OKS. In contrast, the control group who viewed the identical but static dot pattern, showed neither change in their ASMP during this condition, nor any significant change at 30 min or 24h poststimulation. In Study 2, we show in two samples of neglect patients (N = 3 each) that repetitive leftward OKS with smooth pursuit eye movements as a therapy induces lasting improvements in auditory (the ASMP) and visual neglect while visual scanning therapy yielded no measurable effects on auditory and significantly smaller effects on visual neglect. In conclusion, the experiments show that a single session of OKS induces rapid though transient recovery from auditory neglect including a sustained effect after termination of stimulation, while repetitive OKS therapy yields enduring and multimodal recovery from auditory and visual neglect. OKS therapy with pursuit eye movements therefore represents a multimodally effective and easily applicable technique for the treatment of auditory and visual neglect.

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.

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.

Smooth Pursuit “Bedside” Training Reduces Disability and Unawareness During the Activities of Daily Living in Neglect A Randomized Controlled Trial

Background. Neglect is associated with disability, unawareness, poor long-term outcome, and dependence from caregivers. No randomized trial has evaluated the effects of smooth pursuit eye movement training (SPT) and visual scanning training (VST) at the bedside on these variables. Objective. To compare the effects of SPT and VST in postacute stroke at 1 month with left neglect. Methods: We carried out an assessor-blinded, randomized controlled trial. The 24 participants were randomly allocated to either SPT or VST (n = 12 each). They received 20 treatment sessions lasting 30 minutes each at the bedside over 4 weeks. Outcome measures included the Functional Neglect Index (FNI) based on 4 tasks: find objects on a tray, stick bisection, picture search, and gaze orientation. In addition, the Unawareness and Behavioral Neglect Index (UBNI) with 6 items about unawareness and 4 about neglect in activities of daily living, the Help index (required assistance in 10 functional activities), the Barthel Index, and the rehabilitation phase were rated by treatment-blinded assessors. Outcome measures were obtained before and immediately after the end of the interventions and at a 2-week follow-up. Results. Significantly greater improvements were obtained after SPT versus VST treatment in the FNI and UBNI, and there were continued improvements selectively in the SPT group 2 weeks later. Conclusions. SPT accelerates recovery from functional neglect and reduces unawareness significantly. Bedside neglect treatment using SPT is effective and feasible early after stroke.

Smooth Pursuit Eye Movement Training Promotes Recovery From Auditory and Visual Neglect A Randomized Controlled Study

Background. No treatment for auditory neglect and no randomized controlled trial evaluating smooth pursuit eye movement therapy (SPT) for multimodal neglect are available. Objective. To compare the effects of SPT and visual scanning therapy (VST) on auditory and visual neglect in chronic stroke patients with neglect. Methods. A randomized, prospective trial was conducted. Fifty patients with left auditory and visual neglect were randomly assigned. Twenty-four patients completed SPT therapy and 21 patients VST. Five patients (4 VST, 1 SPT) were lost. Each group received 1-hour sessions of neglect therapy for 5 consecutive days totaling 5 hours. Outcome measures in visual neglect (digit cancellation, visuoperceptual- and motor line bisection, paragraph reading) and auditory neglect (auditory midline) were assessed twice before therapy, thereafter, and at 2-week follow-up. The SPT group practiced smooth pursuit eye movements while tracking stimuli moving leftward. The VST group systematically scanned the same but static stimuli. Both groups were divided into subgroups, and effects were separately investigated for mild and severe neglect. Results. Both groups did not differ before therapy in clinical/demographic variables or neglect severity (auditory/visual). After treatment, the SPT group showed significant and lasting improvements in all visual measures and normal performance in the auditory midline. Neither visual nor auditory neglect impairments changed significantly after VST. Moreover, the treatment effect sizes (Cohen’s d) were considerably higher for visual and auditory neglect after SPT versus VST, both for mild and severe neglect. Conclusions. Repetitive contralesional, smooth pursuit training induces superior, multimodal therapeutic effects in mild and severe neglect.

