Investigation of Subcortical Deficits in Unilateral Adult Amblyopia by fMRI

Purpose: This study used functional magnetic resonance imaging (fMRI) to investigate layer-specific deficits in the retino-geniculo-striate pathway and functional alterations in the retino-tectal pathway in adult unilateral amblyopia. Methods: Sixteen adult patients (mean age ± SD = 28.4 ± 5.2 years; 9 men and 7 women) with unilateral amblyopia and 12 matched healthy controls (mean age ± SD = 27.1 ± 4.8 years; 7 men and 5 women) underwent 3T fMRI scanning. The lateral geniculate nucleus (LGN) and superior colliculus (SC) were chosen as regions of interest (ROIs) to assess functional status. Responses of the M and P layers were analyzed with general linear models, and stimulus-specific beta values were extracted for quantitative comparison. Results: A significant interaction between stimulus type and subject group was observed in the LGN P layer but not in the M layer. The P-layer responses to P stimuli were significantly reduced in amblyopic eyes, whereas M responses remained relatively preserved, this reduction may partly reflect reduced effective contrast in the amblyopic eye, and input-level factors cannot be fully excluded. In the SC, fellow eyes showed decreased M responses and a shift toward P-preference, whereas no clear deficits were observed in amblyopic eyes. Moreover, MT responses in both amblyopic and fellow eyes were significantly reduced compared with healthy controls, suggesting broader cortical involvement. However, V1 and V2 responses showed no significant reduction, indicating relatively intact early visual cortex activation. Conclusions: An fMRI allowed noninvasive segregation of M and P divisions in the LGN of amblyopic adults. Under the current stimulus conditions, amblyopic eyes showed a predominant reduction in LGN responses, whereas fellow eyes exhibited M-function loss and P-preference shift in the SC. Reduced MT responses in both eyes may arise from abnormal binocular integration mechanisms rather than primary dysfunction in V1 or the M pathway. These findings suggest pathway-selective alterations in subcortical visual structures, although contributions from interocular differences in contrast sensitivity warrant further investigation.