Daniel P. Spiegel

Anodal Transcranial Direct Current Stimulation Transiently Improves Contrast Sensitivity and Normalizes Visual Cortex Activation in Individuals With Amblyopia

Background. Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia. Objective. We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye. Methods. Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level–dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye. Results. A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS. Conclusions. These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

Dichoptic training improves contrast sensitivity in adults with amblyopia

Dichoptic training is designed to promote binocular vision in patients with amblyopia. Initial studies have found that the training effects transfer to both binocular (stereopsis) and monocular (recognition acuity) visual functions. The aim of this study was to assess whether dichoptic training effects also transfer to contrast sensitivity (CS) in adults with amblyopia. We analyzed CS data from 30 adults who had taken part in one of two previous dichoptic training studies and assessed whether the changes in CS exceeded the 95% confidence intervals for change based on test-retest data from a separate group of observers with amblyopia. CS was measured using Gabor patches (0.5, 3 and 10cpd) before and after 10days of dichoptic training. Training was delivered using a dichoptic video game viewed through video goggles (n=15) or on an iPod touch equipped with a lenticular overlay screen (n=15). In the iPod touch study, training was combined with anodal transcranial direct current stimulation of the visual cortex. We found that dichoptic training significantly improved CS across all spatial frequencies tested for both groups. These results suggest that dichoptic training modifies the sensitivity of the neural systems that underpin monocular CS.

Altered white matter in early visual pathways of humans with amblyopia

Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways.

The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia

Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia.

Ocular dominance plasticity: inhibitory interactions and contrast equivalence

Brief monocular occlusion results in a transient change in ocular dominance, such that the previously patched eye makes a stronger contribution to the binocular percept after occlusion. The previously unpatched eye therefore makes a correspondingly weaker contribution to the binocular sum. To shed light on the mechanism underlying this change we investigate how the relationship between the perception of fusion, suppression, and diplopia changes after short-term monocular deprivation. Results show that fusible stimuli seen by the unpatched eye are actively suppressed as a result of patching and that this can be reversed by an interocular contrast imbalance. This suggests that dichoptic inhibition plays an important role in ocular dominance changes due to short-term occlusion, possibly by altering the contrast gain prior to binocular summation. This may help explain why this form of plasticity affects the perception of both fusible and rivalrous stimuli.

Multisensory attention training for treatment of tinnitus

Tinnitus is the conscious perception of sound with no physical sound source. Some models of tinnitus pathophysiology suggest that networks associated with attention, memory, distress and multisensory experience are involved in tinnitus perception. The aim of this study was to evaluate whether a multisensory attention training paradigm which used audio, visual, and somatosensory stimulation would reduce tinnitus. Eighteen participants with predominantly unilateral chronic tinnitus were randomized between two groups receiving 20 daily sessions of either integration (attempting to reduce salience to tinnitus by binding with multisensory stimuli) or attention diversion (multisensory stimuli opposite side to tinnitus) training. The training resulted in small but statistically significant reductions in Tinnitus Functional Index and Tinnitus Severity Numeric Scale scores and improved attentional abilities. No statistically significant improvements in tinnitus were found between the training groups. This study demonstrated that a short period of multisensory attention training reduced unilateral tinnitus, but directing attention toward or away from the tinnitus side did not differentiate this effect.Tinnitus is the conscious perception of sound with no physical sound source. Some models of tinnitus pathophysiology suggest that networks associated with attention, memory, distress and multisensory experience are involved in tinnitus perception. The aim of this study was to evaluate whether a multisensory attention training paradigm which used audio, visual, and somatosensory stimulation would reduce tinnitus. Eighteen participants with predominantly unilateral chronic tinnitus were randomized between two groups receiving 20 daily sessions of either integration (attempting to reduce salience to tinnitus by binding with multisensory stimuli) or attention diversion (multisensory stimuli opposite side to tinnitus) training. The training resulted in small but statistically significant reductions in Tinnitus Functional Index and Tinnitus Severity Numeric Scale scores and improved attentional abilities. No statistically significant improvements in tinnitus were found between the training groups. This study demonstrated that a short period of multisensory attention training reduced unilateral tinnitus, but directing attention toward or away from the tinnitus side did not differentiate this effect.

Inter-hemispheric wave propagation failures in traumatic brain injury are indicative of callosal damage

Approximately 3.2-5.3 million Americans live with the consequences of a traumatic brain injury (TBI), making TBI one of the most common causes of disability in the world. Visual deficits often accompany TBI but physiological and anatomical evidence for injury in mild TBI is lacking. Axons traversing the corpus callosum are particularly vulnerable to TBI. Hemifield representations of early visual areas are linked by bundles of fibers that together cross the corpus callosum while maintaining their topographic relations. Given the increased vulnerability of the long visual axons traversing the corpus callosum, we hypothesized that inter-hemispheric transmission for vision will be impaired following mild TBI. Using the travelling wave paradigm (Wilson, Blake, & Lee 2001), we measured inter-hemispheric transmission in terms of both speed and propagation failures in 14 mild TBI patients and 14 age-matched controls. We found that relative to intra-hemispheric waves, inter-hemispheric waves were faster and that the inter-hemispheric propagation failures were more common in TBI patients. Furthermore, the transmission failures were topographically distributed, with a bias towards greater failures for transmission across the upper visual field. We discuss the results in terms of increased local inhibition and topographically-selective axonal injury in mild TBI.

Sensitivity to binocular disparity is reduced by mild traumatic brain injury.

Purpose The impairment of visual functions is one of the most common complaints following mild traumatic brain injury (mTBI). Traumatic brain injury-associated visual deficits include blurred vision, reading problems, and eye strain. In addition, previous studies have found evidence that TBI can diminish early cortical visual processing, particularly for second-order stimuli. We investigated whether cortical processing of binocular disparity is also affected by mTBI. Methods In order to investigate the influence of mTBI on global stereopsis, we measured the quick Disparity Sensitivity Function (qDSF) in 22 patients with mTBI. Patients with manifest strabismus and double vision were excluded. Compared with standard clinical tests, the qDSF is unique in that it offers a quick and accurate estimate of thresholds across the whole spatial frequency range. Results Results show that disparity sensitivity in the mTBI patients were significantly reduced compared with the normative dataset (n = 61). The peak spatial frequency was not affected. Conclusions Our results suggest that the reduced disparity sensitivity in patients with mTBI is more likely caused by cortical changes (e.g., axonal shearing, or reduced interhemispheric communication) rather than oculomotor dysfunction.