Subcortical Visual Prosthetics

Ventrolateral Thalamic Nuclei
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The lateral geniculate nucleus extends from ventral posterior tip of the
thalamus, inferior to the pulvinar and lateral to the medial geniculate nucleus.
Image source: http://en.wikipedia.org/wiki/Ventral_lateral_nucleus.

The lateral geniculate nucleus (LGN) of the thalamus has recently received attention as a possible site of visual prosthesis. The LGN is a subcortical structure of early visual processing that is retinotopically organized, easily accessed surgically, and structurally flat in humans, making it an appealing alternative to cortical, retinal, and subretinal implantation. [1] The possibility of LGN prosthesis stems from the ability of electrical stimulation to produce phosphenes, which are percepts of light in the absence of retinal stimulation. [2] If video signals were converted into electrical signals and delivered to the LGN by microelectrodes, then such stimulation could reconstruct a pixelated representation of the visual world. [1] Studies of simulated vision suggest that microelectrode stimulation to the LGN could allow the identification of faces and text; [3] however, the neural signals contained in the LGN are complex with numerous interactions, posing a formidable challenge to the development of an appropriate model of stimulation. [4]

1. Characteristics of the LGN

Information coded in the retina is projected along the optic nerve to the superior colliculus, pretectum, and thalamus. [5] The ventral subregions of the thalamus are known to filter and organize sensory signals en route to the primary

Figure 1. Laminar Organization of the Macaque LGN
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Figure 1. Laminar organization of the macaque LGN. The
LGN is functionally divided by the horizontal meridian into a medial
half coding the lower visual field, and a lateral half coding the upper
visual field. The central field of vision is represented in six main
layers; layers 5-6 are parvocellular and 1-2 are magnocellular.
Koniocellular layers are intercalated between. Layers 1, 4, and 6
received input from the contralateral eye. Image source:
http://web.mit.edu/bcs/schillerlab/research/A-Vision/A4-1.html.

sensory cortices, a function for which these nuclei are colloquially referred to as 'relay nuclei'. [6] The thalamic nucleus that receives and relays visual information is the lateral geniculate nucleus (LGN). In humans, the LGN protrudes from the ventral posterior side of the thalamus, inferior to the pulvinar and lateral to the medial geniculate nucleus. [5] The optic radiation begins at the lateral posterior side of the LGN on either side and extends to the ipsilateral primary visual cortex. [5]

1.1 Primate LGN

1.1a Structure and Organization

The LGN has been well-characterized in nonhuman primates, particularly the macaque. It has a laminar organization that changes with eccentricity along the superior-inferior pole. [7] The most superior segment processes the central binocular field of vision and contains six main layers with six smaller layers intercalated.[7] For the purposes of visual prosthesis, only the main six layers on the superior pole will be considered.
The organization of the macaque LGN is shown in Figure 2. Visual information is delivered to the LGN by the retinogeniculate pathway. The two most ventral layers (1-2) are magnocellular and receive most of their input from parasol ganglion cells. The receptive fields of neurons in these layers are low-contrast, colour-opponent, and small. [9] The four dorsal layers (3-6) are parvocellular and receive most of their input from midget ganglion cells. Parvocellular receptive fields are large, achromatic, and high-contrast. [9] The koniocellular pathway is composed at least partially of large and small bistratified ganglion cells that carry colour-opponent signals and
synapses primarily on the intercalated layers, although little is known about this pathway as of yet. [9]
Either side of the LGN represents the contralateral visual hemifield. Because the contralateral eye contains some information of the appropriate visual field, it is represented on layers 1, 4, and 6. [10] The LGN is functionally divided by the horizontal meridian into a superior and medial half – representing the lower visual field – and an inferior, lateral half representing the upper visual field. [10]

1.1b Foveal Magnification

The LGN is retinotopically mapped, which is to say that is organized like the retina. However, the densely-coded signals coming from the fovea occupy a disproportionate area of the LGN on the dorsal side, in the parvocellular layers. [10] The magnified representation of the fovea is known as foveal magnification, and it allows the visual system to process the central visual field more finely than the periphery. To that end, parvocellular concentrations are 10,000 higher in the central field of vision than in the periphery, and magnocellular cells contribute to only 2.6% of the central 2° of vision. [7]

