Assessment of Cortical Plasticity in the Visual System Following Macular Degeneration in Adult Humans

Ehud Zohary, Ph.D.

The Hebrew University of Jerusalem

Funded in January, 2006: $100000 for 3 years
LAY SUMMARY . ABSTRACT . HYPOTHESIS . SELECTED PUBLICATIONS .

LAY SUMMARY

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Does Cortical Reorganization Occur and Aid Vision in Adults with Macular Degeneration?

Researchers expect that this study will determine whether cortical reorganization occurs in adults who develop macular degeneration and, if so, whether the reorganization facilitates improved vision.

While cortical reorganization occurs in congenitally blind people, enabling them to develop compensatory auditory, verbal, and memory functions, clinicians do not know whether functional reorganization occurs in adults who lose vision due to macular degeneration. This disease obliterates vision in the center of the gaze and produces partial damage to peripheral vision.  Since the central visual field has much greater cortical representation compared to the peripheral regions, the ability to judge the shapes of patterns (such as letters) is better in the center of the gaze than in the visual periphery.  The researchers hypothesize that, if cortical reorganization does occur in macular degeneration, it will be directed by a “remapping” principle.  According to this remapping concept, cortical regions that normally map to central vision will instead map to peripheral vision.   

Using fMRI, the investigators will determine patterns of activity throughout the brain when participants watch a visual stimulus inside the scanner.  They then will test the remapping hypothesis by consistently changing the position of the visual image on the screen and observing cortical activation patterns.  Additionally, the investigators will determine whether, when patients gaze off center, this preferred retinal location is over-represented in the visual cortex and is accompanied by better accuracy in that visual region of the grain.

Significance:  The study is anticipated to provide insight into brain plasticity that might lead to better rehabilitation methods for people with macular degeneration that enables them to maximize visual capacity.

ABSTRACT

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Assessment of Cortical Plasticity in the Visual System Following Macular Degeneration in Adult Humans

Contrary to long held beliefs, there is evidence that sensory maps are not immutable in the adult cerebral cortex. However, the degree to which massive changes in cortical maps indeed take place after a peripheral injury is still hotly disputed (see Smirnakis et al., Nature, 2005). We recently demonstrated that a dramatic cortical reorganization occurs in congenitally blind humans, such that the visual cortex becomes engaged in higher cognitive processes (such as verbal and memory functions; Amedi et al., Nature Neuroscience, 2003, 2004). The objective of the proposed research is to test if cortical reorganization can be observed in humans suffering from partial peripheral damage in adulthood (such as retinal degeneration), and, if so, are the changes functionally adaptive. To that end we plan to study patients suffering from macular degeneration (MD), a disease that typically obliterates foveal vision. Due to the gross over-representation of the fovea, cortical remapping should be readily observed with fMRI. Furthermore, MD patients often adopt a new retinal locus for fixation.

We will study if this preferred retinal locus is over–represented in these patients and whether this is mirrored by superior psychophysical performance in that region of visual space. If so, we will also try to establish the causal implications of such remapping by applying trans-cranial magnetic stimulation to the occipital pole, which normally elicits sensation of faint light (phosphenes) in the central visual field. The remapping hypothesis predicts that in MD patients such stimulation should lead to phosphene sensation in the periphery. Finally, we will try to assess the time course of the putative cortical changes by generating reversible central "virtual" scotomata in healthy humans wearing appropriately designed contact lenses for a week. This research project is bound to be important from both basic research and clinical perspectives. It will provide us with a better understanding of human cortical plasticity and its relationship to behavior, and it should lead to better rehabilitation strategies for people suffering from MD.

HYPOTHESIS

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Hypothesis:
Macular degeneration is typically characterized by loss of central vision in the elderly. This may result in a reorganization of posterior cortical areas mapping the central visual field. We will examine if this putative cortical plasticity is adaptive in its nature, or simply reflects bottom-up neuronal competition processes.

Goals:
To determine if cortical reorganization can be observed in humans suffering from macular degeneration (MD). Furthermore, MD patients often adopt a new retinal locus for fixation. We will study if this preferred retinal locus is over–represented in these patients and whether this is mirrored by superior psychophysical performance in that region of visual space. If we do find clear evidence of cortical reorganization, we will try to assess the time course of the putative cortical changes by generating reversible central “blind zones” in healthy humans wearing appropriately designed contact lenses for a week. This research project will provide us with a better understanding of human cortical plasticity and its relationship to behavior, and should lead to better rehabilitation strategies for people suffering from MD.

Methods:
This study employs functional magnetic resonance imaging (fMRI), as well as psychophysical techniques, to determine visual capabilities. Functional MRI allows us to map changes in metabolic activity in the brain (which is correlated with neural activity) at a millimeter resolution. It is an excellent technique to assess cortical remapping, due to the gross over-representation of the fovea (which is most affected by MD). The participants will perform various visual discrimination tasks during the scan, such as discriminating between word and non–word stimuli, presented in various positions in the visual field.

SELECTED PUBLICATIONS

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Raz N., Amir Amedi A., and Zohary E. Visual cortex activation in the blind is associated with episodic retrieval success. Cereb Cortex. 2005 Sep;15(9):1459-68.

Amedi A., Floel A., Knecht S., Zohary E., and Cohen L.G.  Transcranial magnetic stimulation to the occipital pole interferes with verbal processing in blind subjects. Nat Neurosci. 2004 Nov;7(11):1266-70.

Amedi A., Raz N., Pianka P., Malach R., and Zohary E.  Early ‘visual’ cortex activation correlates with superior verbal-memory performance in the blind.  Nat Neurosci. 2003 Jul;6(7):758-66.