Combining Visual Rehabilitative Training and Noninvasive Brain Stimulation to Enhance Visual Function in Patients With Hemianopia: A Comparative Case Study

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
PM&R (Impact Factor: 1.53). 09/2011; 3(9):825-35. DOI: 10.1016/j.pmrj.2011.05.026
Source: PubMed


To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT).
A comparative case study assessing feasibility and safety.
A controlled laboratory setting.
Two patients, both with right hemianopia after occipital stroke damage. METHODS AND OUTCOME MEASUREMENTS: Both patients underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2 sham tDCS with VRT was performed. The primary outcome, visual field border, was defined objectively by using high-resolution perimetry. Secondary outcomes included subjective characterization of visual deficit and functional surveys that assessed performance on activities of daily living. For patient 1, the neural correlates of visual recovery were also investigated, by using functional magnetic resonance imaging.
Delivery of combined tDCS with VRT was feasible and safe. High-resolution perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient 1 also showed greater recovery of function in activities of daily living. Contrary to the expectation, patient 2 perceived greater subjective improvement in visual field despite objective high-resolution perimetry results that indicated otherwise. In patient 1, visual function recovery was associated with functional magnetic resonance imaging activity in surviving peri-lesional and bilateral higher-order visual areas.
Results of preliminary case comparisons suggest that occipital cortical tDCS may enhance recovery of visual function associated with concurrent VRT through visual cortical reorganization. Future studies may benefit from incorporating protocol refinements such as those described here, which include global capture of function, control for potential confounds, and investigation of underlying neural substrates of recovery.

