Amblyopia, commonly known as "lazy eye," is a prevalent visual developmental disorder typically characterized by reduced vision in one eye. Previous research has generally suggested that visual signals from the amblyopic eye are weakened during transmission. However, the specific alterations in cortical microcircuits involved in feedforward, lateral, and feedback processing at the mesoscopic scale, as well as the mechanisms of binocular interaction, remain unclear.

On April 11, 2025, a collaborative study published in Imaging Neuroscience by researchers from the Institute of Biophysics, Chinese Academy of Sciences, and the Eye & ENT Hospital of Fudan University employed ultra-high-resolution 7 Tesla (7T) functional magnetic resonance imaging (fMRI) along with frequency-tagged electroencephalography (EEG) to reveal abnormal neural activity in the microcircuitry of the visual cortex in human patients with amblyopia.

The researchers found that in the primary visual cortex (V1) of amblyopic patients, visual signals from the amblyopic eye were significantly weakened as early as the input layer-an intracortical sublayer primarily responsible for receiving thalamic input-and that this weakened signal was subsequently transmitted forward to downstream visual areas. This suggests that the abnormalities in amblyopia originate from a very early stage of visual information input.

Furthermore, an imbalance in the lateral inhibition mechanisms between the two eyes led to a loss of signals in the superficial layers of V1. The dominant (non-amblyopic) eye exerted strong inhibitory effects on the amblyopic eye's signal transmission, while the amblyopic eye showed significantly reduced inhibition of the dominant eye.

Frequency-tagged EEG data further indicated that this imbalance in interocular inhibition was accompanied by a marked decline in the brain's ability to integrate visual information from both eyes. In addition to reduced signal amplitude, visual signals from the amblyopic eye also showed noticeably slower transmission, indicating an overall decline in visual processing efficiency.

This study is the first to characterize, with sub-millimeter spatial and millisecond temporal resolution, the microcircuit-level abnormalities in the visual cortex of amblyopic individuals. It reveals how abnormal visual experiences during critical developmental periods can shape the functional architecture of human cortical microcircuits.

The findings offer significant insights into the neural mechanisms underlying amblyopia and provide a new theoretical foundation for treatment. "Visual training aimed at enhancing the function of input-layer neurons, improving binocular information integration, and correcting imbalanced inhibition may represent new directions for future amblyopia therapy," said Prof. ZHANG.

Figure. Visual signals from the amblyopic eye are already impaired upon entering the cortex. Binocular inhibition is imbalanced, integration is weakened, and signal transmission is delayed.

(Image by ZHANG Peng's group)

Article link: https://doi.org/10.1162/imag_a_00561

Contact: ZHANG Peng

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

E-mail: zhangpeng@ibp.ac.cn

(Reported by Prof. ZHANG Peng's group)