BACKGROUND:Visual field defects after posterior cerebral artery stroke can be improved by vision restoration training (VRT), but when combined with transcranial direct current stimulation (tDCS), which alters brain excitability, vision recovery can be potentiated in the chronic stage. To date, the combination of VRT and tDCS has not been evaluated in postacute stroke rehabilitation.OBJECTIVES:To determine whether combined tDCS and VRT can be effectively implemented in the early recovery phase following stroke, and to explore the feasibility, safety and efficacy of an early intervention.DESIGN:Open-label pilot study including a case series of 7 tDCS/VRT versus a convenience sample of 7 control patients (ClinicalTrials.gov ID: NCT02935413).SETTING:Rehabilitation center.SUBJECTS:Patients with homonymous visual field defects following a posterior cerebral artery stroke.METHODS:Seven homonymous hemianopia patients were prospectively treated with 10 sessions of combined tDCS (2.mA, 10 daily sessions of 20 minutes) and VRT at 66 (±50) days on average poststroke. Visual field recovery was compared with the retrospective data of 7 controls, whose defect sizes and age of lesions were matched to those of the experimental subjects and who had received standard rehabilitation with compensatory eye movement and exploration training.RESULTS:All 7 patients in the treatment group completed the treatment protocol. The safety and acceptance were excellent, and patients reported occasional skin itching beneath the electrodes as the only minor side effect. Irrespective of their treatment, both groups (treatment and control) showed improved visual fields as documented by an increased mean sensitivity threshold in decibels in standard static perimetry. Recovery was significantly greater (P < .05) in the tDCS/VRT patients (36.73% ± 37.0%) than in the controls (10.74% ± 8.86%).CONCLUSION:In this open-label pilot study, tDCS/VRT in subacute stroke was demonstrated to be safe, with excellent applicability and acceptance of the treatment. Preliminary effectiveness calculations show that tDCS/VRT may be superior to standard vision training procedures. A confirmatory, larger-sample, controlled, randomized, and double-blind trial is now underway to compare real-tDCS- versus sham-tDCS-supported visual field training in the early vision rehabilitation phase.LEVEL OF EVIDENCE:IV.

Background Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. Methods We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. Results The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. Conclusion rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. Trial Registration ClinicalTrials.gov NCT01280877

Aim This study addresses the examination of the factorial validity of the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ 39) and the neuro-ophthalmological supplement in a German sample.Method Eighty-one patients with visual field defects affecting at least one eye answered the NEI-VFQ 39 and the supplement. Theoretical factor structures reported in the manuals were examined in confirmatory factor analysis. Because of a misfit, items retained after itemanalysis were subjected to exploratory factor analysis.Results The originally postulated factor structures could not be replicated. Many items revealed floor effects. The 21 remaining items could be assigned to two factors - "visual functioning" and "socio-emotional impairment".Conclusion The weakness of the theoretical factors can be avoided by using the 2-scale model.

Introduction: Stroke patients with predominantly visual symptoms due to posterior circulation ischemia rarely receive thrombolytic treatment despite the often debilitating nature of their homonymous visual field deficits. In addition to stroke physicians’ judgment of risks and benefits, perhaps influenced also by low scores on the National Institutes of Health Stroke Scale, lack of thrombolytic treatment may be caused by delayed admission to a stroke center. Hypothesis: We hypothesized that patients with occipital infarcts presenting with predominantly visual field symptoms would show less direct routes and longer onset-to-admission delays to a stroke center compared to the general stroke population, of which approximately half are admitted within 4h of symptom onset. Methods: All patients with visual field deficits as their primary symptom of occipital infarction treated at the Helsinki University Central Hospital between 2010 and 2013 were retrospectively identified from all cases of ischemic stroke by careful review of medical records and radiological data. All patients with acute stroke within the Greater Helsinki area (catchment area of 1.5 million) are brought to our emergency room (ER). Data were gathered on admission route and length of delay from symptom onset to admission. Results: Of the 179 occipital ischemic stroke patients with hemianopia as their main symptom or sign, 32 (18%) were admitted within 4h of symptom onset and a further 64 (36%) within 4-24h. Only 17 patients (9.5%) arrived as pre-notified thrombolysis candidates. 10 patients (5.6%) received thrombolysis, but half of them were only recognized as thrombolysis candidates after ER admission. Of all patients, 35 (20%) arrived directly at our ER, whereas 45 (25%) had visited two or more points of care or had been initially discharged, with a significant proportion of all patients, 30%, having visited an ophthalmologist prior to admission. Conclusions: Recognizing ischemic stroke presenting with visual field symptoms is challenging. Complexity of patient routes and long admission delays likely contribute to the low rates of thrombolytic therapy in this patient group.

