An fMRI Study of Word-Level Recognition and Processing in Patients with Age-Related Macular Degeneration

PURPOSE. To compare the cortical networks that underlie word recognition and processing in patients with age-related macular degeneration (AMD) with those of normally sighted control subjects using functional magnetic resonance imaging (fMRI). METHODS. Six patients with bilateral geographic atrophy who were using an eccentrically located preferred retinal location were recruited. Six younger and six older control subjects were also recruited. Patients and control subjects were asked to perform a three-letter (3Let) and a six-letter (6Let) word recognition task during fMRI on a 3.0-Tesla MRI scanner. The fMRI tasks were two-condition, blocked-design paradigms in which central fixation was alternated with a word recognition task requiring a forced, two-choice reaction time living/nonliving judgment. RESULTS. When contrasted with controls, patients showed increased brain activation in a widespread cortical network that included regions identified as the frontal eye fields, both superior and inferior parietal lobules, and regions within the prefrontal cortex. Peak activation within these prefrontal regions was correlated with increased accuracy (r = 0.875, P = 0.024; r = 0.848, P = 0.033) and decreased reaction times (r = -0.861, P = 0.028; r = -0.842, P = 0.036) for the 3Let task within the group of patients. Correlations between peak activity and behavioral performance were also found in both the right (-0.818, P = 0.047) and left (r = -0.839, P = 0.037) superior parietal lobules for the 3Let task. Similar relationships were found for the 6Let task. CONCLUSIONS. Patients with AMD demonstrate increased prefrontal and parietal activation compared with controls. The authors posit that these increases reflect increased top-down involvement in basic word recognition to compensate for decreased sensory function. ( Invest Ophthalmol Vis Sci. 2009;50:4487-4495) DOI:10.1167/iovs.08-2258