Early-stage visual perception impairment in schizophrenia, bottom-up and back again

Abstract

Visual perception is one of the basic tools for exploring the world. However, in schizophrenia, this modality is disrupted. So far, there has been no clear answer as to whether the disruption occurs primarily within the brain or in the precortical areas of visual perception (the retina, visual pathways, and lateral geniculate nucleus [LGN]). A web-based comprehensive search of peer-reviewed journals was conducted based on various keyword combinations including schizophrenia, saliency, visual cognition, visual pathways, retina, and LGN. Articles were chosen with respect to topic relevance. Searched databases included Google Scholar, PubMed, and Web of Science. This review describes the precortical circuit and the key changes in biochemistry and pathophysiology that affect the creation and characteristics of the retinal signal as well as its subsequent modulation and processing in other parts of this circuit. Changes in the characteristics of the signal and the misinterpretation of visual stimuli associated with them may, as a result, contribute to the development of schizophrenic disease.

Fig. 1. Retinal layers.

The composition of the individual layers of the retina in the area of the optic nerve. NFL nerve fiber layer, GCL ganglion cell layer, IPL inner plexiform layer, INL inner nuclear layer, OPL outer plexiform layer, ONL outer nuclear layer, ELM external limiting membrane, IS/OS rod and cone inner and outer segments, RPS retinal pigment epithelium. Redrawn from retinareference.com.

Fig. 2. Schema of ERG signal from retinal cells.

An illustration of the retina (left) and a representative ERG comparing HCs and schizophrenia patients (right). In the dark-adapted retina, a light stimulus elicits a presynaptic response from photoreceptor cells, represented by the downward-deflecting a-wave. The subsequent postsynaptic response, mediated largely by bipolar and Müller cells, produces the b-wave. The a-wave amplitude (measured from the baseline to the trough of the a-wave) depends on the intensity of the light stimulus and the integrity of the photoreceptors. The b-wave amplitude (measured from the trough of the a-wave to the peak of the b-wave) depends on the a-wave and the integrity of signal transmission within the retina. Redrawn from Hanjin Deivasse web illustration.

Fig. 3. Distribution of DA receptors in retinal cells.

Schematic of the retinal circuitry with cell types expressing specific DA receptors in the retina. The DA receptors D₁R, D₂R, and D₄R and D₂ autoreceptors localized on various cell types are indicated in purple, green, yellow, and red. The dopaminergic amacrine cells (DACs; orange) stratify primarily in the outermost layers of the IPL and send axon-like dendritic projections to cone terminals in the OPL and to the inner layers of the IPL, where they contact AII amacrine cells (ACs). Synaptic excitation and inhibition are illustrated by arrows and bar-line (green). Gap-junctions are shown as sawtooth symbols. The two concentric circles at the top represent OFF-center and ON-center RGCs, which respond oppositely to light in the center and surroundings of their receptive fields. DAC: aopaminergic amacrine cell, HC horizontal cell, RBC rod bipolar cell, CBC cone bipolar cell, AC amacrine cell, RGC retinal ganglion cell, ipRGC intrinsically photosensitive RGC. Redrawn from Roy & Fieldl.

Fig. 4. Structure of the LGN with three distinct layers.

Simplified diagram of visual thalamic circuitry and the LGN. A Diagram of feedforward and feedback inhibitory pathways that influence LGN RCs. Excitatory inputs are indicated in purple. Inhibitory inputs are indicated in black. TRN: thalamic reticular nucleus; LGN lateral geniculate nucleus; Int LGN interneuron. Modified from Casagrande & Xu. B LGN diagram with ganglion cells type. RGCs retinal ganglion cells. Redrawn from Kim et al..

Fig. 5. Visual pathways and brain streams.

A The ventral (purple) and dorsal (yellow) streams of visual information processing. B A detailed scheme of signal distribution from PC, MC, and KC visual pathways to the LGN and further to the primary (V1) and secondary (V2) visual cortex and subsequently to the dorsal or ventral stream. Redrawn from Casagrande & Xu.

Fig. 6. Aberrant signal propagation and subsequent physiological changes.

This simplified scheme illustrates the hypothesis of the early spread of an aberrant signal within the visual circuit and the physiological changes associated with it. 1 In the early stages of the disease, an aberrant signal is formed on the retina and further propagates within the precortical and cortical visual circuit. 2a/b The first areas that are likely to fail to adapt to the unstable signal and where there is GMV thinning are the thalamus and areas of the frontal lobe. 3a/b From there, the pathophysiological changes spread into the lower visual processing areas (4 and 5). SPL superior parietal lobule, IPL inferior parietal lobule, V5/MT middle temporal visual area, IT inferior temporal cortex, V4 visual area 4, V2 secondary visual cortex, LGN lateral geniculate nucleus.