A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes (‘chip’), each with its own amplifier and local stimulation electrode. At the implant's tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron–electrode interface. Visual scenes are projected naturally through the eye's lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals.

Subretinal electric stimulation can yield reliable, predictable percepts. Patterned perception is feasible, enabling blind persons to recognize shapes and discriminate different letters. Stimulation paradigms must be optimized, to further increase spatial resolution, demanding a better understanding of physical and biological effects of single versus repetitive stimulation (ClinicalTrials.gov number, NCT00515814).

Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro-metabolic and neuro-vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus-driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato-sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo-Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (615) mL/100 g min and baseline oxygen consumption to be 6.7 (61.3) mL O 2 /100 g min. We calculate parametric, linear increases in arterial dilation (R 2 = 0.96) and CMRO 2 (R 2 = 0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version. Blood Flow & Metabolism (2007) 27, 1262-1279 doi:10.1038/sj.jcbfm.9600435; published online 3 January 2007 Keywords: CBF and oxidative metabolism; human and experimental studies; hemodynamics; optical imaging and spectroscopy; NIRS (near-infrared spectroscopy); MRI hemodynamics Journal of Cerebral IntroductionThe ability of magnetic resonance imaging or optical techniques to measure functional changes in blood volume, flow, or hemoglobin oxygenation has led to important advances in modern neuroscience and has contributed to our current understanding of the functional anatomy of the brain (reviewed by Nair, 2005). However, the interpretation of these hemodynamic-derived measurements is complicated by the fact that these changes are the result of the competing effects of the increased metabolic demand for oxygen to support glycolysis and the increased supply of oxygen offered by the elevated regional perfusion of blood via the dilation of feeding arteries (reviewed by Buxton et al, 2004;Mintun et al, 2001). Imaging methods, such as the blood oxygen level-dependent signal in functional magnetic resonance imaging (fMRI) or optical imaging, measure these composite changes and are less reveal...