Javitt Daniel C
Division of Experimental Therapeutics, Columbia University Medical Center, New York, NY, USA.
Schizophrenia Research Division, Nathan Kline Institute, Orangeburg, NY, USA.
Curr Top Behav Neurosci. 2025;74:1-40. doi: 10.1007/7854_2025_582.
Schizophrenia is a severe mental disorder and a leading cause of global disability. Increasing evidence ties impairments in both auditory and visual perceptual processing to impaired functional outcomes. In the auditory system, deficits are observed in the ability to process changes in tonality, leading to deficits in the detection of nonverbal aspects of auditory communication, including emotion and sarcasm. In the auditory sytem, these deficits are indexed by impaired generation of mismatch negativity (MMN), which has become a widely utilized index of auditory perceptual dysfunction. In the visual system, deficits are especially observed in functions related to the magnocellular visual pathway, which projects preferentially to the dorsal visual stream. Dorsal stream dysfunction, in turn, contributes to impairments in processes such as fragmented object recognition, face emotion recognition, and social cognition. Indices of visual perceptual dysfunction include visual P1 responses to magnocellular-biased stimuli, as well as fMRI activation levels within the dorsal and ventral streams. Perceptual level deficits are tied most directly to impaired function of N-methyl-D-aspartate glutamate receptors (NMDAR) and thus may serve both as pathophysiologically based nosological biomarkers and as targets for neuromodulatory and pharmacological treatment development.
精神分裂症是一种严重的精神障碍，也是导致全球残疾的主要原因。越来越多的证据表明，听觉和视觉感知处理方面的损伤与功能预后受损有关。在听觉系统中，人们观察到处理音调变化的能力存在缺陷，这导致在检测听觉交流的非语言方面（包括情感和讽刺）时出现缺陷。在听觉系统中，这些缺陷通过失匹配负波（MMN）产生受损来表征，MMN已成为广泛使用的听觉感知功能障碍指标。在视觉系统中，尤其在与大细胞视觉通路相关的功能中观察到缺陷，该通路优先投射到背侧视觉流。反过来，背侧流功能障碍会导致诸如碎片化物体识别、面部表情识别和社会认知等过程受损。视觉感知功能障碍的指标包括对大细胞偏向刺激的视觉P1反应，以及背侧和腹侧流内的功能磁共振成像激活水平。感知水平的缺陷与N-甲基-D-天冬氨酸谷氨酸受体（NMDAR）的功能受损最为直接相关，因此既可以作为基于病理生理学的疾病生物标志物，也可以作为神经调节和药物治疗开发的靶点。
