Typical resting-state activity of the brain requires visual input during an early sensitive period.

Sensory deprivation, following a total loss of one sensory modality e.g. vision, has been demonstrated to result in compensatory plasticity. It is yet not known to which extent neural changes, e.g. higher resting-state activity in visual areas (cross-modal plasticity) as a consequence of blindness, reverse, when sight is restored. Here, we used functional MRI to acquire blood oxygen level-dependent resting-state activity during an eyes open and an eyes closed state in congenital cataract-reversal individuals, developmental cataract-reversal individuals, congenitally permanently blind individuals and sighted controls. The amplitude of low frequency fluctuation of the blood oxygen level-dependent signal-a neural marker of spontaneous brain activity during rest-was analyzed. In accordance with previous reports, in normally sighted controls we observed an increase in amplitude of low-frequency fluctuation during rest with the eyes open compared with rest with eyes closed in visual association areas and in parietal cortex but a decrease in auditory and sensorimotor regions. In congenital cataract-reversal individuals, we found an increase of the amplitude of slow blood oxygen level-dependent fluctuations in visual cortex during rest with eyes open compared with rest with eyes closed too but this increase was larger in amplitude than in normally sighted controls. In contrast, congenital cataract-reversal individuals lagged a similar increase in parietal regions and did not show the typical decrease of amplitude of low-frequency fluctuation in auditory cortex. Congenitally blind individuals displayed an overall higher amplitude in slow blood oxygen level-dependent fluctuations in visual cortex compared with sighted individuals and compared with congenital cataract-reversal individuals in the eyes closed condition. Higher amplitude of low-frequency fluctuation in visual cortex of congenital cataract-reversal individuals than in normally sighted controls during eyes open might indicate an altered excitatory-inhibitory balance of visual neural circuits. By contrast, the lower parietal increase and the missing downregulation in auditory regions suggest a reduced influence of the visual system on multisensory and the other sensory systems after restoring sight in congenitally blind individuals. These results demonstrate a crucial dependence of visual and multisensory neural system functioning on visual experience during a sensitive phase in human brain development.