Optokinetic stimulation affects word omissions but not stimulus-centered reading errors in paragraph reading in neglect dyslexia

Patients with right hemisphere lesions often omit or misread words on the left side of a text or the initial letters of single words, a phenomenon termed neglect dyslexia (ND). Omissions of words on the contralesional side of the page are considered as egocentric or space-based errors, whereas misread words can be viewed as a type of stimulus-centered error where the left part of a single perceptual entity (the word) is neglected. Previous patient studies have shown that optokinetic stimulation (OKS) significantly modulates many facets of the neglect syndrome, including the subjective body midline, line bisection and size distortions. An open question is whether OKS can also influence omissions and stimulus-centered errors in paragraph reading in ND. The current study compared the influence of OKS on both types of reading errors using controlled indented paragraph reading tests in a group of 9 right-hemisphere lesioned patients with ND, 7 patients without ND and 9 matched healthy controls. Leftward OKS significantly reduced omissions on the left side of the text in ND. In contrast, the pattern of stimulus-centered reading errors remained unchanged. In conclusion egocentric manipulations like OKS only appear to influence space-based attentional processes evident as omissions in paragraph reading but have no impact on stimulus-centered attentional processes evident as word-based errors during paragraph reading in ND.

Subliminal galvanic-vestibular stimulation recalibrates the distorted visual and tactile subjective vertical in right-sided stroke

Stroke of the right cerebral hemisphere often causes deficits in the judgement of the subjective visual vertical (SVV) and subjective tactile vertical (STV) which are related to central vestibular functioning. Clinically, deficits in the SVV/STV are linked to balance problems and poor functional outcome. Galvanic Vestibular Stimulation (GVS) is a non-invasive, save stimulation technique that induces polarity-specific changes in the cortical vestibular systems. Subliminal GVS induces imperceptible vestibular stimulation without unpleasant side effects. Here, we applied bipolar subliminal GVS over the mastoids (mean intensity: 0.7 mA, 20 min duration per session) to investigate its online-influence on constant errors, difference thresholds and range values in the SVV and STV. 24 patients with subacute, single, unilateral right hemisphere stroke were studied and assigned to two patient groups (impaired vs. normal in the SVV and STV) on the basis of cut-off scores from healthy controls. Both groups performed these tasks under three experimental conditions on three different days: a) sham GVS where electric current was applied only for 30s and then turned off, b) left-cathodal GVS and c) right-cathodal GVS, for a period of 20 min per session. Left-cathodal GVS, but not right-cathodal GVS significantly reduced all parameters in the SVV. Concerning STV GVS also reduced constant error and range numerically, though not significantly. These effects occurred selectively in the impaired patient group. In conclusion, we found that GVS rapidly influences poststroke verticality deficits in the visual and tactile modality, thus highlighting the importance of the vestibular system in the multimodal elaboration of the subjective vertical.

Subliminal galvanic-vestibular stimulation influences ego- and object-centred components of visual neglect

Neglect patients show contralesional deficits in egocentric and object-centred visuospatial tasks. The extent to which these different phenomena are modulated by sensory stimulation remains to be clarified. Subliminal galvanic vestibular stimulation (GVS) induces imperceptible, polarity-specific changes in the cortical vestibular systems without the unpleasant side effects (nystagmus, vertigo) induced by caloric vestibular stimulation. While previous studies showed vestibular stimulation effects on egocentric spatial neglect phenomena, such effects were rarely demonstrated in object-centred neglect. Here, we applied bipolar subsensory GVS over the mastoids (mean intensity: 0.7mA) to investigate its influence on egocentric (digit cancellation, text copying), object-centred (copy of symmetrical figures), or both (line bisection) components of visual neglect in 24 patients with unilateral right hemisphere stroke. Patients were assigned to two patient groups (impaired vs. normal in the respective task) on the basis of cut-off scores derived from the literature or from normal controls. Both groups performed all tasks under three experimental conditions carried out on three separate days: (a) sham/baseline GVS where no electric current was applied, (b) left cathodal/right anodal (CL/AR) GVS and (c) left anodal/right cathodal (AL/CR) GVS, for a period of 20min per session. CL/AR GVS significantly improved line bisection and text copying whereas AL/CR GVS significantly ameliorated figure copying and digit cancellation. These GVS effects were selectively observed in the impaired- but not in the unimpaired patient group. In conclusion, subliminal GVS modulates ego- and object-centred components of visual neglect rapidly. Implications for neurorehabilitation are discussed.