Damage along the visual pathway prevents bottom-up visual input from reaching further processing stages and consequently leads to loss of vision. But perception is not a simple bottom-up process rather it emerges from activity of widespread cortical networks which coordinate visual processing in space and time. Here we set out to study how vision loss affects activity of brain visual networks and how networks activity is related to perception. Specifically, we focused on studying temporal patterns of brain activity. To this end, resting-state eyes-closed EEG was recorded from partially blind patients suffering from chronic retina and/or optic-nerve damage (n = 19) and healthy controls (n = 13). Amplitude (power) of oscillatory activity and phase locking value (PLV) were used as measures of local and distant synchronization, respectively. Synchronization time series were created for the low- (7-9 Hz) and high-alpha band (11-13 Hz) and analyzed with three measures of temporal patterns: (i) length of synchronized-/desynchronized-periods, Higuchi Fractal Dimension (HFD), and (iii) Detrended Fluctuation Analysis (DFA). We revealed that patients exhibit less complex, more random and noise-like temporal dynamics of high-alpha band activity. More random temporal patterns were associated with worse performance in static (r = -.54, p = .017) and kinetic perimetry (r = .47, p = .041). We conclude that disturbed temporal patterns of neural synchronization in vision loss patients indicate disrupted communication within brain visual networks caused by prolonged deafferentation. We propose that because the state of brain networks is essential for normal perception, impaired brain synchronization in patients with vision loss might aggravate the functional consequences of reduced visual input. (C) 2015 Elsevier Ltd. All rights reserved.

Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain.

Posterior cerebral artery (PCA) stroke usually results in visual field defects varying in size and extent of the blind field. Vision restoration training (VRT) may reduce the visual field impairment. Combined application of anodal transcranial direct current stimulation (tDCS) over visual cortex together with VRT indicates that tDCS may accelerate VRT-effects in the post-acute stage. We investigated safety, applicability and efficacy in 7 post-acute PCA stroke patients and compared their visual field changes to 7 control subject who were matched with respect to lesion-age and defect-size and underwent standard rehabilitation.

BACKGROUND:While there are reports on vision-related quality of life in patients with vision impairment caused by both ophthalmic and brain diseases, little is known about mental distress. In fact, mental distress after cerebral visual injury has been widely ignored.METHODS:Mental health symptoms were assessed in 122 participants with visual field defects after brain damage (72 male, mean age 58.1 ± 15.6 years), who completed the German Brief Symptom Inventory (BSI) at their homes after they had been asked by phone for their participation.RESULTS:Clinically relevant mental distress was present in 25.4% of participants with cerebral visual injury. In case of multisensory impairment, an increased amount and intensity of mental distress symptoms was observed compared to the subsample with only visual impairment.CONCLUSION:Assessment of comorbid mental health symptoms appears to be clinically meaningful in brain-damaged patients with visual sensory impairment. In case of clinically relevant mental distress, psychological supportive therapies are advisable especially in subjects with cerebral visual injury and comorbidities affecting other sensory modalities as well.

Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: "compensation" and "restoration". Existing methods can be classified into three groups: Visual Scanning Training (VST), Audio-Visual Scanning Training (AViST) and Vision Restoration Training (VRT). VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local "within-system" interactions (i.e., relying on plasticity within peri-lesional spared tissue) and changes in more global 'between system" networks (i.e., recruiting alternative visual pathways) contribute to both vision restoration and compensatory rehabilitation, which ultimately have implications for the rehabilitation of cognitive functions.

Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: “compensation” and “restoration”. Existing methods can be classified into three groups: Visual Scanning Training (VST), Audio-Visual Scanning Training (AViST) and Vision Restoration Training (VRT). VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local “within-system” interactions (i.e., relying on plasticity within peri-lesional spared tissue) and changes in more global “between-system” networks (i.e., recruiting alternative visual pathways) contribute to both vision restoration and compensatory rehabilitation, which ultimately have implications for the rehabilitation of cognitive functions.

Cognitive and neurological dysfunctions can severely impact a patient's daily activities. In addition to medical treatment, non-invasive transcranial alternating current stimulation (tACS) has been proposed as a therapeutic technique to improve the functional state of the brain. Although during the last years tACS was applied in numerous studies to improve motor, somatosensory, visual and higher order cognitive functions, our knowledge is still limited regarding the mechanisms as to which type of ACS can affect cortical functions and altered neuronal oscillations seem to be the key mechanism. Because alternating current send pulses to the brain at predetermined frequencies, the online- and after-effects of ACS strongly depend on the stimulation parameters so that "optimal" ACS paradigms could be achieved. This is of interest not only for neuroscience research but also for clinical practice. In this study, we summarize recent findings on ACS-effects under both normal conditions and in brain diseases.