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Available from: Alvaro Pascual-Leone, Dec 19, 2013
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    • "Anodal tDCS effects Previous research has shown that anodal tDCS can increase sensitivity in the central visual field (Kraft et al. 2010), that repeated sessions of stimulation may expand the visual field border in hemianopic patients (e.g., Plow et al. 2011, 2012a, b) and that it can improve visual exploratory skills (Bolognini et al. 2010b). When investigating whether these tDCS effects are the same in a group of healthy individuals who had central and peripheral visual fields assessed, we found no effect in the center and a significant effect at the most eccentric area measured (60 o , Fig. 1) for which the average increase of sensitivity from baseline was of ~12.5 %. "
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    ABSTRACT: Recent research suggested that transcranial direct current stimulation (tDCS) can affect visual processing and that it can be useful in visual rehabilitation. Nevertheless, there are still few investigations on the subject. tDCS selectivity and the extent of its outcomes on visual perception are still to be assessed. Here, we investigate whether central and peripheral visual fields are equally affected by tDCS. We also tried to reproduce a previous work that has evaluated tDCS effects on the central visual field only (Kraft et al. 207:283–290, 2010). Fifteen healthy subjects participated in this randomized repeated-measure design study and received 1.5-mA anodal, cathodal and sham stimulation in different sessions, while performing 10-2 and 60-4 protocols in an automated perimeter. Anodal tDCS significantly decreased thresholds, but was limited to the most eccentric regions of the visual field measured (60°). This suggests that tDCS might be used for rehabilitation of peripheral visual field losses. We did not replicate the excitatory tDCS effect in the central visual field as previously reported by another group. Instead, we observed a trend toward an inhibitory (yet not statistically significant) effect of anodal tDCS on the central field. This might be explained by methodological differences. These results highlight that although tDCS is a technique with a low focality in the spatial domain, its effects might be highly focal in a functional domain. When taken together with previous findings, this also suggests that tDCS may have a differential effect on different retinotopic areas in the brain.
    Experimental Brain Research 02/2015; 233(5). DOI:10.1007/s00221-015-4213-0 · 2.04 Impact Factor
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    • "If a greater and/or accelerated benefit were to be achieved with tDCS, then the utility of abridged CIMT would be established. Our rationale is derived from our work where tDCS paired with contracted vision rehabilitation promoted gains equivalent to a traditional, longer paradigm [32,40,71]. Ultimately, our pilot clinical study carries important implications for future trials; utility of an alternate cortical target would inform future transcranial research and investigation of markers of recovery would inform invasive (intracranial) applications of subcortical/deep brain structures that are in translational stages [72,73]. "
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    ABSTRACT: More than 60% of stroke survivors experience residual deficits of the paretic upper limb/hand. Standard rehabilitation generates modest gains. Stimulation delivered to the surviving Primary Motor Cortex in the stroke-affected hemisphere has been considered a promising adjunct. However, recent trials challenge its advantage. We discuss our pilot clinical trial that aims to address factors implicated in divergent success of the approach. We assess safety, feasibility and efficacy of targeting an alternate locus during rehabilitation- the premotor cortex. In anticipating variance across patients, we measure neural markers differentiating response from non-response. In a randomized, sham-controlled, double-blinded pilot clinical study, patients with chronic stroke (n = 20) are assigned to receive transcranial direct current stimulation delivered to the premotor cortex or sham during rehabilitation of the paretic arm/hand. Patients receive the designated intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess hand function and patients' reports of use of paretic hand. A general linear mixed methods model will analyze changes from pre- to post-intervention. Responders and non-responders will be compared upon baseline level of function, and neural substrates, including function and integrity of output tracts, bi-hemispheric balance, and lesion profile. Incidence of adverse events will be compared using Fisher's Exact test, while rigor of blinding will be assessed with Chi-square analysis to ascertain feasibility. Variable success of cortical stimulation in rehabilitation can be related to gaps in theoretical basis and clinical investigation. Given that most patients with severe deficits have damage to the primary motor cortex or its output pathways, it would be futile to target stimulation to this site. We suggest targeting premotor cortex because it contributes substantially to descending output, a role that is amplified with greater damage to the motor cortex. With regards to clinical investigation, paired cortical stimulation in rehabilitation has been compared to rehabilitation alone in unblinded trials or to unconvincing sham conditions. Transcranial direct current stimulation, a noninvasive technique of brain stimulation, which offers a more effective placebo and has a favorable safety-feasibility profile, may improve scientific rigor. Neural markers of response would help inform patient selection for future clinical trials so we can address limitations of recent negative studies.Trial registration
    Trials 10/2013; 14(1):331. DOI:10.1186/1745-6215-14-331 · 1.73 Impact Factor
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    • "The present study contrasts on several grounds with the four published studies investigating repeated tDCS in the visual system, all describing one small clinical trial (n = 4 per treatment condition) into combined anodal tDCS and visual restoration therapy (VRT), which utilized sparser measurement timepoints at baseline and monthly follow-ups (Halko et al., 2011; Plow et al., 2011, 2012a,b). Although significant improvements compared to sham tDCS with VRT were reported, and fMRI correlates of neuroplastic change were demonstrated in a single case study (Halko et al., 2011), potentially representing encouraging indications of neuroplasticity in the lesioned visual cortex, the studies do not greatly inform our understanding of the short- and medium-term timecourse, or nature of isolated tDCS-specific effects in the visual system. "
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    ABSTRACT: Transcranial direct current stimulation (tDCS) is a novel neuromodulatory tool that has seen early transition to clinical trials, although the high variability of these findings necessitates further studies in clinically relevant populations. The majority of evidence into effects of repeated tDCS is based on research in the human motor system, but it is unclear whether the long-term effects of serial tDCS are motor-specific or transferable to other brain areas. This study aimed to examine whether serial anodal tDCS over the visual cortex can exogenously induce long-term neuroplastic changes in the visual cortex. However, when the visual cortex is affected by a cortical lesion, up-regulated endogenous neuroplastic adaptation processes may alter the susceptibility to tDCS. To this end, motion perception was investigated in the unaffected hemifield of subjects with unilateral visual cortex lesions. Twelve subjects with occipital ischemic lesions participated in a within-subject, sham-controlled, double-blind study. MRI-registered sham or anodal tDCS (1.5 mA, 20 min) was applied on five consecutive days over the visual cortex. Motion perception was tested before and after stimulation sessions and at 14- and 28-day follow-up. After a 16-day interval an identical study block with the other stimulation condition (anodal or sham tDCS) followed. Serial anodal tDCS over the visual cortex resulted in an improvement in motion perception, a function attributed to MT/V5. This effect was still measurable at 14- and 28-day follow-up measurements. Thus, this may represent evidence for long-term tDCS-induced plasticity and has implications for the design of studies examining the time course of tDCS effects in both the visual and motor systems.
    Frontiers in Human Neuroscience 06/2013; 7:314. DOI:10.3389/fnhum.2013.00314 · 2.99 Impact Factor
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