Anton Fedorov

Non-invasive alternating current stimulation improves vision in optic neuropathy.

PURPOSE Partial blindness after visual system damage is considered irreversible, yet the brain has residual visual capacities and considerable plasticity potential. We now applied non-invasive alternating current stimulation (ACS) to the visual system of patients with optic nerve damage with the aim to induce recovery of visual functions. METHODS In a prospective, double-blind, randomized, placebo-controlled clinical trial patients with several year old partial optic nerve lesions were treated with ACS (n = 12) or placebo-stimulation (n = 10). ACS was delivered transorbitally for 40 minutes on 10 days. Visual outcome measures and EEG were measured before and after treatment. RESULTS ACS, but not placebo, led to significant improvement of a visual field detection deficit by 69%, and also significantly improved temporal processing of visual stimuli, detection performance in static perimetry, and visual acuity. These changes were associated with alpha-band changes in the EEG power spectra. Visual improvements were stable for at least 2-months. CONCLUSIONS ACS can induce vision restoration many years after optic neuropathy. Though the mechanism is still unclear, EEG changes indicate increased synchronization in posterior brain regions. The present study provides Class Ib evidence that non-invasive transorbital ACS is well tolerated and improves visual function in optic neuropathy.

Brain functional connectivity network breakdown and restoration in blindness

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.

Non-invasive alternating current stimulation induces recovery from stroke.

BACKGROUND Recovery of post-stroke deficits can be achieved by modulating neuroplasticity with non-invasive brain stimulation. To evaluate potential effects of repetitive transorbital alternating current stimulation (rtACS) on stroke recovery we carried out a randomized, drug-controlled clinical trial. METHODS Ninety-eight patients that had suffered ischemic stroke 21.4 months earlier were randomly assigned to either group D (n=30) receiving conventional drug therapy, group ACS (n=32) treated for 12 days with rtACS, or group D/ACS (n=36) receiving combined drug therapy/rtACS. Stroke severity level (SSL) was assessed by the NIH-NINDS stroke scale before and after treatment and at a 1-month follow-up to evaluate motor impairments (weakness, ataxia), sensory loss, visual field defects, and cortical deficits (aphasia, neglect). At each time point standard EEG recordings (10-20 system) were conducted. RESULTS Before therapy SSL was moderate (9.18 ± 0.78) without significant group difference (F =0.86, p=0.43). After 12 days of treatment, SSLs of groups ACS and D/ACS significantly improved by 22.5% and 25.1% over baseline, respectively, with no such change in the control group D (+3%). SSL improvements were mainly due to recovery of motor, sensory, and speech functions. After 1-month follow-up, an additional improvement of 9.7% and 9.4% was seen for the group ACS and D/ACS which led to a total change of +32.3% and +34.7% over baseline. EEG recordings revealed greater interhemispheric synchrony between both temporal lobes which were positively correlated with clinical outcome. CONCLUSIONS Non-invasive rtACS applied to post-stroke patients can modulate brain plasticity and induce recovery from neurological deficits long after the early post lesion recovery is over.

Repetitive transorbital alternating current stimulation in optic neuropathy

BACKGROUND Visual field defects after optic nerve damage typically show a limited capacity for spontaneous and treatment-induced recovery. OBJECTIVE Repetitive transorbital alternating current stimulation (rtACS) was applied to the damaged optic nerve to evaluate visual functions after stimulation. METHODS A 27-years-old male patient suffering left optic nerve atrophy with nearly complete loss of vision 11 years after atypical traumatic damage was treated transorbitally with biphasic 10-15 pulse trains of rtACS (10-30 Hz, < 600 μA, 30-40 min daily for 10 days) which produced phosphenes. RESULTS After rtACS treatment detection ability of super-threshold stimuli increased from 3.44% to 17.75% and mean perimetric threshold from 0 dB to 2.21 dB at final diagnostics. CONCLUSION This improvement of vision may be due to increased neuronal synchronization, possibly involving strengthening of synaptic transmission along the central visual pathway.

Transcorneal alternating current stimulation after severe axon damage in rats results in “long-term silent survivor” neurons

Transcorneal alternating current stimulation (tACS) was proposed to decrease acute death of retinal ganglion cells after optic nerve transection in rats, but it is not known if cell survival is long-term and associated with functional restoration. We therefore evaluated the effects of tACS in a rat model of optic nerve crush using anatomical, electrophysiological and behavioural measures. Rats were trained in a brightness discrimination visual task and the retinal ganglion cell number was quantified with in vivo confocal neuroimaging. Thereafter, severe optic nerve crush or sham crush was performed and rats were treated under anaesthesia either with tACS or sham stimulation immediately after the lesion and on day 3, 7, 11, 15, 19 and 23. Brightness discrimination was evaluated for 6 weeks and retinal ganglion cells were counted in vivo on post-crush days 7 and 28. In additional rats we studied the influence of tACS on bioelectrical activity. On post-lesion day 28, the tACS-treated group showed a neuronal survival of 28.2% which was significantly greater than in sham operates (8.6%). All animals with optic nerve crush were significantly impaired in brightness discrimination and did not recover performance, irrespective to which group they belonged. In accordance with this, there was no significant influence of the stimulation on EEG power spectra. In conclusion, tACS induced long-term neuronal protection from delayed retrograde cell death, but in this case of severe axonal damage tACS did not influence functional restoration and EEG signals recorded over the visual cortex.