1.2 Human LGN

Little is known about the human LGN. Early post-mortem studies revealed that the human LGN in somewhat variable, although the least variability is in the main six layers. [8] Foveal magnification is much greater in the human LGN, with the central 15 ° of the visual field represented across half of its volume. [7]

Recent advances in imaging technology have made it possible to examine the structure and connections of the human LGN. These studies corroborate earlier efforts by showing that the human LGN is anatomically and structurally very similar to the macaque LGN. However, imagining resolution has not been strong enough to distinguish parvocellular from magnocellular layers. A few studies have attempted to determine their distributions through functional analysis of neuronal contrast sensitivity, but more work will need to be done in order to develop a sufficiently usable map. [11]

The Visual Pathway
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The geniculostriate pathway divides parasol, midget, and bistratified ganglion cell
projections onto magnocelullar, parvocellular, and koniocelullar layers of the LGN,
respectively. After being organized and modulated by top-down processes, LGN signals are
sent to the LGN for further processing. Image source: Nassi and Callaway (2009).

1.2a Connections

Although the LGN receives 90% of the signals projected from the retina, the majority of input comes from the TRN (30%), the brainstem (30%), and V1 (30%). [12] The inputs modulate and filter activity in the LGN and likely contribute to how information is filtered. [12] Some have suggested that the LGN has a broader role in cognition and perception, although evidence to date is only speculative. [12]
Outgoing signals from the LGN are projected to the visual cortex for processing. The parvocellular layers project to layers 4Cα of V1 and the magnocellular layers project to layer 4Cβ, and both project to layer 6. [13] Koniocellular layers project to layer 1 and to cytochrome oxidase blobs of layer 2/3 in V1. [9]

2. LGN Prosthesis

There are several features of the LGN that make it a suitable candidate for visual prosthesis: it is conveniently proximal to other structures for which surgical procedures have already been determined, making it easy to access; it is relatively simple and flat in humans, making it easy to determine the arrangement of an implant; and the foveal magnification of the LGN will make it simple to target the central field of vision. [((bibcite 16)]] [1]

2.1 Phosphenes and Vision Restoration

Modern approaches to visual prosthesis are based on the ability to produce percepts without light stimulating the retina. These percepts are called phosphenes and they can be produced by electrically stimulating brain matter along the visual pathway. {14] Recent studies have demonstrated that electrical stimulation of the macaque LGN produces phosphenes comparable to those observed in occipital stimulation, leading to the proposition that a well-organized microelectrode arrangement over this region might restore a pixelated field of vision to the blind. [2] It has been demonstrated that electrical stimulations to the LGN mimicking those observed in natural perception produce a similarly ‘natural’ activation in V1; however, the electrical signals that produce these perceptions have yet to be decoded. {15] Following the compilation of an electrical code, researchers will need to develop a way of transforming video inputs into a signal that will be recognized appropriately by the visual system. {15]

2.2 Microelectrode Arrangement

The possibility of developing a subcortical visual prosthetic is relatively new and methods are less developed than those targeting the eye, the retina, and the visual cortex. Due to a general lack of research, current maps of the LGN are limited to the central field of vision and lack anatomical resolution, making it difficult to create an applicable model of stimulation [1][11] Until the human LGN is better characterized, research must continue to generalize findings from stimulation on the retina, the visual cortex, and most notably the macaque LGN.

Simulated Map of Phosphene Distribution
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Simulated map of phosphene distribution in the macaque LGN using
a three dimensional microelectrode placement. The left axis indicates mean
isotropic Cartesian spacing (µm). Lighter colours represent response fields
from parvocellular tip locations, darker colours from magnocellular tip
locations. Foveal magnification is evidenced in how the central field of vision
(right) is more heavily represented. Image source: Pezaris and Reid (2009)

