Incomplete Cortical Reorganization in Macular Degeneration

Macular degeneration (MD) is an eye condition that affects the fovea and perifoveal retina, resulting in a loss of central vision. Age-related macular degeneration (AMD) is the leading cause of legal blindness and low vision in the United States and one of the most common causes of legal blindness and low vision globally.1 Juvenile macular degeneration (JMD), primarily Stargardt's disease, is a different type of MD that affects children or young adults. Central vision has the highest spatial resolution and is vital for many aspects of visual function such as reading. Early visual cortex contains a retinotopic map in which the central visual field is highly magnified with respect to the peripheral field. Approximately 50% of the primary visual cortex (V1) is devoted to the central 15° of the visual field.2,3 People with advanced AMD often develop bilateral, dense central scotomas subtending 10° to 15° (see Ref. 4 for review). In the absence of any retinotopic reorganization, a 15° bilateral central scotoma would result in no visual responses in the posterior half of V1. Recent fMRI studies have claimed reorganization of visual processing in persons with loss of foveal vision from MD; however, the extent and mechanisms of the reorganization remain unclear.5–10 Further complicating the picture, it has been shown that the activity seen in the lesion projection zone (LPZ) is task dependent,7 and at least some aspects of the cortical system plasticity decrease with aging.11 In this article, reorganization of visual cortex refers to the pattern of cortical responses measured with fMRI in patients with macular degeneration that differs from the expected loss of response in the cortical projection from the retinal scotoma. We consider such changed cortical activity as evidence for functional reorganization, without necessarily implying anatomic changes in cortical structure. For instance, the changed activation patterns observable with fMRI might be due to modification of synaptic connection strength or unmasking of existing signals when bottom-up input is no longer present.12 Our experiments were designed to address three unresolved issues related to cortical reorganization in MD. First, patients with macular degeneration usually adopt a spared location in nonfoveal retina for fixation, called the preferred retinal locus (PRL).4,13 The PRL assumes the role of the former fovea as an oculomotor reference point and may adopt some of the fovea's functional characteristics. Evidence from Schumacher et al.9 supports the view that there is more extensive cortical representation of PRL compared with non-PRL locations, including extension of activation toward the LPZ. In contrast, Dilks et al.8 found similar activation for stimuli at the PRL and comparable non-PRL locations. The discrepant results might be due to differences in task design and methods of data analysis. In our study, we compared cortical responses when a small flickering checkerboard was presented either at the PRL or at another functioning retinal location with comparable eccentricity. Second is the influence on cortical reorganization of the age of onset and the etiology of MD. In previous studies, often only one type of MD was investigated. In our study, we were able to compare cortical reorganization in AMD and JMD subjects by testing groups of comparable size and similar visual function characteristics using the same protocols. Third, task demands and stimulus properties have varied across previous studies. Sometimes, the visual stimuli were meaningful objects5,6,8 and sometimes meaningless patterns.9,10 Sometimes, the subjects actively responded to the stimuli,5 and sometimes viewing was passive.10 Sometimes the stimuli were spatially localized5 and sometimes full field.7 We tested our subjects with separate tasks designed to compare cortical responses during passive and active viewing, similar to the Masuda et al.7 study of JMD subjects. A preview of our results is as follows: Cortical activation with a small stimulus at the PRL was more extensive than at a non-PRL location; full-field stimuli in both passive and active conditions left a silent zone in the posterior pole of the occipital cortex, implying a lack of complete reorganization; the extent of the silent zone was smaller in the active task than the passive task, implying an important role for feedback signals in functional reorganization in the visual system; evidence for functional reorganization was more robust in JMD than AMD subjects.