Neural Mechanism of Blindsight in a Macaque Model

Some patients with damage to the primary visual cortex (V1) exhibit visuomotor ability, despite loss of visual awareness, a phenomenon termed “blindsight”. We review a series of studies conducted mainly in our laboratory on macaque monkeys with unilateral V1 lesioning to reveal the neural pathways underlying visuomotor transformation and the cognitive capabilities retained in blindsight. After lesioning, it takes several weeks for the recovery of visually guided saccades toward the lesion-affected visual field. In addition to the lateral geniculate nucleus, the pathway from the superior colliculus to the pulvinar participates in visuomotor processing in blindsight. At the cortical level, bilateral lateral intraparietal regions become critically involved in the saccade control. These results suggest that the visual circuits experience drastic changes while the monkey acquires blindsight. In these animals, analysis based on signal detection theory adapted to behavior in the “Yes–No” task indicates reduced sensitivity to visual targets, suggesting that visual awareness is impaired. Saccades become less accurate, decisions become less deliberate, and some forms of bottom-up attention are impaired. However, a variety of cognitive functions are retained such as saliency detection during free viewing, top–down attention, short-term spatial memory, and associative learning. These observations indicate that blindsight is not a low-level sensory-motor response, but the residual visual inputs can access these cognitive capabilities. Based on these results we suggest that the macaque model of blindsight replicates type II blindsight patients who experience some “feeling” of objects, which guides cognitive capabilities that we naïvely think are not possible without phenomenal consciousness

Double viral vector technology for selective manipulation of neural pathways with higher level of efficiency and safety

Pathway-selective gene delivery would be critical for future gene therapy against neuropsychiatric disorders, traumatic neuronal injuries, or neurodegenerative diseases, because the impaired functions depend on neural circuits affected by the insults. Pathway-selective gene delivery can be achieved by double viral vector techniques, which combine an injection of a retrograde transport viral vector into the projection area of the target neurons and that of an anterograde viral vector into their somas. In this study, we tested the efficiency of gene delivery with different combinations of viral vectors to the pathway extending from the ventral tegmental area (VTA) to the cortical motor regions in rats, considered to be critical in the promotion of motor recovery from neural injuries. It was found that retrograde recombinant adeno-associated virus 2-retro (rAAV2reto) combined with anterograde AAVDJ (type2/type4/type5/type8/type9/avian/bovine/caprine chimera) exhibited the highest transduction efficiency in the short term (3-6 weeks) but high toxicity in the long term (3 months). In contrast, the same rAAV2reto combined with anterograde AAV5 displayed moderate transduction efficiency in the short term but low toxicity in the long term. These data suggest that the combination of anterograde AAV5 and retrograde rAAV2retro is suitable for safe and efficient gene delivery to the VTA-cortical pathway

Contribution of the Pulvinar and Lateral Geniculate Nucleus to the Control of Visually Guided Saccades in Blindsight Monkeys

After damage to the primary visual cortex (V1), conscious vision is impaired. However, some patients can respond to visual stimuli presented in their lesion-affected visual field using residual visual pathways bypassing V1. This phenomenon is called "blindsight." Many studies have tried to identify the brain regions responsible for blindsight, and the pulvinar and/or lateral geniculate nucleus (LGN) are suggested to play key roles as the thalamic relay of visual signals. However, there are critical problems regarding these preceding studies in that subjects with different sized lesions and periods of time after lesioning were investigated; furthermore, the ability of blindsight was assessed with different measures. In this study, we used double dissociation to clarify the roles of the pulvinar and LGN by pharmacological inactivation of each region and investigated the effects in a simple task with visually guided saccades (VGSs) using monkeys with a unilateral V1 lesion, by which nearly all of the contralesional visual field was affected. Inactivating either the ipsilesional pulvinar or LGN impaired VGS toward a visual stimulus in the affected field. In contrast, inactivation of the contralesional pulvinar had no clear effect, but inactivation of the contralesional LGN impaired VGS to the intact visual field. These results suggest that the pulvinar and LGN play key roles in performing the simple VGS task after V1 lesioning, and that the visuomotor functions of blindsight monkeys were supported by plastic changes in the visual pathway involving the pulvinar, which emerged after V1 lesioning.SIGNIFICANCE STATEMENT Many studies have been devoted to understanding the mechanism of mysterious symptom called "blindsight, " in which patients with damage to the primary visual cortex (V1) can respond to visual stimuli despite loss of visual awareness. However, there is still a debate on the thalamic relay of visual signals. In this study, to pin down the issue, we tried double dissociation in the same subjects (hemi-blindsight macaque monkeys) and clarified that the lateral geniculate nucleus (LGN) plays a major role in simple visually guided saccades in the intact state, while both pulvinar and LGN critically contribute after the V1 lesioning, suggesting that plasticity in the visual pathway involving the pulvinar underlies the blindsight

Protocol for making an animal model of “blindsight” in macaque monkeys

Patients with damage to the primary visual cortex (V1) can respond correctly to visual stimuli in their lesion-affected visual field above the chance level, an ability named blindsight. Here, we present a protocol for making an animal model of blindsight in macaque monkeys. We describe the steps to perform pre-lesion training of monkeys on a visual task, followed by lesion surgery, post-lesion training, and evaluation of blindsight. This animal model can be used to investigate the source of visual awareness. For complete details on the use and execution of this protocol, please refer to Yoshida et al. (2008)1 and Takakuwa et al. (2021)

The tectum/superior colliculus as the vertebrate solution for spatial sensory integration and action

The superior colliculus, or tectum in the case of non-mammalian vertebrates, is a part of the brain that registers events in the surrounding space, often through vision and hearing, but also through electrosensation, infrared detection, and other sensory modalities in diverse vertebrate lineages. This information is used to form maps of the surrounding space and the positions of different salient stimuli in relation to the individual. The sensory maps are arranged in layers with visual input in the uppermost layer, other senses in deeper positions, and a spatially aligned motor map in the deepest layer. Here, we will review the organization and intrinsic function of the tectum/superior colliculus and the information that is processed within tectal circuits. We will also discuss tectal/superior colliculus outputs that are conveyed directly to downstream motor circuits or via the thalamus to cortical areas to control various aspects of behavior. The tectum/superior colliculus is evolutionarily conserved among all vertebrates, but tailored to the sensory specialties of each lineage, and its roles have shifted with the emergence of the cerebral cortex in mammals. We will illustrate both the conserved and divergent properties of the tectum/superior colliculus through vertebrate evolution by comparing tectal processing in lampreys belonging to the oldest group of extant vertebrates, larval zebrafish, rodents, and other vertebrates including primates

The posterior parietal cortex contributes to visuomotor processing for saccades in blindsight macaques

Patients with damage to the primary visual cortex (V1) lose visual awareness, yet retain the ability to perform visuomotor tasks, which is called "blindsight." To understand the neural mechanisms underlying this residual visuomotor function, we studied a non-human primate model of blindsight with a unilateral lesion of V1 using various oculomotor tasks. Functional brain imaging by positron emission tomography showed a significant change after V1 lesion in saccade-related visuomotor activity in the intraparietal sulcus area in the ipsi- and contralesional posterior parietal cortex. Single unit recordings in the lateral bank of the intraparietal sulcus (lbIPS) showed visual responses to targets in the contralateral visual field on both hemispheres. Injection of muscimol into the ipsi- or contralesional lbIPSs significantly impaired saccades to targets in the V1 lesion-affected visual field, differently from previous reports in intact animals. These results indicate that the bilateral lbIPSs contribute to visuomotor function in blindsight