Pezaris in particular has been instrumental in the latter effort by profiling the human LGN and conducting research on microelectrode arrangements. [1][2][16] Recently, Pezaris and Reid (2009) simulated two electrode placement strategies on a model that they developed of the Macaque LGN.[1] The first was a three-dimensional design and the second was a planar design across the axial, sagittal, and coronal planes. Their model indicated that a three dimensional array of microelectrodes produced an optimal number of contact points without anatomical damage. Deep brain stimulation (DBS) electrodes were recommended due to their small size and successful application to the globus pallidus and substantia nigra for other medical purposes.
Virtual reality simulations have been conducted to determine number and distribution of phosphenes required for a functional level of vision. [3] Reflecting the fixed nature of microelectrode stimulation, virtual reality studies recreate visual fields as grids of luminous dots. The general consensus is that spatial navigation, reading, and facial recognition could be achieved with a few hundred pixels distributed across the visual field - something that could be done in the LGN [16] Of course, this method of visual prosthesis results in only a partial restoration of vision, the use of which would demand considerable training. [17]

2.3 Other Challenges

The chronic, electrical stimulation of brain tissues requires careful consideration of neuronal communications. Neural tissues behave non-linearly to electrical stimulation, and as a consequence the specificity of neuronal activation and the prevalence of complex neuronal interactions - particularly in a three-dimensional structure - will require a very delicate microelectrode arrangement. [3] In addition, the structure and layout of the human LGN vary between individuals; thus, a microelectrode implant will need to be applied on a patient-to-patient basis. [2]
Finally, there is much to be learned regarding the functions of the human LGN. The majority of input is from sources outside the visual system that exert top-down control, which suggests that the LGN is influenced by – and may reciprocate in – visual cognition [12] Although more detailed studies of the human LGN will differentiate visual inputs from those of other circuits, the interconnections and their modulatory nature may complicate the development of a prosthetic system.

Bibliography
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2. Pezaris, J. S., & Reid, R. C. (2007). Demonstration of artificial visual percepts generated through thalamic microstimulation. Proceedings of the National Academy of Sciences of the United States of America, 104(18), 7670–7675. doi:10.1073/pnas.0608563104
3. Chen, S. C., Suaning, G. J., Morley, J. W., & Lovell, N. H. (2009). Simulating prosthetic vision: I. Visual models of phosphenes. Vision Research, 49(12), 1493–1506. doi:10.1016/j.visres.2009.02.003
4. Millard, D. C., Wang, Q., & Stanley, G. B. (2011). Nonlinear System Identification of the Thalamocortical Circuit in Response to Thalamic Microstimulation. In 2011 5th International Ieee/Embs Conference on Neural Engineering (ner) (pp. 1–4). New York: Ieee.
5. Troncoso, X. G., Macknik, S. L., & Martinez-Conde, S. (2011). Vision’s First Steps: Anatomy, Physiology, and Perception in the Retina, Lateral Geniculate Nucleus, and Early Visual Cortical Areas. In G. Dagnelie (Ed.), Visual Prosthetics (pp. 23–57). Boston, MA: Springer US.
6. Herrero, M. T., Barcia, C., & Navarro, J. M. (2002). Functional anatomy of thalamus and basal ganglia. Childs Nervous System, 18(8), 386–404. doi:10.1007/s00381-002-0604-1
7. Malpeli, J. G., Lee, D., & Baker, F. H. (1996). Laminar and retinotopic organization of the macaque lateral geniculate nucleus: Magnocellular and parvocellular magnification functions. The Journal of Comparative Neurology, 375(3), 363–377. doi:10.1002/(SICI)1096-9861(19961118)375:3<363::AID-CNE2>3.0.CO;2-0
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14. Brindley, G. S. (1973). Sensory Effects of Electrical Stimulation of the Visual and Paravisual Cortex in Man. In R. Jung (Ed.), Visual Centers in the Brain (Vol. 7 / 3 / 3 B, pp. 583–594). Berlin, Heidelberg: Springer Berlin Heidelberg.
15. Panetsos, F., Diaz-de Cerio, E., Sanchez-Jimenez, A., & Herrera-Rincon, C. (2009). Thalamic visual neuroprostheses: Comparison of visual percepts generated by natural stimulation of the eye and electrical stimulation of the thalamus. In 2009 4th International Ieee/Embs Conference on Neural Engineering (pp. 56–59). New York: Ieee.
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