The Use of Transcranial Direct Current Stimulation (TDCS) to Enhance the Rehabilitative Effect of Vision Restoration Therapy

The specific aim of this study is to improve recovery of visual function after brain injury. A prominent theme of current neuroscience research regarding the sequelae of brain injury posits that activity-dependent plasticity underlies neuro-recovery. If that is the case, there is good reason to believe that neurological changes underling recovery can be facilitated by established means of enhancing cortical activity. Studies suggest that altering cortical excitability may prime or prepare the cortex for subsequent training and furthermore, may improve overall functional outcomes (Webster et al, 2006; Brown & Pilitsis, 2006; Khedr et al, 2005). The working hypothesis of this pilot study is that computer-based visual rehabilitative training (using NovaVision's Vision Restoration TherapyTM; "VRT" software) enhances visual function (defined as an increase in functional visual field) by reinforcing synaptic connections within sensory networks of visual cortex associated with the visual field loss (Kasten et al., 1998; Sabel, 1999). Potentially, this reinforcement can be enhanced by concurrent transcranial direct current stimulation (TDCS) leading in turn, to enhanced visual performance (quantified by the extent of visual field measured by visual perimetry allowing for a direct statistical comparison of visual field change over time and on an individual basis) in patients with partial of complete hemianopic visual field loss caused by brain injury. Both computer based visual rehabilitative training and TDCS are established techniques and this novel approach aims to provide preliminary data regarding the safety and efficacy of a combined intervention.

We expect that results from this study will provide an objective basis for a larger, formal randomized controlled study combining the two therapies. Our long term goals are to maximize the benefits of a modern vision rehabilitative therapy, lay the groundwork for neurophysiological correlates associated with the recovery of visual function following brain injury and propose possible refinements for future neurorehabilitation strategies. Data from our collaborators at Columbia University Medical Center as well as others indicate that a 6 month course treatment therapy of VRT can lead to dramatic improvements in visual function (as quantified by increases in functional visual field) (Kasten et al., 1998; Kasten et al., 2006). TDCS is well known to bring about transient positive changes in both functional as well as electrophysiological measures of cortical brain function. If overall visual function can be further enhanced via a combined synergetic effect of VRT and TDCS, we will conduct a larger randomized controlled study. If there is no enhancement effect with combined TDCS and VRT, we will need to reconsider factors as to why this is the case. For example, a lack of enhancement effect could be related to patient selection including the degree and profoundness of vision loss prior to treatment, the age of the individual and duration of the insult, as well as their level of motivation in participating with the computer-based training program. Other considerations include longer combined treatment duration.

The loss of visual function following brain injury can be highly debilitating for an individual. Typically, damage to the occipital cortex or optic radiations following a brain lesion or trauma leads to a loss of visual function in visuotopically corresponding parts of the visual field while sparing the remaining areas (e.g. half the visual field as in the case with hemianopia). This partial blindness and loss in visual function has generally been considered untreatable due to the fact that the highly specific neuronal organization underlying normal visual function is determined early in development and not regenerative particularly after the "critical period" of development has been reached. More recent evidence (including that from our laboratory) has demonstrated that a considerable degree of plasticity and reorganization of the visual system occurs not only after cerebral damage but also in adulthood, that is, well after the critical period of development has occurred. For example, evidence of spontaneous post-lesion neuroplasticity has been demonstrated in the adult visual system as documented by extensive receptive field reorganization following lesions in the retina or visual cortex (e.g. Kass 1990).

Computer-based training strategies have been developed to train and rehabilitate various cerebral functions such as language learning deficits. Computer-based training has also been extensively studied as a treatment for partial blindness in adult brain-injured patients (Kasten et al., 1998; Sabel and Trauzettel-Klosinksi, 2005; Sabel et al., 2005). However, the neurophysiological mechanisms underlying the reported beneficial effect following VRT remains poorly understood. One important issue is that if the restoration of visual field and function is the result of localized neuroplastic changes in cortical circuitry within visual cortex, one can posit that modulation of cortical excitability should in turn influence the degree of this restorative effect. More specifically, increasing the level of overall cortical excitability of the visual cortex should potentiate synaptic neuroplastic interactions and thus translate into improved visual functional gains.

Transcranial Direct Current Stimulation (TDCS) represents a noninvasive method of brain stimulation that could potentially modulate such an effect. TDCS utilizes low amplitude direct currents applied via scalp electrodes to inject currents in the brain and thus modulate the level of excitability. Direct Current (DC) stimulation has been used in various forms since the inception of modern electrophysiology at the beginning of nineteenth century. There has been a recent upsurge in interest in TDCS as a tool for neuroscience research as well as an assessment and treatment modality for various neurological and neuropsychiatric disorders including depression, Parkinsonism, stroke recovery, and chronic neuropathic pain. TDCS has the distinct advantage of being inexpensive, easy to administer, noninvasive and painless. We have extensive experience with TDCS and are currently running parallel studies. We now wish to extend these principles into the visual rehabilitation domain.