Neurosensory Prosthetics: An Integral Neuromodulation Part of Bioelectronic Device

Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.

The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders. Despite the success and rapid adoption of DBS, crucial questions remain, including which brain areas should be targeted and in which patients. This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet challenges and future directions in the DBS field. Determining the next steps in DBS science will help to define the future role of this technology in the development of novel therapeutics for the most challenging disorders affecting the human brain.

We have measured the spatial density of cones and rods in eight whole-mounted human retinas, obtained from seven individuals between 27 and 44 years of age, and constructed maps of photoreceptor density and between-individual variability. The average human retina contains 4.6 million cones (4.08-5.29 million). Peak foveal cone density averages 199,000 cones/mm2 and is highly variable between individuals (100,000-324,000 cones/mm2). The point of highest density may be found in an area as large as 0.032 deg2. Cone density falls steeply with increasing eccentricity and is an order of magnitude lower 1 mm away from the foveal center. Superimposed on this gradient is a streak of high cone density along the horizontal meridian. At equivalent eccentricities, cone density is 40-45% higher in nasal compared to temporal retina and slightly higher in midperipheral inferior compared to superior retina. Cone density also increases slightly in far nasal retina. The average human retina contains 92 million rods (77.9-107.3 million). In the fovea, the average horizontal diameter of the rod-free zone is 0.350 mm (1.25 degrees). Foveal rod density increases most rapidly superiorly and least rapidly nasally. The highest rod densities are located along an elliptical ring at the eccentricity of the optic disk and extending into nasal retina with the point of highest density typically in superior retina (5/6 eyes). Rod densities decrease by 15-25% where the ring crosses the horizontal meridian. Rod density declines slowly from the rod ring to the far periphery and is highest in nasal and superior retina. Individual variability in photoreceptor density differs with retinal region and is similar for both cones and rods. Variability is highest near the fovea, reaches a minimum in the midperiphery, and then increases with eccentricity to the ora serrata. The total number of foveal cones is similar for eyes with widely varying peak cone density, consistent with the idea that the variability reflects differences in the lateral migration of photoreceptors during development. Two fellow eyes had cone and rod numbers within 8% and similar but not identical photoreceptor topography.