Objective: To characterize brain functional connectivity in subjects with prechiasmatic visual system damage and relate functional connectivity features to extent of vision loss.Methods: In this case-control study, resting-state, eyes-closed EEG activity was recorded in patients with partial optic nerve damage (n = 15) and uninjured controls (n = 13). We analyzed power density and functional connectivity (coherence, Granger causality), the latter as (1) between-areal coupling strength and (2) individually thresholded binary graphs. Functional connectivity was then modulated by noninvasive repetitive transorbital alternating current stimulation (rtACS; 10 days, 40 minutes daily; n = 7; sham, n = 8) to study how this would affect connectivity networks and perception.Results: Patients exhibited lower spectral power (p = 0.005), decreased short- (p = 0.015) and long-range (p = 0.033) coherence, and less densely clustered coherence networks (p = 0.025) in the high-alpha frequency band (11-13 Hz). rtACS strengthened short- (p = 0.003) and long-range (p = 0.032) alpha coherence and this was correlated with improved detection abilities (r = 0.57, p = 0.035) and processing speed (r = 0.56, p = 0.049), respectively.Conclusion: Vision loss in the blind is caused not only by primary tissue damage but also by a breakdown of synchronization in brain networks. Because visual field improvements are associated with resynchronization of alpha band coherence, brain connectivity is a key component in partial blindness and in restoration of vision.

and connectivity between the frontostriatal network. Using resting-state EEG we showed that frontal theta phase-stability is reduced by DBS [3]. Since brain areas communicate by increasing phase-synchrony, decreases in phase-stability reduce the capacity for brain regions to phase-synchronize. Notably, we also found that frontal theta power in response to symptomprovoking stimuli – a potential biomarker for OCD – is normalized to comparable levels of frontal theta power elicited by neutral stimuli, while leaving frontal theta power in response to neutral stimuli intact.

Non-invasive brain stimulation using alternating current stimulation (ACS) has recently been shown to improve vision after optic nerve damage. It is assumed that transorbital ACS induces neuronal networks to propagate synchronous firing probably activating residual areas surviving the injury. The aim of the ‘/INS;Restoration of Vision after Stroke’/INS; (REVIS) network is to determine if bilateral transcranial direct current stimulation (tDCS) and transorbital ACS may also have a positive impact on vision restoration in patients with post-chiasmatic visual pathway lesions. In particular, the potential of non-invasive current stimulation in ameliorating vision impairment following stroke (hemianopia) is the key issue addressed by the REVIS study group.

Introduction: Non-invasive brain stimulation enhances neuronal plasticity in the visual system in normals and patients with visual field loss (Antal et al., RNN 2012; Sabel et al., RNN 2011) with one of the proposed mechanisms being the neuromodulation of oscillatory brain activity (Schmidt et al., Brain Stimul 2013).

Introduction: Repetitive transorbital alternating current stimulation (rtACS) can improve visual deficits in patients with optic nerve damage. Recent retrospective results suggest that rtACS enhances oscillatory brain activity. The exact mechanisms of rtACS are unclear and little is known about possibly frequency-specific neural-plastic mechanisms. An association between bandwidth-confined neural-entrainment and vision recovery maximization could offer a novel therapeutic option for patients with optic neuropathy.Objectives: The goal of this prospective open-label study was to investigate if the enhancement of rhythmic brain activity over 10 days of consecutive rtACS stimulation is associated with visual field recovery. The secondary goal was to investigate neurophysiological mechanisms related to frequency dependent adaptive plasticity.Methods: 18 Patients with visual field impairments resulting from pre-chiasmatic partial optic nerve damage received rtACS on 10 consecutive days. Daily, subject-specific treatment parameters (<500 mu A, 9 -37 Hz, 25-40 min/day) were defined and EEG-spectra collected prior to and after rtACS. Visual field data was collected at day 1 and 10. The change of spectral-power in classic bandwidths were investigated and correlated with visual field deficit recovery.Results: After 10 days of rtACS alpha-power over bilateral occipital electrodes was significantly larger than at baseline (F-Time (x alpha-power) p < 0.01). This effect was progressive over subsequent days of stimulation (cubic-fit, R-2 0.70, RMSE 0.008). Perimetric results improved significantly, but they were not associated with changes in alpha-synchronization.Discussion: rtACS can induce cumulative bandwidth-confined changes in brain rhythms over multiple sessions. These findings are in line with the notion of brain-state dependent [1] and bandwidth-confined entrainment [2] as well as rtACS facilitated visual recovery [3]. (C) 2013 Elsevier Inc. All rights reserved.