Effects of Feedback-Based Visual Line-Orientation Discrimination Training for Visuospatial Disorders After Stroke

Background. Patients with right or more rarely left parietotemporal lesions after stroke may have profound visuospatial disorders that impair activities of daily living (ADL) and long-term outcome. Clinical studies indicate improvements with systematic training of perception. Studies of perceptual learning in healthy persons suggest rapid improvements in perceptual learning of spatial line orientation with partial transfer to nontrained line orientations. Objective. The authors investigated a novel feedback-based perceptual training procedure for the rehabilitation of patients after stroke. Methods. In an uncontrolled trial, 13 participants showing profound deficits in line orientation and related visuospatial tasks within 12 to 28 weeks of onset performed repetitive feedback-based, computerized training of visual line orientation over4 weeks of treatment. Visual line-orientation discrimination and visuospatial and visuoconstructive tasks were assessed before and after training. Results. The authors found (a) rapid improvements in trained but also in nontrained spatial orientation tests in all 13 participants, partially up to a normal level; (b) stability of the obtained improvements at 2-month follow-up; (c) interocular transfer of training effects to the nontrained eye in 2 participants suggesting a central, postchiasmatic locus for this perceptual improvement; and (d) graded transfer of improvements to related spatial tasks, such as horizontal writing, analog clock reading, and visuoconstructive capacities but no transfer to unrelated measures of visual performance. Conclusions. These results suggest the potential for treatment-induced improvements in visuospatial deficits by feedback-based, perceptual orientation training as a component of rehabilitation after stroke.

Line bisection error predicts the presence and severity of neglect dyslexia in paragraph reading

Cancellation tasks and line bisection tasks are commonly used to diagnose spatial neglect after right hemisphere lesions. In such tasks, neglect patients often show leftsided omissions of targets in cancellation tests as well as a pathological rightward deviation in horizontal line bisection. However, double dissociations have also been reported and the relation between performance in both tasks is not clear. Another impairment frequently associated with the neglect syndrome are omissions or misread initial letters of single words, a phenomenon termed neglect dyslexia (ND). Omissions of whole words on the contralesional side of the page are generally considered as egocentric or space-based errors, whereas misreadings of the left part of a word in ND can be viewed as a type of stimulus-centered or word-based, perceptual error. As words, sentences and horizontal lines have a similar spatial layout in the sense that they all are horizontally aligned, long stimuli with a canonical left-right orientation (with a defined beginning on the left and an end on the right side), we hypothesized a significant association between the horizontal line bisection error (LBE) in neglect and the extent (number) of neglected or substituted letters within single words in ND (neglect dyslexia extension, NDE). To this purpose, we computed Center-of-Cancellation (CoC) scores in a cancellation task as well as Center-of-Reading (CoR) scores in an experimental paragraph reading test. We found that the CoR was a better indicator for egocentric word omissions than the CoC in a group of 17 patients with left visuospatial neglect. Furthermore, the LBE predicted the severity of ND, indicated by highly significant correlations between the LBE and the extent of the neglected letter string within single words (NDE; r=0.73, p<0.001) as well as between the LBE and the frequency of ND errors (r=0.61; p=0.009). In contrast, we found no significant correlation between the CoC and the severity of ND. These results indicate two different pathological mechanisms being responsible for contralesional spatial neglect and ND. In conclusion, the LBE is a more sensitive predictor of the presence and severity of the reading disorder in spatial neglect than conventional cancellation tasks.